Key Points: The vascular endothelial growth factor B inhibitor CSL346 (8 or 16 mg/kg q4w) did not reduce urinary albumin-creatinine ratio at week 16 versus placebo in patients with type 2 diabetes mellitus and diabetic kidney disease. CSL346 was generally well tolerated at both doses; however, CSL346 (16 mg/kg) significantly increased diastolic BP versus placebo.
Background: Increased vascular endothelial growth factor B (VEGF-B) expression in patients with diabetic kidney disease (DKD) is associated with increased lipid deposition in glomerular podocytes.
Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.
Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.
Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.
Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications.
View Article and Find Full Text PDFKey Points: Renin-angiotensin system inhibition was favorable for risk of kidney failure (compared with 0% decline with use of placebo or other agents) up to declines in eGFR of 13% over a 3-month period. Relation between eGFR decline after renin-angiotensin system inhibitor initiation and risk of outcomes was stronger in the first 2 years of follow-up and waned over time.
Background: Declines in GFR occur commonly when renin-angiotensin system (RAS) inhibitors are started.
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min per 1.
View Article and Find Full Text PDFSignificance Statement: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years.
View Article and Find Full Text PDFBackground: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope.
View Article and Find Full Text PDFBackground: The cause for differences in serum creatinine between Black and non-Black individuals incorporated into prior GFR-estimating equations is not understood. We explored whether social determinants of health can account for this difference.
Methods: We conducted a secondary analysis of baseline data of the Modification of Diet in Renal Disease and Chronic Renal Insufficiency Cohort studies ( N =1628 and 1423, respectively).
Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further plays a role in the progression of diabetic nephropathy, and the suppression of glomerular albumin leak is a key factor in its prevention. Although microalbuminuria is a classic manifestation of diabetic nephropathy, often progressing to macroalbuminuria or overt proteinuria over time, it does not always precede renal function loss in diabetes.
View Article and Find Full Text PDFRationale & Objective: Thrice-weekly hemodialysis can result in adequate urea clearance; however, the morbidity and mortality rates of patients treated with maintenance dialysis remain unacceptably high, partly because of nonadherence. African Americans have a higher prevalence of kidney failure treated with dialysis, greater dialysis nonadherence, and higher odds of hospitalization. We hypothesized that more precise ways of assessing dialysis treatment adherence will reflect the severity of nonadherence, distinguish patterns of nonadherence, and inform the design of personalized behavioral interventions.
View Article and Find Full Text PDFBackground: Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects.
Methods: To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization.
Introduction: Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of "primary" membranous nephropathy (MN). Crescents in MN in nonlupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and are postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody.
Methods: We studied PLA2R staining in nonlupus patients with MN and crescents.
Background: The concept of multinephron segment diuretic therapy (MSDT) has been recommended in severe diuretic resistance with only expert opinion and case-level evidence. The purpose of this study was to investigate the safety and efficacy of MSDT, combining 4 diuretic classes, in acute heart failure (AHF) complicated by diuretic resistance.
Methods And Results: A retrospective analysis was conducted in patients hospitalized with AHF at a single medical center who received MSDT, including concomitant carbonic anhydrase inhibitor, loop, thiazide, and mineralocorticoid receptor antagonist diuretics.
Hypertension is frequently both a cause and complication of CKD. The optimal blood pressure target in CKD has been of hot debate over the decades with little data to inform the goals. Here, we review the data from the Systolic Blood Pressure Intervention Trial (SPRINT), Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), Ramipril Efficacy in Nephropathy-2 (REIN-2), and Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials to use the available evidence to better inform what blood pressure goal should be recommended in patients with CKD and to answer the question "How low should we go?".
View Article and Find Full Text PDFBackground: Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials.
Methods: In this meta-analysis, we searched PubMed for publications in English from Jan 1, 1946, to Dec 15, 2016, using search terms including "chronic kidney disease", "chronic renal insufficiency", "albuminuria", "proteinuria", and "randomized controlled trial"; key inclusion criteria were quantifiable measurements of albuminuria or proteinuria at baseline and within 12 months of follow-up and information on the incidence of end-stage kidney disease.
In the original publication of the article, the majority of changes stem from misclassification of "medium adherence" when using the Morisky Medication Adherence Scale (MMAS-8) and not using the correct scoring algorithm for one of the responses when calculating MMAS-8 total scores.
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