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BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

BACKGROUND: GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors both improve cardiovascular and kidney outcomes in people with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors. METHODS: We searched MEDLINE and Embase databases from inception until July 12, 2024, for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data. We estimated treatment effects by baseline SGLT2 inhibitor use using inverse variance-weighted meta-analysis. The main cardiovascular outcomes were major adverse cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure. Kidney outcomes included a composite of ≥50% reduction in estimated glomerular filtration rate, kidney failure or death caused by kidney failure, and annualized rate of decline in estimated glomerular filtration rate (estimated glomerular filtration rate slope). Serious adverse events and severe hypoglycemia were also evaluated. This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024565765). RESULTS: We identified 3 trials with 1743 of 17 072 (10.2%) participants with type 2 diabetes receiving an SGLT2 inhibitor at baseline. GLP-1 receptor agonists reduced the risk of major adverse cardiovascular events by 21% (hazard ratio [HR], 0.79 [95% CI, 0.71–0.87]), with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline (HR, 0.77 [95% CI, 0.54–1.09] and HR, 0.79 [95% CI, 0.71–0.87], respectively; P -heterogeneity=0.78). The effect on hospitalization for heart failure was similarly consistent regardless of SGLT2 inhibitor use (HR, 0.58 [95% CI, 0.36–0.93] and HR, 0.73 [95% CI, 0.63–0.85]; P -heterogeneity=0.26). Effects on the composite kidney outcome (risk ratio, 0.79 [95% CI, 0.66–0.95]) and estimated glomerular filtration rate slope (0.78 mL/min/1.73 m2/y [95% CI, 0.57–0.98]) also did not vary according to SGLT2 inhibitor use (P -heterogeneity=0.53 and 0.94, respectively). Serious adverse effects and severe hypoglycemia were also similar regardless of SGLT2 inhibitor use (P -heterogeneity=0.29 and 0.50, respectively). CONCLUSIONS: In people with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use. [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 and Purpose: Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging. Approach: We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR). Background and Key Results: An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR. Conclusions and Impact: These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

Importance: More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis. Observations: Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter–related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure–related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis. Conclusions and Relevance: In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making. This narrative review explores the use of maintenance hemodialysis and peritoneal dialysis in the treatment of dialysis-dependent chronic kidney failure, including diagnosis, pathophysiology, and disease management. [ABSTRACT FROM AUTHOR]

Abstract1. Introduction2. Methods3. Results4. ConclusionThe study aimed to investigate the influence of interleukin (IL)-6 -174 G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation.The study included 115 Caucasian kidney transplant recipients on Tac-based immunosuppression. The patients were followed between 6 and 60 post-transplantation months. Interleukin-6 and CYP3A5 genotyping were performed.Patients carrying the IL-6 -174GG genotype had lower eGFR values compared to the patients with the IL-6 -174GC and −174CC genotypes at the 12th, 48th and 60th post-transplantation months. The linear regression analysis indicated that eGFR at the 6th post-transplantation month and IL-6 -174 G/C polymorphism are independent predictors of eGFR values in the late post-transplantation period. The IL-6 -174GG genotype carriers had lower dose-adjusted trough concentration (C0/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24th month), while this effect was independent of the CYP3A5 genotype within three years post-transplantation.Interleukin-6 genotyping could be an additional tool to categorise patients towards the risk of graft deterioration in the long-term post-transplantation period. The IL-6 genotyping could be supportive in genotype-guided dosing of Tac. [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]

ABSTRACT Background and Aims Methods and Results Conclusion To prevent end‐stage renal disease caused by diabetic kidney disease, we created a predictive model for high‐risk patients using machine learning.The reference point was the time at which each patient's estimated glomerular filtration rate (eGFR) first fell below 60 mL/min/1.73 m2. The input period spanned the reference point to 1 year prior. The primary endpoint was a 50% decrease in eGFR from the mean of the input period over the 3 year evaluation period. We created predictive models for patients’ primary endpoints using time series data of various variables over the input period. Among 2,533 total patients, 1,409 had reference points, 31 had records for their input and evaluation periods and had reached their primary endpoints, and 317 patients had not. The area under the curve (AUC) of the predictive model peaked (0.81) when the minimum eGFR, the difference between maximum and minimum eGFR, and both maximum and minimum urinary protein values were included in the features.The accuracy of prognosis prediction can be improved by considering the variable components of urinary protein and eGFR levels. This model will allow us to identify patients whose renal functions are relatively preserved with eGFR of more than 60 mL/min/1.73 m2 and are likely to benefit clinically from immediate treatment intensification. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is associated with several complications with higher prevalence and intensity at lower glomerular filtration rate. Albuminuria is the traditional biomarker of kidney damage. Although albuminuria can contribute to renal function decline, only a few studies have been published on whether albuminuria is associated with concurrent complications of chronic kidney disease. The aim of this work was to identify the relation between albuminuria and some of concurrent complications of chronic kidney disease among children. Methods: A cross-sectional study included fifty children with chronic kidney disease stages 2–5. Measurement of blood pressure, hemoglobin, serum bicarbonate, calcium, phosphorus, albumin, and lipid profile was done. Urinary albumin/creatinine ratio was determined. The relation between albuminuria and some of the complications of chronic kidney disease among children was studied. Results: The study included 50 patients aged 3–14 years. Dyslipidemia was present in 62% of the patients, acidosis in 56%, anemia in 38%, hyperphosphatemia in 34%, hypertension in 28%, and hypocalcemia in 22%. Eighty-eight percent had albuminuria, 26% had microalbuminuria, and 62% had macroalbuminuria. A statistically significant relation was found between the degree of albuminuria and presence of anemia and hyperphosphatemia. But no significant relation was found between the degree of albuminuria and presence of hypertension, dyslipidemia, acidosis, or hypocalcemia. Conclusion: There is a significant relation between the degree of albuminuria and presence of anemia and hyperphosphatemia among children with chronic kidney disease. Key message: What is already known? Albuminuria is a biomarker of kidney damage and it can contribute to renal function decline. What this study adds? There is a relation between albuminuria and some of CKD complications among children. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions We investigated the association between the ankle reflex and the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.This was a single‐center, retrospective, observational cohort study. A total of 1,387 patients who underwent an ankle reflex examination between January 2005 and December 2015 were included in the analysis for the primary outcome. The findings of the ankle reflex examination were classified into three groups: normal, decreased, or absent. The primary outcome was defined as the incidence of a 40% loss of eGFR from baseline. A survival time analysis using the Kaplan–Meier method and a regression analysis using a Cox proportional hazards model were conducted to evaluate the association between the ankle reflex test results and loss of eGFR.The ankle reflex test results were as follows: normal, n = 678 (48.9%); decreased, n = 270 (19.5%); and absent, n = 439 (31.6%) patients. The median follow‐up period was 5.6 years in the observational period. In the univariate regression analysis, decreased and absent ankle reflexes were significantly associated with loss of eGFR. Moreover, decreased ankle reflex (hazard ratio: 1.83, 95% confidence interval: 1.16–2.87) and absent ankle reflex (hazard ratio: 2.57, 95% confidence interval: 1.76–3.76) were independently associated with loss of eGFR after adjusting for prognostic risk factors.Decreased and absent ankle reflexes are closely and independently associated with loss of eGFR in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionPatients with lupus nephritis (LN), a severe renal manifestation of systemic lupus erythematosus, should be monitored for progression of chronic kidney disease to end-stage renal disease but data on renal function testing in LN patients are limited. This real-world analysis aimed to evaluate nephrologists’ use of renal function tests to support LN diagnosis and monitoring and to examine the impact of disease progression in LN patients in Europe.Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional survey of nephrologists and their next five consulting patients with LN in France, Germany, Italy, Spain, and the United Kingdom in 2021. Nephrologists provided demographic and clinical information for each patient and the same patients completed a self-reported questionnaire. Using a checkbox, patients provided informed consent to take part in the survey.Nephrologists (n = 72) provided data on 376 patients with LN. Estimated glomerular filtration rate (eGFR) or proteinuria testing was not undertaken in around 10% and 50% of these patients, respectively. Regression analysis predicted reduction in renal function (disease progression) following LN diagnosis whilst bivariate analyses showed significantly worse outcomes for patients with progressed disease: worse pain, fatigue, treatment satisfaction, and patient-reported health state and activity impairment.Our study revealed lower-than-expected nephrologist-reported use of renal function testing to support diagnosis/monitoring of patients with LN in real-world clinical settings in Europe. Lower quality of life (QoL) was observed in patients with more progressed disease. Increased use of renal function testing is needed so that all LN patients are monitored closely to manage disease progression and avoid the associated QoL impact. [ABSTRACT FROM AUTHOR]

Edoxaban is an orally active inhibitor of activated factor X (FXa). Population pharmacokinetic (PK) and pharmacodynamic (PD) analyses were performed to characterize the PK and PK–PD relationships of edoxaban in pediatric patients to identify the covariates that may contribute to inter‐subject variability in PK and PD of edoxaban in pediatric patients, and to compare the PK and PD data between pediatric and adult patients. The pediatric PK of edoxaban was best described by a two‐compartment model with transit compartments, first‐order oral absorption, and linear elimination. The estimated glomerular filtration rate (eGFR), body weight, and post‐menstrual age were the significant covariates explaining variability in edoxaban PK among pediatric patients. A function based on renal maturation was applied to edoxaban clearance. The clearance for a 70 kg patient with an eGFR of 110 mL/min/1.73 m2 was estimated to be 42.9 L/h (CV ~ 31.8%). PK simulation showed that exposures across five pediatric age groups were comparable to that in adult patients receiving 60 mg once daily dose. The PK–PD relationship for anti‐factor Xa was best fit with an Emax (8.65 IU/mL) model with an EC50 of 631 ng/mL. The PK–PD relationships for activated partial thromboplastin time and prothrombin time were best fit with linear models (slopes of 0.0467, and 0.0415 s mL/ng, respectively). In addition, due to the small number of efficacy and safety events, an exploratory analysis did not detect a correlation between efficacy events (recurrent venous thromboembolism) or safety events (clinically relevant bleeding) and edoxaban exposure. [ABSTRACT FROM AUTHOR]

Background: Parathyroid cysts account for a small percentage of parathyroid lesions and are more prevalent in females. Cystic parathyroid hyperplasia is exceptionally rare, with only two cases reported thus far. This case report provides the readers with the first multimodality imaging in cystic parathyroid hyperplasia as well as the authors' first experience in using a 4D computed tomography (CT) scan in our institution while the systematic review will comprehensively search and present similar cases. Main text: The literature search started and ended on August 4, 2024. We searched five academic databases: MEDLINE, Cochrane Library, Pubmed, Science Direct, and Google Scholar. The studied population was all patients with cystic parathyroid gland hyperplasia, confirmed by histopathology. A total of 205 articles were initially identified, out of which 29 duplicates were promptly eliminated, leaving 176 unique articles for screening. Following the evaluation of titles and abstracts, ultimately only two studies were included in the systematic review. A 61-year-old male presented with recurrent abdominal pain and weight loss. Ultrasound revealed a left neck mass, cystic. The laryngeal CT scan agreed with the ultrasound while the Technetium-99 sestamibi scan suggested a thyroid lesion. A 4D CT scan confirmed a lobulated cystic lesion in the left parathyroid region. The patient underwent successful surgery, and histopathology confirmed parathyroid hyperplasia with a pseudocyst appearance. Conclusions: This case report presents the first imaging multimodality in cystic parathyroid hyperplasia while highlighting the rarity of this case, with two cases worldwide. In addition, this article describes our institution's first experience with a 4D CT scan. [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]

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]

Introduction: A causal relationship exists between salt intake and hypertension, stroke, and kidney disease. However, whether or not reduced salt intake slows progression of renal diseases has been intensely debated. Methods: In this prospective, open-label, randomized controlled trial, we examined the impact of a low salt diet on renal function, blood pressure, and other metabolic parameters. Herein, 194 patients with chronic kidney disease (CKD) stages 1 to 3 were randomized in low salt (intervention) and control groups. The intervention group was provided a low salt diet (1.5 g/day) for 3 months. The control group consumed their usual diet, and daily food intake was recorded in the control group. Renal function tests, 24-h urinary sodium excretion, urinary protein, serum calcium, phosphorus, and electrolyte levels were recorded monthly. Results: After 3 months, the mean reduction in estimated glomerular filtration rate was significantly higher in the control group (mean reduction in eGFR, −3.011 mL/min/1.73 m2; 95% confidence interval (CI) = −5.367, −0.656, P =.013). Blood pressure (BP) decreased significantly in both groups; systolic and diastolic BP reduction at 3 months was significantly greater in the intervention group (systolic BP mean reduction −6.57/−4.29 mmHg; 95% CI = −10.24, −2.89) and diastolic BP mean reduction −6.95, −1.64 mmHg) compared with the control group (systolic BP mean reduction −0.58/−2.63 mmHg; 95%, CI = −4.33, 3.17 and diastolic BP mean reduction −5.34, −0.08 mmHg). The mean reduction in 24-h urine sodium excretion was greater in the intervention group, reaching a significant level at month 2 (−14.45 mmol/day; 95% CI = −27.63, −1.22). Conclusion: Overall, salt restriction can help slow the progression of renal insufficiency and results in statistically significant and clinically important reductions in BP among patients with CKD. ClinicalTrials.Gov Identifier: NCT05716386 on 28/01/2023. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction is a known predictor of long-term functional dependency after anterior circulation large vessel occlusion (ACLVO) stroke. However, the impact of renal dysfunction on early infarct growth rate (IGR) has not been previously demonstrated. The objective of this study was to define the association of creatinine-based renal biomarkers with fast or slow progressor phenotypes and related clinical outcomes in ACLVO stroke. Methods: This retrospective study examined patients with acute intracranial internal carotid artery or middle cerebral artery-M1 occlusions admitted between 2014 and 2019. Patients were included if they received baseline CT perfusion (CTP) or MRI on presentation within 24 h of estimated stroke onset. Infarct growth rate (IGR) was determined by ischemic core volume on CTP or MRI divided by time from stroke onset to imaging. IGR was used to stratify fast progressor (IGR ≥10 mL/h) and slow progressor (IGR < 10 mL/h) status. Renal dysfunction was assessed based on serum creatinine and estimated glomerular filtration rate (eGFR) on presenting laboratories. Logistic regression models, adjusted for significant covariates, identified independent associations between renal dysfunction biomarkers, progressor status, and clinical outcomes based on modified Rankin Scale (mRS) at 90 days. Results: Among 230 patients with ACLVO, 29% were fast progressors, with median serum creatinine levels higher than slow progressors (1.1 vs. 0.9 mg/dL, p < 0.05) and lower median eGFR (66.2 vs. 69.0 mL/min/1.73m2, p < 0.05). Elevated creatinine (≥1.2 mg/dL) was independently associated with fast progressor status (adjusted OR 2.37, 95% CI 1.18–4.77), worse 90-day mRS (adjusted OR 1.88, 95% CI 1.01–3.51) and mortality (adjusted OR 2.57, 95% CI 1.14–5.79). Reduced eGFR (<60 mL/min/1.73m2) was independently associated with fast progressor status (adjusted OR 2.38, 95% CI 1.14–4.94), but not with 90-day mRS or mortality. Conclusion: Serum creatinine-based biomarkers of renal dysfunction were associated with fast progressor phenotype of ACLVO stroke, and worse clinical outcomes, which may help identify such patients earlier during emergency evaluation for expedited access to EVT. Future prospective studies are warranted to confirm and test implementation of these findings. [ABSTRACT FROM AUTHOR]

ABSTRACT Literature on the association between the cardiometabolic index (CMI) and chronic kidney disease (CKD) risk is limited, especially in hypertensive populations. The objective of the present investigation was to assess the relationship between the CMI and CKD risk in a hypertensive population. The current cross‐sectional study included a total of 13 717 individuals with hypertension. The calculation of the CMI was based on the waist‐to‐height ratio and the triglyceride‐to‐high‐density lipoprotein cholesterol ratio. The definition of CKD was based on an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. The prevalence of CKD was found to be 4.24% in younger adults (aged < 65 years) and 14.93% in the elderly (aged ≥ 65 years). The results of the multivariate regression analysis indicated that in the elderly group, the CMI was positively associated with CKD risk (odd ratio [OR] 1.29; 95% confidence interval [CI]: 1.14, 1.46), while no significant relationship was observed in the younger group (OR 1.04, 95% CI: 0.85, 1.27). Furthermore, subgroup analyses did not identify any potential factors that could modify the relationship between the CMI and CKD risk (all p for interaction > 0.05). Among adults with hypertension, there was an independent and positive correlation between the CMI and CKD risk in the elderly, whereas such a correlation was not observed in younger adults.Trial Registration: ClinicalTrials.gov identifier: ChiCTR1800017274 [China Hypertension Registry Study] [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 and Objectives: Soluble alpha Klotho (s.Klotho) is an emerging marker for chronic kidney disease (CKD) prognosis. The objective was to study the association between s.Klotho and CKD‐related decrease in glomerular filtration rate (GFR), bone and vascular damage. Method: A total of 118 patients with CKD stage 2–4 were enrolled and 107 patients continued in the study. Clinical and laboratory parameters were recorded at time of enrollment and 12 months. A double sandwich ELISA for s.Klotho was recorded in controls (n = 25) and patients' serum samples at 6 months (n = 107) and 12 months (n = 102). Primary endpoints like 40% or more fall in GFR, a requirement for renal replacement therapy (RRT), and death with different grades of s.Klotho deficiency were studied. Results: Of the 107 patients (80 male and 27 female), mean s.Klotho was 3.46 ng/mL (02.3–04.2). The GFR fall was significantly different (p value < 0.0001) in the different grades of s.Klotho deficiency with Grade 4 s.Klotho deficiency (0.1–2.99 ng/mL) having the maximum fall of GFR at 9.2 mL/min/1.73 m2 (04.8–12.0) and minimum in Grade 2 (3–5.99 ng/mL) at 1.35 mL/min/1.73 m2 (03.0–02.75). The Ankle Brachial Pressure Index positively correlated with s.Klotho and the correlation coefficient was 0.536 (0.382–0.662) (p < 0.001). The carotid intimal medial thickness negatively correlated with s.Klotho and the correlation coefficient was −0.712 (95% CI: −0.797–−0.601, p < 0.001). All five deaths had s.Klotho Grade 4 (severe) deficiency. The event‐free survival rate was maximum (100%) in Grade 2 Klotho deficiency and lowest (55%) in Grade 4 s.Klotho deficiency. Conclusions: s.Klotho levels decreased significantly in patients with progressive kidney failure. s.Klotho levels significantly correlated with the presence of vascular disease. Death and need for RRT were significantly more in patients with severe s.Klotho deficiency. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders causing abnormal renal function and progressive decline in the glomerular filtration rate (GFR). This study aimed to investigate the associations of several Environmental factors with CKD in the Iranian population. This is the second phase of a hospital-based case-control study, which was conducted on 700 participants (350 CKD cases and 350 controls, age and gender frequency matched). Multiple logistic regression was applied to measure the associations between the selected factors and CKD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All p-values were two-sided and the results were considered statistically significant at p < 0.05. The results suggested that environmental factors including proximity of residence to mines (OR yes/no=3.98, 95%CI: 2.20–7.21, p < 0.001), proximity of residence to mobile antenna (OR yes/no=2.20, 95%CI: 1.24–3.89, p = 0.006), and exposure to chemicals (OR chemical/no=4.40, 95%CI: 2.27–8.53, p < 0.001), were significantly associated with a higher risk of CKD. The present study covered a large number of factors in association with CKD and highlighted the importance of some environmental factors in development of CKD.‌ One of the main causes of heat in the work environment being a risk factor is dehydration caused by high heat. In order to reduce damage to the kidneys in jobs that deal with high heat, the following tips are recommended: drinking fluids, reducing working hours and shifts, proper ventilation in the workplace, using suitable clothes and heat protection. [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]

The targeted activation or inhibition of specific cell populations using chemogenetics allows the precise dissection of cellular signaling and function. Designer receptors exclusively activated by designer drugs (DREADDs) is a chemogenetic platform initially developed by mutating human muscarinic receptors to be unresponsive to endogenous acetylcholine but exclusively activated by an "inert" designer drug. Compound 21 (C21) is a new and potent DREADD agonist; however, radioligand assays from a recent report indicated its ability to bind to endogenous G protein-coupled receptors (GPCRs), including muscarinic M1–3 receptors. Whether this binding causes off-target effects is unclear. Renal innervation is important for the regulation of renal function, and the advent of chemogenetic tools provides significant opportunities for the mechanistic understanding of renal innervation and function. GPCRs such as adrenergic and muscarinic receptors play a role in renal function; thus, a careful pharmacological characterization of C21 in renal function is a prerequisite for this approach. Unexpectedly, an infusion of 1.0 mg/kg C21 in anesthetized mice caused an ∼4-fold increase in urine output and correspondingly increased the glomerular filtration rate (GFR), suggesting a C21-mediated acute diuretic effect. This acute diuresis effect was further confirmed in awake mice using voiding spot assays. The exact molecular mechanism for C21-mediated diuresis is unclear; however, we demonstrated by in vitro myography that C21 can effectively inhibit bladder smooth muscle contraction by antagonizing M3 receptors at the micromolar level, causing increased voiding size in vivo. In summary, C21 functions as a GPCR antagonist and has significant dose-dependent off-target effects in the renal system. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of robot-assisted partial nephrectomy (RAPN) between completely endophytic tumors (CERT) and non-completely endophytic tumors (non-CERT). Methods: This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. We performed a systematic search in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English up to May 2024. Our analysis primarily evaluated key outcomes, specifically perioperative, functional, and oncological outcomes. Results: A total of 2126 patients across six studies were included in the analysis. Compared to non-CERT, CERT was associated with significantly higher rates of major complications (Odds Ratio [OR]: 2.47; 95% CI: 1.14 to 5.34; p = 0.02), longer warm ischemia times (Weighted Mean Difference [WMD]: 3.27 min; 95% CI: 0.61 to 5.39; p = 0.02), a greater decline in estimated glomerular filtration rate (eGFR) (WMD: 2.93 ml/min/1.73 m2; 95% CI: 0.75 to 5.11; p = 0.008), and relatively lower trifecta achievement rates (OR: 0.63; 95% CI: 0.41 to 0.96; p = 0.03). However, no statistically significant differences were observed between the two groups in terms of operative time, length of stay, blood loss, transfusion rates, intraoperative complications, overall complications, positive surgical margins, and local recurrence. Conclusions: Although CERT was associated with greater declines in eGFR and lower rates of trifecta achievement, it yielded perioperative, functional, and oncologic outcomes comparable to those of non-CERT in RAPN. Our findings suggest that RAPN for completely endophytic renal masses can achieve acceptable outcomes when performed in centers with substantial expertise in robotic surgery. Systematic review registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=555067 , identifier CRD42024555067. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and renal dysfunction often coexist and interact in many complex and bidirectional pathways, leading to detrimental effects on patient outcomes. The treatment of HF patients with renal dysfunction presents a significant clinical challenge. Interestingly, sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), may have beneficial effects on cardiac and renal outcomes in patients with HF with reduced ejection fraction, particularly by slowing the rate of decrease in the estimated glomerular filtration rate compared to a single angiotensin–converting enzyme inhibitor. Recently, more reports have emphasized the renal protection of sacubitril/valsartan in patients with HF. In HF patients with renal dysfunction, however, there is no strong evidence supporting the use of sacubitril/valsartan to reduce the absolute risk of hyperkalemia and worsening renal function; therefore, the administration of ARNI requires a careful balance between the benefits and risks. Furthermore, the lack of evidence‐based management highlights the importance of an individualized approach based on published experience and multidisciplinary collaborations, as well as underlines the need for in‐depth studies investigating the underlying mechanisms in cardiorenal interactions with a focus on treatments. [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: Globally, the prevalence of chronic kidney disease (CKD) is increasing among young people living with HIV (YPLHIV), with inconsistent estimates. Aggregated data on the prevalence of CKD are needed in sub-Saharan Africa (SSA) to inform strategies for early diagnosis and management. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of CKD among YPLHIV in SSA. Methods: We searched Medline/PubMed, EMBASE, African Index Medicus, and African Journals Online for articles reporting the prevalence of CKD among YPLHIV in SSA using predefined search strategies up to 15th January 2024. The reference lists of identified articles were checked for additional eligible studies. The eligibility criteria were studies among YPLHIV aged 10–24 years reporting CKD prevalence defined by either glomerular filtration rate (GFR), albumin-to-creatinine ratio (ACR) or proteinuria. We used a narrative synthesis to report differences between the included studies. The DerSimonian-Laird random effects model was used to pool the CKD prevalence, and heterogeneity was assessed using the Cochrane Q-test and I-squared values. We assessed the risk of bias in each article using the Joanna Briggs Institute checklist and publication bias in a funnel plot and Egger's test. Results: Of 802 retrieved articles, 15 fulfilled the eligibility criteria and were included in the meta-analysis. Of these, 12 (80%) were cross-sectional studies that used estimated GFR to diagnose CKD. Only one study followed the standard definition of CKD. The pooled CKD prevalence from 15 studies was 12% (95% CI 6.0–19.5%), ranging from 0.8% to 53.1% according to the definition used, with a high degree of heterogeneity (I2 = 97.7%, p<0.001). The included studies were of moderate quality, with no evidence of publication bias. Sensitivity analysis showed that the findings were robust to the methodological and analytic approach. Conclusion: CKD prevalence among YPLHIV is moderately high and highly heterogeneous across SSA. The standard definition of CKD should be used to enable estimation of CKD prevalence in different studies and settings. HIV programs enrolling YPLHIV should routinely screen for CKD to ensure early diagnosis and management. Trial registration: PROSPERO registration number: CRD42022347588. [ABSTRACT FROM AUTHOR]

Introduction: Treating extensive burn injury requires an individually tailored resuscitation protocol that includes hourly-titrated intravenous fluid infusion to avert both hypovolemic shock and edema. Due to the complexity of burn pathophysiology and significant variability in treatment protocols, there is an ongoing effort to optimize burn resuscitation. The goal of this work is to contribute to this effort by developing a mathematical model of burn pathophysiology and resuscitation for in silico testing of burn resuscitation protocols and decision-support systems. Methods: In our previous work, we developed and validated a mathematical model consisting of volume kinetics, burn-induced perturbations, and kidney function. In this work, we expanded our previous mathematical model to incorporate novel mathematical models of cardiovascular system and hormonal system (renin-angiotensin-aldosterone (RAAS) system and antidiuretic hormone) which affect blood volume and pressure regulation. We also developed a detailed mathematical model of kidney function to regulate blood volume, pressure, and sodium levels, including components for glomerular filtration rate, reabsorption rates in nephron tubules, Tubuglomerular feedback, and myogenic mechanisms. We trained and validated the expanded mathematical model using experimental data from 15 pigs and 9 sheep with extensive burns to quantitatively evaluate its prediction accuracy for hematocrit, cardiac output, mean arterial pressure, central venous pressure, serum sodium levels, and urinary output. We then trained and tested the mathematical model using a clinical dataset of 233 human burn patients with demographic data and urinary output measurements. Results: The mathematical model could predict all tested variables very well, while internal variables and estimated parameters were consistent with the literature. Discussion: To the best of our knowledge, this is the first mathematical model of burn injury and resuscitation which is extensively validated to replicate actual burn patients. Hence, this in silico platform may complement large animal pre-clinical testing of burn resuscitation protocols. Beyond its primary purpose, the mathematical model can be used as a training tool for healthcare providers delivering insight into the pathophysiology of burn shock, and offering novel mathematical models of human physiology which can be independently used for other purposes and contexts. [ABSTRACT FROM AUTHOR]

Background: In addition to hypertension or diabetes, elderly people are also considered one of the high-risk groups for chronic kidney disease (CKD). Although niacin is recognized for its renal protective properties, the link between dietary niacin intake and CKD remains uncertain. This study investigated this relationship in the elderly. Methods: We included participants aged 60 and older from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2018. Dietary niacin intake was assessed through two non-consecutive 24-hour dietary recalls. CKD was diagnosed in individuals with a urine albumin-to-creatinine ratio exceeding 30 mg/g or an estimated glomerular filtration rate below 60 mL/ min per 1.73 m^2. The study cohort comprised 4,649 participants, 1,632 of whom had CKD. Propensity score matching (PSM) was utilized to adjust for baseline differences between the groups. Results: Our analysis, using smooth curve fitting and generalized additive models both before and after PSM, found a U-shaped curve depicting the relationship between dietary niacin intake and CKD risk, confirmed by a log-likelihood ratio test (P < 0.05). Threshold effect analysis (after PSM) indicated a reduced risk of CKD in older adults with a niacin intake below 38.83 mg per day [odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.97-1.00]. In contrast, higher intake levels significantly increased the risk (OR = 1.03, 95% CI 1.00-1.06). Subgroup analysis indicated that these associations were consistent across different stratification variables (P for interaction > 0.05). Conclusion: Our findings suggested a U-shaped association between dietary niacin intake and CKD risk among older Americans. However, further prospective cohort studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Backgrounds: Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Methods: Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. Results: The results showed that with the crushing weight increased, the kidney function assessment's gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. Conclusion: We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI. [ABSTRACT FROM AUTHOR]

Introduction: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients. Methods: In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN. Results: By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. Discussion: These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN. [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) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition. Methods: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values. Results: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m2) = 0.375 × PV (cm3) + (− 0.395) × age (years) + (− 2.93) × male sex + (− 13.3) × hypertension + (− 14.0) × diabetes + (− 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001). Conclusions: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is associated with both beneficial and harmful effects, and the role of alcohol consumption in chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the relationship between alcohol consumption and CKD or estimated glomerular filtration rate (eGFR). Methods: This study enrolled adults from the second Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and Hyperlipidemia, conducted in 2007. Participants were categorized into frequent drinkers, occasional drinkers, and nondrinkers. The amount of alcohol consumption was assessed by standard drinks per week. The primary outcome was the presence of CKD, and the secondary outcome was the eGFR. Results: Among 3967 participants with a mean age of 47.9 years and a CKD prevalence of 11.7%, 13.8% were frequent drinkers, and 23.1% were occasional drinkers. The average amount of alcohol consumed was 3.3 drinks per week. Frequent drinkers (odds ratio [OR] 0.622, 95% confidence interval [CI] 0.443–0.874) and occasional drinkers (OR 0.597 95% CI 0.434–0.821) showed a lower prevalence of CKD than nondrinkers. Consumption of a larger number of standard drinks was associated with a lower prevalence of CKD (OR 0.872, 95% CI 0.781–0.975). Frequent drinkers and those who consumed a larger number of standard drinks per week showed higher eGFRs. Conclusion: Within the range of moderate alcohol intake, those who consumed more alcohol had a higher eGFR and reduced prevalence of CKD. The potentially harmful effects of heavy drinking should be taken into consideration, and alcohol intake should be limited to less than light to moderate levels. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are significant risks for kidney cancer (KC) patients undergoing partial (PN) or radical nephrectomy (RN) and for living kidney donors (LKD). This study compares AKI and CKD incidence in these groups with a pre-operative glomerular filtration rate (GFR) over 60 mL/min/1.73 m2. Methods: This study included 465 KC patients with cT1-2N0M0 kidney mass and 256 LKD who underwent nephrectomy at four Italian institutions from 2014 to 2021. Data on demographics, comorbidities, and therapies were analyzed. Serum creatinine and estimated GFR (eGFR) were measured before and after surgery. Outcomes were AKI (per KDIGO guidelines) and CKD stage progression. Analyses included descriptive statistics, ANOVA, logistic regression, and Kaplan–Meier survival. Results: Among 721 patients, significant age and gender differences were noted. Hypertension (41%) and diabetes (7.1%) were prevalent in RN and PN groups. Post-surgery AKI was more common in donors (84%), while CKD stage progression varied by surgery type (CKD stage G3 after 60 months: RN 48.91%, PN 18.22%, LKD 26.56%). Age, pre-surgery CKD, and surgery type predicted CKD progression. Limitations include retrospective design and bias. Conclusions: Both LKD and KC patients face similar AKI and CKD risks. Surgery type significantly influences AKI and CKD incidence, highlighting the importance of approach. [ABSTRACT FROM AUTHOR]

Background and Aims: Dehydration is a prevalent and costly healthcare concern, linked to heightened risks of acute kidney injury and in-hospital mortality. Despite its significance, limited evidence exists regarding its prevalence and correlation with renal function decline in apparently healthy individuals. This retrospective cohort study aimed to investigate the prevalence and association of dehydration with renal function decline and the development or progression of chronic kidney disease (CKD) in the general population. Methods: The medical records of subjects undergoing annual health check-ups from 2016 to 2019 at a single center in Taiwan were analyzed, and those with CKD stage V, insufficient data, or an increased estimated glomerular filtration rate (eGFR) were excluded. Serum osmolality, eGFR, and relevant parameters were measured. Logistic regression and Kaplan–Meier analyses were used to assess associations between osmolality and CKD-related outcomes. Results: Among the 4449 eligible subjects, those in the higher osmolality quartiles had an elevated risk of CKD or CKD progression. Multivariate analyses identified age, systolic blood pressure, serum osmolality, uric acid, proteinuria, and a history of diabetes as independent risk factors, with high-density lipoprotein being protective. Cumulative incidence curves demonstrated a significant increase in the risk of CKD with increasing osmolality levels. Restricted cubic spline analyses confirmed a nonlinear relationship between osmolality and CKD risk. Conclusions: Elevated serum osmolality independently predicted renal function decline and CKD development in apparently healthy individuals, and this effect persisted after adjusting for established risk factors. Our findings underscore the importance of addressing dehydration as a modifiable risk factor for CKD. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of mannitol administration on postoperative renal function during robot-assisted partial nephrectomy (RAPN) in patients with renal cell carcinoma (RCC). Methods: Patients with RCC who underwent RAPN at eight Japanese facilities between March 2016 and November 2023 were enrolled. In this study, patients were categorized into two groups according to those who received mannitol during RAPN (Group I) and those who did not receive mannitol (Group II). Differences in covariates between the two groups were adjusted using propensity score matching (PSM). Results: The study included 1530 patients with RCC who underwent RAPN. PSM was performed on 531 participants in each group. No difference was observed in perioperative outcomes between the two groups in terms of length of hospital stay, surgical outcomes, achievement ratio of Trifecta, and estimated glomerular filtration rate at 28 days, 90 days, and 1 year postoperatively. Conclusions: Intraoperative mannitol administration during RAPN for improving renal function may be unnecessary. [ABSTRACT FROM AUTHOR]

Background/Objectives: Recent studies show conflicting results regarding sex-related differences in outcomes following aortic surgery. This study primarily evaluated 20-year mortality rates, along with 30-day and one- and five-year rates, and postoperative complications in female and male patients who underwent elective and acute ascending aortic surgery at a tertiary care centre. Methods: This retrospective observational study analysed data from 676 adult patients who underwent ascending aortic surgery in Amsterdam UMC, between January 2001 and December 2020. Descriptive statistics, Fisher's Exact test, Kaplan–Meier survival analysis, and logistic regression were used to assess differences in mortality rates. Results: Patient characteristics for elective and acute procedures were different. Females were generally older (elective: 69 vs. 62 years, p < 0.001, acute: 70 vs. 62 years, p = 0.002), with smaller body surface area (elective/acute: 1.8 vs. 2.1 m2, p < 0.001), lower preoperative haemoglobin (elective: 8.3 vs. 8.9 mmol/L, p < 0.001, acute: 7.8 vs. 8.4 mmol/L, p < 0.001) and estimated glomerular filtration rate (elective: 64 vs. 91 mL/min, p < 0.001; acute: 67 vs. 83 mL/min, p = 0.004). Females undergoing elective procedures had a lower body mass index (25.0 vs. 26.6 kg/m2, p = 0.006), better left ventricle function (p = 0.048) and higher incidence of chronic obstructive pulmonary disease (15 vs. 8%, p = 0.032). In elective procedures, the 20-year mortality rate (49% vs. 30%, p < 0.001) was significantly higher in females, especially those under 60 years (OR of 3.158 [1.2–8.6], p = 0.024). Mortality rates up to one year were comparable. Five-year mortality rate (26% vs. 16%, p = 0.027) was higher. Females had longer ventilation times (32% vs. 15%, p < 0.001) and intensive care unit stays (2 vs. 1 days, p = 0.005). For acute procedures, morbidity and mortality rates were comparable between sexes. Conclusions: Females under 60, undergoing elective ascending aortic surgery showed higher long-term all-cause mortality rates. Implementing sex-specific management strategies and extended follow-up could be essential for improving outcomes in this group. [ABSTRACT FROM AUTHOR]

Background and Objectives: One of the main objectives of partial nephrectomy is to preserve as much renal function as possible. However, the removal of functioning nephrons and ischemic damage secondary to the clamping of the renal pedicle can be associated with a certain degree of renal function loss. We aim to evaluate the relationship between tumor volume and other factors on renal function in the short term (1–3 months) and long term (6–12 months) in our series of partial nephrectomies. Methods: A retrospective study was conducted on 147 patients who underwent open or laparoscopic partial nephrectomy between 2018 and 2022. Tumor volume was estimated through reconstructions from the computed tomography images. Univariate and multivariate analyses of the data were performed. Results: The mean age was 58.2 years, with an average glomerular filtration rate (GFR) of 79 mL/min/m2. Of all partial nephrectomies, 76.2% were laparoscopic, 57.1% were T1a tumors, and the mean volume was 17 cc. The average ischemia time during surgery was 14.3 min, with a mean hemoglobin loss of 2.8 g/dL in the immediate postoperative period. No significant differences were found either in the short or long term regarding ischemia time (p = 0.57, p = 0.32) or tumor volume (p = 0.57, p = 0.33). However, in the multivariate analysis, it was observed that the variable with the greatest influence on short-term renal function was perioperative glomerular filtration, while in the long term, ischemia time, age, and tumor volume also had an influence. Conclusions: Tumor volume is not an independent factor for renal function deterioration in the short or long term. Short-term renal function is primarily determined by perioperative glomerular filtration. Perioperative glomerular filtration, ischemia time, age, and tumor volume can jointly predict long-term renal function. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a globally widespread complication of diabetes mellitus (DM). Research indicates that pioglitazone and linagliptin mitigate the risk of DN by reducing inflammation, oxidative stress, and fibrosis. The role of tamsulosin in DN is less studied, but it may contribute to reducing oxidative stress and inflammatory responses. The protective effects of combining pioglitazone, linagliptin, and tamsulosin on the kidneys have scarcely been investigated. This study examines the individual and combined effects of these drugs on DN in Wistar rats. Diabetic rats were treated with tamsulosin, pioglitazone, and linagliptin for six weeks. We assessed food and water intake, estimated glomerular filtration rate (eGFR), histological markers, urea, creatinine, glucose, NF-κB, IL-1, IL-10, TGF-β, and Col-IV using immunofluorescence and qPCR. The DN group exhibited hyperglycaemia, reduced eGFR, and tissue damage. Tamsulosin and linagliptin improved eGFR, decreased urinary glucose, and repaired tissue damage. Pioglitazone and its combinations restored serum and urinary markers and reduced tissue damage. Linagliptin lowered serum creatinine and tissue injury. In conclusion, tamsulosin, linagliptin, and pioglitazone demonstrated renoprotective effects in DN. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a severe and prevalent syndrome, primarily observed in intensive care units (ICUs) and perioperative settings. The discovery of a new biomarker for kidney function and injury, capable of overcoming the limitations of traditional markers, has the potential to improve the diagnosis and management of AKI. Proenkephalin A 119–159 (PENK) has emerged as a novel biomarker for AKI and has been validated in various clinical settings. It has demonstrated a faster response to AKI compared to creatinine and has been shown to predict successful weaning from renal replacement therapy in the ICU. PENK has also shown promise as an AKI biomarker in perioperative patients. Additionally, PENK has been proven to be effective in estimating mortality and morbidity in patients undergoing cardiac surgery, and those with traumatic brain injury or ischemic stroke. Incorporating PENK into a novel estimation of the glomerular filtration rate, referred to as the PENK-Crea equation, has yielded promising results. [ABSTRACT FROM AUTHOR]

La glomérulonéphrite fibrillaire (GNF) est une pathologie glomérulaire décrite depuis 1977, rare, ayant une prévalence inférieure à 1 % des prélèvements de biopsies rénales. Elle se présente par une insuffisance rénale, une protéinurie, une hématurie et une hypertension artérielle chez l'adulte d'âge moyen. Sa définition est histologique, passant par la microscopie optique, qui retrouve des dépôts organisés de fibrilles d'environ 20 nm négatives pour la coloration au rouge Congo. La microscopie électronique, premier gold standard du diagnostic, est désormais supplantée par l'immunohistochimie avec l'anticorps anti-DNAJB9. La découverte de cette molécule a permis une révolution dans le diagnostic de la GNF grâce à ses excellentes sensibilité et spécificité (respectivement 98 et 99 %). L'association au virus de l'hépatite C, aux maladies auto-immunes et aux néoplasies ou hémopathies est débattue. Le pronostic rénal est réservé, avec une évolution vers l'insuffisance rénale terminale chez 50 % des patients dans les 2 à 4 ans après le diagnostic. Le traitement recommandé, faute d'étude randomisée contrôlée, repose sur les mesures de néphroprotection, une corticothérapie et éventuellement un immunosuppresseur en seconde ligne comme le rituximab. Après transplantation rénale, la guérison ou la récidive sont possibles. La physiopathologie est encore mal connue et des études supplémentaires seraient nécessaires. Fibrillary glomerulonephritis (FGN) is a glomerular disease described since 1977, with a prevalence in renal biopsies of less than 1%. It presents as renal failure, proteinuria, haematuria and hypertension in middle-aged adults. It is defined histologically, using light microscopy, which reveals organised deposits of fibrils measuring around 20 nm, which are negative for Congo red staining. Electron microscopy, the first gold standard for diagnosis, has now been superseded by immunohistochemistry using the anti-DNAJB9 antibody. The discovery of this molecule has revolutionised the diagnosis of GNF, thanks to its excellent sensitivity and specificity (98% and 99% respectively). The association of GNF with hepatitis C virus, autoimmune diseases, neoplasia or haemopathy is debated. Renal prognosis is guarded, with 50% of patients progressing to end-stage renal failure within 2 to 4 years of diagnosis. In the absence of randomised controlled trials, the recommended treatment is based on nephroprotective measures, corticosteroid therapy and possibly a second-line immunosuppressant such as rituximab. After renal transplantation, recovery or recurrence is possible. The pathophysiology of the disease is still poorly understood, and further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is common in older adults, especially those with renal dysfunction. We aimed to investigate the complex relationships among renal function, nutritional status, and CI in older people free from late chronic kidney disease (CKD) and severe CI. Methods: A study of older people (≥60 years old) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and Montreal Cognitive Assessment (MoCA) scores of >10 (n = 237) was conducted at Beijing Tongren Hospital. Their eGFR was determined using the CKD‐EPI‐cr‐Cysc equation. Cognitive function was evaluated with the MoCA. We tested the relationship between eGFR and MoCA scores using Spearman correlation analysis and multivariate logistic regression analysis. We then conducted a mediation analysis to figure out the mediating roles of nutritional indicators (Mini Nutritional Assessment‐Short Form (MNA‐SF) scores, albumin (ALB), and haemoglobin (HGB)) between the eGFR and MoCA scores. Results: The incidence of CI was 48.5% (115/237) in older people. Spearman correlation analysis revealed that the better the kidney function, the better the cognitive function (R = 0.297, P < 0.001). Multivariate logistic regression analysis revealed that eGFR decrease per 15 mL/min/1.73 m2 (OR: 1.415, 95% confidence interval: 1.055–1.896, P = 0.020) was related to CI after adjusting for age and sex. However, the eGFR was not associated with cognitive decline after adjusting for nutritional indicators, behavioural risk factors, other biomarkers, and chronic conditions, suggesting that eGFR is not independently associated with CI. Mediation analysis revealed that the MNA‐SF scores (a*b = 0.006 (0.0002–0.012)) and HGB (a*b = 0.008 (0.001–0.017)) were mediating factors between the eGFR and MoCA scores. Conclusions: A decline in renal function can directly lead to CI and can also exacerbate cognitive deficits through intermediary factors such as MNA‐SF scores and HGB. Therefore, correcting anaemia and improving nutritional status are significantly important for enhancing cognitive function in older patients, especially those with renal dysfunction. [ABSTRACT FROM AUTHOR]

Aim: Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers. Methods: We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43‐multiparametric renal function assessment between January 1, 2021, and June 30, 2023. Results: All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte‐free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m2 (95% CI 6–29) and +9 mL/min/1.73 m2 (95% CI 2–15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease ‐ Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate‐ and measured creatinine clearance‐based assessments. Conclusions: This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute‐free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis. [ABSTRACT FROM AUTHOR]