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Higher baseline urinary neutrophil gelatinase-associated lipocalin was associated with worse cognitive scores at baseline. Lower concentrations of baseline serum bicarbonate (higher is better) were associated with lower cognitive scores at baseline. We found no associations with urine markers with longitudinal changes in cognition.

Tubulointerstitial damage in diabetes and chronic kidney disease (CKD) is poorly captured by estimated glomerular filtration rate (eGFR) and albuminuria. Urine biomarkers of kidney health may better elucidate disease progression in persons with diabetes and CKD.Per case-cohort design, we randomly selected a subcohort of 560 study participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study from 1092 adults with diabetes and baseline eGFR 60 ml/min per 1.73 mAt baseline, subcohort participants had mean age of 70 ± 9 years, mean eGFR of 40 ±13 ml/min per 1.73 mAmong adults with diabetes and eGFR 60 ml/min per 1.73 m

Earlier identification of individuals at high risk of chronic kidney disease (CKD) may facilitate improved risk factor mitigation.We evaluated the association of novel plasma biomarkers with incident CKD using a case-cohort design in participants without diabetes and with baseline estimated glomerular filtration rate (eGFR) ≥ 60 ml/min per 1.73 mIn MESA (median follow-up of 9.2 years), there were 497 individuals in the random subcohort and 163 incident CKD cases. In REGARDS (median follow-up of 9.4 years), there were 497 individuals in the random subcohort and 497 incident CKD cases. Each 2-fold higher plasma KIM-1 (adjusted HR 1.38 [95% CI 1.05-1.81]), suPAR (1.96 [1.10-3.49]), TNFR-1 (1.65 [1.04-2.62]), TNFR-2 (2.02 [1.21-3.38]), and YKL-40 (1.38 [1.09-1.75]) concentrations were associated with incident CKD in MESA. In REGARDS, TNFR-1 (1.99 [1.43-2.76]) and TNFR-2 (1.76 [1.22-2.54]) were associated with incident CKD.Plasma concentrations of soluble TNFR-1 and TNFR-2 are consistently associated with incident CKD in nondiabetic community-living individuals in MESA and REGARDS.

Background Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. Methods We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary efficacy period (weeks 24–36). Results Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups (hazard ratio 1.10; 95% CI 0.62, 1.93). In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was −0.10 g/dL (95% CI −0.33, 0.12) in the primary efficacy period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively. Conclusions In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

Introduction: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. Methods: To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm. Results: In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events. Discussion/Conclusion: Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Currently, thrice-weekly in-center hemodialysis for 3 to 5 hours per session is the most common therapy worldwide for patients with treated kidney failure. Outcomes with thrice-weekly in-center hemodialysis are poor. Emerging evidence supports the overarching hypothesis that a more physiological approach to administering dialysis therapy, including in the home through home hemodialysis or peritoneal dialysis, may lead to improvement in several cardiovascular risk factors and cardiovascular outcomes compared with thrice-weekly in-center hemodialysis. The Advancing American Kidney Health Initiative, which has a goal of increasing the use of home dialysis, is aligned with the American Heart Association’s 2024 mission to champion a full and healthy life and health equity. We conclude that incorporation of interdisciplinary care models to increase the use of home dialysis therapies in an equitable manner will contribute to the ultimate goal of improving outcomes for patients with kidney failure and cardiovascular disease.

RATIONALE AND OBJECTIVE. Achievement of decongestion in acute heart failure (AHF) is associated with improved survival and cardiovascular outcomes, but can be associated with acute declines in estimated glomerular filtration rate (eGFR). We sought to examine whether rate of in-hospital decongestion is associated with longer term kidney function decline. STUDY DESIGN. Post hoc analysis of trial data. SETTINGS & PARTICIPANTS. Patients with ≥2 measures of kidney function (n=3,500) from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. EXPOSURE. In-hospital rate of change in assessments of volume overload, including b-type natriuretic peptide (BNP), N-terminal pro b-type natriuretic peptide (NT-proBNP) and clinical congestion score (0–12); and rate of change in hemoconcentration including measures of hematocrit, albumin and total protein. OUTCOMES. Incident chronic kidney disease (CKD) Stage ≥4 (defined by a new eGFR40%. ANALYTICAL APPROACH. Multivariable cause-specific hazards models. RESULTS. Over median 10-month follow-up, faster decreases in volume overload and more rapid increases in hemoconcentration were associated with decreased risk of incident CKD Stage ≥4 and eGFR decline of >40%. In adjusted analyses, for every 6% faster decline in BNP per week, there was a 32% lower risk of both incident CKD Stage ≥4 (HR=0.68, 95% CI 0.58, 0.79) and eGFR decline by >40% (HR=0.68, 95% CI 0.57, 0.80). For every 1% faster increase per week in absolute hematocrit, there was a lower risk for both incident CKD Stage ≥4 (HR=0.73 [0.64, 0.84]) and eGFR decline by >40% (HR=0.82 [0.71, 0.95]), with results consistent for other biomarkers. LIMITATIONS. Possibility of residual confounding. CONCLUSION. These results provide reassurance that more rapid decongestion in patients with AHF do not increase the risk of adverse kidney outcomes in patients with HF.

Cardiovascular disease (CVD) is a major cause of mortality among people with diabetic kidney disease (DKD). The pathophysiology is inadequately explained by traditional CVD risk factors. The uremic solutes trimethylamine-N-oxide (TMAO) and asymmetric and symmetric dimethylarginine (ADMA, SDMA) have been linked to CVD in kidney failure with replacement therapy (KFRT), but data are limited in populations with diabetes and less severe kidney disease.Observational cohort.Random subcohort of 555 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants with diabetes and estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 mADMA, SDMA, and TMAO assayed by liquid chromatography-mass spectrometry in plasma and urine.Cardiovascular mortality (primary outcome); all-cause mortality and incident KFRT (secondary outcomes).Plasma concentrations and ratios of urine to plasma concentrations of ADMA, SDMA, and TMAO were tested for association with outcomes. Adjusted Cox regression models were fitted and hazard ratios of outcomes calculated per standard deviation and per doubling, and as interquartile comparisons.The mean baseline eGFR was 44 mL/min/1.73 mSingle cohort, restricted to patients with diabetes and eGFR 60 mL/min/1.73 mHigher plasma concentrations and lower ratios of urine to plasma concentrations of uremic solutes were independently associated with cardiovascular and all-cause mortality in DKD. Associations of ratios of urine to plasma concentrations with mortality suggest a connection between renal uremic solute clearance and CVD pathogenesis.

RATIONALE & OBJECTIVE: Most circulating biomarkers of chronic kidney disease (CKD) progression focus on factors reflecting glomerular filtration. Few biomarkers capture non-glomerular pathways of kidney injury or damage, which may be particularly informative in populations at high risk for CKD progression such as individuals with diabetes. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 594 participants (mean age 70, 53% women) of the Reason for Geographic and Racial Differences in Stroke study who had diabetes and an estimated glomerular filtration rate (eGFR)