Chatzikyrkou C, Herzog C, Ganz MJ
… +4 more, Wiech T, Gröne HJ, Mertens PR, Scurt FG
Clin Kidney J
· 2026 Apr · PMID 41993676
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BACKGROUND: In the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), accurate prognostication of renal outcome is critical. However, the clinical utility of highly precise multi-varia...BACKGROUND: In the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), accurate prognostication of renal outcome is critical. However, the clinical utility of highly precise multi-variable models, such as the ANCA Kidney Risk Score (AKRiS), is often hampered by their complexity. This study aimed to validate a simple alternative: the "Normal" Glomerular Score (NGS), defined as the percentage of normal glomeruli. METHODS: We retrospectively analyzed 188 consecutive patients with biopsy-proven AAV-glomerulonephritis (GN) from a single European center (2001-24). Patients were categorized by NGS: high (>50%), moderate (26%-50%), low (10%-25%) and very low (<10%). We assessed concordance between NGS, Berden classification and AKRiS to determine whether NGS serves as a valid proxy for complex systems. The primary endpoint was death-censored progression to end-stage kidney disease. RESULTS: The NGS strongly indicated presentation renal function; median estimated glomerular filtration rate (eGFR) was 31.4 mL/min in the high NGS group vs 10.8 mL/min in the low cohort ( < .001). It correlated moderately-to-strongly with AKRiS (Rho = -0.714, < .001). Over a 46.6-month median follow-up, dialysis rates were 12.8%, 23.7%, 42.9% and 42.6% in the high, moderate, low and very low NGS groups ( = .003). There was no statistical difference in dialysis rates ( = .98) or long-term eGFR (28 vs 30 mL/min, = .51) between the low and very low groups, indicating a prognostic plateau below 25% normal glomeruli. Cox regression showed a significant hazard ratio for dialysis of 1.432 with each worsening category (95% confidence interval 1.144-1.792). The NGS achieved a C-index of 0.812, statistically inferior to AKRiS (0.831). Subanalysis of post-2015 patients confirmed NGS's prognostic validity with modern rituximab-based induction. CONCLUSION: NGS predicts long-term renal survival in AAV-GN. While not replacing multi-variable models like AKRiS for precise risk assessment in clinical trials, it offers a rapid, accessible estimation of functional nephron mass for bedside stratification.
Bodapati N, Hajat S, Steenkamp R
… +3 more, Gray T, Plummer Z, Nitsch D
Clin Kidney J
· 2026 Apr · PMID 41987872
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BACKGROUND: Acute kidney injury (AKI) incidence is rising and while heat-AKI associations are established, the demographic and clinical groups most vulnerable remain unclear. Identifying these groups is essential for kid...BACKGROUND: Acute kidney injury (AKI) incidence is rising and while heat-AKI associations are established, the demographic and clinical groups most vulnerable remain unclear. Identifying these groups is essential for kidney-specific heatwave guidance. METHODS: A total of 947 342 AKI alerts in England from April to September 2017-21, from UK Renal Registry data, were linked to HadUK-Grid dataset and hospital admission data. We utilized a time-stratified, bidirectional case-crossover design with distributed lag models estimated odds ratios (ORs) for AKI associated with temperatures above 25°C, stratified by demographic characteristics and admission diagnosis. RESULTS: Heat exposure was associated with AKI [OR 1.038; 95% confidence interval (CI) 1.036-1.040 per 1°C rise above 25°C] with highest odds for stage 3 AKI (OR 1.047; 95% CI 1.039-1.055). Associations were more marked in males (OR 1.041; 95% CI 1.037-1.044) than females (OR 1.035; 95% CI 1.032-1.039); odds doubled in those aged ≥85 years (OR 1.054; 95% CI 1.049-1.060) compared with the 45-64 years age group (OR 1.027; 95% CI 1.021-1.032). Ethnic risks varied between Chinese (OR 1.054, 95% CI: 1.012-1.098), White (OR 1.041; 95% CI 1.038-1.044), Indian (OR 1.033; 95% CI 1.019-1.047), Pakistani/Bangladeshi (OR 1.027; 95% CI 1.011-1.044), Caribbean (OR 1.024; 95% CI 1.005-1.042) and African (OR 1.001; 95% CI 0.982-1.021), with differences partly explained by younger age distribution in ethnic minority groups. Heat-related AKI was more marked for admissions of patients with delirium (OR 1.061; 95% CI 1.029-1.094) and with respiratory diseases (OR 1.044; 95% CI 1.037-1.052). CONCLUSIONS: There was effect modification by age for heat-related AKI risk, with especially high risks amongst older individuals; those admitted with delirium or respiratory illness and some ethnic groups. These findings support the development of targeted kidney-specific hot weather guidance to protect the vulnerable populations identified.
Auñón P, Lopes V, Minguez I
… +11 more, Pérez-Romero P, Peña-Ordónez K, Serrano-Soto M, Rivera M, Alonso F, Mercado VR, Moliz C, Cabello V, Morales E, Gutiérrez E, Cavero T
Clin Kidney J
· 2026 Apr · PMID 41987871
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BACKGROUND: Immune-mediated acute tubulointerstitial nephritis (ICI-AIN) is the most common form of immune-mediated renal toxicity induced by immune checkpoint inhibitors (ICIs). It has an excellent response to corticost...BACKGROUND: Immune-mediated acute tubulointerstitial nephritis (ICI-AIN) is the most common form of immune-mediated renal toxicity induced by immune checkpoint inhibitors (ICIs). It has an excellent response to corticosteroids, but there is no consensus on the most suitable steroid regimen. METHODS: A multicentre retrospective study including 62 patients diagnosed with ICI-AIN treated with corticosteroids was conducted. Patients were categorized into two groups based on the duration of corticosteroid treatment: 'short course of steroids (SCS)' (<12 weeks) and 'long course of steroids (LCS)' (≥12 weeks). The study aims to compare the efficacy and toxicity of these two regimens. RESULTS: Twenty-eight patients received SCS and 34 received LCS. Renal recovery was achieved in 89% of patients, with no differences between groups (= 1). Serum creatinine levels were also similar (1.2 mg/dL, = .71) at the end of follow-up. ICI rechallenge was attempted in 18 patients, and ICI-AIN recurred in 5 (28%). Among these, four recurrences occurred in LCS patients, 67% still receiving ≥10 mg of prednisone. Steroid-related adverse events per patient-month were lower in the SCS group (0.027 vs 0.072, 95% confidence interval 0.20-0.68; = .001). At 12 and 18 months, progression-free survival and overall survival were significantly better in the SCS group, even after adjusting for confounders. CONCLUSIONS: SCS is an effective and safe approach for the management of ICI-AIN. It offers a comparable rate of renal recovery, fewer adverse events and possibly more favourable oncological outcomes, compared with a prolonged regimen. Future prospective studies are warranted.
Kinguchi S, Tamura K, Yano Y
… +20 more, Nangaku M, Isaka Y, Maruyama S, Kanegae H, Heerspink HL, Nakagawa N, Nishio S, Asahi K, Yamagata K, Fukui A, Okada H, Narita I, Tsuruya K, Wada J, Terada Y, Mukoyama M, Imai E, Yokota N, Kobayashi K, Kashihara N
Clin Kidney J
· 2026 Apr · PMID 41982250
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BACKGROUND: Hypertriglyceridemia has attracted considerable attention as a residual cardiovascular risk factor in patients with chronic kidney disease (CKD). Pemafibrate, a selective peroxisome proliferator-activated rec...BACKGROUND: Hypertriglyceridemia has attracted considerable attention as a residual cardiovascular risk factor in patients with chronic kidney disease (CKD). Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, is a novel therapeutic option for hypertriglyceridemia in patients with CKD, and is associated with fewer kidney adverse events in this population compared with conventional fibrates. Although appropriate management of hypertriglyceridemia may contribute to improved kidney outcomes, evidence regarding the efficacy and safety of pemafibrate to reduce CKD progression is unknown. The aim of this study is to investigate the effect of pemafibrate on the rate of change in estimated glomerular filtration rate (eGFR) slope in patients with CKD. METHODS: The Japan Kidney Association-Pemafibrate Intervention for Chronic Kidney Disease patients (JKAPI-CKD) study is a prospective, multicenter, open-label, parallel-group, randomized controlled trial. The study will enroll 2200 adults with CKD, defined as eGFR ≥20 ml/min/1.73 m and <60 ml/min/1.73 m, and hypertriglyceridemia [triglyceride level ≥150 mg/dl (fasting) or ≥175 mg/dl (non-fasting)] who have not received pemafibrate or conventional fibrates within 12 weeks prior to consent. Participants will be randomized in a 1:1 ratio to the pemafibrate group (guideline-based conventional therapy plus pemafibrate 0.1-0.4 mg/day) or the control group (guideline-based conventional therapy excluding fibrates). The observation period will be 104 weeks. The primary endpoint is the chronic eGFR slope, defined as the eGFR slope from weeks 12 to 104 after study initiation. RESULTS: On 1 December 2025, a total of 2328 participants had been enrolled, completing the participant enrollment. CONCLUSIONS: The JKAPI-CKD study is anticipated to yield novel insights into the renoprotective effects of pemafibrate in patients with CKD and establish new evidence supporting its use for the management of dyslipidemia in this population.Trial registration: Japan Registry of Clinical Trials (jRCTs031240097).
Xu L, Ng JK, Fung WW
… +4 more, Chan GC, Pang WF, Chow KM, Szeto CC
Clin Kidney J
· 2026 Apr · PMID 41982249
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BACKGROUND: Sarcopenia is a common and serious complication of dialysis patients. In addition to the reduction in total muscle mass, fat infiltration of skeletal muscle as represented by the percentage of intermuscular a...BACKGROUND: Sarcopenia is a common and serious complication of dialysis patients. In addition to the reduction in total muscle mass, fat infiltration of skeletal muscle as represented by the percentage of intermuscular adipose tissue (IMAT%) affects muscle quality and may have prognostic implications. METHODS: We investigated 86 incident peritoneal dialysis (PD) patients. Their total muscle area, skeletal muscle index and IMAT% at the level of third lumbar vertebra (L3) was measured by computer tomography. The relation with functional assessment, bioimpedance spectroscopy (BIS) parameters, survival and peritonitis rate were analyzed. RESULTS: L3 total muscle area and IMAT% had opposite but both significant correlation with functional scores (Morse Fall Scale and Norton Scale) and lean tissue mass measured by BIS, but IMAT% did not have correlation with adipose tissue mass by BIS. IMAT%, but not total muscle area, was independently associated with peritonitis-free survival (adjusted hazard ratio 1.084, 95% confidence interval (CI) 1.027 to 1.144, = .004) and peritonitis rate (adjusted β = 1.091, 95% CI 1.032 to 1.155, = .002). Neither total muscle area nor IMAT% was associated with patient survival or hospitalization rate. CONCLUSION: IMAT% is an independent predictor of peritonitis-free survival and peritonitis rate in incident PD patients. Further studies are needed to validate our results and to develop convenient non-invasive methods for the assessment of IMAT%.
Oba Y, Kamido H, Yoshimoto M
… +9 more, Kurihara S, Ikuma D, Mizuno H, Yamanouchi M, Suwabe T, Ubara Y, Kono K, Ohashi K, Sawa N
Clin Kidney J
· 2026 Apr · PMID 41982248
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BACKGROUND: Kidney biopsy is the gold standard diagnostic technique for nephrologists. Appropriate patient positioning facilitates physiological stability and access to target anatomy. Factors such as patient weight, siz...BACKGROUND: Kidney biopsy is the gold standard diagnostic technique for nephrologists. Appropriate patient positioning facilitates physiological stability and access to target anatomy. Factors such as patient weight, size and medical history, including respiratory or circulatory disorders, should guide position selection. However, most kidney biopsies are performed exclusively in the prone position and procedures are often deferred when this is not feasible. Although lateral kidney biopsy has been reported, it remains uncommon and its applications are not well established. We aimed to demonstrate the safety and utility of lateral kidney biopsies. METHODS: We retrospectively reviewed patients who underwent lateral kidney biopsy at Toranomon Hospital Kajigaya between October 2015 and February 2025. Vital signs and blood test results pre- and post-biopsy were analysed. RESULTS: Twenty-five patients underwent lateral kidney biopsies; six had abdominal aortic aneurysms (AAAs), 12 had respiratory distress (7 with massive ascites or pleural effusions, 2 with obesity, 2 with organomegaly and 1 with pericardial effusion), 6 had major joint pain (4 thin, 1 with scoliosis and 1 with arthritis) and 1 had stoma. All patients were histologically diagnosed and received appropriate treatment. Vital signs remained stable and only one patient with splenomegaly experienced a bleeding complication, which was not readily predictable and unlikely related to biopsy position. CONCLUSIONS: Lateral kidney biopsy offers a viable alternative for the accurate diagnosis of kidney diseases in patients in whom the prone position is challenging, including those with AAA, anasarca-induced respiratory distress or significant joint pain due to body habitus.
Gemander N, Dao M, Kalbacher E
… +4 more, Fantoni JC, Provot F, Correas JM, Joly D
Clin Kidney J
· 2026 Apr · PMID 41982247
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BACKGROUND: Renal angiomyolipomas (AMLs) drive substantial morbidity in tuberous sclerosis complex (TSC) through haemorrhage and repeated invasive procedures. While mammalian target of rapamycin inhibitors (mTORis) reduc...BACKGROUND: Renal angiomyolipomas (AMLs) drive substantial morbidity in tuberous sclerosis complex (TSC) through haemorrhage and repeated invasive procedures. While mammalian target of rapamycin inhibitors (mTORis) reduce AML volume, long-term real-world data on clinically meaningful bleeding and procedure outcomes remain limited, particularly in cohorts enriched for high-risk imaging phenotypes. METHODS: We conducted a multicentre observational study (2004-2020) in three French tertiary centres. Among 103 included patients, the 96 with TSC constituted the primary analysis set. We assessed AML-related haemorrhage and selective arterial embolization (SAE). For patients initiating mTORi, follow-up was split into pre- and post-initiation periods and incidence rate ratios (IRRs) were estimated using Poisson regression with patient-time offsets and patient-clustered robust standard errors; generalized estimating equation Poisson and negative binomial models were used as sensitivity analyses. RESULTS: Total follow-up was 694.3 patient-years. Thirty-nine patients (40.6%) initiated an mTORi (everolimus 94.9%). Haemorrhage rates decreased from 0.061 to 0.007 events per patient-year after mTORi initiation {IRR 0.11 [95% confidence interval (CI) 0.02-0.62]} and SAE rates decreased from 0.197 to 0.020 sessions per patient-year [IRR 0.10 (95% CI 0.04-0.29)]. Therapeutic inertia remained substantial: among 57 never-treated patients, high-risk imaging features and active complications were frequent at the last assessment. CONCLUSIONS: In this long-term real-world cohort of TSC-associated renal AMLs, mTORi initiation was associated with markedly lower rates of AML haemorrhage and SAE. Despite these benefits, many high-risk patients remained untreated in routine care, supporting earlier nephrology referral, systematic risk stratification and timely treatment initiation to reduce preventable AML-related morbidity.
Welberry Smith M, Wrigley A, Kojro A
… +3 more, Emmanouilidou A, O'Callaghan J, Woywodt A
Clin Kidney J
· 2026 Apr · PMID 41982246
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To date, the environmental impact of kidney transplantation has received much less attention than that of dialysis. Facilitating a pre-emptive transplant is probably one of the most environmentally friendly interventions...To date, the environmental impact of kidney transplantation has received much less attention than that of dialysis. Facilitating a pre-emptive transplant is probably one of the most environmentally friendly interventions available in kidney care, as it avoids dialysis, with its requirements for water and energy. However, transplant assessment also requires scrutiny, as it involves a multitude of tests, often with duplication of tests and sometimes with little, if any, evidence (e.g. cardiac testing of asymptomatic patients). Organ retrieval often involves air travel of either the organ or a surgical team, although more innovative approaches, such as drone transport, are being tested. Transplant anaesthesia also has an environmental footprint linked to volatile substances. Surgical tray optimization is well established in other surgical specialties to reduce the effects of repeatedly sterilizing instruments that are only rarely used. Post-transplant patients have a lot of regular blood tests, and it is time we scrutinise those and find a better balance between safe care and environmental footprint. Virtual appointments have become much more common since the COVID-19 pandemic and we should use them where appropriate, for example in long-term care of stable transplant patients. Transplantation is a very research-oriented specialty, and this also has an environmental footprint that is amenable to intervention. In addition, our congresses and conferences have an environmental footprint, and it is for us to promote meetings with just as much learning and interaction but less travel, waste and energy use. The opportunities are there for us to take and our tips provide ideas for clinical teams to turn kidney transplantation into a showcase for excellent, safe and environmentally friendly care in nephrology.
Agur T, Steinmetz T, Haran M
… +7 more, Rahamimov R, Goldman S, Nagel N, Meisel E, Zingerman B, Nesher E, Rozen-Zvi B
Clin Kidney J
· 2026 Apr · PMID 41969627
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BACKGROUND: Kidney transplant recipients (KTRs) face a heightened risk of cardiovascular disease but the impact of post-transplant mineral and bone disorders on this risk remains unclear. This study investigated the asso...BACKGROUND: Kidney transplant recipients (KTRs) face a heightened risk of cardiovascular disease but the impact of post-transplant mineral and bone disorders on this risk remains unclear. This study investigated the association between serum calcium, phosphate and calcium-phosphate (Ca × P) product levels and cardiovascular outcomes. METHODS: In this retrospective cohort study, adult KTRs transplanted between 2005 and 2014 at a large centre were analysed. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality and a composite of MACE and mortality. Cumulative exposure to abnormal mineral levels was assessed using time-weighted average calculations. Cox proportional hazards models were used to evaluate associations adjusting for confounders, including estimated glomerular filtration rate (eGFR). Mineral abnormalities were analysed both as continuous variables and by quartiles. RESULTS: The study included 649 KTRs (median follow-up 2943 days), with 109 patients (16.8%) experiencing MACE. Over time, calcium exposure decreased, while phosphate and Ca × P product exposure increased. Hypercalcaemia was not significantly associated with MACE, all-cause mortality or the composite outcome. In contrast, hyperphosphataemia remained significantly associated with an increased risk of MACE {hazard ratio [HR] 1.414 [95% confidence interval (CI) 1.044-1.916]) and the composite outcome [HR 1.353 (95% CI 1.064-.721)] even after adjustment for eGFR. Elevated, Ca × P product levels were similarly associated with increased cardiovascular risk [HR 1.055/mg/dl (95% CI 1.015-1.096) and HR 1.043/mg/dl (95% CI 1.013-1.075), respectively]. CONCLUSIONS: While hypercalcaemia does not independently predict cardiovascular outcomes post-transplant, sustained hyperphosphataemia and elevated Ca × P product are significant risk factors for adverse cardiovascular events in KTRs.
Beauregard N, Vinson AJ, McIsaac DI
… +10 more, Girard C, Sood MM, Kendall CE, Sweet A, Singla R, Motazedian P, Hundemer GL, Knoll G, Dhaliwal S, Bugeja A
Clin Kidney J
· 2026 Apr · PMID 41948120
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BACKGROUND: Females develop hypertension later and are less likely to receive chronic kidney disease (CKD) prevention treatments. The long-term impact of these differences remains unclear. We aimed to investigate sex-bas...BACKGROUND: Females develop hypertension later and are less likely to receive chronic kidney disease (CKD) prevention treatments. The long-term impact of these differences remains unclear. We aimed to investigate sex-based differences in the in CKD outcomes among older adults with hypertension. METHODS: We conducted a population-based retrospective cohort study of adults aged ≥66 years with new hypertension using linked health data from Ontario, Canada (1 January 2010, to 31 December 2021). The primary composite outcome was a 40% decline in estimated glomerular filtration rate (eGFR) or kidney failure. We used Cox proportional hazards models to calculate hazard ratios (HRs) and Fine-Gray models accounting for death as a competing risk (subdistribution HRs, sHRs). RESULTS: Incident hypertension developed in 121 490 individuals (57.7% female; mean age 73.1 years; mean eGFR 83.2 mL/min/1.73 m²; median follow-up 6.8 years), 17 343 (14.3%) experienced the composite kidney outcome. The crude incidence rate per 1000 person-years was higher for females compared with males (22.0 in females vs 21.1 in males; < .001). Females had a higher adjusted risk of the primary outcome, after accounting for death {sHR 1.10 [95% confidence interval (CI) 1.07-1.14]}. Females had a higher crude incidence of eGFR <60 mL/min/1.73 m² than males (66.6 vs 59.4; < .001), and a higher adjusted risk [sHR 1.15 (95% CI 1.13-1.18)]. For eGFR <45 mL/min/1.73 m², females had a higher crude incidence (19.2 vs 17.5; < .001) and a higher adjusted risk [sHR 1.13 (95% CI 1.10-1.17)] compared with males. CONCLUSION: Older females with new onset hypertension were more likely to develop a 40% decline in eGFR or kidney failure compared with older males. This study will inform hypertension management practices in aging populations.
Polderman N, Shaw V, Anderson CE
… +11 more, Desloovere A, McAlister L, Nelms CL, Paglialonga F, Pugh P, Qizalbash L, Snauwaert E, Renken-Terhaerdt J, Tuokkola J, Greenbaum LA, Shroff R
Clin Kidney J
· 2026 Apr · PMID 41948119
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Optimal nutrition is central to growth and development in all children, and is particularly relevant in those with chronic illnesses. This document provides 10 practical, evidence-informed tips on the assessment and mana...Optimal nutrition is central to growth and development in all children, and is particularly relevant in those with chronic illnesses. This document provides 10 practical, evidence-informed tips on the assessment and management of the nutritional prescription in children with chronic kidney disease (CKD) and those receiving dialysis. The 10 tips synthesize work of the Paediatric Renal Nutrition Taskforce, an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations for the nutritional management of children with kidney diseases. We describe a comprehensive, three-dimensional nutritional assessment (anthropometry, dietary intake, biochemical markers) and regular monitoring tailored to age, CKD stage and treatment modality. Energy prescriptions should approximate requirements of healthy peers, adjusting toward the upper end of the suggested dietary intake (SDI) for faltering growth, and accounting for dialysate-derived glucose in peritoneal dialysis (PD). Protein targets should align with the SDI, avoiding restriction to prevent impaired linear growth and protein-energy wasting; higher intakes are needed in children on PD to replace dialysate protein losses. Early, proactive strategies should address feeding barriers through fortification, oral supplements, timely initiation of enteral tube feeding and planning for gastrostomy insertion in patients on PD. A diet emphasizing fiber-rich, nutrient-dense foods is recommended, with individualized management of calcium, phosphate, potassium and sodium, and targeted micronutrient monitoring and supplementation. Reducing ultra-processed foods supports improved diet quality and mitigates cardiometabolic risk. Multidisciplinary care and ongoing outcome-focused research remain essential to refine nutritional targets and delivery approaches that optimize growth and long-term health in pediatric CKD.
Clin Kidney J
· 2026 Apr · PMID 41948118
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We describe a case of immunoglobulin A nephropathy (IgAN) treated with targeted-release budesonide (Nefecon) that resulted in notable systemic adverse effects. The patient developed cushingoid features, weight gain, hype...We describe a case of immunoglobulin A nephropathy (IgAN) treated with targeted-release budesonide (Nefecon) that resulted in notable systemic adverse effects. The patient developed cushingoid features, weight gain, hyperglycaemia and leucocytosis within 3 months of therapy. During dose tapering he experienced symptomatic adrenal insufficiency confirmed by low morning cortisol, requiring hydrocortisone replacement. Despite Nefecon's design for terminal ileum absorption, and hence assumed minimal systemic exposure, this case demonstrates clinically significant adverse effects and adrenal suppression. These findings underscore the need for careful monitoring and patient education when initiating and tapering Nefecon in IgAN management.
Zuo L, Gan L, Guan T
… +9 more, He W, Ye H, Peng Q, Liu B, Dai H, Ba Y, Xue L, Lowe M, Enoiu M
Clin Kidney J
· 2026 Apr · PMID 41948117
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BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a common and debilitating condition in patients receiving in-centre haemodialysis. This study evaluated the efficacy and safety of difelikefalin (a new,...BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a common and debilitating condition in patients receiving in-centre haemodialysis. This study evaluated the efficacy and safety of difelikefalin (a new, intravenous treatment for moderate-to-severe CKD-aP approved in >40 countries) in a Chinese population receiving haemodialysis. METHODS: This Phase 3, multicentre, randomized placebo-controlled study included a 12-week double-blind treatment period, during which patients received either difelikefalin or placebo, followed by an optional 14-week open-label extension, in which all patients received difelikefalin. Endpoints included change from baseline in the Worst Itching Intensity Numerical Rating Scale (WI-NRS) at Week 4 (primary endpoint), the percentage of patients achieving a clinically relevant ≥3-point change in WI-NRS, patient-reported health-related quality-of-life measures, and incidence of adverse events. RESULTS: Difelikefalin-treated patients showed significantly greater improvements in least squares mean change from baseline in WI-NRS at Week 4 of the double-blind period compared with placebo [difelikefalin minus placebo: -0.81 (95% confidence interval: -1.25, -0.37); = .0003], and patients with ≥3-point improvement in WI-NRS at Week 12 (48.7% versus 33.8%, nominal = .0235). Difelikefalin also improved health-related quality of life, with clinically relevant changes observed in 5-D itch and Skindex-10 in most patients at Week 4 of the open-label extension (estimated ≥62% and ≥56%, respectively). Adverse events were mostly mild or moderate in severity and generally consistent with the known safety profile of difelikefalin. CONCLUSION: Difelikefalin effectively reduced pruritus intensity and improved quality of life in Chinese patients with CKD-aP receiving haemodialysis, supporting its use in this population.
Chen HR, Tang H, Zhang M
… +7 more, Lin JA, Lin XQ, Zhang JY, Lu JY, Xia HM, Gao X, Liao X
Clin Kidney J
· 2026 Apr · PMID 41948115
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BACKGROUND: This study sought to explore the bone metabolism clinical features of pediatric nephrotic syndrome (NS) patients receiving glucocorticoid (GC) therapy and evaluate the bone-protective and renal-protective eff...BACKGROUND: This study sought to explore the bone metabolism clinical features of pediatric nephrotic syndrome (NS) patients receiving glucocorticoid (GC) therapy and evaluate the bone-protective and renal-protective efficacy of alfacalcidol in this cohort. METHODS: A prospective randomized cohort study was conducted at the Department of Nephrology, Guangzhou Women and Children's Medical Center, enrolling 86 children from January 2021 to June 2022. Participants were randomized into two groups ( = 43 each): the alfacalcidol group administered 0.05 µg/kg alfacalcidol plus 300 mg calcium daily, and the control group given 400 IU vitamin D3 plus 300 mg calcium daily. Primary outcomes included bone mineral density (BMD) and cumulative GC dose, measured at baseline, 3 months, 6 months and study endpoint. Secondary outcomes covered bone metabolism biomarkers (type I collagen C-terminal telopeptide and type I procollagen N-terminal propeptide), urine protein-to-creatinine ratio and proteinuria remission status. RESULTS: Multivariate regression identified cumulative GC dose as a risk factor for BMD reduction, while alfacalcidol treatment correlated with BMD improvement. Lumbar spine BMD increased by 0.028 ± 0.008 g/cm² in the alfacalcidol group versus 0.002 ± 0.008 g/cm² decrease in the control group ( = .035). Alfacalcidol recipients had lower cumulative GC doses, shorter time to initial urinary protein negativity (7 vs 11 days, = .004), higher 1-year GC discontinuation rate (67.9% vs 38.7%, = .025), lower proteinuria relapse rate (7.9% vs 41.9%, = .045) and more favorable proteinuria remission survival curves ( = .035). CONCLUSIONS: Alfacalcidol may have potential bone-protective and renal-protective effects in pediatric NS patients undergoing GC therapy (Trial registration: ChiCTR2200055790).
Martínez-Castelao A, Hasegawa T, Fernández-Fernández B
… +18 more, Górriz JL, Ortiz A, Quero M, Fernández-Fresnedo G, Zamora JI, Soler MJ, Primo-Alvarez JC, Robles NR, Venegas NI, Ojeda FI, Gil-Paraíso A, Llorente-Cortijo IM, Martínez-Villanueva C, Poch E, Sanchez-Rodriguez J, Li Y, Yuko S, Navarro-González JF
Clin Kidney J
· 2026 Apr · PMID 41948114
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BACKGROUND: Chronic kidney disease (CKD) is frequently associated with systemic inflammation. However, the relationship between inflammatory cytokines and CKD progression remains incompletely understood. METHODS: The PRO...BACKGROUND: Chronic kidney disease (CKD) is frequently associated with systemic inflammation. However, the relationship between inflammatory cytokines and CKD progression remains incompletely understood. METHODS: The PROGRESER study (Factores de PROGRESion en Enfermedad Renal) was a multicentre, prospective observational cohort that included patients with CKD stage G3. A total of 17 plasma and 10 urinary inflammatory cytokines were measured in 165 participants, at baseline, 18 months and 36 months, using a fully automated HISCL immune analyser. Unsupervised cluster analysis identified six distinct patient clusters. Associations between cytokine levels and kidney outcomes [estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), KDIGO risk scores, kidney replacement therapy (KRT)], cardiovascular outcomes (cardiovascular hospitalization) and death was assessed during a follow-up of up to 10 years. The primary outcome was a combination of KRT or death. RESULTS: Plasma levels of 15 cytokines and 6 urinary cytokines differed between patients with CKD and 30 healthy controls. Of these, plasma interleukin (IL)-8 levels were inversely associated with uACR slopes, while IL-22, tumour necrosis factor (TNF)-α and Growth Differentiation Factor 15 (GDF-15) levels showed positive correlations with uACR progression. Additionally, plasma TNF-α and GDF-15 were associated with KRT and/or death with 10 years.Cluster analysis of plasma IL-8, IL-22, TNF-α and GDF-15 identified six distinct patient clusters. Clusters 3 (elevated levels of IL-22, TNF-α, GDF-15), 4 (elevated levels of all four cytokines) and the uncommon Cluster 5 (high GDF-15 only) were associated with worse kidney, cardiovascular and survival outcomes, while Cluster 6 (low cytokine levels) represented patients with slower disease progression and the best long-term outcomes. Over time, patients frequently transitioned to more severe clusters. CONCLUSION: In CKD G3 patients, systemic inflammation can be stratified using cytokine profiles. Specific cytokine clusters are linked to faster progression of CKD and cardiovascular disease, and to worse long-term outcomes including kidney failure and mortality.
Xie S, Thomas A, Ponte B
… +4 more, Ackermann D, Pruijm M, Marques-Vidal P, Bochud M
Clin Kidney J
· 2026 Apr · PMID 41939824
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BACKGROUND: Chronic kidney disease (CKD) is a global public health issue. Heavy metals and trace elements may influence kidney function. This study aimed to investigate the association between plasma concentrations of 24...BACKGROUND: Chronic kidney disease (CKD) is a global public health issue. Heavy metals and trace elements may influence kidney function. This study aimed to investigate the association between plasma concentrations of 24 heavy metals and trace elements and kidney function, including estimated glomerular filtration rate (eGFR) and CKD status in European adults. METHODS: This study included adult participants from the Swiss Kidney Project on Genes in Hypertension cohort (2008-2013). Associations with eGFR and CKD were assessed using multivariable linear and logistic regression, and restricted cubic spline models for non-linear trends. Mixture effects were evaluated using least absolute shrinkage and selection operator for variable selection, followed by weighted quantile sum (WQS) regression. Multiple sensitivity analyses were conducted to assess robustness. RESULTS: Of the 988 participants (mean age 47.0 years, 52.3% female), 72 (7.3%) had CKD. In multivariable linear models with continuous exposures, higher plasma tin, antimony and iodine were associated with lower eGFR, but none remained significant after false discovery rate (FDR) correction. In quartile analyses, lower eGFR was observed in the highest exposure quartile for zinc and thallium, with a borderline trend for iodine. Arsenic showed a significant non-linear relationship with eGFR, with a turning point at ≈11.7 μg/l and an estimated decline of 3.27 ml/min/1.73 m from the 25th percentile. For CKD, elevated levels of molybdenum, copper and iodine were linked to higher odds, whereas aluminum and silver were inversely associated. After FDR correction, only molybdenum remained significant. WQS regression indicated that tin, antimony, iodine, molybdenum and cadmium contributed most to lower eGFR, while iodine, arsenic, palladium, manganese and copper showed the strongest associations with CKD. CONCLUSIONS: After FDR adjustment across 24 elements, no individual element remained associated with eGFR, whereas molybdenum remained linked to CKD. Findings involving iodine were nominal and should be considered exploratory. Longitudinal and mechanistic studies are needed to validate these observations and clarify causality.
Calabrese V, Tripepi GL, Santoro D
… +4 more, Cernaro V, Mezzatesta S, Mattace-Raso F, Torino C
Clin Kidney J
· 2026 Apr · PMID 41929583
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BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASIs) are widely used antihypertensive drugs. Due to the hyperkalaemic effect, previous 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines dis...BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASIs) are widely used antihypertensive drugs. Due to the hyperkalaemic effect, previous 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines discouraged RAASI use in patients with severe chronic kidney disease (CKD). However, due to the recently discovered cardioprotective and nephroprotective effects, the 2022 KDIGO guidelines suggest their use in CKD stage 4-5. To our knowledge, few studies have explored the use of RAASIs in dialysis patients. This study aims to evaluate the impact of RAASIs on kalaemia and on mortality in a large sample of dialysis patients. METHODS: We included 4764 dialysis patients from the Sicilian Registry of Nephrology, Dialysis and Transplantation. The longitudinal association between RAASI intake and serum potassium was analysed by univariate and multivariate linear mixed models. The survival models were computed through univariate and multivariate Cox models and Cox models with mixed effects. RESULTS: The study included 4764 patients, of whom 1207 (25%) were treated with RAASis. Multivariate longitudinal models showed a direct association between RAASI intake and serum potassium {adjusted β = 0.10 [95% confidence interval (CI) 0.05-0.15], < .001}. However, multivariate Cox analysis did not show any association between RAASI intake and mortality [adjusted hazard ratio 0.76 (95% CI 0.43-1.30), = .31]. No differences in the impact of RAASIs on mortality were found in the analysis stratified for potassium levels (cut-off 5.1 mmol/l). CONCLUSIONS: In the present study we found, in a large cohort of dialysis patients, an independent, direct association between RAASIs and serum potassium. However, no association was found between RAASI intake and mortality. Although specific randomized controlled trials are needed to confirm our findings, RAASI intake did not seem to have a negative impact on patients' survival, thus suggesting a re-evaluation of RAASI use in this population.