Key Points Patients with IgA nephropathy and proteinuria are at risk of kidney failure despite use of guideline-recommended renin-angiotensin system and sodium-glucose cotransporter 2 (SGLT2) inhibition. Atrasentan reduces proteinuria in IgA nephropathy, but its efficacy as adjunct to renin-angiotensin system and SGLT2 inhibition has not been rigorously tested. Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy treated with renin-angiotensin system and SGLT2 inhibitors. Background Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of atrasentan has not been rigorously determined. Methods We performed a randomized, double-blind, placebo-controlled crossover study of atrasentan in adults with IgA nephropathy, eGFR ≥30 ml/min per 1.73 m 2 , and urinary protein >0.5 g/d while on maximal, stable RASi and SGLT2i. Participants were randomized 1:1 to either sequence AB or sequence BA (0.75 mg atrasentan [A] once daily during period 1 and matching placebo [B] during period 2, or vice versa), with a 12-week washout period in between. The primary end point was the change in urinary protein-to-creatinine ratio (UPCR) to week 12. The secondary end point was the change in UPCR to week 24. Safety end points included the type, incidence, severity, seriousness, and relatedness of adverse events (AEs). Results We recruited 54 participants with mean age 48 years (SD 12), 43% female, mean (SD) eGFR 63 (22) ml/min per 1.73 m 2 , and median UPCR 1.0 g/g (Q1–Q3, 0.7–1.4). Treatment with atrasentan versus placebo resulted in a difference in geometric mean percentage change in UPCR at week 12 of −25.3% (95% confidence interval, −36.8 to −11.7; P < 0.001). The treatment difference in UPCR between atrasentan versus placebo during treatment period 2 at week 24 was −26.4% (95% confidence interval, −45.8 to −0.0). There was one unrelated serious adverse event. Fluid retention events were uncommon, and none required hospitalization. There were no study drug discontinuations due to treatment-related adverse events and no deaths. Conclusions Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy and proteinuria ≥0.5 g/d treated with RASi and SGLT2i therapy. Atrasentan was well tolerated, and no new safety signals emerged. Clinical Trial registry name and registration number: NCT05834738.

Arteriovenous fistula (AVF) creation induces substantial haemodynamic alterations through increased venous return and reduced systemic vascular resistance. Although cardiovascular remodelling after AVF creation has been described in haemodialysis populations, prospective echocardiographic data in pre-dialysis chronic kidney disease (CKD) patients remain limited. This prospective observational study enrolled adult pre-dialysis CKD patients undergoing elective AVF creation at the University of Malaya Medical Centre between March 2021 and December 2022. Transthoracic echocardiography was performed before AVF creation, at early follow-up (4–12 weeks), and at late follow-up ( ≥ ≥ 6 months). Parameters assessed included left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), stroke volume (SV), left ventricular mass index (LVMI), cardiac index (CI), pulmonary artery systolic pressure (PASP), and right ventricular functional indices. Paired analyses were performed using paired t-tests or Wilcoxon signed-rank tests according to normality of paired differences. Thirty-four patients underwent baseline echocardiography, with 27 completing early follow-up and 14 completing late follow-up. Mean age was 65.2 ± 8.9 years, and 52.9

The human leukocyte antigen (HLA) system is central to immune function, transplantation compatibility, and disease susceptibility. However, comprehensive data on HLA allele and haplotype distributions in Southeast Asia, particularly Malaysia, remain limited despite the region's rich genetic diversity. In this study we analyzed HLA class I (A, B, C) and class II (DRB1, DQB1) alleles in 4,882 individuals of Malay, Chinese, Indian, and Indigenous descent from genotyping data collected between 2000 and 2020. HLA genotyping was performed using PCR-SSP and PCR-SSO methods. Haplotype frequencies (HF) were resolved using haplotype segregation analysis (HSA) and the expectation-maximization (EM) algorithm, with linkage disequilibrium (LD) and Hardy-Weinberg equilibrium (HWE) evaluated across loci. The most frequent alleles included HLA-A*11, -A*02, -B*15, -B*40, -C*07, -C*03, -DRB1*15, and -DQB1*03, with notable variation among ethnic groups. A total of 1,416 unique A ∼ B ∼ DRB1 ∼ DQB1 haplotypes and 1,317 A∼C∼B∼DRB1∼DQB1 haplotypes were identified, with A*33∼C*03∼B*58∼DRB1*03∼DQB1*02 being the most prevalent overall (4.0 %). Ethnic-specific haplotypes were also delineated, underscoring the population's complex genetic architecture. Principal component analysis demonstrated genetic relatedness between Malaysian groups and other East and South Asian populations. This study represents the largest multiethnic HLA dataset in Malaysia to date. The findings contribute valuable insights for population genetics, donor registry optimization, and future disease association and immunogenomic research in Southeast Asia.

Abstract Background and objectives Cardiac surgery associated acute kidney injury can lead to increased morbidity, mortality, and hospitalization. The available risk assessment tools have limited predictive ability. Machine learning has been increasingly utilized to predict acute kidney injury in cardiac surgery patients in recent times due to its ability to handle complex clinical data. However, its predictive value remains uncertain. This study evaluates the predictive performance of machine learning models for acute kidney injury post-cardiac surgery. Methods A systematic review and meta-analysis was conducted by searching Web of Science, PubMed, Science Direct, Google Scholar, Scopus, and Cochrane Library up to 31st December 2025. PRISMA guidelines were followed. Included studies were assessed for machine learning model performance and acute kidney injury predictors, with effect measures including area under the receiver operator characteristic curve (AUC), sensitivity, and specificity. Pooled estimates were calculated using a random-effects model with 95% confidence intervals. Risk of bias was assessed using PROBAST. The meta-analysis in our study was performed using R version 4.5.0. Results The systematic search yielded 45 studies that met our inclusion criteria, encompassing 13 distinct model types, which include 81 models for training and 162 for validation. The overall pooled AUC was 0.83 (95% CI: 0.79–0.85) in the training and 0.76 (95% CI: 0.75–0.78) in the validation cohorts. Pooled sensitivity and specificity in the training dataset were 0.75 (95% CI: 0.71–0.79) and 0.81 (95% CI: 0.72–0.87), respectively. In the validation dataset, pooled sensitivity was 0.61 (95% CI: 0.53–0.69), while specificity was 0.82 (95% CI: 0.77–0.86). Analysis showed an overall 44.4% high risk of bias, particularly due to the analysis domain of PROBAST. Conclusion This study suggests that machine learning based models could potentially serve as a viable framework for predicting the risk of post-cardiac surgery AKI, however, highlighting the need for model optimization and validation in a diverse population before clinical implementation. Trial registration The study was registered with PROSPERO (CRD42024576556).

KEY POINTS:Patients with IgA nephropathy and proteinuria are at risk of kidney failure despite use of guideline-recommended renin-angiotensin system and sodium-glucose cotransporter 2 (SGLT2) inhibition. Atrasentan reduces proteinuria in IgA nephropathy, but its efficacy as adjunct to renin-angiotensin system and SGLT2 inhibition has not been rigorously tested. Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy treated with renin-angiotensin system and SGLT2 inhibitors. BACKGROUND:Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of atrasentan has not been rigorously determined. METHODS:We performed a randomized, double-blind, placebo-controlled crossover study of atrasentan in adults with IgA nephropathy, eGFR ≥30 ml/min per 1.73 m 2 , and urinary protein >0.5 g/d while on maximal, stable RASi and SGLT2i. Participants were randomized 1:1 to either sequence AB or sequence BA (0.75 mg atrasentan [A] once daily during period 1 and matching placebo [B] during period 2, or vice versa), with a 12-week washout period in between. The primary end point was the change in urinary protein-to-creatinine ratio (UPCR) to week 12. The secondary end point was the change in UPCR to week 24. Safety end points included the type, incidence, severity, seriousness, and relatedness of adverse events (AEs). RESULTS:We recruited 54 participants with mean age 48 years (SD 12), 43% female, mean (SD) eGFR 63 (22) ml/min per 1.73 m 2 , and median UPCR 1.0 g/g (Q1-Q3, 0.7-1.4). Treatment with atrasentan versus placebo resulted in a difference in geometric mean percentage change in UPCR at week 12 of -25.3% (95% confidence interval, -36.8 to -11.7; P < 0.001). The treatment difference in UPCR between atrasentan versus placebo during treatment period 2 at week 24 was -26.4% (95% confidence interval, -45.8 to -0.0). There was one unrelated serious adverse event. Fluid retention events were uncommon, and none required hospitalization. There were no study drug discontinuations due to treatment-related adverse events and no deaths. CONCLUSIONS:Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy and proteinuria ≥0.5 g/d treated with RASi and SGLT2i therapy. Atrasentan was well tolerated, and no new safety signals emerged. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:NCT05834738 .

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterised by progressive cyst growth leading to loss of kidney function. The Mayo Clinic ADPKD prognostic tool stratifies patients by risk of progression based on height-adjusted total kidney volume (HtTKV) and age. This study evaluated the tool's applicability in Southeast Asians using data from 50 Malaysian ADPKD patients. HtTKV was measured by MRI. Kidney function was estimated by CKD-EPI-based eGFR. The Mayo model eGFR strongly correlated with actual eGFR over 24 months (cc 0.748–0.815, p < 0.001). Bland-Altman analysis showed high accuracy with P30 of Mayo eGFR values more than 90% of measured eGFR. Results indicate the Mayo prognostic tool provides accurate disease progression predictions in Southeast Asian ADPKD patients.

BACKGROUND:Proteinuria and chronic metabolic acidosis may negatively impact renal allograft survival. This study aims to evaluate dietary intervention in reducing proteinuria and correcting metabolic acidosis among kidney transplant recipients (KTRs). METHODS:This is a prospective dietary intervention study. KTRs who have proteinuria ≥ 0.5g/d or chronic metabolic acidosis with serum bicarbonate ≤ 22 mmol/L for at least two readings in the past 6 months were recruited. All recruited subjects were given one-to-one diet counseling for moderate dietary protein restriction at 0.8 g/kg of ideal body weight (IBW) and high vegetable and fruit intake by a research dietitian. All subjects were encouraged to replace animal protein with plant protein. The duration of the study was 3 months. Changes in proteinuria and serum bicarbonate levels pre- and postintervention were analyzed. RESULTS:A total of 30 KTRs (26 with proteinuria and four with chronic metabolic acidosis) were enrolled and completed the intervention phase. Proteinuria reduced significantly after 1 month of the intervention (z = -2.643, P = .008) in alignment with a significant reduction in dietary protein (z = -2.376, P = .018) and dietary acid load (z = -2.149, P = .032). However, this effect was not sustainable when the dietary protein intake was increased at 3 months. Significant weight reduction was observed after 1 month (z = -3.379, P = .001) and 3 months (z = -3.503, P < .001) after dietary intervention. No statistically significant change in serum bicarbonate was found. CONCLUSIONS:Dietary intervention can induce favorable dietary changes, leading to reductions in proteinuria and body weight in KTRs. Hence, dietary counseling should be part of the multiprong approach to managing KTRs.

BACKGROUND:Polypharmacy in chronic kidney disease (CKD) is substantial. Clinicians and patients are often reluctant to add medications to already complex regimens, partly due to concerns about diminishing efficacy and increased adverse effects. We assessed whether efficacy and safety of canagliflozin is modified by polypharmacy status in patients with type 2 diabetes and CKD. METHODS:We conducted a post-hoc analysis of the CREDENCE trial, which evaluated the effects of canagliflozin on outcomes in patients with type 2 diabetes and CKD. Participants were categorized as no polypharmacy (0-4 medicines), polypharmacy (5-9 medicines), or hyperpolypharmacy (≥10 medicines). We assessed the relative effects of canagliflozin on clinical and safety outcomes by polypharmacy status using Cox proportional hazards models. We assessed absolute benefits using Poisson regression. The primary outcome was a composite of doubling of serum creatinine, kidney failure or death due to cardiovascular or kidney disease. RESULTS:Among 4401 participants, 612 (14%), 2404 (55%), and 1385 (31%) were categorized as no polypharmacy, polypharmacy and hyperpolypharmacy, respectively. Mean number of medications was 8.3 (SD 3.77). The effect of canagliflozin on kidney and cardiovascular outcomes was consistent irrespective of polypharmacy status, with no interaction observed for safety outcomes (all P-interaction > 0.06). Rates of treatment discontinuation increased with medication burden, but were lower with canagliflozin versus placebo, regardless of polypharmacy status (P-interaction = 0.16). Incidence of all-cause hospitalization, and heart failure hospitalization or cardiovascular death increased with higher medication burden, thus absolute risk reductions were estimated to be substantially greater in patients with polypharmacy and hyperpolypharmacy. CONCLUSION:Among patients with type 2 diabetes and CKD, the efficacy and safety of canagliflozin appears consistent regardless of polypharmacy status, with larger estimated absolute reductions in hospitalizations and cardiovascular events in those experiencing polypharmacy or hyperpolypharmacy. These findings suggest that polypharmacy alone should not preclude consideration of SGLT2 inhibitor therapy in patients with CKD and type 2 diabetes for whom treatment is otherwise indicated.