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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

Purpose To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) > 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (>38 °C) within 48 hours of drug administration. Results Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 °C P <.001) but remained below 38 °C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P =.009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P =.8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P =.004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. Method: This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a 'sequential feature selector' and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs' scores to determine the importance of the original variables in contracting COVID-19. Results: HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. Conclusion: The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor. [ABSTRACT FROM AUTHOR]

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals. Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure. Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors. Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics. [ABSTRACT FROM AUTHOR]

Background: Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels. Methods: A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985–1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women. Results: Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30–59 ml/min/1.73 m2) had a higher risk of AF compared to those with normal eGFR (60–89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29–2.30; HR = 1.10, 95% CI: 1.03–1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72–1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64–4.07). Conclusion: Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed is combined with cisplatin to treat cancer. Whether pemetrexed-cisplatin combination chemotherapy exacerbates cisplatin nephrotoxicity is unclear. Here, we investigated kidney injury in mice administered a non-lethal low-dose regimen of pemetrexed or cisplatin alone and compared it with a pemetrexed-cisplatin combination. Methods: Mice were randomly divided into four groups and administered intraperitoneally the experimental drugs solubilized in captisol (sulfobutylether β-cyclodextrin). Group 1 received captisol, Group 2 pemetrexed (10 mg/kg), Group 3 cisplatin (1 mg/kg), and Group 4 pemetrexed (10 mg/kg) plus cisplatin (1 mg/kg). The mice were treated every other day for two weeks, three times per week. Glomerular filtration rate (GFR) was determined on the third day after the last treatment, followed by a necropsy. Results: Whereas the relative kidney weight was comparable in the control vs. pemetrexed or cisplatin alone group, it was significantly increased in the combination group. Mice treated with cisplatin and pemetrexed-cisplatin combination exhibited reduced GFR. The pemetrexed-cisplatin combination caused significant increases in the plasma or urinary levels of kidney injury biomarkers, renal lipid peroxidation, and nitrosative stress compared with pemetrexed or cisplatin alone. Histopathology revealed that pemetrexed or cisplatin alone had minimal effects on the kidneys. By contrast, the pemetrexed-cisplatin combination caused tubular degeneration, dilatation, and granular casts. Live-cell imaging showed that the pemetrexed-cisplatin combination caused more severe apoptosis of primary renal epithelial cells than individual concentrations. Conclusions: These findings suggest that combining pemetrexed and cisplatin causes oxidative kidney damage at individual doses that do not cause significant nephrotoxicity. Hence, the renal function of patients undergoing treatment with the pemetrexed-cisplatin combination needs extensive monitoring. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD. [ABSTRACT FROM AUTHOR]

Background: The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China. Methods: A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60–90 ml·min–1·(1.73 m2)–1. The relationship between changes in SUA levels and the eGFR was assessed. Results: (1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min–1·(1.73 m2)–1, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001). Conclusion: In people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR. [ABSTRACT FROM AUTHOR]

Background: Altitude influences bicarbonate levels, it is a variable that is hardly considered in diagnosing Renal Tubular Acidosis (RTA), so it should be a factor to consider when diagnosing this pathology, especially at 2250 mts over the sea level as it is the case of Mexico City. RTA is most often misdiagnosed. Regarding of this, the present study established reference limits for bicarbonate levels in healthy children without pathologies associated with alterations in the acid-base balance in Mexico City and it´s metropolitan area. Methods: A total of 267 healthy pediatric patients were included, within normal estimated glomerular filtration rate (eGFR), and without any associated pathology of any alteration in the acid-base balance. Results: Compared to older children, children younger than two years of age showed statistically higher levels of calcemia and cystatin C. On the other hand, this same group showed lower values of creatininemia, pCO2, and HCO3-. Percentile 50 of bicarbonate in children under two years of age were 19.9 mEq/L and 21.9 mEq/L in those over that age. A correlation was identified between HCO3- levels and pCO2 (r = 0.68; p < 0.001). Conclusions: In the study population, an effect of altitude on blood levels of pCO2 and HCO3- was observed. [ABSTRACT FROM AUTHOR]

Background: Perioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias. Objective: We aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant. Methods: This single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes. Results: Twenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05). Conclusion and Relevance: Both AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications. [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 preclinical 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: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. −3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios. [ABSTRACT FROM AUTHOR]

Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis—after controlling for age, BMI, and treatment duration—the eGFR value (ß = −0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = −0.7915, SE 0.37, p = 0.03) and eGFR (ß = −0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis. [ABSTRACT FROM AUTHOR]

Empirical maturation models (e.g., Johnson and Rhodin models) for glomerular filtration rate (GFR) are commonly used as scaling factors for predicting pediatric renal clearance, but their predictive performance for drugs featured with tubular reabsorption is poorly understood. This study investigated the adequacy of GFR‐based scaling models for predicting pediatric renal clearance in drugs with passive tubular reabsorption by comparing with a mechanistic kidney model (Mech‐KiM) that encompasses the physiological processes of glomerular filtration, tubular secretion, and reabsorption. The analysis utilized hypothetical drugs with varying fractions of tubular reabsorption (Freabs), alongside the model drug metronidazole, which has a Freabs of 96%. Our simulations showed that when Freabs is ≤70%, the discrepancies between the GFR‐based scaling methods and the Mech‐KiM model in predicting pediatric renal clearance were generally within a twofold range throughout childhood. However, for drugs with substantial tubular reabsorption (e.g., Freabs > 70%), discrepancies greater than twofold were observed between the GFR‐based scaling methods and the Mech‐KiM model in predicting renal clearance for young children. In neonates, the differences ranged from 5‐ to 10‐fold when the adult Freabs was 95%. Pediatric physiologically based pharmacokinetic (PBPK) modeling of metronidazole revealed that using a GFR‐based scaling method (Johnson model) significantly overestimated drug concentrations in children under 2 months, whereas utilizing the Mech‐KiM model for renal clearance predictions yielded estimates closely aligned with observed concentrations. Our study demonstrates that using GFR‐based scaling models to predict pediatric renal clearance might be inadequate for drugs with extensive passive tubular reabsorption (e.g., Freabs > 70%). [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Despite the development of transient elastography (TE)‐based Agile scores for diagnosing fibrotic burden in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), their applicability in predicting kidney outcomes remains unclear. We aimed to investigate the association between liver fibrotic burden, as assessed by Agile scores, and the risk of incident chronic kidney disease (CKD) in patients with MASLD. Methods: A total of 3240 participants with MASLD but without pre‐existing CKD who underwent TE between July 2006 and October 2018 were selected. The primary outcome was incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ on dipstick) on two consecutive measurements. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. Results: During a median follow‐up of 3.6 years, 187 participants (5.8%) developed incident CKD. When stratified into three groups according to Agile 3+ scores, multivariable Cox models revealed that risk of incident CKD was 2.77‐fold (95% confidence interval [CI], 1.89–4.07; p < 0.001) higher in the high‐risk group (Agile 3+ >0.68), compared to the low‐risk group (Agile 3+ <0.45). During a median follow‐up of 3.4 years, the high‐risk group had a 2.41‐fold higher risk (95% CI, 1.86–3.12; p < 0.001) of experiencing the secondary outcome, compared to the low‐risk group. Similar findings were observed for Agile 4 scores. Prediction testing revealed that Agile scores were better predictors of kidney outcomes, compared to liver stiffness measured by TE. Conclusions: In patients with MASLD, but without CKD, advanced liver fibrosis measured by Agile scores was significantly associated with a higher risk of incident CKD. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aimed to examine the association between the triglyceride‐glucose (TyG) index and chronic kidney disease (CKD) in normotensive adults with hypertension and further investigate potential effect modifiers of this association. A total of 7975 normoweight hypertensive participants were enrolled from the Chinese H‐type hypertension registry (CHHRS) cohort. The TyG index was calculated using the formula: ln (fasting triglyceride [mg/dL] × fasting plasma glucose [mg/dL])/2. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 of body surface area. Multivariate logistic regression analysis revealed a 50% increased risk of CKD (OR: 1.50, 95% CI: 1.26–1.79) for each unit increase in the TyG index. A linear dose‐response relationship between the TyG index and CKD risk was observed using restricted cubic spline analysis. Compared to the first quartile of the TyG index, the fourth quartile showed a significantly higher risk of CKD (OR: 1.88; 95% CI: 1.41–2.50). Subgroup analysis identified a stronger association between the TyG index and CKD risk in males and individuals with a history of alcohol consumption (all p values for interaction < 0.05). In conclusions, the TyG index was significantly associated with an increased risk of CKD in normoweight adults with hypertension, particularly in males and those with a history of alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. Methods: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. Results: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. Conclusions: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions. Methods: Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification. Results: Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy. Conclusion: Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association. [ABSTRACT FROM AUTHOR]

Purpose: The identification of patients with chronic hypoparathyroidism who are adequately (AC) or not adequately controlled (NAC) has clinical interest, since poor disease control is related to complications and mortality. We aimed to assess the prevalence of NAC patients in a cohort of subjects with postsurgical hypoparathyroidism. Methods: We performed a multicenter, retrospective, cohort study including patients from 16 Spanish hospitals with chronic hypoparathyroidism lasting =3 years. We analyzed disease control including biochemical profile and clinical wellness. For biochemical assessment we considered three criteria: criterion 1, normal serum calcium, phosphorus and calcium x phosphorus product; criterion 2, the above plus estimated glomerular filtration rate =60 ml/min/1.73 m2; and criterion 3, the above plus normal 24-hour urinary calcium excretion. A patient was considered AC if he or she met the biochemical criteria and was clinically well. Results: We included 337 patients with postsurgical hypoparathyroidism (84.3% women, median age 45[36-56] years, median time of follow-up 8.9[6.0-13.0] years). The proportions of NAC patients with criteria 1, 2 and 3 were, respectively, 45.9%, 49.2% and 63.1%. Patients who had dyslipidemia at the time of diagnosis presented a significantly higher risk of NAC disease (criterion 3; OR 7.05[1.44-34.45]; P=0.016). NAC patients (criterion 2) had a higher proportion of subjects with incident chronic kidney disease and eye disorders, and NAC patients (criterion 3) had a higher proportion of incident chronic kidney disease, nephrolithiasis and dyslipidemia than AC patients. Conclusion: The present study shows a strikingly high prevalence of NAC patients in the clinical practice of Spanish endocrinologists. Results suggest that NAC disease might be associated with some prevalent and incident comorbidities. [ABSTRACT FROM AUTHOR]

This systematic review explores the relationship between the gut microbiota metabolite trimethylamine N-oxide (TMAO) and heart failure (HF), given the significant impact of TMAO on cardiovascular health. A systematic search and meta-analysis of peerreviewed studies published from 2013 to 2024 were conducted, focusing on adult patients with heart failure and healthy controls. The review found that elevated levels of TMAO are associated with atherosclerosis, endothelial dysfunction, and increased cardiovascular disease risk, all of which can exacerbate heart failure. The analysis also highlights that high TMAO levels are linked to reduced left ventricular ejection fraction (LVEF) and glomerular filtration rate (GFR), further supporting TMAO's role as a biomarker in heart failure assessment. The findings suggest that interventions targeting gut microbiota to reduce TMAO could potentially benefit patients with heart failure, although further research is needed to evaluate the effectiveness of such approaches. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this. Methods: Individuals aged 18–75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography–mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10–25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups. Results: 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols. Conclusions: We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression. [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: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73 m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (β = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working ≤ 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (β = 1.159, 95% CI: 0.699, 1.619) compared to low PA ( < 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours. [ABSTRACT FROM AUTHOR]

Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function. Methods: The study used genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score <4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function. Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-tocreatinine ratio (UACR) (rg = 0.202, P-value = 5.0E-04), between serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg = -0.094; P-value = 1.4E-05), and between serum25(OH)D and blood urea nitrogen (BUN) (rg = 0.127; P-value = 1.7E-06). In univariableMR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P-value 2.0E-03; beta 0.13, P-value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P-value 2.0E-04; beta -0.005, P-value 2.0E -03) and an increase in BUN (beta 0.02, P-value 3.0E-03; beta 0.02, P-value 7.5E -07). The influence of serum P on kidney function was further supported in multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function. Conclusions: Elevated serum Ca or P levels could both impair kidney function, whereas 25(OH)D has no impact on renal function. [ABSTRACT FROM AUTHOR]

Background: Primary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit. Methods: This prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022. Results: At follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group. Conclusion: For PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment. [ABSTRACT FROM AUTHOR]

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up. [ABSTRACT FROM AUTHOR]

Malnutrition early in life increases the later-life risk of noncommunicable diseases, and previous epidemiologic studies have found a link between famine and renal impairment, but no consensus has been reached. This meta-analysis and systematic review were conducted to assess the correlation between early-life famine exposure and the risk of developing renal impairment. Search in Embase, Scopus, Web of Science, PubMed, and Cochrane using keywords that report the correlation between early famine exposure and renal function indicators. RevMan and Stata software were used for data analysis. This meta-analysis contained twelve observational studies. The findings demonstrated a link between prenatal famine exposure and a higher risk of developing chronic kidney disease (CKD) (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.25, 2.39), a decreased estimated glomerular filtration rate (eGFR) (mean difference (MD) = −10.05, 95% CI: −11.64, −8.46), and increased serum creatinine (Scr) (MD = 0.02, 95% CI: 0.01, 0.03) compared to unexposed individuals. Famine exposure in childhood was associated with decreased eGFR (MD = −9.43, 95% CI: −12.01, −6.84) and increased Scr (MD = 0.03, 95% CI: 0.01, 0.04), but not with CKD (OR = 0.980, 95% CI: 0.53, 1.81). Famine exposure in adolescence and adulthood was associated with decreased eGFR (MD = −20.73, 95% CI: −22.40, −19.06). Evidence certainty was deemed to be of low or extremely low quality. Famine exposure early in life could pose a greater risk of developing renal impairment in adulthood, but this outcome may be driven by uncontrolled age differences between famine-births and post-famine-births (unexposed). [ABSTRACT FROM AUTHOR]

Background: Kidney replacement therapy (KRT) needs preparation and its timing is difficult to predict. Nephrologists' predictions of kidney failure risk tend to be more pessimistic than the Kidney Failure Risk Equation (KFRE) predictions. We aimed to explore how physicians' risk estimate related to referral to KRT education, vs. the objective calculated KFRE. Methods: Prospective observational study of data collected in chronic kidney disease (CKD) clinics of the Veterans Affairs Medical Center San Diego and the University of California, San Diego. The study included 257 participants who were aged 18 years or older, English speaking, prevalent CKD clinic patients, with estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 (MDRD equation). The exposure consisted of end stage kidney disease (ESKD) risk predictions. Nephrologists' kidney failure risk estimations were assessed: "On a scale of 0–100%, without using any estimating equations, give your best estimate of the risk that this patient will need dialysis or a kidney transplant in 2 years." KFRE was calculated using age, sex, eGFR, serum bicarbonate, albumin, calcium, phosphorus, urine albumin/creatinine ratio. The outcomes were the pattern of referral to KRT education (within 90 days of initial visit) and kidney failure evaluated by chart review. The population was divided into groups either by nephrologists' predictions or by KFRE. Referral to KRT education was examined by group and sensitivity and specificity were calculated based on whether participants reached kidney failure at 2 years. Results: A fifth were referred for education by 90 days of enrollment. Low risk patients by both estimates had low referral rates. In those with nephrologists' predictions ≥ 15% (n = 137), sensitivity was 71% and specificity 76%. In those with KFRE ≥ 15% (n = 55), sensitivity was 85% and specificity 41%. Conclusions: Although nephrologists tend to overestimate patients' kidney failure risk, they do not appear to act on this overestimation, as the rates of KRT education referrals are lower than expected when a nephrologist identifies a patient as high risk. Clinical Trial Number: Not applicable [ABSTRACT FROM AUTHOR]

Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing. [ABSTRACT FROM AUTHOR]

Background: Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Results: Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77–0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85–0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82–0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). Conclusions: As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. Trial registration: Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1. Highlights: The mFRI is a rapid, cost-effective and easily accessible biomarker. The mFRI exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers and cytokines in cardiac surgical patients with mild to moderate AKI. Combining the functional biomarker mFRI with a urinary injury biomarker (uNAG or uNGAL) enhanced predictive accuracy for adverse renal outcomes. [ABSTRACT FROM AUTHOR]

Cyclophilin A (CypA) is a novel renal inflammation biomarker, with levels altered in various diseases, particularly in patients with diabetes mellitus (DM) and kidney damage. This study aimed to investigate the correlation between urinary cyclophilin A (uCypA) and chronic kidney disease (CKD) conditions with and without type 2 diabetes mellitus (T2DM) using an in-house enzyme-linked immunoassay (ELISA) method. A uCypA strip-test prototype was also developed. An indirect ELISA was performed to determine the uCypA levels. A 0.48 µg/mL uCypA cutoff differentiated healthy patients from those with early-stage CKD (stages I and II). The uCypA levels were significantly increased in patients with progression of renal deterioration, especially in the T2DM with late-stage CKD group, compared to the control group. Fasting blood sugar (FBS), estimated glomerular filtration rate (eGFR), albumin/creatinine ratio, and metformin use were associated with uCypA levels. Multinomial logistic regression analysis revealed an association between uCypA levels and T2DM diagnosed for over five years and early-stage CKD. This finding shows that uCypA could be used as a biomarker for distinguishing early-stage CKD as well as T2DM complications, which is beneficial for patients to be aware of their health status and change their behavior to slow kidney deterioration. [ABSTRACT FROM AUTHOR]

Background: Morphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. Methods: This single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events. Results: Oxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m2. The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment. Conclusions: This study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. Methods: National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. Results: The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically nonsignificant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). Conclusion: ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. Methods: In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. Results: The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76 cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. Conclusion: Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors. [ABSTRACT FROM AUTHOR]

Objective To establish the association of the SEPP1 gene's (rs7579) polymorphism with enzymatic, metabolic and hormonal activity in patients with chronic pancreatitis (CP) and primary hypothyroidism. Materials and methods Eighty CP patients (40 with comorbid hypothyroidism) and 30 healthy controls participated in the case-control study. Pancreatic enzymes, Selenoprotein P, NO metabolites (NO2-+NO3-), glucose, total cholesterol (TC), triglycerides (TG) and low/high density lipoprotein cholesterol (LDL-, HDL-C), Atherogenicity Index (AI), thyroid-stimulating hormone (TSH), Thyroxine (T4), glomerular filtration rate (GFR) were studied. SEPP1 (rs7579) genotyping performed by PCR (FlexCycler BU). Results and discussion SEPP1 (rs7579) gene's A-allele increases the risk of hypothyroidism twice in CP [OR=2.0; OR 95%CI:1.09-3.66; p=0.023]. Pancreatic patients with hypothyroidism and SEPP1 gene's (rs7579) AA-genotype had 60.0% (pAA=0.013) lower elastase and 13.78% (p=0.003) higher α-amylase as well as TSH by 10.81% (pAA=0.009) and 15.64% (pAA=0.009), especially in women 14.55-45.18% (p<0.001) at a lower value of Selenoprotein P - by 28.65-48.08% (p≤0.048) regardless of the SEPP1 gene (rs7579) variants. Women have 17.43-18.14% (pW≤0.032) higher NO metabolites than men; A-allele women have free T4 value 2.62 times lower (pGG=0.01) than GG-women and 2.97 times lower (pW=0.011) than men. Comorbid patients with A-allele had elevated TC and LDL-C, by 11.77-26.45% (pAA≤0.01) and 18.06-26.21% (pAA≤0.019), respectively. Women have 54.50% (pW=0.002) higher AI with 39.30% lower (pW=0.034) Selenoprotein P and 21.96-24.56% (pW≤0.033) GFR than men. Conclusion SEPP1 (rs7579) gene polymorphism influences the risk of hypothyroidism in CP patients, changes of pancreatic enzymes, dyslipidaemia particular in AA-genotype carriers, mainly women. There was no dependence of SEPP1 and total NO metabolites values on the SEPP1 gene (rs7579) polymorphism. [ABSTRACT FROM AUTHOR]

Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively analyzed data of 4011 patients with a single, unilateral cT1a-b renal mass treated with laparoscopic or robot-assisted partial nephrectomy. The operations were performed by 119 surgeons at 22 participating institutions between 1997 and 2022. Multivariable models investigated the association between surgical experience (number of prior operations) and acute kidney injury (AKI) and recovery of at least 90% of baseline estimated glomerular filtration rate (eGFR) 1 yr after partial nephrectomy. The adjustment for case mix included age, Body Mass Index, preoperative serum creatinine, clinical T stage, PADUA score, warm ischemia time, pathologic tumor size, and year of surgery. Results: A total of 753 (19%) and 3258 (81%) patients underwent laparoscopic and robot-assisted partial nephrectomy, respectively. Overall, 37 (31%) and 55 (46%) surgeons contributed only to laparoscopic and robotic learning curves, respectively, whereas 27 (23%) contributed to the learning curves of both approaches. In the laparoscopic group, 8% and 55% of patients developed AKI and recovered at least 90% of their baseline eGFR, respectively. After adjusting for confounders, we did not find evidence of an association between surgical experience and AKI after laparoscopic partial nephrectomy (odds ratio [OR]: 0.9992; 95% confidence interval [CI]: 0.9963, 1.0022; p = 0.6). Similar results were found when 1-year renal function was the outcome of interest (OR: 0.9996; 95% CI: 0.9988, 1.0005; p = 0.5). Among patients who underwent robot-assisted partial nephrectomy, AKI occurred in 11% of patients, whereas 54% recovered at least 90% of their baseline eGFR. On multivariable analyses, the relationship between surgical experience and AKI after surgery was not statistically significant (OR: 1.0015; 95% CI: 0.9992, 1.0037; p = 0.2), with similar results when the outcome of interest was renal function one year after surgery (OR: 1.0001; 95% CI: 0.9980, 1.0022; p = 0.9). Virtually the same findings were found on sensitivity analyses. Conclusions: In patients treated with laparoscopic or robot-assisted partial nephrectomy, our data suggest that the surgical experience of the operating surgeon might not be a key determinant of functional recovery after surgery. This raises questions about the use of serum markers to assess functional recovery in patients with two kidneys and opens the discussion on what are the key steps of the procedure that allowed surgeons to achieve optimal outcomes since their initial cases. [ABSTRACT FROM AUTHOR]

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = −0.250 and p = 0.04, citric acid with r = −0.296 and p = 0.014, formic acid with r = −0.349 and p = 0.004, and glycine with r = −0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population. Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD. Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years. Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a very prevalent and insidious disease, particularly with initially poorly manifested symptoms that progressively culminate in the manifestation of an advanced stage of the condition. The gradual impairment of kidney function, particularly decreased filtration capacity, results in the retention of uremic toxins and affects numerous molecular mechanisms within the body. The dysbiotic intestinal microbiome plays a crucial role in the accumulation of protein-bound uremic toxins such as p-cresol (pC), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) through the ongoing fermentation process. The described phenomenon leads to an elevated level of oxidative stress and inflammation, subsequently resulting in tissue damage and complications, particularly an increase in cardiovascular risk, representing the predominant cause of mortality in chronic kidney disease (CKD). Therefore, exploring methods to reduce uremic toxins is currently a pivotal therapeutic strategy aimed at reducing the risk of organ damage in patients with chronic kidney disease (CKD). This review aims to summarize recent discoveries on modifying the composition of the intestinal microbiota through the introduction of special probiotic and synbiotic supplements for CKD therapy. The potential to connect the gut microbiota with CKD opens the possibility for further extensive research in this area, which could lead to the incorporation of synbiotics and probiotics into the fundamental treatment and prevention of CKD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD), which has a significant prevalence of 15.7 % in Turkey, is a global health problem that particularly affects elderly. It is difficult to distinguish between age-related and CKD-related declines in kidney function with current glomerular filtration rate (GFR) estimation methods. The “HUGE” formula, incorporating haematocrit, urea, and gender, offers improved differentiation, targeting individuals over 40. This study aims to evaluate the effectiveness of the HUGE formula in estimating GFR in this demographic group and to establish a better diagnostic threshold.A retrospective study of 500 participants over 40 years was conducted and divided into CKD (252) and non-CKD (248) based on demographics, laboratory tests and ultrasound evaluation. Renal function was classified by the HUGE equation (HUGE<0 for age-related decline; ≥ 0 for CKD) and GFR estimates were compared with KDIGO guidelines via CKD-EPI, FAS and BIS1.We observed significant discrepancies in estimated glomerular filtration rate (eGFR) and its staging among different formulas. The HUGE formula showed better agreement with eGFR staging after the cut-off point was set as “−1.58” and improved diagnostic accuracy, especially in stages 3a and 3b.The study validates the HUGE formula improved accuracy in diagnosing CKD, especially for stages 3a and 3b, with a new cut-off value of “−1.58”. It supports the inclusion of the HUGE formula into current diagnostic practices to improve the identification and staging of CKD in individuals over the age of 40, while also demonstrating the necessity for further clinical evaluations. [ABSTRACT FROM AUTHOR]

Objective: The current cross-sectional study determines the prevalence and associated factors of microalbuminuria in a focused population in Eastern India. Methods: The study was conducted in Kolkata from June to December 2022 among type 2 diabetes mellitus (T2DM) patients. Patients with T2DM aged more than 18 were included in the study, and those with overt albuminuria (>300 mg/day), congestive cardiac failure, urinary tract infection, pregnancy, human immunodeficiency virus, hepatitis B, or hepatitis C infection were excluded. Results: Among 297 T2DM patients, 130 (43.8%) had high albumin creatinine ratio (> 30 mg/g). Diabetic patients with elevated blood pressure (BP > 130/80 mm Hg) were 1.68 times (95% CI, 1.12-2.53) at risk of developing microalbuminuria. Similarly, patients with a diabetes duration of 5 years or more were 1.48 (95% CI 1.09-2.02) times more likely to develop microalbuminuria. Logistic regression also concluded that elevated blood pressure (BP > 130/80 mm Hg, P = .027) and duration of diabetes (>5 years, P = .016) were predictive of microalbuminuria. Conclusion: The current study observes a high prevalence of microalbuminuria among diabetes patients. This indicates the need for the implementation of preventive strategies for diabetic nephropathy, especially among patients with long-standing diabetes and elevated blood pressure. [ABSTRACT FROM AUTHOR]

One of the more common diseases affecting zoo-managed cheetahs (Acinonyx jubatus) is chronic renal disease, which can impact their welfare and ultimately shortens their lifespan. Early diagnosis, for which estimating Glomerular Filtration Rate (GFR) is one such tool, is imperative to help mitigate the negative impacts of this insidious disease. GFR was determined by measuring the serum clearance of iohexol in nine clinically normal, cheetahs managed under human care that presented for voluntary blood collection. A 2-sample iohexol clearance method was performed, along with serum symmetric dimethylarginine (SDMA) determination. SDMA has shown promise in humans, dogs, and cats, as an early biomarker of renal disease. Additionally, the relationship between GFR and SDMA, along with serum creatinine and BUN were analyzed. The mean values for the uncorrected GFR and corrected GFR were 2.08 ± 0.215 mL/min/kg body weight and 1.87 ± 0.173 mL/min/kg body weight, respectively. No significant correlations were observed between GFR, SDMA, serum creatinine, or BUN. Both the uncorrected and corrected iohexol-based GFR values were similar to an inulin-based GFR reference interval determined in zoo managed cheetahs and a reported domestic cat iohexol-based GFR reference interval. Serum SDMA values support previous research suggesting cheetahs have a separate reference interval from domestic cats (0–14 μg/dL). Measuring GFR by the serum clearance of iohexol shows promise as a readily available, cheap, and easily administered clearance marker that can be used in cheetahs trained for voluntary blood collection, thereby avoiding the need for anesthesia. [ABSTRACT FROM AUTHOR]

Aim/Introduction: Xanthine oxidoreductase (XOR) inhibitor treatment, which reduces reactive oxygen species (ROS) production and increases adenosine triphosphate (ATP) synthesis, has been reported to improve glycemic control. The possible protective effects of XOR inhibitor treatment on insulin secretory capacity were investigated in patients with type 2 diabetes. Materials and Methods: This retrospective cross‐sectional study included 428 patients with type 2 diabetes. Insulin secretory capacity was assessed based on fasting serum C‐peptide concentration (CPR) and C‐peptide index (CPI) in all subjects, while insulin resistance in non‐insulin users (n = 312) was determined using the homeostasis model assessment of insulin resistance (HOMA‐IR) index. Results: Median values for CPR and CPI in all subjects were 2.4 ng/mL and 1.5, respectively, while that for HOMA‐IR in non‐insulin users was 3.2. The XOR inhibitor users (n = 72) had significantly (P < 0.001) higher CPR and CPI levels than non‐users (n = 356). Multivariable regression analyses showed XOR inhibitor use was positively associated with CPR (β = 0.153, P = 0.001) and CPI (β = 0.144, P = 0.001). Similar results were observed in propensity score analyses. In subgroup analyses of patients with a preserved estimated glomerular filtration rate (≥60 mL/min/1.73 m2) and non‐insulin users, these associations remained significant. Furthermore, the associations were significant in patients with lower (≤6.0 mg/dL) but not with higher (>6.0 mg/dL) uric acid levels (P for interaction <0.05). On the other hand, XOR inhibitor use showed no significant association with HOMA‐IR. Conclusions: The results of XOR inhibitor treatment, especially a sufficient reduction in serum uric acid level, may provide protective effects on insulin secretory capacity in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The time course of chronic kidney disease in young‐onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young‐onset (aged ≤40 years) and late‐onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. Materials and Methods: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young‐ and late‐onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. Results: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young‐onset and 548 (87.6%) had late‐onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young‐onset type 2 diabetes mellitus group. The Kaplan–Meyer curve showed that young‐onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late‐onset type 2 diabetes mellitus. In the multivariate Cox analysis, young‐onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03–2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. Conclusions: Young‐onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late‐onset type 2 diabetes mellitus, indicating that young‐onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end‐stage renal disease. We aimed to identify factors contributing to long‐term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. Materials and Methods: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20‐year period. Baseline risk factors – in particular, the effect of plasma glucose levels on the eGFR – were extracted and evaluated by using Fine and Gray analysis. Results: During the 20‐year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). Conclusions: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for DM content and nitrogen concentration. Data on milk urea and protein concentrations and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure of SAS, with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t -test. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows: 5.46 ± 0.19 versus 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 versus 93.07 ± 1.50 mmol/L (creatinine), and 16.78 ± 0.69 versus 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs. 21.8 ± 0.7 mg/dL) and protein content in milk (3.70% ± 0.08% vs. 3.45% ± 0.07%) than in HO cows. Urea and creatinine concentrations in urine and saliva did not differ between breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and BW were similar in BS and HO cows. Despite greater urea, creatinine, and SDMA concentrations in blood, as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal. [ABSTRACT FROM AUTHOR]