Am J Kidney Dis
· 2025 May · PMID 41744068
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Historically, the paradigm for all maladies was associated with an imbalance of the 4 humors: blood, black bile, yellow bile, and phlegm. Although our understanding of disease has evolved significantly since the time of...Historically, the paradigm for all maladies was associated with an imbalance of the 4 humors: blood, black bile, yellow bile, and phlegm. Although our understanding of disease has evolved significantly since the time of Hippocrates, a similar cornerstone of inpatient and ambulatory care involves understanding and correcting imbalances of volume. The kidneys are the principal organs controlling extracellular volume, capable of both sensing and altering salt retention through multiple redundant pathways, including the sympathetic nervous system and the renin-angiotensin-aldosterone system. Various disease states including sepsis, heart failure, and liver cirrhosis can dramatically alter the movement of volume across body compartments, leading to pathologic responses. Greater understanding of the role of the endothelial glycocalyx, the harms of volume overload among critically ill patients, and the impact of venous congestion on kidney function has challenged the traditional paradigms of volume management. Because both hypovolemia and hypervolemia are symptomatic conditions associated with adverse outcomes, managing volume is an essential skill for the nephrologist. In this Core Curriculum, we review the physiology of volume disorders and management strategies through a series of clinical cases.
Liu P, Caffrey N, Donald M
… +10 more, Smekal M, Harris M, Tam-Tham H, Duquette D, Garg AX, Hundemer G, Christiansen CF, Sawhney S, Ravani P, Elliott MJ
Am J Kidney Dis
· 2026 May · PMID 41722887
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RATIONALE & OBJECTIVE: Many mortality risk prediction models for individuals with kidney failure are available; however, their development did not involve end-users during the design process, and none are widely used in...RATIONALE & OBJECTIVE: Many mortality risk prediction models for individuals with kidney failure are available; however, their development did not involve end-users during the design process, and none are widely used in clinical practice. We identified the needs and preferences of end-users to inform the development and enhance the usability of a mortality risk prediction tool for people with kidney failure. STUDY DESIGN: A half-day, online consensus workshop was conducted using a modified nominal group technique. SETTING & PARTICIPANTS: People with lived experience of kidney failure (patients with or without receipt of kidney replacement therapy and their caregivers) or kidney failure management (health care providers and policymakers) recruited from across Canada. ANALYTICAL APPROACH: Preferences were elicited in 3 topic areas: the tool's intended use, timing (prediction horizon and update frequency), and relevant predictor variables. Conventional content analysis of discussion transcripts was conducted to elaborate on the findings. RESULTS: Eighteen individuals from across 5 provinces participated in the workshop, including 7 patients, 3 caregivers, and 8 health care providers or policymakers. Participants prioritized the following: (1) tool use within clinics and in consultation with nephrologists; (2) personalization of the prediction time horizons and reassessment of risk prediction following changes in clinical condition; and (3) inclusion of coexisting conditions, kidney failure characteristics (eg, unplanned dialysis start), and frailty status as key predictor variables. Analysis of transcripts identified several factors influencing the tool's usability, including provider trust, comfort in discussing mortality risk, patient privacy, availability of follow-up and support systems, patient readiness, and feasibility of incorporating desired predictor variables. LIMITATIONS: Media-based recruitment and participation barriers may have limited the representativeness of the patient sample. CONCLUSIONS: End-users of mortality prediction tools for people with kidney failure prioritized design and use considerations. Co-design of future tools to align with end-user preferences may enhance their usability and enhance their uptake. PLAIN-LANGUAGE SUMMARY: Many calculators predict survival for people with kidney failure on dialysis, but few are used in practice, in part because they were not created with input from people who need them. To learn what users want, we conducted an online consensus workshop involving individuals living with kidney failure, caregivers, clinicians, and policymakers from across Canada. The participants discussed how and when the tool should be used and on which factors the tool should be based. They prioritized the use of the tool during clinic visits, personalizing the prediction horizon, and taking into account health conditions and frailty. The participants emphasized the importance of trust, comfort in communication, and support systems when using the tool. Involving users in tool design may enhance its usability and adoption.
Peschard VG, Yang W, Zhang X
… +13 more, Shlipak MG, Brown RT, Tangri N, Lagunes AC, Unruh ML, Taliercio JJ, Weir MR, Rincon-Choles H, He J, Chen J, Tamura MK, Lash JP, Schrauben SJ
Am J Kidney Dis
· 2026 May · PMID 41713837
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RATIONALE & OBJECTIVE: Physical function is essential for independent living and good health. The trajectory of physical function and its association with important clinical outcomes is understudied in chronic kidney dis...RATIONALE & OBJECTIVE: Physical function is essential for independent living and good health. The trajectory of physical function and its association with important clinical outcomes is understudied in chronic kidney disease (CKD). We describe the associations of baseline and longitudinal self-reported physical function with cardiorenal outcomes among individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Participants of the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Physical Component Summary (PCS) score and PCS slope. OUTCOME: Incident heart failure (HF), incident end-stage kidney disease (ESKD), and all-cause mortality. ANALYTICAL APPROACH: Multivariable adjusted Cox regression models examined associations of baseline PCS score with outcomes and in separate models assessed associations of PCS slope with outcomes. Effect modification was assessed by age, sex, race, and estimated glomerular fitration rate groups. RESULTS: Lower baseline PCS scores (per 10 points) were independently associated with higher risks of incident HF (HR, 1.21 [95% CI, 1.11-1.32]) and all-cause mortality (HR 1.21 [95% CI, 1.16-1.26]) but not with incident ESKD (HR, 0.98 [95% CI, 0.93-1.04]). PCS change (per 4 points annually) was also independently associated with higher risks for all 3 outcomes: incident HF (HR, 1.22 [95% CI, 1.05-1.42]), all-cause mortality (HR, 1.22 [95% CI, 1.13-1.32]), and incident ESKD (HR, 1.11 [95% CI, 1.01-1.22]). LIMITATIONS: Residual confounding, selection bias, and linearity assumption. CONCLUSIONS: Among individuals with CKD, baseline self-reported physical function was significantly associated with increased risk of incident HF and mortality after full adjustment. In addition, longitudinal changes in self-reported physical function were associated with incident HF, incident ESKD, and mortality, even after accounting for baseline self-reported physical function. These findings support monitoring for and testing of early interventions to preserve physical function and potentially prevent or delay adverse outcomes. PLAIN-LANGUAGE SUMMARY: People with chronic kidney disease (CKD) often experience a decline in physical function, but it is unclear how the decline impacts important outcomes in CKD. This study explored how both initial physical function and changes over time relate to important outcomes in CKD, including heart failure, kidney failure, and death. We found that people who rated their physical function lower or whose physical function declined over time were more likely to experience heart failure, kidney failure, and death. These patterns held true even after accounting for other heatlh conditions. These findings suggest that early interventions to preserve physical function could potentially prevent or delay these outcomes in patients but should be tested.
Am J Kidney Dis
· 2026 May · PMID 41713836
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RATIONALE & OBJECTIVE: Reducing central venous catheter (CVC) use for hemodialysis among patients with kidney failure receiving maintenance hemodialysis is an important priority. Previous reports have suggested that part...RATIONALE & OBJECTIVE: Reducing central venous catheter (CVC) use for hemodialysis among patients with kidney failure receiving maintenance hemodialysis is an important priority. Previous reports have suggested that partnerships between hemodialysis facilities and vascular access surgeons lead to reduced rates of CVC use. We studied whether a greater intensity of these relationships was associated with less use of CVCs. STUDY DESIGN: National retrospective cohort study. SETTING & PARTICIPANTS: 109,293 patients with kidney failure receiving maintenance hemodialysis within 4,402 facilities. EXPOSURE: Facility-level Herfindahl-Hirschman index (HHI), an established measure of market concentration used as a proxy for closeness of the relationship between hemodialysis facilities and vascular access surgeons, with higher indices suggesting closer relationships. OUTCOME: Greater than 90 days of continuous CVC use for hemodialysis in 2018. ANALYTICAL APPROACH: Mixed-effects logistic regression model including patient-level covariates, facility-level covariates, and facility random effects. Dialysis facilities were divided into quartiles based on increasing HHI. Multiple sensitivity analyses were conducted using similar models. RESULTS: Patients in facilities in the highest HHI quartile were less likely to have continued catheter use for more than 90 days than those in the lowest quartile (odds ratio, 0.80; 95% confidence interval, 0.75-0.87; P < 0.001). This association was also observed in multiple sensitivity analyses. LIMITATIONS: Misclassification of the exposure, inclusion of patients insured by Medicare Fee-for-Service, unmeasured confounding. CONCLUSIONS: More extensive partnerships between dialysis facilities and vascular access surgeons reflected by the HHI were associated with lower rates of CVC use for hemodialysis. PLAIN-LANGUAGE SUMMARY: The goal of this study was to learn if patients in dialysis facilities that partnered with surgeons (measured using a marker of market concentration) who place and maintain permanent hemodialysis vascular access grafts and fistulas experienced lower use of a temporary form of vascular access for hemodialysis, central venous catheters, which are associated with an increased risk of infection. We found that closer partnerships between hemodialysis centers and surgeons were associated with less use of catheters for the patients served by those dialysis centers. These findings may inform strategies to reduce the use of central venous catheters and improve outcomes for patients with kidney failure requiring dialysis.
Hemodialysis allows people with kidney failure to survive vital organ failure; however, most do not recover premorbid functional status. Despite early efforts focused on increased removal of small molecular weight solute...Hemodialysis allows people with kidney failure to survive vital organ failure; however, most do not recover premorbid functional status. Despite early efforts focused on increased removal of small molecular weight solutes, high levels of morbidity and mortality persist due to the condition underlying kidney failure, comorbid medical conditions, and poor clearance of larger molecules. Early studies demonstrated that hemodiafiltration increases the removal of larger molecules through convective clearance. Recent studies have documented improvements in cardiovascular events, quality of life, and mortality. We review the mechanics of hemodiafiltration and the scientific data supporting improved outcomes.
Am J Kidney Dis
· 2026 Feb · PMID 41577383
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The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2025 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Management of Nephrotic Syndrome in Ch...The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2025 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Management of Nephrotic Syndrome in Children. The KDOQI work group reviewed the KDIGO guideline statements and practice points and provided perspective for implementation within the context of clinical practice in the United States. The updated guidelines reflect contemporary US practice and offer highly relevant guidance that is harmonized with the International Pediatric Nephrology Association's guidelines published in 2020 and 2022. A focus on close monitoring and characterization of the disease status for children with nephrotic syndrome remains central to treatment and management decisions, noting that the lack of insurance coverage for urine dipsticks in the United States is a significant barrier to optimal disease management. As more treatment options become available to children with nephrotic syndrome, the detailed practice points are a sound tool to help providers engage patients and their families in joint decision making. The clinical utility of the guidelines would be enhanced by inclusion of practice points on the incorporation of genetic testing results into treatment decisions, as well as factors to consider when treating and managing patients at high risk for progression to end-stage kidney disease-those with secondary steroid-resistant nephrotic syndrome and those with the chronic kidney disease high-risk APOL1 genotype. The research needs detailed in the updated guidelines reflect the exciting direction of the practice landscape to provide patient-centered, precision-based care.
Am J Kidney Dis
· 2026 May · PMID 41564997
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The clinical challenges and safety concerns associated with the use of erythropoiesis-stimulating agents (ESAs) have provided the rationale for developing novel therapeutic approaches that address the complex pathophysio...The clinical challenges and safety concerns associated with the use of erythropoiesis-stimulating agents (ESAs) have provided the rationale for developing novel therapeutic approaches that address the complex pathophysiology of anemia in chronic kidney disease (CKD). Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral agents that effectively increase and maintain hemoglobin levels in patients with CKD. These agents stimulate the endogenous production of erythropoietin and enhance iron metabolism by activating hypoxia-inducible factors. Despite their efficacy, the use of some HIF-PHIs has been limited to patients on maintenance dialysis in some countries, including the United States, due to unresolved cardiovascular safety concerns in patients with CKD not on dialysis. In this review, we examine the mechanisms of action and erythropoietic effects of HIF-PHIs, evaluate undesirable on-target and off-target effects, and address cardiovascular and other safety concerns that have been raised in comparison to ESAs. We discuss how this novel class of oral anemia drugs may impact clinical practice, including their potential use in kidney transplant recipients.
Yamamoto S, Kaimori JY, Motooka D
… +12 more, Taniguchi H, Lee G, Inoue M, Imanaka T, Yasuda S, Nishimura K, Kajiwara N, Kawano Y, Doi Y, Oka T, Sakaguchi Y, Isaka Y
This case report investigates the genetic basis of collagenofibrotic glomerulopathy (CG), a type of collagen type III glomerulopathy. It is a rare kidney disease characterized by collagen III deposition. A 47-year-old ma...This case report investigates the genetic basis of collagenofibrotic glomerulopathy (CG), a type of collagen type III glomerulopathy. It is a rare kidney disease characterized by collagen III deposition. A 47-year-old man with CG, born to consanguineous parents, underwent whole-exome sequencing. A homozygous truncating variant in STAB2 and a heterozygous variant in STAB1 were identified. Neither of the proteins encoded by STAB2 and STAB1 was expressed in the kidney glomeruli, suggesting a systemic mechanism for CG development. The patient's mother and brother, with homozygous or heterozygous STAB1 and heterozygous STAB2 variants, were unaffected. These observations suggest that the homozygous truncating variant of STAB2 was crucial for CG in our patient. This study provides initial evidence implicating STAB1 and STAB2 in CG pathogenesis. Further studies are needed to confirm the present findings, elucidate the roles of stabilin-1 and stabilin-2 in CG, and investigate their potential for systemic involvement.
Am J Kidney Dis
· 2026 May · PMID 41548738
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RATIONALE & OBJECTIVE: Unemployment is common among patients receiving maintenance dialysis, and peritoneal dialysis (PD) may better facilitate employment and employer-sponsored health insurance compared with hemodialysi...RATIONALE & OBJECTIVE: Unemployment is common among patients receiving maintenance dialysis, and peritoneal dialysis (PD) may better facilitate employment and employer-sponsored health insurance compared with hemodialysis (HD). This study assessed the employment status of dialysis recipients and examined the association between dialysis modality and the likelihood of insurance transitions after dialysis initiation using employer-sponsored health insurance status as a proxy for patient or household employment. STUDY DESIGN: National retrospective cohort study. SETTING & PARTICIPANTS: Patients represented in the United States Renal Data System who initiated dialysis between January 1, 2013, and December 31, 2018, were followed for between 3 and 30 months. A total of 18,408 in-center HD (IHD) and PD recipients who were employed on a full-time basis at the time of dialysis initiation and had employer-sponsored health insurance for 3 months after dialysis were followed for loss of employer-sponsored health insurance. A total of 104,952 IHD and PD recipients who were unemployed at the time of dialysis initiation and had no employer-sponsored health insurance at 3 months after dialysis initiation were followed for initiation of employer-sponsored health insurance. EXPOSURE: Dialysis modality 3 months after dialysis initiation categorized as IHD with an HD fistula, IHD without a fistula, or PD. OUTCOMES: Employer-sponsored health insurance loss or gain. ANALYTICAL APPROACH: Cause-specific hazards modeling. RESULTS: Compared with patients receiving PD, patients receiving IHD without a fistula (HR, 1.26; 95% CI, 1.18-1.36) and with a fistula (HR, 1.14; 95% CI, 1.05-1.24) were more likely to lose employer-sponsored health insurance. Compared with patients receiving PD, patients receiving IHD without a fistula (HR, 0.55; 95% CI, 0.49-0.61) and with a fistula (HR, 0.59; 95% CI, 0.52-0.67) were less likely to gain employer-sponsored insurance. LIMITATIONS: Employer-sponsored health insurance may not be a fully accurate proxy for employment status, and there is potential for residual confounding. CONCLUSIONS: PD was associated with higher probabilities of maintaining and gaining employer-sponsored health insurance after dialysis initiation compared with IHD. These findings may inform policies that influence the uptake of PD, potentially improving rates of employer-sponsored health insurance and employment among dialysis recipients or their households. PLAIN-LANGUAGE SUMMARY: Unemployment remains a challenge for patients receiving maintenance dialysis. Furthermore, the impact of dialysis modality on employment loss and gain after dialysis initiation has not been well studied because of a lack of longitudinal measures of these outcomes. Using cause-specific hazards modeling and considering the loss or gain of employer-sponsored health insurance as a proxy for employment changes at the patient or household levels, we found that patients receiving peritoneal dialysis are less likely to lose and more likely to gain employer-sponsored health insurance than patients receiving in-center hemodialysis. These findings may inform policies that influence the uptake of peritoneal dialysis, potentially improving rates of employer-sponsored health insurance and employment among dialysis recipients or their households.
Lin W, Chang AR, Crews DC
… +4 more, Purnell TS, Appel LJ, Ishigami J, CRIC Study Investigators
Am J Kidney Dis
· 2026 Apr · PMID 41547465
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RATIONALE & OBJECTIVE: Kidney disease is often clustered within families, including Black families, which could be due in part to shared adverse social determinants of health (SDoHs) and/or genetic factors. We hypothesiz...RATIONALE & OBJECTIVE: Kidney disease is often clustered within families, including Black families, which could be due in part to shared adverse social determinants of health (SDoHs) and/or genetic factors. We hypothesize that the association between family history of kidney failure and chronic kidney disease (CKD) progression is largely attenuated when adjusting for adverse SDoHs and apolipoprotein L1 (APOL1) risk allele. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 5,623 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. EXPOSURE: Self-reported family history of kidney failure defined as a first-degree relative treated for kidney failure with dialysis or transplant. OUTCOME: CKD progression defined as incident end-stage kidney disease or 50% decrease in estimated glomerular filtration rate versus baseline. ANALYTICAL APPROACH: Logistic regression models were fitted to estimate adjusted odds ratio (aORs) of the outcome of family history of kidney failure according to the main exposures of (1) race/ethnicity combined with APOL1 risk allele status and (2) SDoHs. Next, Cox proportional hazards models were fitted to assess the association of family history of kidney failure with the outcome of CKD progression. RESULTS: Among all participants (mean age, 59.6 ± 10.7 years; 44% female; 43% Black), 948 (17%) reported a family history of kidney failure. Compared with White participants, Black participants were more likely to report a family history of kidney failure regardless of APOL1 status (aOR, 2.25; 95% CI, 1.74-2.91 for 0 or 1 risk allele; aOR, 3.46; 95% CI, 2.39-5.02 for 2 risk alleles). Adverse SDoHs such as lower income and lower educational attainment were positively associated with a family history of kidney failure in unadjusted analyses, but not in multivariable models. In a prospective analysis, a family history of kidney failure was significantly associated with an increased risk of CKD progression in crude (HR, 1.33; 95% CI, 1.19-1.49) and multivariable models adjusting for demographic characteristics, APOL1 risk allele status, SDoHs, and clinical factors (HR, 1.16; 95% CI, 1.02-1.33). LIMITATIONS: Possible residual confounding. CONCLUSIONS: Among people with CKD, Black race was significantly associated with a family history of kidney failure, even in those without high-risk APOL1 allele status. After adjusting for SDoHs and APOL1 status, family history of kidney failure remained associated with the risk of CKD progression. These findings highlight the importance of collecting information on family history and the need for further efforts to understand the reasons for familial aggregation of CKD. PLAIN-LANGUAGE SUMMARY: Kidney disease sometimes runs in families. We studied more than 5,600 people with kidney problems to determine whether having a close family member with kidney failure makes someone more likely to experience worse kidney disease. We found that people, especially Black individuals, with family members who had kidney failure were more likely to have worsening kidney problems themselves. This was true even when we considered other health problems like high blood pressure or diabetes. Our study suggests that doctors should ask about family history because it may help identify people who are at higher risk. More research is needed to understand why kidney disease is often clustered within families.