Search

Introduction: Data about impact of switch to dolutegravir (DTG)-based antiretroviral therapy (ART) on estimated glomerular filtration rate (eGFR) in Asians are scarce. RV254/SEARCH010 is a prospective observational cohort in Bangkok, Thailand with ART initiation during acute HIV infection (AHI) where participants switched to DTG-based ART. Methods: Participants started Efavirenz (EFV)-based ART during AHI (n = 214) and switched to DTG-based ART after a median of 97 weeks (IQR 61–145). GFR was estimated by serum creatinine (eGFRcre) every 24 weeks before and after switch. Estimated GFR by cystatin C (eGFRcystC) was ordered at clinician's discretion for decreased eGFRcre after switch. Random-effect linear regression model was used to assess changes in eGFRcre over 96 weeks from starting ART, and from switching to DTG. Results: At study entry, 20 participants (9.3%) had eGFRcre < 90 ml/min/1.73 m2. During EFV-based ART, an additional 17 (8%) developed eGFRcre < 90 ml/min/1.73 m2, nearly all transient, while mean eGFRcre remained stable and within normal range. At switch to DTG, 21 (9.8%) had eGFRcre < 90 ml/min/1.73 m2 but an additional 116 (54%) developed eGFRcre < 90 ml/min/1.73 m2 during follow-up with eGFRcre decrease being mostly persistent. Mean eGFRcre decreased 20.8% from 117.0 to 92.4 ml/min/1.73 m2 (p < 0.001). Among 20 post-switch participants with eGFRcystC measured within 4 weeks of eGFRcre < 90 mL/min/1.73 m2, 13 (65%) had normal kidney function by eGFRcystC. Conclusions: Persistent eGFRcre decrease to < 90 ml/min/1.73 m2 after switch to DTG was common in this Thai population. eGFRcystC was helpful to identify individuals with clinically significant decrease in kidney function and obviate unnecessary ART modifications. Trial registration Clinical Trials Registry Number: ClininicalTrials.gov NCT00796146. [ABSTRACT FROM AUTHOR]

Background: Lithium is extensively used for mood stabilization in bipolar disorder, but its long-term use can lead to nephrotoxicity, characterized by a reduction in glomerular filtration rate (GFR) and potential progression to end-stage renal disease (ESRD). Exercise has been shown to have protective effects on renal function, yet the impact of varying exercise intensities on lithium-induced nephropathy is not well understood. Aim: This study aimed to investigate the effects of different intensities of endurance training on kidney function and inflammation in a rat model of lithium-induced nephropathy, focusing on the expression of aquaporin 2 (AQP2), glycogen synthase kinase 3-beta (GSK-3β), and SIRT1. Methods: Thirty-five male Wistar rats were divided into five groups: control, lithium-only, lithium with low-intensity exercise (LIT), lithium with medium-intensity exercise (MIT), and lithium with high-intensity exercise (HIT). The lithium-induced nephropathy model was established by administering lithium in food. Exercise groups underwent treadmill training at specified intensities for eight weeks. Fractional excretion of sodium (FENa) was measured, and GFR was evaluated by Cr clearance. ELISA and Western blotting assessed inflammatory markers (TNF-α, IL-10), SIRT1, GSK-3β, and AQP2 expressions in kidney tissues. Results: Lithium significantly reduced Cr clearance and increased FENa compared to controls. All exercise intensities improved Cr clearance and reduced FENa, with HIT showing the most significant improvement. Exercise at all intensities reduced TNF-α levels and increased IL-10 levels, with MIT and HIT significantly enhancing SIRT1 levels. Lithium reduced the expression of GSK-3β and AQP2, whereas exercise increased their expression across all intensities. Conclusion: Endurance training, particularly at high intensity, significantly mitigates lithium-induced renal impairment by improving GFR, reducing inflammation, and enhancing the expression of renal protective proteins. These findings suggest that tailored exercise regimens could be beneficial for patients undergoing long-term lithium therapy to prevent renal damage. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association between hypomagnesemia and dynapenia in older women with different nutritional status. Methods: This cross-sectional study included older women who attended one outpatient geriatric clinic. Undernutrition was defined according to the Mini Nutritional Assessment score (MNA) (< 23,5), and handgrip strength of < 16 kg on dynamometer was defined as dynapenia. The association between hypomagnesemia (serum magnesium < 1.7 mg/dL) and dynapenia was determined by logistic regression analysis. Results: Among the 933 older women (mean age 81 ± 8), the prevalences of undernutrition and hypomagnesemia were 61% and 15%, respectively. The risk of hypomagnesemia increased with each step of decline in nutritional status, and undernutrition was associated with hypomagnesemia (OR 1.64, 95% CI 1.11–2.43, p = 0.013) In the entire cohort, hypomagnesemia was associated with dynapenia (OR 2.01, 95% CI 1.35-3.00, p = 0.001). In well-nourished patients, hypomagnesemia was not associated with dynapenia, even when unadjusted. However, in the undernourished group, hypomagnesemia was associated with dynapenia after adjusting for age, diabetes mellitus, hypertension, coronary heart disease, Barthel and Lawton scores, polypharmacy, glomerular filtration rate, serum albumin, hemoglobin, and MNA score (OR 2.95, 95% CI 1.04–8.32, p = 0.040). The coexistence of hypomagnesemia and undernutrition (versus neither of them) was significantly associated with dynapenia (OR 4.44, 95% CI 2.67–7.41, p < 0.001). Conclusion: The prevalence of hypomagnesemia increases with worsening nutritional status. Hypomagnesemia is associated with dynapenia in older women who are undernourished, even after adjusting for nutritional status, but not in those who are well nourished. The coexistence of undernutrition and hypomagnesemia increase the risk of dynapenia substantially. Highligths: The prevalence of hypomagnesemia increases with worsening of nutritional status. The relationship between hypomagnesemia and dynapenia varies according to nutritional status; hypomagnesemia is associated with an increased risk of dynapenia in undernourished patients but not in their well-nourished counterparts. In the presence of malnutrition, the level of magnesium should also be assessed, and both malnutrition and hypomagnesemia should be treated. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is defined by a sharp decrease in the estimated glomerular filtration rate (eGFR). However, the impact of medication history on the survival of AKI patients has received little attention. Hence, it is necessary to investigate the potential of medication history as a predictor of survival outcomes among AKI patients in the intensive care unit (ICU). Methods: Critically ill AKI patients were sourced from the MIMIC-IV database. To ascertain significant, drug-related, independent predictors of survival, univariate Cox analysis and stepwise Cox regression were performed. Based on the identified predictor, a nomogram was developed to estimate the individualized survival probability for AKI patients. Additionally, to address potential confounders among patients with medications referenced in the nomogram, a propensity score matching procedure was applied. Ultimately, a comparative analysis was performed to elucidate the prognostic disparities among these patient subgroups. Results: This study enrolled 1,208 patients and developed a nomogram incorporating oxygen flow rate, respiratory frequency, continuous venovenous hemodiafiltration status, age, and medication use (including ibuprofen, epinephrine, cefazolin, warfarin, and vasopressin). The predictive model demonstrated diagnostic accuracy, with AUC values for 1-year, 3-year, and 5-year survival among AKI patients of 0.827, 0.799, and 0.777 in the training dataset, and 0.760, 0.743, and 0.740 in the internal validation dataset, respectively. Kaplan–Meier survival analyses revealed significant differences in survival outcomes among AKI patients based on their exposure to different medications. Conclusions: In summary, the developed prediction model demonstrated accuracy for AKI patients in the ICU and helped clinical decision-making. However, future studies will require external validation to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: To describe the clinical characteristics, comorbidity, and medical treatment in a primary care population with chronic kidney disease (CKD). Additionally, to investigate how primary care physicians (PCPs) diagnose, manage and treat impaired kidney function, including uptake of cardio-renoprotective renin–angiotensin–aldosterone system inhibitors (RAASis) and sodium glucose co-transporter 2 inhibitors (SGLT2is). Design: An observational study of CKD prevalence, treatment patterns and comorbidities in primary care based on patient record data combined with a questionnaire on diagnosis, management and treatment of impaired kidney function in a real-world, primary care setting. Setting: In all 128 primary care clinics in Denmark of 211 randomly invited and a quetionnaire completed by 125/128 participating PCPs. Methods: A computerized selection identified 12 random individuals with CKD per clinic with ≥ 2 measurements of eGFR < 60 mL/min/1.73 m2 or UACR > 30 mg/g within two years (N = 1 497). Pre-specified data collected from individual electronic health records included demographics, clinical variables, comorbidities, and relevant prescribed medications. Results: Of the CKD study population (N = 1 497), 80% had hypertension, 32% diabetes (DM), 13% heart failure (HF), 59% no DM/HF. ACEis/ARBs were prescribed to 65%, statins to 56%, SGTL2is to 14%, and MRAs to 8% of all individuals. Treatment patterns differed between individuals with varying comorbidities, e.g., ACEis/ARBs usage was higher in DM (76%) or HF (74%) vs. no DM/HF (58%), as was statin usage (76% in DM vs. 45% in no DM/HF). SGTL2i usage in no DM/HF was low. Most PCPs identified CKD using eGFR < 60 mL/min/1.73 m2 (62%) or UACR > 30 mg/g (58%) and 62% reported initiating treatment to retard kidney function decline. Conclusions: Despite good PCP awareness and wish to use relevant guidelines, a gap exists in implementation of cardio-renoprotective treatment, especially in individuals without DM/HF. This offers an opportunity for clear recommendations to PCPs to optimize early cardio-renal protection in individuals with CKD. [ABSTRACT FROM AUTHOR]

Objective and background: Hyperspectral imaging (HSI) is an innovative, noninvasive technique that assesses tissue and organ perfusion and oxygenation. This study aimed to evaluate HSI as a predictive tool for early postoperative graft function and long-term outcomes in living donor (LD) and deceased donor (DD) kidney transplantation (KT). Patients and methods: HSI of kidney allograft parenchyma from 19 LD and 51 DD kidneys was obtained intraoperatively 15 minutes after reperfusion. Using the dedicated HSI TIVITA Tissue System, indices of tissue oxygenation (StO2), perfusion (near-infrared [NIR]), organ hemoglobin (OHI), and tissue water (TWI) were calculated and then analyzed retrospectively. Results: LD kidneys had superior intraoperative HSI values of StO2 (0.78 ± 0.13 versus 0.63 ± 0.24; P = 0.001) and NIR (0.67 ± 0.10 versus 0.56 ± 0.27; P = 0.016) compared to DD kidneys. Delayed graft function (DGF) was observed in 18 cases (26%), in which intraoperative HSI showed significantly lower values of StO2 (0.78 ± 0.07 versus 0.35 ± 0.21; P < 0.001) and NIR (0.67 ± 0.11 versus 0.34 ± 0.32; P < 0.001). Receiver operating characteristic curve analysis demonstrated an excellent predictive value of HSI for the development of DGF, with an area under the curve of 0.967 for StO2 and 0.801 for NIR. Kidney grafts with low StO2 values (cut-off point 0.6) showed reduced renal function with a low glomerular filtration rate and elevated urea levels in the first two weeks after KT. Three years after KT, graft survival was also inferior in the group with initially low StO2 values. Conclusion: HSI is a useful tool for predicting DGF in living and deceased KT and may assist in estimating short-term allograft function. However, further studies with expanded cohorts are needed to evaluate the association between HSI and long-term graft outcomes. [ABSTRACT FROM AUTHOR]

Background: To explore the prevalence of hyperuricemia and its associated factors in uremic patients undergoing maintenance hemodialysis (MHD). Methods: Two hundred two uremic patients undergoing MHD for ≥ 3 months, in Jinshan Hospital, Fudan University, were enrolled. Pre-dialysis blood samples were tested during March 1st, 2023 to April 30th, 2023. Demographic characteristics were recorded. The prevalence of hyperuricemia, defined as serum uric acid (SUA) ≥ 420 μmol/L, was investigated. Individuals were divided into hyperuricemia (HUA) and non-hyperuricemia (n-HUA) groups. The demographic characteristics, residual kidney function, nutritional status, acid–base metabolism, electrolyte and lipid metabolism were compared between groups. The associated factors for hyperuricemia in MHD patients were identified by logistic regression. Results: The median SUA level of the enrolled patients was 458.50 (392.25, 510.75) μmol/L. 134 (66.34%) candidates met the diagnostic criteria of hyperuricemia. The median SUA level in HUA group was 491.00 (459.50, 543.50) μmol/L. Compared to those in n-HUA group, subjects in HUA group showed lower estimated glomerular filtration rate and blood CO2 level, but higher levels of body mass index, geriatric nutritional risk index, plasma phosphate, potassium, pre-albumin, albumin, serum creatinine (Scr) and urea nitrogen. Logistic regression indicated that Scr (OR 1.002, 95% CI 1.001–1.004, P = 0.003), albumin (OR 1.165, 95%CI 1.011–1.342, P = 0.035), and blood potassium (OR 1.673, 95% CI 1.009–2.773, P = 0.046) were associated factors for hyperuricemia in uremic patients undergoing MHD. Conclusion: Hyperuricemia was highly prevalent among uremic MHD patients. Elevated levels of Scr, albumin and plasma potassium were independent associated factors for hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Creatinine-based estimated glomerular filtration rate (eGFR) equations are widely used in clinical practice but exhibit inherent limitations. On the other side, measuring GFR is time consuming and not available in routine clinical practice. We developed and validated machine learning models to assess the trustworthiness (i.e. the ability of equations to estimate measured GFR (mGFR) within 10%, 20% or 30%) of the European Kidney Function Consortium (EKFC) equation at the individual level. Methods: This observational study used data from European and US cohorts, comprising 22,343 participants of all ages with available mGFR results. Four machine learning and two traditional logistic regression models were trained on a cohort of 9,202 participants to predict the likelihood of the EKFC creatinine-derived eGFR falling within 30% (p30), 20% (p20) or 10% (p10) of the mGFR value. The algorithms were internally and then externally validated on cohorts of respectively 3,034 and 10,107 participants. The predictors included in the models were creatinine, age, sex, height, weight, and EKFC. Results: The random forest model was the most robust model. In the external validation cohort, the model achieved an area under the curve of 0.675 (95%CI 0.660;0.690) and an accuracy of 0.716 (95%CI 0.707;0.725) for the P30 criterion. Sensitivity was 0.756 (95%CI 0.747;0.765) and specificity was 0.485 (95%CI 0.460; 0.511) at the 80% probability level that EKFC falls within 30% of mGFR. At the population level, the PPV of this machine learning model was 89.5%, higher than the EKFC P30 of 85.2%. A free web-application was developed to allow the physician to assess the trustworthiness of EKFC at the individual level. Conclusions: A strategy using machine learning model marginally improves the trustworthiness of GFR estimation at the population level. An additional value of this approach lies in its ability to provide assessments at the individual level. [ABSTRACT FROM AUTHOR]

Background: Limited studies have explored the relationship between estimated Glomerular Filtration Rate(eGFR) and in-hospital mortality(IHM) in low-income sub-Saharan African countries. This study aimed to explores this association, offering insights into its impact in resource-limited settings. Methods and results: We retrospectively included 226 patients(age 45.35 ± 18.85yrs, 54.4% women) admitted to Naguru-referral hospital between January 1st and June 30th, 2024. Baseline demographics and clinical variables, including eGFR, were recorded at admission. Patients were followed from date of admission to discharge and primary outcome was IHM. Multivariable Hazard regression analysis assessed the association between eGFR and IHM, respectively. During follow-up, 45(19.9%) of patients died. Per-standard deviation(SD) increase in eGFR(48.60 mL/min/1.73m2) was associated with Hazard Ratio(HR) of 0.46[95%CI: 0.282–0.759, p = 0.002, β = -0.77] for IHM in fully adjusted models. When stratified by eGFR quartiles, using highest quartile(≥ 120 mL/min/1.73m2) as reference, HR was 1.08[95%CI: 0.276–4.226, p = 0.912, β = + 0.08] for 99.0–120 mL/min/1.73m2; 4.08[95%CI: 1.284–12.954, p = 0.017, β = + 1.41] for 66.8–99.0 mL/min/1.73m2, and 4.08[95%CI: 1.284–12.954, p = 0.037, β = + 1.25] for < 66.8 mL/min/1.73m2. Among age stratification-subgroups: age < 40yrs: 0.93[95%CI: 0.89–0.97, p < 0.001, β = -0.07]; 40-60yrs: 0.98[95%CI: 0.966–0.999, p = 0.039, β = -0.02]; ≥ 60yrs, p < 0.005 with p-value-interaction for age = 0.046; and HIV-positive: 0.94[95%CI: 0.905–0.974, p < 0.001, β = -0.06] with p-value-interaction = 0.021. Significant Pearsons-correlation(r) was observed only in: [< 40yrs, HIV(-)] with p = 0.016, r = -0.275; [40-60yrs, HIV(+)] with p = 0.020, r = -0.397; and [≥ 60yrs,HIV(+)] with p = 0.003, r = -0.997. Conclusions: We report that eGFR was associated with in-hospital mortality, with a stronger association observed in HIV-negative patients(< 40yrs) and HIV-positive patients (aged ≥ 60yrs yrs). Further research is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study. Methods: Data from 18,694 subjects were analyzed from Uric acid Right foR heArt Healt (URRAH) database. The study evaluated the association between TG/HDL-C ratio and SUA/GFR ratio, as well as their impact on the development of outcomes during the follow-up study period. The primary endpoint was CV mortality. Results: After a mean follow-up of 124 ± 64 months, 2,665 (14.2%) CV deaths occurred. The incidence of fatal and non-fatal CV events increased in parallel with the increase of TG/HDL-C quintiles. TG/HDL-C ratio showed a positive association with increasing of SUA/GFR ratio, even in non-diabetic patients. Multivariate analysis showed that the TG/HDL-C ratio increases the mortality risk even after adjustment for potential confounding factors. Finally, IR and GFR-adjusted hyperuricemia showed an additive effect on CV mortality. Conclusions: Both IR and SUA/GFR ratio independently predict CV mortality, regardless of age, gender, BMI, diabetes, hypertension and statin use. The joint effect of the TG/HDL-C ratio and the elevated SUA/GFR ratio was greater than the presence of each single risk factor on CV mortality. This highlights the importance of monitoring these markers to better assess cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: The standard treatment for periprosthetic joint infections (PJI) typically involves a two-stage resection arthroplasty using antibiotic-loaded bone cement (ALBC) spacers. This study hypothesizes that there is no significant correlation between antibiotic levels in blood and synovial fluid and the patient's kidney function, and that the success rates of staged resection arthroplasty are comparable between groups, specifically targeting gram-positive bacterial infections. Methods: This retrospective review included patients treated from 2017 to 2022 with two-stage arthroplasty using vancomycin-loaded ALBC spacers, selectively targeting gram-positive infections. Patients with non-gram-positive infections or those with allergies or treatments affecting serum antibiotic levels were excluded. The study assessed comorbidities, renal function, specifics of the spacers, and vancomycin concentrations in joint fluid and blood. Results: Among 62 PJI cases analyzed (22 hips and 40 knees), 34 patients (54.8%) had renal insufficiency (RI), associated with significantly lower albumin (2.64 g/dL vs. 3.43 g/dL, p < 0.05) and estimated glomerular filtration rate (eGFR) (58.17 mL/min/1.73 m² vs. 121.74 mL/min/1.73 m², p < 0.05). No significant differences were found in comorbidities, antibiotic regimen, or the weight of the ALBC spacers between the groups (p > 0.05). Both groups exhibited high vancomycin levels in joint fluid, with peak blood vancomycin levels inversely correlated with eGFR (coefficient − 3.612, 95% CI -8.543 to -2.753, p < 0.001). RI patients displayed higher peak blood vancomycin levels (1.23–5.43 mg/L) but remained below toxicity thresholds. The infection-free interval, aseptic revision rates, and bacterial profiles specific to gram-positive species showed no significant differences between the groups. Conclusion: Systemic absorption of vancomycin from ALBC spacers was evident in patients with RI and inversely correlated with eGFR, yet remained well below toxic thresholds across all patients. These findings suggest that the use of vancomycin-loaded ALBC spacers appears to be safe for managing gram-positive infections in patients with varying renal function. Additionally, renal insufficiency did not adversely affect the infection-free interval, aseptic revision rates, or bacterial diversity. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Background: A number of UK transplantation centres use isotope studies to estimate the relative contribution from each kidney in living kidney donor assessment. The evidence that the estimation of pre-donation split function of the non-donated kidney influences post-donation renal recovery is limited. The aim of this study was to analyse whether, in the context of other donor factors, the split function of the non-donated kidney predicts the percentage recovery of glomerular filtration rate (GFR) at one-year post-donation. Methodology: A retrospective cohort analysis was undertaken on 291 living kidney donors in the Glasgow Renal and Transplant Unit between 1st January 2011 and 1st June 2022. Univariable and multivariable linear regression analysis was used to analyse the impact of donor factors on recovery of renal function at one year relative to baseline isotope GFR (iGFR) or to estimated GFR (eGFR by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula). Sub-analyses of donor outcome (% recovery of iGFR and eGFR at one year) were undertaken using single-measures ANOVA and grouping of donors by pre-donation isotope uptake of the non-donated kidney. Results: Median recovery of pre-donation GFR at 1 year was 70.0% (IQR 64.8-75.5). On linear regression analysis there was no significant association found between split function of the non-donated kidney and the percentage recovery of iGFR, although a small significant association was found for eGFR. There was no significant difference between mean iGFR or eGFR recovery on sub-analysis of donor outcomes. Conclusions: This study demonstrated no clinically important predictive relationship between percentage recovery of renal function at 1 year after living kidney donation and pre-donation split function within the range accepted for donation in our centre. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and is an important cause of chronic kidney disease (CKD) and kidney failure. Outcomes are heterogeneous, and accurate risk stratification is important to identify the highest risk individuals for treatment and to help prevent disease progression. The Oxford classification (OC) is an internationally adopted standard for renal biopsy reporting in IgAN, which measures the degree of histological abnormalities and predicts prognosis. The kidney failure risk equation (KFRE) was developed to predict kidney failure in all causes of CKD and has been shown to be highly accurate across diverse etiologies. This review aimed to compare the KFRE with formulae incorporating the OC in accurately determining the risk of kidney failure in IgAN. Methods: A systematic review was conducted in accordance with the Cochrane library guidelines and PRISMA statement for reporting of systematic reviews. Studies comparing the accuracy of the KFRE with the OC in predicting disease progression and kidney failure in IgAN were evaluated. The search strategy and analysis were performed independently by two reviewers. Studies that were eligible for inclusion compared the KFRE with any tool incorporating the OC in a cohort of individuals with IgAN. Eligible outcomes were reduction of estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD), and prognostic tools were required to assess the accuracy of these formulae by discrimination and/or calibration. Results: After searching several databases, only one study was eligible for inclusion in the review. This study of 2300 Chinese individuals with IgAN had a median follow-up of 2.5 years. Two-hundred eighty-eight individuals had a composite outcome of 50% decline in eGFR or ESRD, and 214 individuals developed ESRD. Both the KFRE and the IgAN Risk Prediction (IRP) tool (incorporating the OC) were highly accurate at predicting ESRD with a C-statistic of 0.90 and 0.91, respectively. Subgroup analysis demonstrated improved performance of IRP over KFRE in discrimination for individuals with preserved eGFR (> 60 ml/min/1.73 m2) at baseline. The risk of bias was high due to insufficient follow-up and handling of missing data, so overall confidence in findings is very low. Conclusion: There is currently insufficient evidence to compare the accuracy of the KFRE and OC in determining outcomes in IgAN. Further research is required in this field. Systematic review registration: PROSPERO CRD42022364569. [ABSTRACT FROM AUTHOR]

Background: The factors influencing diffuse crescentic glomerulonephritis renal survival and prognosis remain uncertain. Additionally, there's no literature on the clinical outcomes of IgA nephropathy, lupus nephritis, and IgA vasculitis nephritis in type II patients. Methods: This study retrospectively examined 107 patients diagnosed with diffuse crescentic glomerulonephritis through biopsy. Analytical methods included Cox regression models and Kaplan-Meier survival analysis to assess the data. Results: Among the 107 enrolled patients, 12 patients had Type I diffuse crescentic glomerulonephritis, 70 patients had Type II, and 25 patients had Type III. The respective 5-year kidney survival rates were 0%, 57.5%, and 18.6% for type I, type II, and type III. Furthermore, among Type II patients, IgA nephropathy emerged as the most prevalent condition. The cumulative 5-year kidney survival rates were 50% for patients with IgA nephropathy, 64% for lupus nephritis, and 70% for Henoch-Schönlein purpura nephritis. A significant association between the risk of ESKD development and several factors was revealed by a multivariate Cox regression analysis: estimated glomerular filtration rate (P = 0.004), initial kidney replacement therapy (KRT) at presentation (P = 0.002), global glomerulosclerosis (P<0.001). Conclusions: Type II diffuse crescentic glomerulonephritis was the most prevalent type in DCGN, and favors better renal prognosis than type I and III DCGN, in which IgA nephropathy was the most common entity of Type II DCGN. Additionally, estimated glomerular filtration rate, initial KRT at presentation and global glomerulosclerosis were identified as predictors of renal outcomes in diffuse crescentic glomerulonephritis. [ABSTRACT FROM AUTHOR]

Background and hypothesis: Gut dysbiosis characterized by an imbalance in pathobionts (Enterobacter, Escherichia and Salmonella) and symbionts (Bifidobacterium, Lactobacillus and Prevotella) can occur during chronic kidney disease (CKD) progression. We evaluated the associations between representative symbionts (Bifidobacterium and Lactobacillus) and pathobionts (Enterobacteriaceae) with kidney function in persons with autosomal dominant polycystic kidney disease (ADPKD). Methods: In this cross-sectional study, 29 ADPKD patients were matched to 15 controls at a 2:1 ratio. Clinical data and biological samples were collected. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine concentration using the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Microbial DNA extracted from stool specimens and amplified by qPCR was used to quantify Enterobacteriaceae, Bifidobacterium and Lactobacillus abundance. Differences between ADPKD subgroups and controls were assessed using nonparametric tests. Results: The mean age (SD) of the 44 participants was 40.65 (± 11.9) years. Among the participants with ADPKD, 62.1% experienced flank pain, and 48.3% had hypertension. Their median eGFR [IQR] was 74.4 [51.2–94.6] ml/min/1.73m2. All stool samples had Enterobacteriaceae. Lactobacillus abundance was lower in ADPKD participants with more pronounced kidney function decline (CKD G3-5: 0.58 ng/μL) than in those with milder damage and controls (G1-2: 0.64 ng/μL, p = 0.047; controls: 0.71 ng/μL, p = 0.043), while Enterobacteriaceae abundance was greater in ADPKD patients with lower kidney function (CKD G3-5: 78.6 ng/μL) than in those in the other two groups (G1-2: 71.6 ng/μL, p = 0.048; controls: 70.5 ng/μL, p = 0.045). Conclusion: Decreased kidney function was associated with decreased symbiont and increased pathobiont abundance in ADPKD patients, suggesting a potential role for the microbiota in disease progression and possible targets for further research. [ABSTRACT FROM AUTHOR]

Background: The impact of chronic kidney disease (CKD) on healthy life expectancy and healthcare costs requires research. This study examined associations between CKD and healthy life expectancy, and its economic burden. Methods: This study of community-dwelling adults residing in Hakui City, Ishikawa Prefecture, Japan used data from the National Health Insurance database between 2012 and 2022. Participants were grouped by baseline estimated glomerular filtration rate (eGFR) (< 45, ≥ 45 to < 60, ≥60 to < 75, ≥75 to < 90, and ≥ 90 mL/min/1.73 m²). The primary endpoint was a composite of becoming a care level ≥ 2 or death. Multivariable Cox proportional hazards models were used to calculate the risk regarding time to the primary endpoint. Secondary endpoints were the annual medical and long-term care costs. Results: The 5,592 participants had a mean follow-up of 6.4 years. The hazard ratio was 1.86 (95% confidence interval [CI]: 1.35 to 2.55) for the eGFR < 45 group and 1.60 (95% CI: 1.13 to 2.25) for the eGFR ≥ 90 group, both compared with the eGFR ≥ 60 to < 75 group. Both annual costs were significantly higher in the lower eGFR groups than in the higher eGFR groups. For the eGFR < 45 group, the median medical care cost was 0.38 million yen/year in all participants and the median long-term care cost was 0.40 million yen/year in primary endpoint achievers. A lower eGFR was correlated with longer unhealthy years of life. Conclusions: Higher and lower eGFRs were associated with increased risks of reduced healthy life expectancy. A lower eGFR was associated with higher medical and long-term care costs. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a leading cause of death in the United States, and renal fibrosis represents a pathologic hallmark of CKD. Extracellular cold-inducible RNA-binding protein (eCIRP) is a stress response protein involved in acute inflammation, tissue injury and regulated cell death. However, the role of eCIRP in chronic inflammation and tissue injury has not been elucidated. We hypothesize that eCIRP is involved in renal ischemia/reperfusion (RIR)-induced CKD and that C23, an antagonist to eCIRP, is beneficial in attenuating renal fibrosis and ferroptosis in RIR-induced CKD. Methods: C57BL/6 (WT) or CIRP−/− mice underwent renal injury with total blockage of blood perfusion by clamping bilateral renal pedicles for 28 min. In the WT mice at the time of reperfusion, they were treated with C23 (8 mg/kg) or vehicle. Blood and kidneys were harvested for further analysis at 21 days thereafter. In a separate cohort, mice underwent bilateral RIR and treatment with C23 or vehicle and were then subjected to left nephrectomy 72 h thereafter. Mice were then monitored for additional 19 days, and glomerular filtration rate (GFR) was assessed using a noninvasive transcutaneous method. Results: In the RIR-induced CKD, CIRP−/− mice showed decreased collagen deposition, fibronectin staining, and renal injury as compared to the WT mice. Administration of C23 ameliorated renal fibrosis by decreasing the expression of active TGF-β1, α-SMA, collagen deposition, fibronectin and macrophage infiltration to the kidneys. Furthermore, intervention with C23 significantly decreased renal ferroptosis by reducing iron accumulation, increasing the expression of glutathione peroxidase 4 (GPX4) and lipid peroxidation in the kidneys of RIR-induced CKD mice. Treatment with C23 also attenuated BUN and creatinine. Finally, GFR was significantly decreased in RIR mice with left nephrectomy and C23 treatment partially prevented their decrease. Conclusion: Our data show that eCIRP plays an important role in RIR-induced CKD. Treatment with C23 decreased renal inflammation, alleviated chronic renal injury and fibrosis, and inhibited ferroptosis in the RIR-induced CKD mice. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is prevalent among elderly patients with type 2 diabetes mellitus (T2DM). The association between dietary patterns and CKD in elderly T2DM patients remains understudied. This study aimed to investigate the relationship between dietary patterns and CKD in elderly Chinese patients with T2DM. Methods: This community-based cross-sectional study included 5,713 elderly T2DM patients (aged ≥ 65 years) from Xiangcheng District, Suzhou, China. Dietary intake was assessed using a validated food frequency questionnaire, and dietary patterns were identified using factor analysis. Each participant was assigned a score for each identified dietary pattern, with higher scores indicating a greater alignment of their diet with the respective pattern. Quartiles of these pattern scores were utilized as the primary exposures in the analysis. CKD was defined as albuminuria, reduced estimated glomerular filtration rate (eGFR), or both. Logistic regression models assessed CKD prevalence across quartiles of dietary pattern scores, expressed as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: CKD prevalence was 45.7%. Four dietary patterns were identified: "traditional southern", "high-protein", "balanced" and "imbalanced". A balanced dietary pattern, featured with high intake of fruits, dairy products, eggs, snacks, crab and shellfish, and fish and shrimp, was associated with lower CKD prevalence. The adjusted ORs for CKD across ascending quartiles were 0.99 (95% CI: 0.85–1.16), 0.89 (95% CI: 0.76–1.04), and 0.73 (95% CI: 0.62–0.86). The imbalanced dietary pattern, characterized by high intake of green leafy vegetables, refined grains, and red meat but low dietary diversity, was associated with increased CKD prevalence, with ORs of 1.01 (95% CI: 0.86–1.18), 1.15 (95% CI: 0.98–1.35), and 1.25 (95% CI: 1.07–1.46) across quartiles. No significant associations were observed for "traditional southern" or "high-protein" dietary patterns. Conclusions: Dietary patterns were associated with CKD prevalence in elderly Chinese T2DM patients. A "balanced dietary pattern", consistent with local dietary customs, was associated with a lower risk of CKD. Further longitudinal and intervention studies are needed to confirm these associations. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) is estimated to be about 13.4% worldwide. Studies have shown that CKD accounts for up to 2% of the health cost burden. Various factors, such as genetic polymorphisms, metabolic disorders, and unhealthy lifestyles, can contribute to the occurrence of CKD. Therefore, the present study aimed to investigate the relationship between renal function and cardiometabolic risk factors, anthropometric characteristics, and the dietary inflammatory index (DII) in an Iranian population. Methods: This study was conducted on 2472 male and female employees of Shiraz University of Medical Sciences (SUMS), selected through census between 2018 and 2019. In this cross-sectional study, renal function was evaluated using serum creatinine (sCr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR). Biochemical indices including sCr, BUN, fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) were measured using standard laboratory methods. eGFR was calculated using the Modification of Diet in Renal Disease formula. Systolic (SBP) and diastolic (DBP) blood pressure as well as anthropometric indices such as height (Ht), weight (Wt), hip circumference (HC), waist circumference (WC), body mass index (BMI), conicity index (C-Index), visceral adiposity index (VAI), abdominal volume index (AVI), body adiposity index (BAI), and body shape index (ABSI) were measured and calculated using standard methods and formulas. Diet was evaluated through a 113-item food frequency questionnaire, and the DII was calculated according to its specific instructions. To predict the factors influencing renal function and to remove the impact of confounders, multivariable linear regression was employed using the backward elimination method. Results: There was a significant direct relationship between sCr and FBS, TG, HDL, DBP, Wt, and BAI as well as between BUN and age, TG, HDL, and BAI. In addition, there was a significant inverse relationship between eGFR and SBP, Wt, BAI, and VAI. In women compared to men, sCr and BUN values were significantly lower, while eGFR levels were significantly higher. Conclusions: It seems that age, gender, lipid profile, glycemic status, BP, BAI, VAI, and Wt can be considered factors associated with renal function. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the predictive value of renal function status [estimating glomerular filtration rate (eGFR)] in conjunction with inflammatory biomarkers [white blood cell(WBC) and C-reactive protein (CRP)] for in-hospital outcomes in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Methods: We retrospectively screened a total of 409 AIS patients treated with IVT. The study participants were classified into two groups according to post-stroke pneumonia or functional outcome. They were divided into four groups according to the cut-offs of inflammatory biomarkers and eGFR by receiver operating characteristics(ROC) curves for two outcomes of post-stroke pneumonia and functional status: WBC↓/eGFR↑, WBC↓/eGFR↓, WBC↑/eGFR↑, and WBC↑/eGFR↓for post-stroke pneumonia; and CRP↓/eGFR↑, CRP↓/eGFR↓, CRP↑/eGFR↑, and CRP↑/eGFR↓for functional outcome. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of post-stroke pneumonia or at-discharge functional outcome, using the WBC↓/eGFR↑group or CRP↓/eGFR↑group as the reference. The Net Reclassification Index (NRI) and the Integrated Discrimination Improvement (IDI) were calculated to analyze the combined predictive value. Results: Compared with patients in WBC↓/eGFR↑group, those in WBC↑/eGFR↑group had increased risk of post-stroke pneumonia (OR 5.15, 95% CI 1.67–15.87) and poor functional outcome (OR 5.95, 95% CI 2.25–15.74). Furthermore, patients in WBC↑/ eGFR↓group had the highest risk of clinical outcomes (all P value for trend < 0.001), the multivariable-adjusted ORs (95% CIs) were 7.04 (2.42–20.46) for post-stroke pneumonia and 8.64 (3.30–22.65) for poor functional outcome. The addition of WBC and eGFR to the basic model significantly improved risk prediction for post-stroke pneumonia (category-free NRI 69.0%, 95% CI 47.3%–90.7%; IDI 5.4%, 95% CI 2.6%–8.3%) and functional outcome (category-free NRI 59.4%, 95% CI 39.2%–79.9%; IDI 5.3%, 95% CI 2.9%–7.8%). Similarly, when we added CRP and eGFR to the basic model with conventional risk factors, the risk discrimination and prediction for post-stroke pneumonia and functional outcome was also significantly improved. Conclusion: Combining renal function status and inflammatory biomarkers within 4.5 h after onset could better predict in-hospital outcomes of AIS patients with IVT. [ABSTRACT FROM AUTHOR]

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of this research. Methods: We built and internally validated a prediction model on 3,893 patients from the Wisconsin Allograft Recipient Database (WisARD) who had a functioning graft 6 months after kidney transplantation. The landmark analysis approach was used to build a proof-of-concept dynamic prediction model to address the aforementioned methodological issues: the prediction of graft failure, accounted for competing risk of death, as well as the future eGFR value, are updated at each post-transplant time. We used 21 predictors including recipient characteristics, donor characteristics, transplant-related and post-transplant factors, longitudinal eGFR, hospitalization, and rejection history. A sensitivity analysis explored a less conservative variable selection rule that resulted in a more parsimonious model with reduced predictors. Results: For prediction up to the next 1 to 5 years, the model achieved high accuracy in predicting graft failure, with the AUC between 0.80 and 0.95, and moderately high accuracy in predicting eGFR, with the root mean squared error between 10 and 18 mL/min/1.73m2 and 70%-90% of predicted eGFR falling within 30% of the observed eGFR. The model demonstrated substantial accuracy improvement compared to a conventional prediction model that used only baseline predictors. Conclusion: The model outperformed conventional prediction model that used only baseline predictors. It is a useful tool for patient counseling and clinical management of KTx and is currently available as a web app. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the impact of the COVID-19 pandemic and resulting changes to diabetes care, especially concerning disease control, the use of (tele)consultation and lessons worth implementing to improve diabetes care, with a specific focus on ethnic minority groups. Methods: A mixed-methods prospective cohort study among people with type 2 Diabetes Mellitus (T2DM) treated in primary care during the COVID-19 pandemic. A survey was sent regionally, including items related to teleconsultation and amount of contact with the healthcare professional. We conducted interviews based on the chronic care model with individuals from various ethnic backgrounds living in a deprived neighbourhood. Change in diabetes control (HbA1c, fasting glucose, LDL, systolic BP, BMI, eGFR) was evaluated based on routine care data. Latent class analysis was performed to identify groups who were more at risk for decreased glycaemic control. Results: Most people maintained face-to-face (59%) or telephone (44%) contact with their healthcare provider. A decrease in consultations was observed. Based on the interviews, factors important for maintaining good glycaemic control were the use of medical devices, religion, routines and social support from family and friends. We did not find a clinically relevant change in diabetes control and no specific group was identified as at risk for worse diabetes regulation. Conclusions: In the context of proactive care, remote healthcare and self-regulation have a crucial role for people with T2DM. It is important to identify barriers and facilitators for maintaining good glycaemic control among vulnerable groups, such as ethnic minority groups. [ABSTRACT FROM AUTHOR]

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have been proven to prevent decline in kidney function and failure. Whether SGLT2i affect the risk of contrast-associated acute kidney injury (CA-AKI) remains uncertain. Methods: Use of SGLT2i was assessed in consecutive diabetics undergoing coronary angiography (CA) or percutaneous coronary intervention (PCI) from January 2020 to May 2023 at a tertiary hospital in Chongqing, China. Propensity-matched analysis was used to adjust for baseline variables. CA-AKI was defined by the Acute Kidney Injury Network (AKIN) as creatinine increase ≥ 0.3 mg/dl (26.4 μmol/l), or a percentage increase in the serum creatinine level of ≥ 50%. Results: A total of 604 new users of SGLT2i, and 298 chronic users of SGLT2i were matched with non-users. New use of SGLT2i was not associated with an increased incidence of AKIN-defined CA-AKI (OR 1.60; 95% CI 0.97–2.63; p = 0.065), in-hospital new-onset dialysis (OR 0.50; 95% CI 0.09–2.73; p = 0.422), or death (OR 0.55; 95% CI 0.18–1.66; p = 0.289). However, it was associated with a minor (> 25%) creatinine elevation (OR 1.55; 95% CI 1.04–2.30; p = 0.030), a 0.3 mg/dl increase in creatinine (OR 1.66; 95% CI 1.01–2.75; p = 0.048), and CMSC-defined CA-AKI (OR 1.51; 95% CI 1.02–2.24; p = 0.039). By 90 days, there was no evidence creatinine elevation differed between the two groups (p = 0.590). Chronic use of SGLT2i was not associated with AKIN-defined CA-AKI (OR, 0.92; 95% CI 0.41–2.05; p = 0.838). Conclusions: New use of SGLT2i during CA or PCI was not associated with an AKIN-defined CA-AKI, and it did not translate into new-onset dialysis or death during hospital stay. Chronic usage of SGLT2i did not affect creatinine. Further randomized clinical trials are warranted to confirm this finding. Key learning points: What was known: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have a renal protective effect; however, they cause an acute increase in the creatinine level and dip in glomerular filtration rate (GFR) upon treatment initiation. This study adds: New use of SGLT2i during coronary angiography or percutaneous coronary intervention was associated with an acute increase in the creatinine level, but it did not translate into new-onset dialysis or death during hospital stay, causing a pseudo contrast-associated acute kidney injury, and the creatinine level seemed return to normal thereafter. Continuation of SGLT2i did not affect creatinine elevation. Potential impact: Usage of SGLT2i may be safe during coronary angiography or percutaneous coronary intervention. Randomized controlled trials and other observational studies are needed to validate our observation. [ABSTRACT FROM AUTHOR]

Background: The advent of Alzheimer's disease-modifying drugs requires accurate biological diagnosis to identify candidates for these therapies. So far, the most promising single plasma biomarker is phosphorylated tau at threonine 217 (p-tau217). To understand its biological features, it is essential to know its longitudinal trajectory and factors influencing it in cognitively unimpaired subjects with no brain pathology. Methods: We analyzed longitudinal plasma p-tau217 values (mean follow-up time = 768.3 days) in a cohort of 209 healthy volunteers. We have studied factors associated with plasma p-tau217 changes by using different linear mixed-effects models. Results: In amyloid-negative cognitively healthy subjects (n = 151) carriers of ApoE ε4 allele had significantly higher p-tau217 values than non-carriers (0.85 pg/mL; p-value < 0.001) and also a greater rate of change (0.01 pg/mL/year; p-value < 0.001). In the overall sample, including subjects with amyloid and tau pathology we have seen that amyloid positive subjects had higher predicted baseline plasma p-tau217 values than amyloid negative subjects (0.16 pg/mL; p-value < 0.001) and a greater rate of change (0.00004 pg/mL/day; p-value < 0.001). Subjects considered tau positive also showed a greater rate of change of p-tau217 with respect to tau negative (0.00005 pg/mL/day; p-value < 0.001). A + T + N + participants showed a higher baseline p-tau217 levels than A-T-N- subjects (0.2 pg/mL; p-value < 0.001) and also a greater rate of change (0.00006 pg/mL/day; p-value = 0.002). ApoE ε4 carriers had a greater rate of change than non-carriers (0.00003 pg/mL/day; p-value = 0.03). Conclusion: In amyloid-negative cognitively unimpaired subjects, ApoE4 status influenced both baseline levels and rate of change of plasma p-tau217. Other factors such as age, sex or glomerular filtration rate have not shown significant influence on plasma p-tau217 levels in this group. [ABSTRACT FROM AUTHOR]

Background: Major abdominal surgery is a kind of high-risk surgery type for postoperative acute kidney injury (AKI) among non-cardiac surgeries. Despite dexmedetomidine exerts significant renal protective effects in cardiac surgeries and animal studies, whether it is associated with a lower incidence of AKI in major abdominal surgeries remains unclear. Methods: From January 2019 to July 2021, patients undergoing elective major abdominal surgery in West China Hospital were enrolled. Participants were divided into two groups based on exposure to continuous intravenous dexmedetomidine: the Dex group (exposed) and the Control group (not exposed). The primary outcome was the incidence of AKI in the postoperative 7 days. Secondary outcomes included intraopertive average urine output, renal function on the first day after surgery, incidence of postoperative dialysis, postoperative intensive care unit (ICU) admission, in-hospital mortality, length of hospital stay, incidence of intraoperative hypotension and bradycardia, and intraoperative use of inotropes and vasopressors. Propensity score matching (PSM), based on participants' baseline and intraoperative characteristics, was performed to minimize potential bias. Furthermore, a subgroup analysis was conducted based on the infusion rate and the use of a loading dose to explore the effects of different methods of dexmedetomidine administration on AKI. The subgroups included: loading dose, non-loading dose, low-infusion rate (infusion rate ≤ 0.4 µg/kg/h), and high-infusion rate (infusion rate > 0.4 µg/kg/h). Results: After PSM with a ratio of 1:1, a total of 8836 patients were successfully matched. Dexmedetomidine administration had no association with the incidence of postoperative AKI, serum creatinine (Scr) level on the first postoperative day, incidence of postoperative dialysis, postoperative ICU admission, in-hospital mortality, length of hospital stay, intraoperative hypotension, or the use of inotropes and vasopressors, but had association with increased intraoperative average urine output (122.95 (76.80, 189.27) vs. 104.65 (67.04, 161.07) ml/h, P < 0.001), higher value of estimated glomerular filtration rate (eGFR) (97.33 ± 15.95 vs. 96.13 ± 16.35 ml/min/1.73m2, P < 0.001) on the first day after surgery and a higher incidence of intraoperative bradycardia (37.0% vs. 30.6%; P < 0.001). In the loading dose subgroup, dexmedetomidine use was significantly associated with a reduced incidence of postoperative AKI (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.23–0.76, P = 0.006).The association between dexmedetomidine and postoperative AKI was absent in subgroups of high or low infusion rate and no loading dose use. Conclusion: In this single-center retrospective propensity-matched study, we did not detect a significant overall difference in post-operative AKI rates between patients treated with or without dexmedetomidine during major abdominal surgery. However, though additional prospective data are needed, our study found that administering dexmedetomidine with a loading dose may be associated with lower rates of AKI, potentially indicating a renoprotective effect of loading-dose dexmedetomidine in this setting. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum klotho level and albuminuria is unknown in middle-aged and elderly participants without diabetes mellitus (DM). Therefore, we will investigate the association between serum klotho level and albuminuria in middle-aged and elderly participants without DM. Methods: Participants (aged 40–79) were from the five continuous cycles (2007–2016) of the National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression was performed to investigate the association between serum klotho level and albuminuria. Results: 9217 participants were included in the present study. 47.6% of the participants were male. The average age of the overall participants was 56.3 years (40–79 years). Overall, 823 participants with albuminuria were identified. After adjusted confounders (age, gender, marital status, ethnicity, family income to poverty ratio, education, body mass index, smoke, charlson comorbidity index, hypertension, hyperlipidemia, angiotensin converting enzyme inhibitor/angiotonin receptor blocker, and estimated glomerular filtration rate), participants with a high serum klotho level had a decreased risk for albuminuria. Compared with the lowest serum klotho level (Tertile 1), participants in Tertile 2 (odds ratio [OR] 0.83, 95% CI 0.70–0.99, P = 0.044) and Tertile 3 (OR 0.76, 95% CI 0.63–0.91, P = 0.003) had a lower risk of albuminuria (P for trend = 0.002). The stratified analysis showed that serum klotho level was still negatively associated with albuminuria in the subgroups, and statistically significant interactions were not observed in the subgroups (all P values for interactions > 0.05, except for the hypertension subgroup). Conclusions: In middle-aged and elderly participants without DM, a high serum klotho level is associated with a decreased risk of albuminuria. In the future, the mechanism of the interaction between klotho and albuminuria needs to be elucidated to find new treatment targets for individuals without DM who suffer from albuminuria. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes increases the risk of coronary artery disease (CAD). High-throughput metabolomics may be utilized to identify metabolites associated with disease, thus, providing insight into disease pathophysiology, and serving as predictive markers in clinical practice. Urine is less tightly regulated than blood, and therefore, may enable earlier discovery of disease-associated markers. We studied urine metabolomics in relation to incident CAD in individuals with type 1 diabetes. Methods: We prospectively studied CAD in 2501 adults with type 1 diabetes from the Finnish Diabetic Nephropathy Study. 209 participants experienced incident CAD within the 10-year follow-up. We analyzed the baseline urine samples with a high-throughput targeted urine metabolomics platform, which yielded 54 metabolites. With the data, we performed metabolome-wide survival analyses, correlation network analyses, and metabolomic state profiling for prediction of incident CAD. Results: Urinary 3-hydroxyisobutyrate was associated with decreased 10-year incident CAD, which according to the network analysis, likely reflects younger age and improved kidney function. Urinary xanthosine was associated with 10-year incident CAD. In the network analysis, xanthosine correlated with baseline urinary allantoin, which is a marker of oxidative stress. In addition, urinary trans-aconitate and 4-deoxythreonate were associated with decreased 5-year incident CAD. Metabolomic state profiling supported the usage of CAD-associated urinary metabolites to improve prediction accuracy, especially during shorter follow-up. Furthermore, urinary trans-aconitate and 4-deoxythreonate were associated with decreased 5-year incident CAD. The network analysis further suggested glomerular filtration rate to influence the urinary metabolome differently between individuals with and without future CAD. Conclusions: We have performed the first high-throughput urinary metabolomics analysis on CAD in individuals with type 1 diabetes and found xanthosine, 3-hydroxyisobutyrate, trans-aconitate, and 4-deoxythreonate to be associated with incident CAD. In addition, metabolomic state profiling improved prediction of incident CAD. [ABSTRACT FROM AUTHOR]

Introduction: Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. Methods: A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR < 60 ml/min/1.73m2 or < 90 ml/min/1.73m2 or ACR above 30 mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. Results: A total of 500 participants were enrolled. Most were female (56%; n = 280) and aged 10 to 17 years (66.9%; n = 335). CKD prevalence ranged from 0 to 23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30 mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR = 1.42; 95% CI:1.30–1.51) and male sex (aOR = 3.02; 95% CI:1.68–5.43). Conclusion: CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: In the contemporary management of heart failure with reduced ejection fraction (HFrEF), the recommended quadruple guideline-directed medical therapy (GDMT) consists of angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This study explored the impact of adding implantable cardioverter-defibrillator (ICD) therapy to this comprehensive regimen in HFrEF patients. Methods: Utilizing deidentified data from the National Electronic Database of the Turkish Ministry of Health, we conducted a nationwide retrospective cohort study on 5450 HFrEF patients receiving quadruple GDMT, including ARNI. Among them, 709 patients underwent additional ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Propensity score matching ensured balanced baseline characteristics between groups. Primary endpoint was determined as all-cause mortality. Results: In the matched cohort, all-cause mortality occurred in 108 out of 619 patients (17.4%) in the GDMT group and 101 out of 619 patients (16.3%) in the ICD group, with a hazard ratio (HR) of 0.74 and a 95% confidence interval (CI) ranging from 0.57 to 0.98. The median follow-up time was 1365 days in the matched cohort, 1283 days in the GDMT group. Subgroup analyses consistently demonstrated benefits, particularly among individuals aged 61 years and older (HR: 0.60, 95% CI: 0.42–0.87, p = 0.006), those with sinus rhythm (HR: 0.55, 95% CI: 0.34–0.89, p = 0.013), individuals not using amiodarone (HR: 0.61, 95% CI: 0.42–0.89, p = 0.011), and those with an estimated glomerular filtration rate lower than 61.9 (HR: 0.66, 95% CI: 0.48–0.91, p = 0.011). Conclusions: This study may offer a glimmer of hope that even after achieving the best current optimal medical therapy, the addition of device therapy could still yield positive outcomes in the management of patients with HFrEF. [ABSTRACT FROM AUTHOR]

Background: With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population. Methods: By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis. Result: One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2). Conclusion: We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 and European Kidney Function Consortium (EKFC) 2023 both recently updated the equations to estimate the glomerular filtration rate (eGFR) using cystatin C; however, little is known about the benefits of using the equations for the risk stratification of health outcomes. We conducted this longitudinal study to compare the cystatin C CKD-EPI and EKFC equations to track the risks of cardiovascular disease and all-cause mortality among Chinese adults. Methods: We used data from China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Adjusted logistic regression models and restricted cubic spline functions were used to evaluate the relationships of cystatin C-based eGFR values with incidence of cardiovascular disease and mortality. Results: A total of 6 496 participants were finally included in this study. The mean age of the participants was 59.6 (± 9.5) years, including 2996 (46.1%) males. There were 473 deaths and 1996 cases of cardiovascular disease observed during a maximum follow-up of 7.0 years. Using cystatin C-based CKD-EPI equation, people of eGFR < 60 mL/min/1.73 m2 had an increased risk of mortality (risk ratio [RR], 1.527; 95% CI, 1.068–2.178) and incident cardiovascular disease (RR, 1.363; 95% CI, 1.006–1.844), compared to those of eGFR ≥ 90 mL/min/1.73 m2. On the contrary, we did not observe significant associations of eGFR levels by EKFC equation with mortality nor cardiovascular disease. Conclusions: The findings indicated that cystatin C-based eGFR using CKD-EPI equation is more closely associated with all-cause mortality and cardiovascular disease compared to EKFC equation among Chinese adults. The cystatin C-based eGFR by CKD-EPI equation should be monitored in health practice, which needs further validation in other populations. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi). Methods: This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed. Results: After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15 ml/min/1.73 m², OKT: 64.53 ml/min/1.73 m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81 min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22 min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180–4.096, p = 0.848). Conclusions: RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients. Trial registration: The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008||https://www.clinicaltrials.gov/) [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause of significant morbidity and mortality. Acute kidney injury (AKI) has been seen in COVID-19-infected subjects, and it has frequently resulted in an abnormal estimated glomerular filtration rate. Colchicine, an immunomodulatory drug, was used in several studies in the early stages of the pandemic. Colchicine has been shown to prevent the development of renal failure in patients with Familial Mediterranean Fever (FMF). It has also been reported to reduce fibrosis, which plays a role in chronic kidney disease. We, therefore, aimed to investigate whether using Colchicine, in addition to standard care, was associated with better renal function in patients with severe COVID-19 infection. Methods: This retrospective cohort study comprised 118 out of 605 hospitalized COVID-19 subjects. Some of the subjects (n = 50) received oral Colchicine plus standard care, called the Col (+) group. The others (n = 68) received only the standard care, called the Col (-) group. The estimated glomerular filtration rate (eGFR) and other laboratory findings, including lymphocytes, D-dimer, and CRP, were analyzed. Results: The D-dimer and serum creatine levels were significantly reduced in both groups. The number of lymphocytes showed a significant increase in both groups at discharge. The level of C-reactive protein (CRP) was significantly higher in the Col (+) group than in the Col (-) group at admission. The reduction of SCr was considerably higher in the Col (+) group than in the Col (-) group. Similarly, the improvement of eGFR was higher in the Col (+) group than in the Col (-) group at discharge and 6–12 mounts follow-up. Conclusion: Our findings indicated the use of Colchicine plus standard care was associated with improved renal function in hospitalized patients with severe COVID-19 infection. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry. Patients and methods: Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73 m². Kaplan–Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables. Results: A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060–1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829–4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229–2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS. Conclusion: In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness and safety of enzyme replacement therapy (ERT) for treating Fabry disease in clinical practice. Methods: The clinical data of patients with Fabry disease were retrospectively collected and screened according to inclusion and exclusion criteria. The effectiveness of ERT was evaluated by analyzing the improvement in renal dysfunction (decreased estimated glomerular filtration rate (eGFR) and proteinuria), cardiac system injury (mainly increased left ventricular mass index (LVMI)), and neuropathic pain after ERT treatment. The safety of ERT was measured by summarizing the occurrence of adverse events (AE) and adverse drug reactions (ADR) before and after ERT. Results: Sixteen patients with Fabry disease who underwent ERT treatment 2–36 times over a period of 2–89 weeks were enrolled in the study. Among them, 13 received symptomatic treatment based on the involvement of various organs, 14 were treated with anti-inflammatory and anti-allergic drugs, and 16 had no AE or ADR. After ERT, there was no significant difference in (eGFR, microalbumin (mALB), 24 h urinary protein quantitation (24 h PRO), urinary albumin/creatinine ratio (ACR), uric acid (UA), and β2 microglobulin (β2MG) (P > 0.05), and the renal function remained stable or improved; ERT could significantly reduce left ventricular mass index (LVMI) (P = 0.043) and lactate dehydrogenase (LDH) (P = 0.031), and other cardiac function indexes had an improvement trend or remained stable, but the difference was not significant (P > 0.05). After ERT, the degree of limb pain in three of the four minor patients improved. Conclusions: ERT could effectively stabilize or improve renal and cardiac function and relieve neuropathic pain in patients with Fabry disease, and no AE occurred during treatment, and the clinical effectiveness and safety were satisfactory. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a common condition that increases the risk of fracture and mortality. In Taiwan, clinical guidelines recommend pharmaceutical therapy for patients with a T-score of ≤ − 2.5; however, Taiwan's National Health Insurance (NHI) only covers these medications for those with a history of fragility fractures. This gap in coverage necessitates a discussion of out-of-pocket treatment options. To address this, we provided an integrated care program with patient education and shared decision-making by nurse case managers specializing in osteoporosis. We evaluated whether education by nurse case managers influences patients with a T-score ≤ − 2.5, who are not covered by the NHI, to choose out-of-pocket pharmaceutical therapy. Methods: We retrospectively reviewed medical records of patients who underwent bone density scanning at our hospital between January 2014 and December 2021. We identified 4,462 patients with a T-score of ≤ − 2.5 who were ineligible for NHI-covered anti-osteoporotic therapy and analyzed trends in out-of-pocket medication use. Since the integrated care program began in 2018, we evaluated whether education by nurse case managers between 2018 and 2021 influenced patients' decisions to pay out-of-pocket for therapy. After the implementation of the integrated care program, we identified 2,910 patients with a T-score ≤ -2.5 who were ineligible for NHI-covered anti-osteoporotic therapy. Of these, 640 opted for out-of-pocket treatment, while 2,270 chose conservative care. After a 1:1 propensity score match based on age and sex, logistic regression was used to analyze the impact of nurse case manager education on these decisions. Results: Between 2014 and 2021, 888 of the 4,462 patients chose out-of-pocket pharmaceutical therapy. Before the implementation of the integrated care program and patient education by nurse case managers (2014–2017), 16% of the patients opted to pay out-of-pocket for anti-osteoporotic therapy. After the program was implemented (2018–2021), the rate increased significantly to 22% (P < 0.001). A multivariate logistic regression model showed that a history of osteoarthritis (adjusted odds ratio = 1.576; P = 0.009) and education provided by the nurse case managers (adjusted odds ratio = 5.044; P < 0.001) were significantly associated with choosing out-of-pocket therapy. Conclusions: Education from nurse case managers significantly increased the likelihood of patients choosing out-of-pocket anti-osteoporotic therapy in our hospital, thereby bridging the gap between clinical guidelines and NHI reimbursement criteria. [ABSTRACT FROM AUTHOR]

Background: The quantification of mRNA expression in urinary sediments is a reliable biomarker for various diseases. However, few studies have investigated the clinical relevance of urinary mRNA levels in IgA nephropathy (IgAN). Thus, we investigated the expression of urinary mRNAs and their clinical significance in IgAN. Methods: Overall, 200 patients with biopsy-proven IgAN, 48 disease controls, and 76 healthy controls were enrolled. We identified the differential expression of mRNAs in renal tissue between patients with IgAN and normal subjects using the Gene Expression Omnibus dataset and selected candidate mRNAs. mRNA expression in the urinary sediment was measured using quantitative real-time polymerase chain reaction. Associations between urinary mRNA levels and clinicopathological parameters were analyzed and the predictive value of mRNAs for disease progression was evaluated. Results: The urinary expression of CCL2, CD14, DNMT1, FKBP5, Nephrin, and IL-6 was significantly upregulated in patients with IgAN compared with healthy controls. C3, FLOT1, and Podocin levels were significantly correlated with renal function, where C3, FLOT1, and TfR levels were significantly correlated with urinary protein excretion. During follow-up, 26 (13.0%) patients with IgAN experienced disease progression, defined as a greater than 50% reduction in the estimated glomerular filtration rate or progression to end-stage renal disease. Urinary mRNA levels of FLOT1 (HR 3.706, 95% CI 1.373–10.005, P = 0.010) were independently associated with an increased risk of disease progression. Conclusions: Our results suggest that urinary sediment mRNAs are a useful biomarker in IgAN patients. Further studies with larger sample sizes and longer follow-up durations are required. [ABSTRACT FROM AUTHOR]

Aim: Studies have shown that renal hypertrophy seen in experimental hyperthyroidism induced by thyroxine (T4) is due to angiotensin (Ang) II. However, other renal effects of Ang II in experimental hyperthyroidism have not been investigated. In addition, Ang 1–7 is believed to be protective against renal injury, but its possible role in thyroxine-induced renal injury is not known. The aim of this study is to elaborate the role of Ang II in thyroxine-induced renal injury and the possible protective role of Ang 1–7. We hypothesize that Ang 1–7 will be as protective against thyroxine-induced renal injury as the use of an ACE inhibitor or an Ang II receptor blocker. Methods: Adult Sprague Dawley rats were used in this study and were divided into 5 groups: (1) Control (treated with vehicle), (2) Treated with thyroxine (T4, 100 µg/kg), (3) Treated with T4 and Ang 1–7 (500 µg/kg), (4) Treated with T4 and captopril (20 mg/kg), and (5) Treated with T4 and losartan (10 mg/kg). Parameters tested after fourteen days of treatment were creatinine clearance, protein excretion rate, glomerular volume, renal ACE1 and ACE2 protein expression. Data were compared using One-way-ANOVA followed by Tukey's HSD post hoc test. Results: Thyroxine caused glomerular hypertrophy and proteinuria but had no effect on glomerular filtration rate (GFR). Glomerular hypertrophy was prevented by losartan and captopril, but not by Ang 1–7. Captopril and losartan had no effect on GFR; however, Ang 1–7 caused an increase in GFR in T4-treated rats. The increase in protein excretion rate was prevented by losartan but not by captopril or Ang 1–7. Renal expression of ACE1 protein was not altered in any of the treatment groups except in captopril treated rats were ACE1 expression was increased. Renal ACE2 protein expression was only increased in T4-losartan-treated rats and not affected by any of the other treatments. Conclusion: We conclude that losartan was more protective than captopril against thyroxine-induced renal changes while Ang 1–7 offered no protection. [ABSTRACT FROM AUTHOR]

Background: Multivessel disease(MVD) is linked to a poorer prognosis, increased complications, longer hospital stays, and higher in-hospital mortality when compared to single-vessel disease(SVD).The purpose of this study is to explore the clinically relevant predictors of acute cornary syndrome (ACS) combined with MVD. Methods: This multicenter retrospective study included 68,378 ACS patients from 240 hospitals.The clinical data were retrospectively analyzed with univariate and multivariate analyses to identify the predictive factors for MVD. Results: When compared to SVD group, the MVD group showed a higher incidence of Major Adverse Cardiovascular Events(MACCEs), including all-cause death, myocardial infarction, stent thrombosis, and ischemic stroke during hospitalization, These differences were found to be statistically significant (P < 0.05).The multivariate analysis revealed that age over 75 years (OR: 1.246, 95% CI: 1.176, 1.319), LDL/HDL ratio > 1.98 (OR: 1.245, 95% CI: 1.192, 1.302), history of heart failure (OR: 1.446, 95% CI: 1.143, 1.829), hypertension (OR: 1.274, 95% CI: 1.225, 1.325), diabetes (OR: 1.341, 95% CI: 1.278, 1.406), eGFRs < 60 ml/min·1.73m2 (OR: 1.179, 95% CI: 1.112, 1.249), family history of CAD (OR: 1.236, 95% CI: 1.108, 1.379), and high homocysteine levels (OR: 1.209, 95% CI: 1.029, 1.420) are independent predictors of MVD. The incidence of multivessel disease increased from 37.7 to 58.6% with an increase in the number of predictive factors, while the incidence of single vessel disease decreased from 62.3 to 41.4%. This trend was statistically significant (P trend < 0.001). Conclusions: MVD is strongly correlated with a range of risk factors including diabetes, hypertension, LDL/HDL ratio greater than 1.98, hyperhomocysteinemia, family history of CAD, reduced glomerular filtration rate (< 60 ml/(min·1.73m2), age over 75 years, and a history of heart failure. Furthermore, as the number of predictive factors increases, the odds ratio (OR) for patients with MVD also increases, reaching 2.344 times the OR for patients without any predictive factors. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a major complication following cardiac surgery with a high incidence in those with existing kidney dysfunction. Platelet distribution width (PDW) reflects variability in platelet size and serves as an indicator of platelet activation. Recent investigations linked PDW changes to kidney pathology, suggesting its utility in identifying individuals at risk for AKI, thus necessitating exploration of its predictive value. Methods: Patients with preoperative renal dysfunction [15 ≤ estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2] who underwent cardiac surgery from January 2018 to December 2021 were retrospectively enrolled. PDW values were measured preoperatively and again upon admission to the ICU immediately after cardiac surgery, with the change in PDW (dPDW) defined as the difference between these two measurements. The primary outcome was postoperative AKI, defined base on the Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria. Multivariate regression models were performed to identify the association between dPDW and AKI and its potential trend. Restricted cubic spline analysis assessed non-linear associations between dPDW and AKI. The Youden index identified an optimal dPDW cut-off for AKI prediction. Subgroup analysis was performed to elucidate the consistency of these associations across the various subgroups. Results: AKI occurred in 53.10% (513/966) of patients, accompanied by significant PDW increases in cases of AKI (P < 0.001). After adjusting confounders, dPDW was identified as a significant risk factor for AKI [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.02 ~ 1.16), P = 0.012]. Patients in the highest dPDW quartile (Q4) had a 195% higher AKI risk compared to those in the lowest quartile (Q1) (OR = 2.95, 95% CI:1.78 ∼ 4.90, P < 0.001). Trend analysis indicates that the risk of AKI increased with higher dPDW quartiles (P for trend < 0.001). Youden index showed that dRDW = 1.1 was identified as the optimal diagnostic cut-off value for AKI. Subgroup analyses and interaction tests showed a robust association between dPDW and AKI in all subgroups (P for interaction > 0.05). Conclusions: This study underscored perioperative PDW changes as a significant predictor of postoperative AKI in patients with renal insufficiency, highlighting its potential in refining risk stratification and management strategies. Clinical trial number: Not applicable for this observational retrospective study. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify the factors most strongly associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk score in patients with type 2 diabetes (T2D). Methods: This cross-sectional study included 4698 patients with T2D over an 11-year period (2010–2021). Patients were categorized into four groups based on their 10-year ASCVD risk score (< 5%, 5–7.5%, 7.5–20%, and > 20%). Multinominal regression analysis was used to evaluate the association between various modifiable and non-modifiable risk factors and the ASCVD risk score. Results: Of the patients, 35.9% had a 10-year ASCVD risk score below 5%, 12.6% had a score between 5% and 7.5%, 30.8% had a score between 7.5% and 20%, and 19.7% had a score above 20%. Higher ASCVD risk scores were significantly associated with elevated waist-to-hip ratio (WHR > 0.93), pulse pressure, uric acid, triglycerides, and decreased glomerular filtration rate (all p-values < 0.05). WHR demonstrated the strongest association with higher ASCVD risk scores (OR: 4.55, 95% CI: 2.94–7.03, p < 0.001) when comparing patients with ASCVD scores > 5% to those with scores < 5%. Conclusion: WHR was independently associated with higher ASCVD risk scores in patients with T2D. Incorporating WHR, along with traditional risk factors, could improve ASCVD risk assessments in this population. [ABSTRACT FROM AUTHOR]

Background: The developing kidney is vulnerable to prenatal environmental factors such as metal exposure, potentially altering the risk of later-life kidney dysfunction. This study examines the relationship between prenatal metal exposures, individually and as mixtures, and adolescent kidney function in Project Viva, a prospective longitudinal birth cohort in Massachusetts, USA. Methods: We used data on metals measured in blood during pregnancy including 15 in the first trimester and four in the second trimester. We calculated estimated glomerular filtration rate (eGFR) in adolescents (mean: 17.7 years) using cystatin C- (eGFRcys) and creatinine-based (eGFRcreat) equations for children. We used linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses, adjusting for relevant covariates. To account for multiple comparisons in the single metal analyses, we applied the Holm-Bonferroni procedure to control the false discovery rate. Results: This study included 371 participants with first trimester metals and adolescent eGFR, and 256 with second trimester metals. Each doubling in first trimester cadmium concentration was associated with lower adolescent eGFRcys (β:-1.51; 95% CI:-2.83, -0.18). Each doubling in first trimester chromium (β:-1.45; 95% CI:-2.71, -0.19), nickel (β:-1.91; 95% CI:-3.65, -0.16), and vanadium (β:-1.69; 95% CI:-3.21, -0.17) was associated with lower adolescent eGFRcreat. After adjusting for multiple comparisons, p-values for associations between adolescent eGFR and chromium, nickel, vanadium and cadmium did not meet the criteria for significance. Metal mixture analyses did not identify statistically significant associations with adolescent eGFR. Conclusions: These findings have important implications for future studies investigating the potential mechanisms through which prenatal metal exposures affect long-term kidney health in children. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) poses a global health challenge with high morbidity and mortality rates. Early detection and prompt intervention are critical in preventing progression to end-stage kidney disease (ESKD) and cardiovascular complications. Effective CKD management requires comprehensive care packages that integrate both pharmacological and non-pharmacological interventions within collaborative, team-based models, aiming to enhance patient outcomes and overall quality of life. The goal of the Strategies for Kidney Outcomes Prevention and Evaluation (SKOPE) study is to establish effective multicomponent intervention (MCI) strategies for evaluating and preventing kidney outcomes in patients with moderate to advanced CKD within primary care settings in Singapore. Methods: This study is a 3-year randomized controlled trial among 896 participants aged between 40 and 80 years with moderate or advanced CKD in five government-subsidized polyclinics in Singapore. The components of the MCI are (1) nurses/service coordinators trained as health coaches for motivational conversation and CKD-specific lifestyle counseling on diet and exercise, using a hybrid follow-up approach of in-person, telephone, and secure video meetings; (2) training physicians in algorithm-based standardized management of CKD; (3) subsidy on SGLT2i medications for CKD; and (4) regular CKD case review meetings. The primary outcome is the estimated glomerular filtration rate (eGFR) total slope from randomization to final follow-up at 36 months. Discussion: If shown to be effective, cost-effective, and acceptable, SKOPE should be considered for scaling country-wide and in similar regional healthcare systems. Trial registration: ClinicalTrials.gov NCT05295368. Registered on March 25, 2022. [ABSTRACT FROM AUTHOR]

Background: Community pharmacists commonly see individuals with chronic kidney disease (CKD) and are in an ideal position to mitigate harm from inappropriate prescribing. We sought to develop a relevant medication list for community pharmacists to dose adjust or avoid in individuals with an estimated glomerular filtration rate (eGFR) below 30 mL/min informed through a scoping review and modified Delphi panel of nephrology, geriatric and primary care pharmacists. Methods: A scoping review was undertaken to identify higher risk medications common to community pharmacy practice, which require a dose adaptation in individuals with advanced CKD. A 3-round modified Delphi was conducted, informed by the medications identified in our scoping review, to establish consensus on which medications community pharmacists should adjust or avoid in individuals with stage 4 and 5 CKD (non-dialysis). Results: Ninety-two articles and 88 medications were identified from our scoping review. Of which, 64 were deemed relevant to community pharmacy practice and presented for consideration to 27 panel experts. The panel consisted of Canadian pharmacists practicing in nephrology (66.7%), geriatrics (18.5%) and primary care (14.8%). All participants completed rounds 1 and 2 and 96% completed round 3. At the end of round 3, the top 40 medications to adjust or avoid were identified. All round 3 participants selected metformin, gabapentin, pregabalin, non-steroidal anti-inflammatory drugs, nitrofurantoin, ciprofloxacin and rivaroxaban as the top ranked medications. Conclusion: Medications eliminated by the kidneys may accumulate and cause harm in individuals with advanced chronic kidney disease. This study provides an expert consensus of the top 40 medications that community pharmacists should collaboratively adjust or avoid to enhance medication safety and prescribing for individuals with an eGFR below 30 mL/min. [ABSTRACT FROM AUTHOR]

Objective: To analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR. Results: In total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR. Conclusion: Peripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment. [ABSTRACT FROM AUTHOR]

Background: A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. Methods: The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). Results: With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. Conclusion: Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min− 1·1.73 m− 2, but virtually no impact on mortality prediction. Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008. [ABSTRACT FROM AUTHOR]

Background: At present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI). Methods: In this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups. Results: After surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P < 0.05). Meanwhile, the incidences of ARs during hospitalization between patients in the Exp and Ctrl groups were all 8%, showing no observable difference (P > 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization. Conclusion: Taken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety. [ABSTRACT FROM AUTHOR]

Background: Living kidney donors (LKD) experience an abrupt decline in glomerular filtration rate (GFR) resulting in abnormalities of mineral and bone metabolism (MBD), and this may have implications for skeletal health. We prospectively studied acute and long term MBD adaptation of LKD from two kidney transplant centers (São Paulo, Brazil and Miami, USA). Methods: Renal function and MBD parameters longitudinally after kidney donation (baseline – D0, day 1, 14, 180 and 360 post-operatively) were measured in 74 patients (40 y, 73% female, 54% Brazilian). A subset of 20 donors from Brazil were reassessed after 10 years of nephrectomy. Results: At baseline, Brazilian donors presented lower intact FGF23 (20.8 vs. 80.1 pg/mL, P < 0.01) and higher PTH (47.4 vs. 40.1, P = 0.04) than their US counterparts. GFR decreased to 63% of its baseline levels just after donation but improved 10% during the first year. PTH levels increased on D1, returning to baseline levels on D14, while FGF23 remained higher than baseline over the first year. LKD had a significant reduction of serum phosphate on D1, which returned to baseline levels on D180. A higher fractional excretion of phosphate (FEP) was noted since D14. After 10 years of donation, 20 LKD presented a sustained reduction in GFR (74.8 ± 14mL/min). There was a return to baseline in serum FGF23 [21.8 (18–30) pg/mL] and FEP, accompanied by an increase in serum calcium. PTH remained elevated (57.9 ± 18 pg/mL), whereas serum calcitriol and Klotho were lower than before the donation. Conclusions: The abrupt decline in kidney mass is associated with an increase in PTH and FGF23 that is not explained by phosphate retention. In a long-term evaluation, LKD showed a sustained drop in GFR, with lower serum calcitriol and Klotho, and higher PTH. The effects of these changes should be investigated in further studies. [ABSTRACT FROM AUTHOR]

Objective: Accumulation of extracellular matrix (ECM) proteins in the glomerular mesangial region is a typical hallmark of diabetic nephropathy (DN). However, the molecular mechanism underlying ECM accumulation in the mesangium of DN patients remains unclear. The present study aims to establish a connection between extracellular proteins and DN with the goal of identifying potential biomarkers for this condition. Methods: Differentially expressed genes (DEGs) between DN kidney tissue and healthy kidney tissue were analyzed using the public data GSE166239. Two gene lists encoding extracellular proteins were then utilized to identify extracellular protein-differentially expressed genes (EP-DEGs). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed on these EP-DEGs. A protein–protein interaction (PPI) network was established to identify key EP-DEGs. Furthermore, the diagnostic ability, immune cell infiltration, and clinical relevance of these EP-DEGs were investigated. Immunohistochemistry (IHC) staining of paraffin-embedded renal tissues was performed to validate the accuracy of the bioinformatic results. Results: A total of 1204 DEGs were identified, from which 162 EP-DEGs were further characterized by overlapping with extracellular protein gene lists. From the PPI network analysis, five EP-DEGs (e.g., TNF, COL1A1, FN1, MMP9, and TGFB1) were identified as candidate biomarkers. TNF, COL1A1, and MMP9 had a high diagnostic accuracy for DN. Assessment of immune cell infiltration revealed that the expression of TNF was positively associated with resting dendritic cells (DCs) (r = 0.85, P < 0.001) and M1 macrophages (r = 0.62, P < 0.05), whereas negatively associated with regulatory T cells (r = − 0.62, P < 0.05). Nephroseq v5 analysis demonstrated a negative correlation between the estimated glomerular filtration rate (eGFR) and TNF expression (r = − 0.730, P = 0.025). Gene set enrichment analysis (GSEA) revealed significant enrichment of glycosaminoglycan (GAG) degradation in the high-TNF subgroup. IHC staining of renal tissues confirmed significantly elevated TNF-a expression and decreased hyaluronic acid (HA) levels in the DN group compared to controls (both P < 0.05), with a negative correlation observed between TNF-a and HA (r = − 0.691, P = 0.026). Conclusion: Our findings suggest that TNF may play a pivotal role in the progress of DN by driving ECM accumulation, and this process might involve GAG degradation pathway activation. [ABSTRACT FROM AUTHOR]

Background: Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression. Methods: We conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis. Results: Serum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737—0.960), sensitivity of 81%, and specificity of 71%. Conclusion: This study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis. [ABSTRACT FROM AUTHOR]