Background The new European Kidney Function Consortium (EKFC) eGFR equation utilizes rescaled serum creatinine to an age- and sex-specific normal median value, making it applicable across the entire age spectrum. We evaluated the performance of the recalibrated EKFCcrea equation using Indian-specific Q (median serum creatinine) and K (normal GFR) in a large Indian cohort and the ability to correctly classify CKD. Methods Indian adults (healthy and patients with CKD) were recruited. Plasma iohexol clearance was used to measure glomerular filtration rate (mGFR). Indian-specific Q values were derived from healthy individuals, and K from those under the age of 40 years. We evaluated EKFCcrea, CKD-EPI2021, and recalibrated the EKFCcrea equations, incorporating the Indian Q (ISQ), Indian constant (ISK), and both (ISQ + ISK). We evaluated bias and accuracy (P30) for all equations. Results A total of 1,174 participants (615 healthy, 559 CKD), mean age 48 years, with equal gender distribution, were recruited. The EKFCcrea equation showed a mean bias of 9.9 (95% CI: 8.7, 11.1) mL/min/1.73 m2 with P30; 58.1%. EKFCISQ reduced bias to 4.9 (95% CI: 3.7, 6.0) mL/min/1.73 m2 and improved P30 to 64%. EKFCISK achieved a bias of -1.2 (95% CI: -0.1, -2.2) mL/min/1.73 m2 and P30 of 69%. 30%, 48%, and 67% of CKD patients were categorized into lower categories using the EKFCISQ, EKFCISK, and EKFCISQ+ISK equations, respectively, against the CKD-EPI 2021. Conclusion Recalibrating EKFCcrea with Indian-specific Q and K reduced bias and improved accuracy, with EKFCISK emerging as the best model. Adopting this recalibrated equation in clinical practice and public health initiatives after validation in diverse cohorts could lead to more accurate CKD diagnosis and staging in India.

Introduction: The new European Kidney Function Consortium (EKFC) eGFR equation uses rescaled serum creatinine (SCr) to an age-and sex-specific normal median value, making it applicable across the entire age spectrum. We evaluated the performance of the recalibrated EKFCcrea equation using Indian-specific Q (for median SCr) and K (for normal glomerular filtration rate [GFR]) in a large Indian cohort and the ability to correctly classify chronic kidney disease (CKD). Methods: Indian adults (healthy and patients with CKD) were recruited. Plasma iohexol clearance was used to assess measured GFR (mGFR). Indian-specific Q values were derived from healthy individuals, and K from those under the age of 40 years. We evaluated EKFCcrea, CKD-Epidemiology Collaboration (EPI)2021, and recalibrated the EKFCcrea equations, incorporating the Indian Q (ISQ), Indian constant (ISK), and both (ISQ + ISK). We evaluated bias and accuracy (P 30 ) for all equations. Results: A total of 1174 participants (615 healthy, 559 CKD), mean age 48 years, with equal sex distribution were recruited. The EKFCcrea equation showed a mean bias of 9.9 (95% CI: 8.7-11.1) ml/min per 1.73 m 2 with P 30 ; 58.1%. EKFCISQ reduced bias to 4.9 (95% CI: 3.7 6.0) ml/min per 1.73 m 2 and improved P 30 to 64%. EKFCISK achieved a bias of-1.2 (95% CI:-0.1 to-2.2) ml/min per 1.73 m 2 and P 30 of 69%. 30%, 48%, and 67% of CKD patients were categorized into lower categories using the EKFCISQ, EKFCISK, and EKFCISQ+ISK equations, respectively, against the CKD-EPI 2021 . Conclusion: Recalibrating EKFCcrea with Indian-specific Q and K reduced bias and improved accuracy, with EKFCISK emerging as the best model. Adopting this recalibrated equation in clinical practice and public health initiatives after validation in diverse cohorts could lead to more accurate CKD diagnosis and staging in India.

Pigment cast nephropathy can cause an acute decline in renal function. The cause of pigment casts in renal allografts is poorly understood, although it has been observed in recipients of road traffic accident donors. We describe a case of pigment cast nephropathy in a renal allograft identified through several sequential biopsies performed for allograft dysfunction. A 27-year-old man underwent a deceased donor kidney transplant and developed delayed graft function with elevating creatinine levels. Early biopsies showed calcineurin inhibitor toxicity and pigment casts, and although tacrolimus was adjusted, kidney function continued to fluctuate. Over the following months, repeated biopsies consistently revealed pigment casts coexisting with pyelonephritis and antibody-mediated rejection. Despite treatment with antibiotics and intensified immunosuppression, the casts persisted. Further evaluation confirmed that the casts contained hemoglobin, and further investigations confirmed glucose-6-phosphate dehydrogenase (G6PD) deficiency as the underlying cause. After managing infections and rejection, his kidney function stabilized with creatinine at 1.55 mg/dl. Pigment cast nephropathy in the posttransplant setting can be triggered by a myriad of causes, which in the index case were deceased donor trauma–related myoglobinuria, infections, and finally G6PD deficiency–related hemoglobinuria. The trigger factors for G6PD deficiency include certain drugs and infections.

Background Vitamin D deficiency is common in CKD and associated with cardiovascular disease (CVD) and bone mineral metabolism. The long-term impact of cholecalciferol supplementation on CVD is unknown. We tested the effects of cholecalciferol supplementation on CVD outcomes [major adverse cardiovascular events (MACE)], progression of CKD, and markers of bone mineral metabolism and inflammation in patients with pre-dialysis CKD. Materials and Methods The study was a single-center, prospective, randomized, placebo-controlled, double blind clinical trial. Patients with CKD, between 18-75 years, estimated glomerular filtration rate 10-45 mL/min/1.73m 2 , serum 25(OH)D levels 20-50 ng/mL were enrolled. Participants received either cholecalciferol 60000 IU once/2 weeks or a matching placebo and followed up at every 3 months till 36 months after enrolment. All clinical, demographic, and biomarker characteristics were analyzed at baseline and at annual follow-up. Results 692 participants were screened, of which 126 were enrolled. However, 37 participants dropped before randomization. 89 participants were randomized: 46 to the cholecalciferol group and 43 to the placebo group. Both groups were similar with respect to MACE events, need for renal replacement therapy, and all-cause mortality. Over one year, serum 25(OH)D increased in the cholecalciferol group [Mean diff between groups: 31.89, 95% CI: 20.46 to 43.32, p <0.001]. Serum calcium increased, whereas C-reactive protein and bone-specific alkaline phosphatase levels decreased in the cholecalciferol group. Conclusions In this feasibility phase of a randomized double-blind clinical trial, Cholecalciferol treatment was safe and effective in modulating surrogate markers of inflammation and bone metabolism, but its effect on CVD outcome or progression of CKD in vitamin D-insufficient patients with stage G3-G4 CKD remains uncertain.

Background:Circulating levels of fibroblast growth factor 23 (FGF23) increase early in chronic kidney disease and are associated with a faster progression and increased mortality. However, evidence from South Asia is limited. We investigated the association between baseline intact FGF23 levels and adverse kidney outcomes in the ICKD cohort. Methods:A prospective cohort of adult participants with mild to moderate CKD enrolled at 11 Indian hospitals was included if baseline FGF-23 levels were available. Plasma iFGF-23 was measured using a two-site ELISA. The primary endpoint was major adverse kidney events (MAKE: a composite of kidney failure, ≥50% decline in eGFR, or kidney death). Secondary endpoints included individual MAKE components, all-cause mortality, and cardiovascular mortality. Cox proportional hazards models were used to evaluate the associations between iFGF23 and time-to-event outcomes. Results:A total of 602 participants were followed up for a median duration of 5.3 years. MAKE developed in 266 (49.3%) participants; 223 (41.3%) progressed to kidney failure; 211 (43.5%) reached ≥50% eGFR decline; and 66 (11.0%) died. iFGF23 was significantly associated with MAKE (SHR 1.23, 95% CI 1.02-1.47, p = 0.027), kidney failure (SHR 1.28, 95% CI 1.04-1.58, p = 0.02), and all-cause mortality (HR 1.39, 95% CI 1.05-1.83, p = 0.02) in unadjusted and age- and sex-adjusted Cox proportional hazards models. However, in the fully adjusted model with clinical variables, none of the associations remained statistically significant. Conclusion:In this prospective cohort of Indian CKD patients, iFGF23 levels did not provide independent prognostic information after accounting for established risk factors. Routine iFGF23 testing has limited incremental prognostic value in this setting.

Background Kidney transplantation, especially from a living donor, is the best treatment for patients with end-stage kidney disease (ESKD). Compared to healthy non-donors, kidney donors have shown a higher incidence of ESKD, increased long-term risk for cardiovascular and all-cause mortality, although the absolute risk is small. In this study, we explored the changes in the urinary proteome after living kidney donation and their possible association with renal adaptations in kidney donors. Materials and Methods Voluntary kidney donors aged >18 years were enrolled in the study. Proteomic analysis of urine samples from the study subjects at baseline and 6-month follow-up was performed using liquid chromatography-mass spectrometry (LC-MS). Results 20 out of 25 enrolled subjects completed 6 6-month follow-ups. Mean eGFR significantly reduced at follow-up (106 to 80 mL/min/1.73m 2 ). eGFR reached ∼76% of the pre-donation value. We identified 350 differentially expressed proteins (DEPs), of which 149 were upregulated and 201 were downregulated after kidney donation. Gene ontology enrichment analysis shows that these DEPs are involved in various molecular, biological functions and pathways. Conclusion The study identifies potential biological processes and pathways involved in adaptation following unilateral nephrectomy. These observations require confirmation and validation.

Background: Autosomal dominant kidney disease (ADPKD) is the most common monogenic disorder leading to renal failure with limited therapeutic options. We aimed to assess the efficacy and safety of metformin in nondiabetic ADPKD patients and its role in slowing disease progression. Materials and Methods: We conducted a prospective, randomized controlled, open labelled clinical trial and enrolled 52 nondiabetic adults aged 18-60 years with typical ADPKD, estimated glomerular filtration rate (eGFR) > 45 mL/min/m(2), and no risk factors of rapid disease progression. Participants were randomized in a 1:1 ratio by a computer-generated random number table into metformin + standard of care group (metformin arm) and standard of care group (Control arm). Primary outcome of the study was to evaluate the effects of metformin versus control arm on the percentage and absolute change in eGFR over a 6-month period. Results: Mean (SD) age of the cohort was 37.15 (10.16) years with half of them being females. The mean (SD) baseline htTKV and eGFR were 335.67 (153.3) mL/m and 100.23 (25.95) mL/min/m(2), respectively. Clinical exome sequencing was available in nine (17.3%) patients of which two-thirds had PKD1 mutation. Baseline characteristics were distributed equally across randomized groups. Baseline proteinuria was significantly higher in the metformin arm (p = 0.014). The eGFR difference and percentage change in eGFR was not different between the groups at 6 months (p = 0.53 and 0.48, respectively). There was no statistically significant difference in htTKV and percentage change in htTKV at 6 months between the groups, although an increase in htTKV was numerically smaller in the metformin group (p = 0.769, 0.805). Blood pressure, body weight, body mass index (BMI), and proteinuria also did not differ between the two groups. Only half of the cohort tolerated the maximum dose of metformin. Around two-thirds of patients reported adverse effects, most commonly asthenia. Conclusion: Metformin appears to be safe and well tolerated in nondiabetic patients with ADPKD.

Vitamin D has been shown to improve immunity as well as vascular function. We investigated the effect of cholecalciferol on T-cell phenotype in cultured peripheral blood mononuclear cells (PBMCs) from twenty vitamin D-deficient, non-diabetic chronic kidney disease (CKD) subjects. We also studied vitamin D effects on endothelial and vascular function markers in human aortic endothelial cells (HAECs) and in human aortic smooth muscle cells (HASMCs), respectively. We studied endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinase 38 (p38 Map kinase), protein kinase B (Akt), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in HAECs and α-smooth muscle actin (α-SMA), smooth muscle calponin (SM-Calponin), smooth muscle myosin heavy chain (SM-MHC), and calcium-sensing receptor (CaSR) in HASMCs. Vitamin D receptors (VDRs) and CYP27B1 were studied in both cell types. In cultured PBMCs isolated from CKD subjects, the percentage of T helper 1(TH1) cells significantly decreased while that of T helper 2 (TH2) cells increased after cholecalciferol treatment. No significant change in intracellular and surface markers of T helper 17 (TH17) and T regulatory (Treg) cells was observed. In vitro treatment of HASMCs and HAECs with cholecalciferol led to significant and favorable alterations in mRNA expression of markers of vascular smooth muscle cells, i.e., α-SMA, SM-Calponin, and SM-MHC. Regarding endothelial cell markers, mRNA encoding eNOS, p38 Map kinase, protein kinase B (Akt), NADPH oxidase, VDR, and CYP27B1 were also significantly changed. Finally, the expression levels of the following proteins were notably altered: NADPH oxidase and protein kinase B (Akt) (in HAECs); SM-MHC and SM-Calponin (in HASMCs). In vitro treatment of PBMCs with cholecalciferol led to a favorable change in T-cell population, decreasing TH1 and increasing TH2 cell percentage, along with beneficial alterations in mRNA expression of HASMCs and HAECs’ cell markers. This study provides evidence that cholecalciferol can influence immune and vascular function in CKD.

Background and aims:Vitamin D deficiency, widely prevalent in patients with chronic kidney disease (CKD) could play a role in the pathogenesis of cardiovascular disease (CVD) by causing alterations in endothelial and immune function. We investigated the change in immune and vascular functions following vitamin D supplementation in non-diabetic subjects with stage 3-4 CKD and vitamin D deficiency. Methods:In this single-arm study, non-diabetic CKD subjects aged 18-75 years, eGFR 15-60 ml/min/1.73m2, and serum 25-hydroxyvitamin D3 levels <20 ng/ml were enrolled. Enrolled subjects received a directly observed oral dose of 300,000 IU cholecalciferol at baseline and 8 weeks. Outcome assessments, including immunological, vascular, endothelial, inflammatory, and biochemical parameters, were measured at baseline and 16 weeks. Results:In total, 62 subjects were studied. The mean age was 44 ± 12 years with 58% men. TH1 cells decreased from 17% (9%, 27%) to 11% (6%, 16%) (p=0.002) and TH2 cells increased from 9% (5%, 16%) to 16% (10%, 27%) (p=0.001) after cholecalciferol treatment. A significant increase in mRNA expression of vitamin D-responsive genes (cathelicidin, IL-10, VDR, and CYP27B1) was observed. The levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-23, and IL-6) decreased whereas anti-inflammatory cytokines (IL-4, IL-10, and IL-13) showed an increase. Cholecalciferol treatment improved flow-mediated dilatation (FMD): 8.2% (6.2%, 12.1%) at baseline to 14.1% (10.0%, 20.1%) at 16 weeks (p<0.001). Conclusions:This study confirms that cholecalciferol supplementation influenced immune function as it favored the TH2/TH1 phenotype, favorably affected the levels of inflammatory markers and mRNA expression of vitamin D responsive genes, and improved vascular function in CKD. Clinical Trial Registration:https://www.ctri.nic.in, identifier CTRI/2019/10/021494.

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. While both haemodialysis (HD) and peritoneal dialysis (PD) are commonly used treatment options for ESKD, the choice of dialysis modality in diabetic ESKD patients remains a critical decision influenced by various patient-related, healthcare system, and socio-economic factors. This article examines the factors influencing the selection of dialysis modalities for diabetic patients, with a focus on the challenges and opportunities in low-resource settings. Key considerations include the impact of comorbidities such as peripheral arterial disease and CKD-related mineral bone disorder (MBD), as well as patient preferences, caregiver burden, and the availability of healthcare infrastructure. The article highlights the need for personalized approaches to dialysis selection, considering both clinical outcomes and quality of life. It also emphasizes the potential benefits of home dialysis, including home HD and PD, in improving patient autonomy and long-term survival. The article advocates for better government policies, increased awareness, and improved support systems to enhance the accessibility and efficacy of dialysis treatments, particularly in underserved populations. Further research comparing the outcomes of different dialysis modalities across diverse settings is essential to guide global treatment strategies for diabetic ESKD patients.