Egfr slope as endpoint

In several therapeutic areas, including chronic kidney disease (CKD) and immunoglobulin A nephropathy (IgAN), there is a growing interest in how best to analyze estimated glomerular filtration rate (eGFR) data over time in randomized clinical trials including how to best accommodate situations where the rate of change is not anticipated to be linear over time, often due to possible short term hemodynamic effects of certain classes of interventions. In such situations, concerns have been expressed by regulatory authorities that the common application of single slope analysis models may induce Type I error inflation...

BACKGROUND: Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area...

Estimated glomerular filtration rate is considered the principal measure of kidney function and, together with albuminuria, is a relevant prognostic factor for the development of end-stage kidney disease. Due to the strong association between estimated glomerular filtration rate and clinical events, such as commencement of dialysis, cardiovascular outcomes and all-cause death, estimated glomerular filtration rate is crucial for clinical decision-making in terms of scheduling follow-up and pharmacological interventions, and planning renal replacement therapies in advanced chronic kidney disease...

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BACKGROUND: The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown. OBJECTIVE: We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex. DESIGN: Prospective randomized placebo-controlled trial...

BACKGROUND: Few studies have evaluated the treatment of immunoglobulin A nephropathy (IgAN) patients with nephrotic syndrome (NS) and mesangioproliferative glomerulonephritis (MPGN). The aim of this study was to compare the therapeutic effects of oral glucocorticoids (GCS) combined with intravenous cyclophosphamide (CTX) and oral GCS alone in the treatment of the MPGN-IgAN patients with NS. METHODS: Biopsy-proven primary IgAN patients who were aged ≥14 years at diagnosis, had coexistent NS and MPGN and estimated glomerular filtration rate (eGFR) ≥15 mL/min/1...

BACKGROUND: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. METHODS: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe...

Random coefficient (RC) models are commonly used in clinical trials to estimate the rate of change over time in longitudinal data. Trials utilizing a surrogate endpoint for accelerated approval with a confirmatory longitudinal endpoint to show clinical benefit is a strategy implemented across various therapeutic areas, including immunoglobulin A nephropathy. Understanding conditional power (CP) and information fraction calculations of RC models may help in the design of clinical trials as well as provide support for the confirmatory endpoint at the time of accelerated approval...

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients...

BACKGROUND: An analysis of European and American individuals revealed that a reduction in estimated glomerular filtration rate (eGFR) slope by 0.5 to 1.0 mL/min/1.73 m2 per year is a surrogate endpoint for end-stage kidney disease (ESKD) in patients with early chronic kidney disease. However, it remains unclear whether this can be extrapolated to Japanese patients. METHODS: Using data from the Japan diabetes comprehensive database project based on an advanced electronic medical record system (J-DREAMS) cohort of 51,483 Japanese patients with diabetes and a baseline eGFR ≥ 30 mL/min/1...

BACKGROUND: In clinical trials targeting early chronic kidney disease (CKD), eGFR slope has been proposed as a surrogate endpoint for predicting end-stage kidney disease (ESKD). However, it is unclear whether the eGFR slope serves as a surrogate endpoint for predicting long-term prognosis in Japanese early CKD populations. METHODS: The data source was the J-CKD-Database, which contains real-world data on patients with CKD in Japan. eGFR slope was calculated from the eGFR of each period, 1-year (1-year slope), 2-year (2-year slope), and 3-year (3-year slope), for participants with a baseline eGFR ≥ 30 ml/min/1...

AIMS: In diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM. METHODS: 489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data...

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1...

BACKGROUND: Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile...

RATIONALE AND OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of multiple kidney cysts that leads to growth in total kidney volume (TKV) and progression to kidney failure. Venglustat is a glucosylceramide synthase inhibitor that has been shown to inhibit cyst growth and reduce kidney failure in preclinical models of ADPKD. STUDY DESIGN: STAGED-PKD was a two-stage, multicenter, double-blind, randomized, placebo-controlled Phase 2/3 study in adults with ADPKD at risk of rapidly progressive disease, selected based on Mayo Kidney Volume Class 1C-1E and an estimated glomerular filtration rate (eGFR) of 30-89...

Background: Chronic kidney disease (CKD) is a global public health issue. Red blood cell distribution width (RDW) is a recently recognized potential inflammatory marker, which mirrors the variability in erythrocyte volume. Studies indicate that elevated RDW is associated with increased risk of mortality in CKD patients, while evidence regarding the impact of RDW on kidney outcome is limited. Methods: Altogether 523 patients with CKD stage 1-4 from a single center were enrolled...

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction. OBJECTIVES: The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial...

Clinical study endpoints that assess the efficacy of interventions in patients with chronic renal insufficiency can be adopted for use in kidney transplantation trials, given the pathophysiological similarities between both conditions. Kidney dysfunction is reflected in the glomerular filtration rate (GFR), and although a predefined (e.g., 50%) reduction in GFR was recommended as an endpoint by the European Medicines Agency (EMA) in 2016, many other endpoints are also included in clinical trials. End-stage renal disease is strongly associated with a change in estimated (e)GFR, and eGFR trajectories or slopes are increasingly used as endpoints in clinical intervention trials in chronic kidney disease (CKD)...

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%])...

Background: Late antibody-mediated rejection (ABMR) after kidney transplantation is a major cause of long-term allograft loss with currently no proven treatment strategy. Design for trials testing treatment for late ABMR poses a major challenge as hard clinical endpoints require large sample sizes. We performed a retrospective cohort study applying commonly used selection criteria to evaluate the slope of the estimated glomerular filtration rate (eGFR) within an early and short timeframe after biopsy as a surrogate of future allograft loss for clinical trials addressing late ABMR...