Clinical Journal of the American Society of Nephrology最新文献

Although the past two decades have seen substantial proportional growth of home hemodialysis in the United States, the absolute number of patients treated with home hemodialysis remains small. Currently available stationary hemodialysis devices for use in the home have inherent limitations that represent barriers for more widespread adoption by a larger proportion of individuals with kidney failure. These limitations include device weight and bulk, ergonomics considerations, technical complexity, vascular access challenges, and limited remote patient monitoring. Recent years have witnessed a resurgence in research and development of prototype wearable kidney replacement devices incorporating innovations in miniaturization, new biomaterials, and new methods for toxin clearance and dialysate regeneration. Recent work has built on five decades of incremental innovation in wearable dialysis concepts and prototypes, starting from the work by Kolff in the 1970s. Wearable dialysis devices that successfully overcome key persistent barriers to successful development and adoption of these technologies will radically reshape the landscape of kidney replacement therapies and have the potential to dramatically improve the lives of individuals living with kidney failure.

Glomerular disease is a leading cause of CKD and ESKD. Although diabetic kidney disease is the most common cause of glomerular disease, nondiabetic causes include malignancy, systemic autoimmune conditions, drug effects, or genetic conditions. Nondiabetic glomerular diseases are rare diseases, with a paucity of high-quality clinical trials in this area. Furthermore, late referral can result in poor patient outcomes. This article reviews the current management of nondiabetic glomerular disease and explores the latest developments in drug treatment in this area. Current treatment of nondiabetic glomerular disease aims to manage complications (edema, hypertension, proteinuria, hyperlipidemia, hypercoagulability, and thrombosis) as well as target the underlying cause of glomerular disease. Treatment options include renin-angiotensin-aldosterone system inhibitors, statins/nonstatin alternatives, loop diuretics, anticoagulation agents, immunosuppressives, and lifestyle and dietary modifications. Effective treatment of nondiabetic glomerular disease is limited by heterogeneity and a lack of understanding of the disease pathogenesis. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs, such as finerenone), with their broad anti-inflammatory and antifibrotic effects, have emerged as valuable therapeutic options for a range of cardiorenal conditions, including CKD. ns-MRAs are an evolving drug class of particular interest for the future treatment of nondiabetic glomerular disease, and there is evidence that these agents may improve kidney prognosis in various subgroups of patients with CKD. The benefits offered by ns-MRAs may present an opportunity to reduce the progression of CKD from a spectrum of glomerular disease. Several novel ns-MRA are in clinical development for both diabetic and nondiabetic CKD.

Background: Social determinants of health shape a child's transplant course. We describe the association between neighborhood socioeconomic deprivation, transplant characteristics, and graft survival in US pediatric kidney transplant recipients.

Methods: US recipients <18 years of age at listing transplanted January 1st, 2010, to May 31st, 2022 (N=9,178) were included from the Scientific Registry of Transplant Recipients. Recipients were stratified into three groups according to Material Community Deprivation Index score, with greater score representing higher neighborhood socioeconomic deprivation. Outcomes were modeled using multivariable logistic regression and Cox proportional hazards models.

Results: Twenty-four percent (N=110) of recipients from neighborhoods of high socioeconomic deprivation identified as being of Black race, versus 12% (N=383) of recipients from neighborhoods of low socioeconomic deprivation. Neighborhoods of high socioeconomic deprivation had a much greater proportion of recipients identifying as being of Hispanic ethnicity (67%, N=311), versus neighborhoods of low socioeconomic deprivation (17%, N=562). The hazard of graft loss was 55% higher (aHR 1.55, 95% CI: 1.24, 1.94) for recipients from neighborhoods of high versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 59% lower odds (aOR 0.41, 95% CI: 0.30, 0.56) of living donor transplantation and, although not statistically significant, 8% lower odds (aOR 0.92, 95% CI: 0.72, 1.19) of preemptive transplantation. The hazard of graft loss was 41% higher (aHR 1.41, 95% CI: 1.25, 1.60) for recipients from neighborhoods of intermediate versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 27% lower odds (aOR 0.73, 95% CI: 0.66, 0.81) of living donor transplantation and 11% lower odds (aOR 0.89, 95% CI: 0.80, 0.99) of preemptive transplantation.

Conclusions: Children from neighborhoods of high socioeconomic deprivation have worse graft survival and lower utilization of preemptive and living donor transplantation. These findings demonstrate inequities in pediatric kidney transplantation that warrant further intervention.

Objective: Limited knowledge exists regarding short-term changes/increases in concentrations of circulating proteins (referred here as deltas) and rapid development of kidney failure (rapid KF) in diabetes mellitus.

Research design and methods: Concentrations of 452 circulating proteins were measured by OLINK proteomics platform at baseline and after a median interval of 3-4 years in 106 individuals with type 1 and 77 with type 2 diabetes in two case-control studies. During 10-year follow-up, 31 and 26 individuals, respectively, developed rapid KF.

Results: Deltas for 40 proteins predicted rapid KF in both studies. All were better predictors than delta urine albumin-creatinine ratio, and half were better than delta glomerular filtration rate. Comparing the delta proteins with 46 circulating proteins of which elevated baseline concentrations were predictors of rapid KF risk in our previous study, 61 unique proteins were identified. Among these proteins, 21 were good predictors of rapid KF only when measured at baseline (predictors of initiation), 15 were good predictors when measured as deltas (predictors of progression) and 25 were good predictors when both baseline and delta concentrations were used (predictors of initiation and progression). An index score, developed for the latter 25 proteins, provided superior prediction of rapid KF. A subset of these latter proteins was associated with apoptotic processes/tumor necrosis factor (TNF) receptor signaling pathways.

Conclusion: Development of rapid KF in diabetes was preceded by elevated concentrations of multiple circulating proteins both at baseline and during short follow-up. Comparing baseline and short-term changes in concentrations of circulating proteins classified predictors of rapid KF risk into those associated with initiation, progression, or both. Predictors of both initiation & progression flagged apoptosis processes and TNF receptor signaling pathways. Multi-protein prognostic algorithms using proteins associated with both initiation and progression improved prediction of rapid KF risk beyond clinical variables.