Am J Kidney Dis
· 2026 May · PMID 42025332
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The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Th...The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. The KDOQI work group reviewed the Kidney Disease: Improving Global Outcomes (KDIGO) guideline statements and practice points and provided perspective for implementation within the context of clinical practice in the United States. Overall, the KDOQI work group agrees with the majority of the KDIGO guideline statements. Throughout this commentary, the KDOQI work group provides clarifications and additional areas for consideration when implementing these practice points.
Am J Kidney Dis
· 2026 Jul · PMID 42019602
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RATIONALE & OBJECTIVE: Creatinine-based estimated glomerular filtration rate (eGFR) and cystatin C-based eGFR (eGFR) may be inaccurate for patients with rheumatoid arthritis (RA) due to sarcopenia and inflammation. This...RATIONALE & OBJECTIVE: Creatinine-based estimated glomerular filtration rate (eGFR) and cystatin C-based eGFR (eGFR) may be inaccurate for patients with rheumatoid arthritis (RA) due to sarcopenia and inflammation. This study characterized changes in eGFR and eGFR after 2 RA treatment regimens and their association with RA disease activity biomarkers. STUDY DESIGN: Secondary observational analysis of randomized controlled trial of tumor necrosis factor (TNF) inhibitor plus methotrexate (MTX) versus triple therapy (MTX, sulfasalazine, and hydroxychloroquine). SETTING & PARTICIPANTS: Patients with active RA enrolled at multiple US institutions into an immunomodulatory treatment trial. EXPOSURE: RA disease activity biomarkers. OUTCOME: eGFR and eGFR at baseline and weeks 6, 18, and 24. ANALYTICAL APPROACH: Describing eGFR and eGFR at baseline and during the follow-up period in the overall cohort and by treatment arm. Adjusted mixed-effects linear models to estimate the associations of RA activity biomarkers with eGFR. RESULTS: The study included 157 eligible trial participants (median age, 58 years; 75% female). At baseline, the mean eGFR was lower than the eGFR (63.3 vs 84.2; difference, -20.9 mL/min/1.73 m [95% CI, -24.7 to -17.0]). Over 24 weeks, neither eGFR nor eGFR changed overall (1.74 mL/min/1.73 m [95% CI, -0.77 to 4.24] and -0.28 mL/min/1.73 m [95% CI, -3.71 to 3.15], respectively). Multiple disease activity biomarkers, including vascular cell adhesion protein 1, interleukin 6, tumor necrosis factor receptor 1 (TNFR1), leptin, and resistin, were inversely associated with eGFR and/or eGFR at baseline in adjusted models. During the follow-up period, only TNF-RI change was inversely associated with eGFR change (-2.91 mL/min/1.73 m [95% CI, -4.48 to -1.33]) in adjusted models whereas no biomarker change was significantly related to eGFR change. LIMITATIONS: No measured GFR, a relatively short follow-up period, and potential false discovery because of the large number of associations examined. CONCLUSIONS: Among patients with actively treated RA, eGFRcys is consistently lower than eGFRcr. Overall, neither eGFRcys nor eGFRcr demonstrated a significant change following RA treatments, despite reductions in disease activity biomarkers. Further studies incorporating directly measured GFR are warranted. PLAIN-LANGUAGE SUMMARY: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can also affect the kidneys. Doctors often check kidney function using blood tests for creatinine or cystatin C, but inflammation and RA medications may influence these tests differently. We studied patients with RA who began either a conventional drug combination (triple therapy) or a tumor necrosis factor (TNF) inhibitor. We measured kidney function and inflammation markers over a 6-month period after the treatment. We found that both cystatin C-based and creatinine-based estimates of kidney function were unchanged overall. An analysis of trial participants who received triple therapy showed an increase in cystatin C-based kidney function, along with a decrease in 1 inflammatory biomarker, TNF receptor 1 (TNFR1); however, the creatinine-based estimates remained unchanged. Understanding how RA treatment and inflammation affect kidney function tests may help develop better ways to monitor kidney function in people with inflammatory diseases.
RATIONALE & OBJECTIVE: Denosumab, an osteoporosis medication, may induce hypocalcemia, secondary hyperparathyroidism (SHPT), and hypophosphatemia. We studied these risks compared with zoledronate and whether the risks di...RATIONALE & OBJECTIVE: Denosumab, an osteoporosis medication, may induce hypocalcemia, secondary hyperparathyroidism (SHPT), and hypophosphatemia. We studied these risks compared with zoledronate and whether the risks differ based on underlying kidney function. STUDY DESIGN: Observational study, new-user design with active comparator. SETTING & PARTICIPANTS: Patients aged 50 year or older initiating denosumab (n = 5,085) or zoledronate (n = 3,599) in Stockholm, Sweden (2011-2021). EXPOSURE: Denosumab or zoledronate initiation. OUTCOME: Hypocalcemia, with secondary outcomes of SHPT and hypophosphatemia assessed within 180 days of dispensing of study medications. ANALYTICAL APPROACH: Cox regression to estimate hazard ratios (HRs), Aalen-Johansen estimators to compute absolute risks (ARs) and risk differences (RDs), and splines to explore effect modification by baseline estimated glomerular filtration rate (eGFR). RESULTS: Twenty-five percent of the study population had eGFR < 60 mL/min/1.73 m (chronic kidney disease [CKD] stage 3a [15%] and 3b [8%]). Compared with zoledronate, denosumab initiation was associated with higher rates of hypocalcemia (HR, 2.10 [95% CI, 1.28-4.33]; RD, 0.72% [95% CI, 0.26-1.18]), SHPT (HR, 2.85 [95% CI, 1.94-5.48]; RD, 1.33% [95% CI, 0.91-1.85]), and hypophosphatemia (HR, 1.96 [95% CI, 1.30-3.38]; RD, 0.85% [95% CI, 0.33-1.38]), which occurred mainly within the first 2 weeks of treatment. Adverse event rates were greater with lower kidney function and mainly limited to people with eGFR < 60 mL/min/1.73 m. The denosumab-associated absolute risk differences for hypocalcemia (RD, 2.12% versus 0.19%; P for interaction = 0.04) and SHPT (RD, 4.84% versus 0.03%; P for interaction < 0.001) were greater in patients with eGFR < 60 versus ≥60 mL/min/1.73 m. For hypophosphatemia, the RDs were numerically higher, but no multiplicative interaction was observed across lower eGFR strata (P for interaction = 0.1). The results were similar when restricting previous users of oral bisphosphonates, when requiring sustained abnormal laboratory values, and across different testing rate scenarios. LIMITATIONS: Residual confounding inherent to observational studies and lack of generalizability to other populations. CONCLUSIONS: Compared with zoledronate, denosumab was associated with higher risks of hypocalcemia, SHPT, and hypophosphatemia, particularly among users with moderate-to-advanced CKD, highlighting the need for careful monitoring of these parameters, especially immediately after treatment initiation. PLAIN-LANGUAGE SUMMARY: Denosumab is a drug used to prevent fractures, but it can affect calcium, phosphate, and parathyroid hormone levels in the blood. We studied adults aged 50 years or older in Stockholm, Sweden, to examine whether these risks differ by kidney function. Compared with zoledronate, denosumab was associated with higher risks of low calcium, low phosphate, and high parathyroid hormone levels. These adverse events occurred mainly within the first 2 weeks after starting treatment and were largely limited to people with moderate to advanced chronic kidney disease. Our findings suggest that patients with chronic kidney disease treated with denosumab should receive careful monitoring of mineral and hormone levels, especially at treatment initiation.
COPA (coatomer protein complex subunit α) syndrome is a rare inborn error of immunity associated with constitutive activation of type I interferon signaling. Organ inflammation and damage (eg, lungs, kidneys, joints) usu...COPA (coatomer protein complex subunit α) syndrome is a rare inborn error of immunity associated with constitutive activation of type I interferon signaling. Organ inflammation and damage (eg, lungs, kidneys, joints) usually develops early in life. Kidney involvement occurs in a subset of COPA syndrome patients, with the potential for rapid progression to kidney failure. Through an international collaboration, we identified COPA syndrome patients who developed kidney failure and underwent a kidney transplantation. The aim of the present report was to describe (1) the kidney involvement at presentation, (2) the immunosuppressive strategies used before and after transplant, (3) the kidney graft outcomes, and (4) the evolution of the underlying COPA disease after transplantation. Five COPA syndrome patients were included. Kidney failure manifested at young age (range, 5-40 years). Kidney involvement was heterogenous between patients (ANCA-associated vasculitis-like disease, lupus or immune complex-mediated glomerulonephritis or overlapping phenotypes), and all had advanced histological damage at clinical presentation. Pulmonary disease of variable severity was also present in all patients. Kidney disease responded poorly to multiple lines of immunosuppression, justifying kidney transplantation between the ages of 7.5 and 42 years. After a follow-up of 10 months to 12 years, we report favorable graft outcomes in all patients (CKD stage 2-3b), although 1 patient developed polyomavirus infection (skin, kidney graft) and another died of progressive lung disease.
Am J Kidney Dis
· 2026 Mar · PMID 41921740
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Individuals are increasingly exposed to a diverse array of chemicals through the environment, consumer products, and occupational settings. These exposures, often involving substances with unknown or emerging implication...Individuals are increasingly exposed to a diverse array of chemicals through the environment, consumer products, and occupational settings. These exposures, often involving substances with unknown or emerging implications for human health, may pose significant kidney health risks because many are processed by the kidneys and excreted in the urine. Kidneys are particularly vulnerable to injury from inorganic chemicals such as lead, cadmium, and mercury. These originate from geogenic sources, but their exposures are multiplied by anthropogenic activities. Emerging data detail possible kidney risks from chemicals derived entirely from anthropogenic activities as well such as from per- and polyfluoroalkyl substances (PFAS), melamine, and agrochemicals. Chronic kidney disease resulting from these environmental exposures is likely underdiagnosed in clinical practice. This review describes the sources of exposure, systemic effects, and potential nephrotoxicity of implicated chemicals, aiming to increase the recognition of environmental exposures as contributors to unexplained new kidney disease. A thorough exposure history and specialized laboratory evaluation may be used for diagnosis in high-risk individuals. Increased clinical awareness and dedicated research efforts are essential to understand and mitigate environmental nephrotoxic exposures and protect kidney health.
Complement 3 glomerulopathy (C3G) is a rare complement-mediated kidney disease characterized by overactivation of the alternative pathway (AP). C3G encompasses 2 subtypes, dense deposit disease and C3 glomerulonephritis,...Complement 3 glomerulopathy (C3G) is a rare complement-mediated kidney disease characterized by overactivation of the alternative pathway (AP). C3G encompasses 2 subtypes, dense deposit disease and C3 glomerulonephritis, both of which lead to C3 deposition in the glomeruli, progressive kidney dysfunction, and, ultimately, kidney failure. The pathophysiology of C3G and the underlying complement AP overactivation are often driven by genetic variants and/or acquired autoantibodies. These systemic drivers can affect native and transplanted kidneys; thus, C3G is associated with a high risk of recurrence in allografts. Recurrence of C3G in posttransplant kidneys has a particularly poor prognosis and leads to a high rate of graft loss. Therapeutic strategies for native and posttransplant recurrent C3G that are largely supportive have shown limited benefit in improving kidney survival, as have therapies targeting the terminal complement cascade downstream of pathogenic AP overactivation. In contrast, emerging therapies that target AP overactivation are showing promise for more effective disease modification. In light of the evolving treatment landscape, this review provides an update on the current state of knowledge regarding the pathophysiology, prognosis, and treatment options for native and posttransplant recurrent C3G.
Am J Kidney Dis
· 2026 Mar · PMID 41905620
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Online hemodiafiltration (OL-HDF) and medium cut-off (MCO) dialyzers augment diffusion-based hemodialysis (HD) with convective clearance to enhance removal of middle molecules. In large-scale randomized trials, OL-HDF ap...Online hemodiafiltration (OL-HDF) and medium cut-off (MCO) dialyzers augment diffusion-based hemodialysis (HD) with convective clearance to enhance removal of middle molecules. In large-scale randomized trials, OL-HDF appears to reduce all-cause, cardiovascular, and infection-related mortality compared with high-flux HD, particularly when convection volumes exceed 23 L per session. Data suggest a graded effect; higher achieved convection volumes are associated with greater benefit, and advantages have been observed across the analyzed subgroups. Evidence also indicates better preservation of patient-reported quality of life compared with high-flux HD. Large-scale observational registry data, while subject to inherent limitations, support beneficial outcomes and generalizability to routine clinical practice. MCO membranes enhance middle-molecule clearance on conventional hemodialysis machines via enlarged pore size and internal-filtration back-filtration. However, the long-term clinical data remain limited, and the convective component is not externally measured or prescribed. This perspective distils mechanistic and clinical insights on both OL-HDF and MCO-HD and evaluates the published evidence, including solute clearance studies, mortality outcomes, and patient-reported quality-of-life data. We outline actionable prescription strategies and opportunities for individualized treatment optimization. Our goal is to provide clinicians with a concise roadmap to personalize and integrate convection-enhancing therapies in everyday practice.
Obesity is highly prevalent among patients with end-stage kidney disease (ESKD) and remains a major barrier to kidney transplantation, the optimal kidney replacement therapy for improving survival and quality of life. We...Obesity is highly prevalent among patients with end-stage kidney disease (ESKD) and remains a major barrier to kidney transplantation, the optimal kidney replacement therapy for improving survival and quality of life. Weight loss strategies tailored to the ESKD population are urgently needed to expand access. This review examines the role of lifestyle interventions, pharmacotherapy, and bariatric surgery in supporting transplant candidacy. Although lifestyle modification is foundational, its effectiveness in ESKD is limited by metabolic, physical, and psychosocial barriers. Pharmacologic agents, particularly glucagon-like peptide-1 receptor agonists, offer promising weight loss and metabolic benefits although access and safety data in ESKD remain limited. Bariatric surgery, increasingly performed in this population, provides durable weight loss, especially for patients requiring ≥20% reduction in weight to meet the transplant body mass index criterion. We also highlight the systemic barriers, including payor policies, program-level variability, and disparities in access, that shape patient outcomes. An integrated approach combining clinical strategies with supportive policies is essential to reduce inequities and expand timely access to kidney transplantation for patients with ESKD and obesity.
Choi D, Xu F, Zaganjor I
… +3 more, Onufrak S, Han S, Pavkov ME
Am J Kidney Dis
· 2026 Jun · PMID 41881385
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RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is one of the most highly prevalent chronic conditions in the United States and associated with a high risk of premature death, particularly from cardiovascular disease...RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is one of the most highly prevalent chronic conditions in the United States and associated with a high risk of premature death, particularly from cardiovascular disease. However, contemporary national trends in all-cause mortality among adults with CKD in the United States remain unclear. This study examined trends in all-cause mortality among US adults with CKD from 1999 to 2019. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adults aged ≥20 years who participated in the 1999-2016 National Health and Nutrition Examination Survey (NHANES), with mortality follow-up through December 2019. EXPOSURE: CKD defined by an estimated glomerular filtration rate < 60 mL/min/1.73 m or a urinary albumin-creatinine ratio ≥ 30 mg/g. OUTCOME: All-cause mortality. ANALYTICAL APPROACH: Age-standardized all-cause mortality rates were estimated for 3 survey periods: 1999-2004, 2005-2010, and 2011-2016. Average percent change (APC) in age-standardized mortality and adjusted relative risk (RR) of CKD-associated mortality for each survey period were estimated. RESULTS: Age-standardized mortality rate was 23.0 deaths/1,000 person-years (95% CI, 19.8-26.2) among adults with CKD surveyed 1999-2004 and 21.8 deaths/1,000 person-years (95% CI, 18.8-24.9) for those surveyed 2011-2016 (APC, -0.4% [95% CI, -1.4 to 0.5]). In contrast to men whose mortality declined (APC, -3.0 [95% CI, -3.5 to -2.6]), mortality rates increased among women with CKD (APC, 2.3 [95% CI, 1.7-3.0]). Adjusted RRs for CKD-associated mortality remained approximately 2-fold higher compared with adults without CKD across all time periods. LIMITATIONS: The cross-sectional design of NHANES precludes analysis of CKD progression or incident CKD during follow-up. CONCLUSIONS: All-cause mortality remained stable among adults with CKD and was about 2 times higher than for those without CKD. However, increasing mortality trends in specific demographic subpopulations may indicate the need for focused public health strategies and further research to address and reduce mortality disparities.