搜索结果：Clinical journal of the American Society of Nephrology : CJASN

Point-of-care ultrasound could provide important information to guide fluid administration in AKI. This study demonstrates the feasibility assessing fluid tolerance through lung and venous ultrasound and implementing it in a trial. Point-of-care ultrasound influenced management in half of patients and lead to higher rate of early diuretic use without negatively affecting kidney function. Indiscriminate fluid administration in AKI can be harmful, and point-of-care ultrasound (POCUS) could be used to assess for fluid tolerance. The objective of pilot study was to determine the feasibility of a randomized trial comparing a fluid management strategy, including POCUS, with usual care. This is a single-center, open-label, pilot randomized controlled trial that recruited noncritically ill patients with AKI for whom fluid administration had begun or was considered. The intervention consisted in the transmission to the nephrology team of a POCUS report on fluid tolerance (assessment of pulmonary B-lines and systemic venous congestion with the venous excess ultrasound score). The control was usual care without POCUS. The primary outcome was feasibility, defined as protocol adherence. Eighty patients underwent randomization, 40 were randomized in the POCUS group and 40 in the usual care group, but one withdrew consent before initiating trial procedures. Protocol adherence was achieved in all patients. In the intervention arm, 50% of initial ultrasound reports led to a change in clinical conduct, and the provided information was perceived as useful by clinicians (median 4.5/5 [interquartile range, 4.0-5.0]). The intervention led to a higher use of diuretics during the first day after randomization (40% versus 15%, P = 0.01), but did not result in difference in cumulative fluid balance or diuretic use at 5 days, progression to higher stages of AKI, or composite outcome of death and escalation of care. This pilot trial demonstrate the feasibility of a randomized trial investigating the clinical effect of providing a POCUS fluid tolerance evaluation in AKI. Its effect on clinical management and perceived usefulness support the rationale for future, larger-scale studies.Clinical Trial registry name and registration number: NCT06411080 .

In ideal situations, contrast agents used in radiologic procedures should provide sufficient image enhancement without high doses and without eliciting any adverse effects. Regrettably, this has not been the case, particularly in states of kidney disease. Standard use, and oftentimes contrast overuse, has highlighted the risk of developing nephrogenic systemic fibrosis and gadolinium toxicity from gadolinium-based contrast agents. Conflicting reports lead to confusion regarding the types of agents that cause injury, the overall injury rates, acceptable defining terms, and even which patient population is most at risk. This confusion can lead to withholding contrast-enhanced examinations in patients for fear of kidney injury. However, at the other end of the spectrum, many providers question the risk or reality of complications, citing conflicting reports. In truth, the risk of complications lies somewhere in between. Educated patients are knowledgeable about the risks associated with gadolinium-based contrast agent administrations, but many of their concerns are often dismissed by health care providers. Transparency is key because there is still much to learn about the overall risk of gadolinium exposures in states of kidney disease and normal kidney function. A learned provider will be foundational for mitigating patient concerns. To provide a foundational understanding of the risks associated with gadolinium exposure, this review focuses on the complications of gadolinium-based contrast agents.

Between 2016 and 2022 the proportion of US patients starting hemodialysis with a catheter increased from 62% to 74%. Concurrently, placement of a fistula or graft in the first 6 months of dialysis decreased from 34% to 26%. After adjustment for baseline characteristics and patient mortality, fistula or graft placement was 31% lower in 2022 than in 2016. Vascular access practice guidelines recommend placement of a permanent vascular access-arteriovenous fistula (AVF) or graft (arteriovenous graft [AVG])-to avoid complications associated with central venous catheter (CVC). Despite these guidelines, there has been a recent decrease in predialysis AVF placement and an increase in patients starting hemodialysis with a CVC only. We evaluated whether there has been an increase in the placement of an AVF or AVG in the first 6 months after dialysis initiation to offset the increase in patients starting dialysis with a CVC. This was a retrospective cohort study using the United States Renal Data System. We identified 522,598 patients initiating hemodialysis with a CVC between 2016 and 2022. The exposure was the calendar year of hemodialysis initiation, and the main outcome was the proportion of patients with placement of an AVF or AVG within 6 months of hemodialysis initiation. The proportion of patients initiating hemodialysis with a CVC only increased from 62% in 2016 to 74% in 2022 ( P < 0.001), while the proportion receiving an AVF or AVG within 6 months of dialysis initiation declined from 34% to 26% ( P < 0.001). In adjusted Fine-Gray competing risk analysis, compared with 2016 as the reference year, hazard ratios for AVF/AVG placement declined markedly beginning in 2019 (subdistribution hazard ratio, 0.89; 95% confidence interval, 0.87 to 0.90 in 2019; 0.77, 0.76 to 0.78 in 2020; 0.75, 0.74 to 0.76 in 2021; and 0.69, 0.68 to 0.70 in 2022). The standardized 6-month cumulative incidence of AVF/AVG placement decreased from 15% in 2016 to 11% in 2022 ( P < 0.001). Contrary to national vascular access guidelines, there has been a nearly one-third secular decrease in placement of an AVF or AVG among patients initiating hemodialysis with a CVC, compounding the lower rates of access placement prior to dialysis initiation.

Cardiovascular-kidney-metabolic syndrome (CKM) describes the clustering of risk factors and progression of disease at the intersection of metabolic disorders, chronic kidney disease (CKD), and cardiovascular disease (CVD). We aimed to characterize the prevalence of CKM stages and progression of CKM syndrome among diverse U.S. Hispanic/Latino adults. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a population-based longitudinal cohort of 16,415 Hispanic/Latino adults aged 18-74 years from four U.S. communities. Participants completed examinations at visit 1 (V1, 2008-2011) and visit 2 (V2, 2014-2017). Data collected included body mass index, waist circumference, glucose tolerance, lipids, blood pressure, metabolic syndrome, CKD, 10-year CVD risk (to define subclinical CVD), and clinical CVD. CKM stages were defined using American Heart Association criteria: stage 0 (no CKM risk factors), stage 1 (excess/dysfunctional adiposity), stage 2 (metabolic risk factors or CKD), stage 3 (subclinical CVD or risk equivalents), and stage 4 (clinical CVD). We estimated the age-standardized prevalence of CKM stages at V1 (n=16,123) and CKM stage progression from V1 to V2 (n=11,178). All analyses were weighted and accounted for the HCHS/SOL complex survey design. At V1, the mean age was 41.1 years, and 52.3% were female. The distribution of CKM stages was: stage 0, 10.6% (standard error (SE): 0.4); stage 1, 26.1% (SE: 0.6); stage 2, 50.6% (SE: 0.6); stage 3, 2.4% (SE: 0.2); and stage 4, 10.3% (SE: 0.3). Over an average follow-up of six years, 10.3% (SE: 0.5) regressed to a lower CKM stage, while 21.5% (SE: 0.7) progressed to a higher CKM stage. Among diverse U.S. Hispanic/Latino adults, eight in ten had CKM risk factors or subclinical CVD, and one in five experienced CKM progression over six years. These findings highlight the need for targeted, early-stage interventions to prevent CKM progression and improve CKM health in Hispanic/Latino populations.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with inflammation. Although chronic kidney disease (CKD) shares these pathophysiological features, the prognostic role of CHIP on CKD progression remains unclear, particularly in underrepresented East Asian populations. Deep-targeted sequencing of CHIP-driving mutations was used to identify the presence of CHIP, defined as variant allele fraction (VAF) &#x2265;2.0%. CHIP prevalence was compared between 175 Korean patients with CKD in the KNOW-CKD cohort and 700 matched general population controls in the GENIE cohort. The association between CHIP and kidney failure (KF) risk was evaluated using multivariable Cox regression analysis both in the KNOW-CKD cohort and 232 matched UK Biobank participants with CKD. Furthermore, VAF was compared between CHIP-positive participants in the KNOW-CKD and GENIE cohorts. The prevalence of CHIP was significantly higher in the KNOW-CKD than in the GENIE cohort (17% vs. 11%; P = 0.04). Over a median follow-up of 10.0 years, 66 patients (38%) developed KF in the KNOW-CKD cohort. After multivariable adjustment, CHIP was associated with higher risk of KF (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.03-3.51). Furthermore, in the UK Biobank, KF occurred in 43 participants (20%) over a median follow-up of 12.9 years and the association of CHIP with higher risk of KF was consistently observed (aHR, 2.16; 95% CI, 1.15-4.03). Furthermore, among CHIP-positive participants, the median VAF of CHIP-associated mutations was significantly higher in persons within the KNOW-CKD cohort compared to healthy controls in the GENIE cohort (7.3% vs. 4.4%; P = 0.02). CHIP is more prevalent in patients with CKD and serves as an independent risk factor for KF. This association is consistently observed across both an underrepresented East Asian cohort and a European cohort, establishing CHIP as a globally relevant risk factor for CKD progression.

C3 glomerulopathy (C3G) and immune complex-associated membranoproliferative glomerulonephritis (IC-MPGN) are rare complement-mediated kidney diseases with a high risk of progression to kidney failure. Little is known about the natural history of these diseases in children, limiting our understanding of risk factors for progressive kidney disease. Using a computable phenotype algorithm, a pediatric cohort with C3G or IC-MPGN was identified at seven institutions in PEDSnet, a national network of pediatric health systems which aggregate electronic health record data and collaborate on pragmatic research studies. Discrete data elements were captured from electronic health records and additional clinical and histopathologic data were extracted by standardized chart review by pediatric nephrologists. Biopsy diagnosis was classified as C3G or IC-MPGN by applying an algorithm based on immunofluorescence and electron microscopy and supplemented with manual chart review. Kaplan-Meier survival curves were utilized to compare the risk of reaching a composite kidney outcome of 50% reduction in estimated glomerular filtration rate (eGFR), initiation of maintenance dialysis, or kidney transplantation. Of 204 patients with MPGN identified by the computable phenotype algorithm and chart review, 159 could be further classified as C3G or IC-MPGN based on available biopsy data. There were no significant differences in baseline serum albumin, C3 level, urine protein/creatinine ratio, or eGFR between C3G or IC-MPGN. Patients with C3G and IC-MPGN had similar rates of progression to the composite kidney outcome, and a low serum C3 level at baseline was associated with this composite outcome. Using large-scale, real-world multi-institutional data, we investigated the natural history of a large contemporary cohort of children with MPGN. As patients classified as having C3G compared to IC-MPGN had similar baseline clinical characteristics and rates of progressive disease despite untargeted treatment approaches, the availability of newer complement-targeted agents hold the promise of benefit to this population.

In a contemporary UK cohort of 96,809 patients, peritoneal dialysis was associated with lower mortality than hemodialysis across all phenotypes. The magnitude of this association varied by phenotype and attenuated with increasing age. Phenotype-based analyses may support more individualized dialysis modality selection and inform system-level policy decisions. Whether peritoneal dialysis (PD) is associated with lower mortality than hemodialysis in contemporary practice remains debated, particularly across heterogeneous patient populations and in the presence of competing transplantation. We examined modality-associated mortality differences across data-driven phenotypes of incident dialysis patients in the United Kingdom using a competing-risks framework. We analyzed 96,809 adults initiating dialysis in the United Kingdom Renal Registry between 2007 and 2021. Unsupervised k-prototypes clustering was used to derive phenotypes based on age, sex, ethnicity, primary kidney disease, hemoglobin, serum albumin, and transplant-listing status. Mortality during the dialysis phase before transplantation was analyzed using competing-risks methods, treating kidney transplantation as a competing event. Cumulative incidence of death at 1 and 5 years was modeled using jack-knife pseudo-value regression with complementary log-log links, adjusting for demographic and clinical covariates. Dialysis modality (hemodialysis versus PD) was the primary exposure, with stratified analyses performed within each phenotype. A complementary competing-risks analysis examined time to transplantation. Among incident patients, 24% initiated PD and 76% hemodialysis. Three reproducible phenotypes were identified, differing primarily by age, hemoglobin and albumin levels, and transplant-listing status. Across the overall cohort, hemodialysis was associated with a higher cumulative incidence of death before transplantation at both 1 year (subdistribution hazard ratio [sHR], 1.85; 95% confidence interval [CI], 1.75 to 1.96) and 5 years (sHR, 1.47; 95% CI, 1.43 to 1.51). In stratified analyses, hemodialysis was associated with higher mortality across all phenotypes. At 1 year, adjusted sHRs ranged from 1.55 (95% CI, 1.44 to 1.68) to 2.29 (95% CI, 1.87 to 2.80) across clusters. At 5 years, the association persisted but attenuated with increasing age, with adjusted sHRs of 2.42 (95% CI, 2.23 to 2.63) in the youngest phenotype, 1.55 (95% CI, 1.48 to 1.61) in the intermediate phenotype, and 1.14 (95% CI, 1.11 to 1.19) in the oldest phenotype. In complementary analyses, time to transplantation did not differ significantly across phenotypes after adjustment. In contemporary UK practice, hemodialysis was associated with higher mortality during the dialysis phase compared with PD across distinct patient phenotypes, with time-dependent variation in effect magnitude. These registry-based associations support consideration of phenotype-informed modality selection while acknowledging the potential for residual confounding and the influence of health system context.

Estimating glomerular filtration rate (GFR) is challenging due to its dependence on age and body composition, especially in pediatric and elderly populations. Recently, d-serine and d-asparagine, rare amino acid enantiomers, have been identified as GFR biomarkers characterized by their ideal kidney clearance and minimal impacts of body size. We investigated the impact of age and sex on GFR estimation using these d-amino acids. We analyzed data from a cross-sectional observational cohort: 366 adult Japanese living kidney transplant donors and recipients. Using a dataset of 244 patients, we developed GFR estimation formulae based on blood levels of d-Ser and d-Asn using linear regression analyses, and validated the formulas' performance in 122 patients. The d-amino acid-based equation was established as 60.4 x d-Ser-0.450 x d-Asn-0.304 x 0.916 (if female), in which age did not significantly improve model performance and the impact of sex was minor. The performance of the established equations was equivalent to that of creatinine-based equations: bias (absolute difference), 9.1 [8.0-11.2], precision (interquartile range of bias), 11.1 [8.8-14.2], and accuracy (ratios of 30% different from measured GFR [P30]), 0.82 [0.73-0.89]. d-Amino acid-based estimation of GFR exhibits minimal empirical association with age and sex, offering a distinct advantage over models dependent on these demographic variables. This stability may support its broad clinical utility as a reliable diagnostic tool across all age groups and diverse populations.

Patients transitioning from peritoneal dialysis to home hemodialysis experience higher hospitalization rate during this transition period. After peritoneal dialysis-to-home hemodialysis transitions, hospitalization rates normalize and match those of patients starting home hemodialysis directly. Shorter transition periods are associated with an attenuated hospitalization risk, suggesting that timely peritoneal dialysis-to-home hemodialysis transitions may improve outcomes. Initiating dialysis with peritoneal dialysis (PD) followed by a transition to home hemodialysis (HHD) is known as integrated home dialysis . Hospitalization outcomes in this model are poorly known. We aimed to compare the hospitalization risk before, during, and after a PD-to-HHD transition with individuals receiving HHD as first home dialysis modality. We analyzed the Canadian Organ Replacement Register and included individuals initiating home dialysis between 2005 and 2018. Patients transitioning from PD to HHD with <365 days of interim facility hemodialysis ("PD-HHD" group) were matched 1:1 to individuals receiving HHD as their first home dialysis modality ("HHD" group) using a propensity score. Patients were followed until December 2019, death, or a transfer to facility hemodialysis. In the PD-HHD group, the transition window was defined as the last 30 days of PD, the facility hemodialysis period and the first 30 days of HHD. Our primary outcome of all-cause hospitalizations (assessed before, during, and after transition) was analyzed using adjusted negative binomial regression. Three hundred and one patients underwent the PD-to-HHD transition and 711 initiated home dialysis in HHD. Hospitalization rates up to 2.17/patient-year (95% confidence interval [CI], 1.91 to 2.43) were observed during the PD-to-HHD transition, with infectious-related hospitalizations being most frequent (30%). Compared with HHD, the PD-HHD group had higher rates of hospitalization during (incidence rate ratio [IRR], 2.89 [95% CI, 2.01 to 4.16]) and before the transition (IRR, 1.38 [95% CI, 1.03 to 1.85]; predominantly in the year before) but not afterward (IRR, 1.04 [95% CI, 0.80 to 1.36]). Higher risk was not observed for cardiovascular-related hospitalizations and less pronounced in patients with short (<90 days in facility hemodialysis) transitions. Most patients transitioning from PD to HHD experience a higher hospitalization risk before and during the transfer (relative to incident HHD). Yet, their hospitalization risk stabilizes after the transition. This higher risk of hospitalization is less apparent for patients with shorter interim facility hemodialysis.

High-volume hemodiafiltration was associated with a 20% lower all-cause mortality risk compared with hemodialysis in incident patients. High-volume hemodiafiltration was associated with a 29% lower cardiovascular mortality risk compared with hemodialysis in incident patients. Associations between high-volume hemodiafiltration and lower mortality were consistent across demographic and clinical subgroups. Evidence for a survival benefit of hemodiafiltration (HDF) over high-flux hemodialysis largely comes from studies based on prevalent ESKD patients with longer dialysis exposure. By contrast, the effect of HDF on mortality of incident patients-those newly starting dialysis-remains less well understood. We analyzed data from 18,515 incident patients (dialysis vintage <3 months) treated between 2019 and 2022 at Fresenius Medical Care NephroCare Clinics. Patients were classified as HDF or hemodialysis on the basis of their predominant dialysis modality during the first year of follow-up (&#x2265;75% of sessions). To assess the effect of HDF in the early phase after treatment initiation, follow-up was limited to 2 years. Cox proportional hazards models with inverse probability of treatment weighting were applied to estimate all-cause and cardiovascular disease mortality risk. Baseline characteristics between HDF and hemodialysis groups were comparable after inverse probability of treatment weighting. Over a median follow-up of 15.7 months (interquartile range, 6.4-24.0 months), HDF was associated with a lower risk of all-cause mortality compared with hemodialysis (11.7 versus 15.6 per 100 person-years; hazard ratio, 0.80; 95% confidence interval, 0.75 to 0.86). Furthermore, HDF was associated with a lower risk of cardiovascular disease mortality compared with hemodialysis (4.1 versus 6.7 per 100 person-years; hazard ratio, 0.71; 95% confidence interval, 0.63 to 0.80). In the large real-world cohort of incident patients with ESKD who are in the early phase of dialysis treatment, online HDF was associated with a significant survival advantage compared with conventional hemodialysis. These findings reinforce the potential clinical benefits of HDF and support early adoption of HDF upon dialysis initiation.

Mexico has a high burden of chronic kidney disease (CKD). The state of Aguascalientes is among the regions with the highest reported prevalence of end-stage kidney disease worldwide. In this setting, CKD of unknown etiology predominates and has been associated with a low number of nephrons of prenatal origin. This study examines the DNA methylation profile following maternal exposure to fluoride and its relationship with lower kidney volume in neonates. This cross-sectional study included at-term pregnant women without concomitant comorbidities. Neonatal total kidney volume (TKV) was calculated using ultrasound imaging. Maternal urine was collected to quantify xenobiotics, and placental DNA methylation was analyzed using the Illumina MethylationEPIC BeadChip. Neonates were classified by TKV percentile [low kidney volume (LKV) = percentile <10th; control (CTRL) = percentile >10th], and fluoride (F-) exposure (F-&#x2265;1.5 mg/L; NF-<1.5mg/L). Bioinformatic analyses were performed to identify differentially methylated genes (DMGs) and enriched biological pathways associated with kidney volume status and fluoride exposure. Thirty-two women were included in the study between March 2023 and April 2024. Principal component analysis (PCA) revealed distinct placental methylation profiles between the groups (LKV/F and CTRL/NF). Epigenome-wide analysis identified 7,540 differentially methylated sites (6,635 hypomethylated and 905 hypermethylated; adjusted p value (FDR)<0.01 and &#x394;&#x3b2;&#x2265;0.1). Integration of stratified comparisons across kidney volume and fluoride exposure identified a shared epigenetic signature of 244 DMGs, including protocadherin clusters and genes related to kidney development, cell adhesion, and developmental signaling. Functional enrichment analyses highlighted pathways involved in calcium signaling, focal adhesion, and organogenesis. Placental DNA methylation profiles associated with neonatal kidney volume were identified in a population with prenatal fluoride exposure. The consistency and biological relevance of the identified epigenetic signature support an association between fluoride exposure and alterations in placental DNA methylation involving pathways critical for early kidney development.

Chronic kidney disease (CKD) and diabetes disproportionately affect the American Indian or Alaska Native population but understanding of major adverse kidney events (MAKE) in this population is limited. Electronic health records from the Providence health system identified the American Indian or Alaska Native adult population with diabetes during 2013-2022. A one-year window surrounding diabetes cohort entry was used to collect baseline data. Kaplan-Meier analyses assessed MAKE (&#x2265;40% estimated glomerular filtration rate [eGFR] decline, eGFR <15 mL/min/1.73 m2, dialysis or kidney transplant, and all-cause death) with propensity score matching (1:3) of American Indian or Alaska Native people to reference individuals (non-Hispanic White) by demographics and clinical characteristics. Cox proportional hazards modeling estimated associations between demographic, clinical, social, and healthcare utilization variables and MAKE. The American Indian or Alaska Native population (N=6,103) was younger (mean&#xb1;standard deviation age 54&#xb1;15 years) with higher HbA1c (mean 7.4&#xb1;2.2 mg/dL) compared to the reference population (N=354,283; age 62&#xb1;14 years; HbA1c 6.9%&#xb1;1.8%). During a median follow-up of 4.1 (interquartile range 2.0-6.4) years, the American Indian or Alaska Native population experienced a higher frequency of MAKE (26%, n=1,614) than the reference population (24%, n=85,920). With propensity score matching, MAKE survival estimates were significantly lower in the American Indian or Alaska Native population (p <0.0001). In the adjusted Cox model, increased MAKE risk was observed for the American Indian or Alaska Native population (versus reference population, hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.15-1.27), higher social vulnerability index (HR 1.05, 95% CI 1.05-1.05), and hospitalization (HR 1.98, 95% CI 1.95-2.01), while more primary care visits were associated with lower MAKE risk (HR 0.78, 95% CI 0.77-0.79). The risk of MAKE was significantly increased in the American Indian or Alaska Native population with diabetes. Social factors and healthcare utilization importantly contributed to risk prediction for MAKE.

In phase 2 ENVISION trial, sibeprenlimab, a selective A PRoliferation-Inducing Ligand (APRIL) inhibitor, significantly decreased proteinuria and stabilized eGFR in adults with IgA nephropathy. This exploratory substudy evaluated COVID-19 severity, SARS-CoV-2-specific antibody responses to vaccine and infection, and circulating B-cell populations in patients with IgA nephropathy treated with sibeprenlimab or placebo. Participants enrolled in ENVISION (NCT04287985) received 12 monthly intravenous infusions of sibeprenlimab (2, 4, or 8 mg/kg) or placebo. COVID-19 infection and vaccination data were recorded for all participants. In a substudy, serum IgG responses to SARS-CoV-2 spike protein, its receptor binding domain (RBD), and nucleocapsid antigen were assessed, with further analysis of serum IgM and IgA and salivary IgA against RBD in a subset of participants. Circulating T cells and B-cell subsets were analyzed by flow cytometry. Overall, symptomatic COVID-19 incidence was comparable between groups (33.3% sibeprenlimab vs 44.7% placebo), indicating no observable excess risk of COVID-19 infection with sibeprenlimab. Of 155 participants, 72 (sibeprenlimab n=52; placebo n=20) consented to the substudy. Within the substudy, COVID-19 seroconversion rates were 100% for IgG against SARS-CoV-2 RBD (IgG-RBD) following vaccination or infection. Peak IgG-RBD titers after mRNA vaccination exceeded protective thresholds in all COVID-19-naive sibeprenlimab recipients, and IgG-RBD durability was comparable between sibeprenlimab and placebo. COVID-19-specific IgG, IgA, and IgM antibody responses to infection were preserved, and IgA-RBD responses detected in saliva suggested preservation of mucosal immunity with sibeprenlimab. No meaningful perturbations in B or T cells were observed. APRIL inhibition with sibeprenlimab reduced pathogenic IgA while preserving mucosal immunity and systemic antibody responses to COVID-19 vaccination and infection. The absence of B-cell perturbations and the apparent absence of an increased risk of impaired vaccine response suggest that sibeprenlimab may not confer clinically significant immunosuppressive risks; the substudy's size and exploratory design preclude definitive conclusions, warranting further evaluation.

Glomerular filtration markers are exogenous or endogenous solutes that are eliminated from the circulation primarily by glomerular filtration. Their rate of elimination is directly related to the GFR, and their plasma concentration is inversely related to the GFR. GFR cannot be measured directly in humans, but it can be assessed by using filtration markers-either as measured GFR (mGFR) from clearance measurements using exogenous filtration markers (such as iothalamate and iohexol) or as eGFR from estimating equations using plasma concentrations of endogenous filtration markers (metabolites, such as creatinine, and low molecular weight proteins, such as cystatin C). Thus, both mGFR and eGFR may differ from true GFR, and understanding the physiologic processes affecting filtration markers is required for clinical evaluation of GFR. Processes other than GFR that affect the plasma concentration of filtration markers are collectively defined as non-GFR determinants. By design, exogenous filtration markers are minimally affected by non-GFR determinants, but both urinary and plasma clearance measurements are associated with error in mGFR. By contrast, by definition, all endogenous filtration markers are affected by non-GFR determinants, but not by error in clearance measurements. The major limitations of mGFR procedures are complexity and inconvenience of clearance measurements, which constrain their utility in clinical practice. The major limitation of eGFR is error because of variation in the non-GFR determinants of the filtration markers, which can be minimized by use of a panel of markers (panel eGFR). There is ongoing interest in the discovery of new exogenous filtration markers that would enable widespread implementation of mGFR procedures and novel metabolite and low molecular weight endogenous filtration markers that would enable a panel eGFR. In this review, we discuss current and emerging insights into existing and novel filtration markers.

The mammalian metanephric kidney evolved in amniotes over 319 million years ago to navigate the extreme environmental variability of terrestrial life. This required a dual physiological capacity: rigorous conservation during periodic scarcity and high-efficiency mechanisms optimized for rapid potassium (K+) excretion following acute dietary abundance. While these homeostatic pathways have historically been viewed as uniform, emerging evidence indicates profound sexual dimorphism driven by the unique teleological demands of reproduction. This review explores the molecular and physiological divergence in K+ handling between the sexes. We discuss how females, possessing a smaller skeletal muscle reservoir for internal K+ distribution, leverage estrogen-mediated upregulation of the Na+-K+-ATPase to maintain extracellular stability. In the kidney, sexual dimorphism manifests as a coordinated shift in functional mass: whereas males exhibit an androgen-driven "proximal-dominant" pattern of reabsorption, females utilize a "distal-dominant" strategy reliant on the upregulation of the thiazide-sensitive sodium-chloride cotransporter. This female-specific architecture, orchestrated by the WNK-SPAK kinase network and structural WNK bodies, allows for the decoupling of sodium retention from K+ secretion, effectively resolving the "aldosterone paradox" inherent to pregnancy. However, this evolutionary adaptation creates a distinct clinical vulnerability in the modern pharmacologic landscape. We detail how the female reliance on distal sodium reclamation renders women disproportionately susceptible to thiazide-induced hypokalemia and hyponatremia, particularly following the menopausal transition when the protective hormonal milieu is lost. We conclude that K+ homeostasis is a sexually dimorphic system, underscoring the importance of recognizing these distinct physiological pathways when anticipating and managing diuretic-induced electrolyte abnormalities.

People with CKD are at high risk of unplanned readmission and death due to multimorbidity and health care complexity. Lower eGFR is strongly associated with 30-day unplanned readmission or death, with congestive heart failure as the most common cause. Targeted, risk-based discharge strategies are needed to reduce readmissions and improve outcomes in CKD populations. People with CKD have higher risk of repeated hospitalization and mortality than the general population. Given many unplanned readmissions may be avoidable, examining risks and reasons for readmission across CKD categories may inform targeted interventions and safer discharge planning. Thus, we estimated the association between eGFR and both readmission and mortality and identified diagnoses for readmission. Adults discharged from hospitals in Alberta, Canada, from 2005 to 2021 were included. Preadmission eGFR was categorized into eight groups (in ml/min per 1.73 m 2 ): &#x2265;60 (G1-2), 45-59 (G3a), 30-44 (G3b), 15-29 (G4), <15 not on dialysis (G5ND), on dialysis (G5D), prevalent kidney transplant recipients (G1T-5T), and unknown. The primary outcome was unplanned readmission or death within 30 days of discharge. Multivariable logistic regression, accounting for multiple admissions per participant, was used to estimate unadjusted and adjusted odds ratios (aOR) of the primary outcome, using G1-2 as the reference. The results were stratified by age and sex. The type and frequency of each unplanned readmission was also determined. The cohort comprised 2,992,810 admissions among 1,249,248 participants (median [interquartile range] admission per participant: 1 [1-3] admission; age: 61 [47-74] years). Among lower eGFR categories, heart failure was the most common readmission diagnosis, followed by AKI. Relative to G1-2, more impaired eGFR groups had significantly higher odds of the primary outcome, with the highest adjusted odds experienced by the G1T-5T group (aOR, 1.47; 95% confidence interval, 1.12 to 1.93) and G5ND group (aOR, 1.40; 95% confidence interval, 1.34 to 1.47). Stratified analyses showed that individuals younger than 65 years and females with reduced eGFR had higher odds compared with counterparts in the G1-2 reference group. People with severe CKD had the highest risk of hospital readmission, suggesting the need to test interventions in this group to target volume and hemodynamic related readmissions such as postdischarge AKI and heart failure.

Two-stage urine chemokine screening improved discrimination and positive predictive value versus blood-only testing while preserving high negative predictive value. In validation, urine chemokine C-X-C motif ligand 9/creatinine screening referred only 79% of samples for donor-derived cell-free DNA testing, reducing blood test use. Standalone blood biomarkers were more consistent for antibody-mediated rejection than cellular rejection; urine chemokine screening improved diagnostic yield. After kidney transplantation, subclinical acute rejection occurs in 20%-25% of clinically stable recipients; surveillance biopsies are invasive and often indicate no rejection. Moreover, the widespread use of noninvasive biomarkers is limited by cost. We developed and sought to validate two-stage diagnostic models integrating urine chemokine assays (chemokine C-X-C motif ligand 9 [CXCL9] and C-X-C motif ligand 10) with confirmatory blood-based gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA). Data from two studies, 476 biopsy-paired samples from 226 recipients (discovery) and 144 samples from 134 recipients (validation), were analyzed retrospectively. Rapid, low-cost urine chemokine assays were used for stage 1 screening; recipients with elevated urine chemokines underwent additional stage 2 testing with GEP and/or dd-cfDNA. In the validation cohort, dd-cfDNA outperformed GEP for overall rejection and antibody-mediated rejection, whereas neither test validated significant discrimination for cellular rejection. CXCL9-based two-stage testing improved the area under the receiver operating characteristic curve and positive predictive value versus standalone stage-2 testing, while maintaining similar negative predictive value and reducing stage 2 test use. At a probability screening threshold of 0.10, the CXCL9/creatinine-based logistic regression, adjusted for BK virus, urinary tract infection, sex, age, time post-transplant, and donor type, followed by dd-cfDNA validated a higher positive predictive value (0.39 versus 0.34), lower sensitivity (0.56 versus 0.62), and similar negative predictive value around 0.94, compared with dd-cfDNA alone, while recommending dd-cfDNA testing in only 0.79 (95% confidence interval, 0.72 to 0.85) of validation cases. Combined GEP and dd-cfDNA testing validated higher area under the receiver operating characteristic curves than dd-cfDNA as a second-stage test for overall (0.85 [0.79 to 0.94] versus 0.82 [0.74 to 0.92]), antibody-mediated (0.96 [0.93 to 1.00] versus 0.90 [0.79 to 1.00]), and cellular rejections (0.69 [0.61 to 0.89] versus 0.63 [0.53 to 0.81]). This staged approach reduces unnecessary biopsies and guides the efficient use of costly blood-based biomarkers while maintaining good clinical performance, particularly for subclinical antibody-mediated rejections. ClinicalTrials.gov, NCT01289717 .

The kidney plays the major role in the maintenance of acid-base balance by reabsorbing the daily filtered load of bicarbonate and generating sufficient base to neutralize the acid produced by metabolism of ingested foodstuffs. Therefore, damage to the kidney caused by CKD can be associated with a decrease in kidney ammonium excretion causing net acid excretion to fall below net acid production resulting in a positive acid balance. The acid retention can lead to eubicarbonatemic metabolic acidosis (tissue retention of acid without a change in systemic acid-base balance) or metabolic acidosis with or without acidemia. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, tissue inflammation, progression of CKD, and increased mortality. Administration of base in the form of sodium bicarbonate, or sodium citrate, may improve acid-base balance and improve cellular function. However, recent large-scale trials have questioned its efficacy in slowing CKD progression, adding complexity to treatment decisions. Evidence that serum bicarbonate concentration >25 mEq/L might be associated with increased cardiovascular disease adds complexity to treatment decisions. Additional study is warranted to determine whether sustained correction of CKD-related metabolic acidosis, with meaningful bicarbonate separation between study arms, improves hard clinical outcomes and to identify which patient subgroups derive net benefit.

Apolipoprotein L1 genetic testing did not reduce potential living donors' willingness to donate, supporting integration of testing into practice. The Apolipoprotein L1 Testing and Counseling Program did not reduce potential living donors' decisional conflict or increase preparedness to donate. The trial demonstrated the feasibility of integrating apolipoprotein L1 genetic testing and counseling into routine living donor clinical evaluation. Living donors of African ancestry have the highest risk of postdonation kidney disease. Apolipoprotein L1 ( APOL1 ) risk variants may contribute to this risk. This study evaluated the effectiveness and implementation of our culturally appropriate APOL1 Testing and Counseling Program to reduce potential donors' decisional conflict for donation. This prospective, nonrandomized, pre-post two-site hybrid type 2 effectiveness-implementation study evaluated the effect of the intervention on decisional conflict about donation, preparedness for decision making about donation and for donation, willingness to donate, and satisfaction with informed consent among potential donors of African ancestry undergoing evaluation. The intervention involved donors: using a chatbot providing APOL1 information, receiving culturally competent counseling, and APOL1 genetic testing. Control arm received routine care. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to longitudinally evaluate implementation outcomes assessed through validated surveys with donors and electronic health record review using linear mixed effects models. Cross-sectional outcomes were assessed using multiple regression models. We enrolled 280 potential donors (75 control arm, 205 intervention arm; 71.07% participation rate). More were female (59%) and had a mean age of 40.2 years (SD, 12.8). No significant differences emerged in most primary and secondary outcomes between the intervention and control groups (decisional conflict &#x3b2; [95% confidence interval (CI)], -1.05 [-4.13 to 2.03]; P = 0.50), preparation for decision making ( &#x3b2; [95% CI], -7.02 [-18.83 to 4.78]; P = 0.24), preparedness to donate ( &#x3b2; [95% CI], 0.04 [-0.48 to 0.56]; P = 0.89), willingness to donate ( &#x3b2; [95% CI], 0.18 [-0.29 to 0.66]; P = 0.45). The right amount of information to make a decision domain for satisfaction with informed consent was significantly lower in the intervention arm ( &#x3b2; [95% CI], -0.34 [-0.65 to -0.02]; P = 0.04). Our APOL1 Testing and Counseling Program had no effect on potential donors' willingness to donate regardless of undergoing APOL1 testing, demonstrating the feasibility of its integration into routine donor clinical evaluation. NCT04910867 .