Surrogate endpoint and ESRD

BACKGROUND: The use of percutaneous mechanical circulatory support (MCS) devices, including Impella and Intra-aortic balloon pump (IABP), in patients with cardiogenic shock has increased in recent times. We aimed to evaluate the impact of the choice of an MCS device on healthcare resource utilization. METHODS: We queried the National Inpatient Sample registry between October 2016 to December 2018 to identify adults admitted for acute coronary syndrome-related cardiogenic shock and who received percutaneous coronary intervention (PCI)...

AIM: The aim of the study was to investigate the effect of a new calcimimetic, Etelcalcetide, on secondary hyperparathyroidism and its effects in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) compared with hemodialysis (HD) patients not treated with calcimimetics. MATERIALS AND METHODS: The cohort study included 203 ESRD patients with secondary hyperparathyroidism (SHPT) who received HD treatment. Total number patients were randomly to two groups...

BACKGROUND: Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is incurable and usually leads to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood, and the genetics of DKD have not yet been extensively studied. In this study, we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease. RESULTS: Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies: one in 26,786 individuals with T2D and the other in 339,080 non-diabetic individuals...

Background: The triglyceride-glucose (TyG) index is a simple, novel and reliable surrogate marker of insulin resistance. However, evidence for the prognostic impact of an elevated TyG index on IgA nephropathy (IgAN) is limited. Therefore, we evaluated the relationship between the TyG index and the risk of renal progression in IgAN. Method: This cohort study involved biopsy-proven IgAN between January 2009 and December 2018 in West China Hospital, in which patients were assigned to two groups based on the cut-off value of TyG using receiver operating characteristic (ROC) curves...

BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD), but currently available treatments do not improve kidney function or prevent the initiation of dialysis/kidney replacement therapy. A previous study demonstrated that bardoxolone methyl improves the estimated glomerular filtration rate (eGFR), but the study was prematurely terminated because of an imbalance in heart failure between treatment groups. The subsequent phase 2 TSUBAKI study demonstrated no incidence of heart failure and an improved eGFR and GFR as determined by inulin clearance in DKD patients...

AIMS: To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events...

IgA nephropathy (IgAN) remains one of the most common forms of glomerulonephritis, especially in developed countries with a low prevalence of infectious diseases. Despite supportive measures that slow the rate of progression of chronic kidney disease (CKD) in IgAN, many patients still progress to end-stage kidney disease. Proteinuria has been shown to be an adverse prognostic factor in IgAN. Data support the use of proteinuria reduction as a reasonably likely surrogate endpoint for a treatment's effect on progression to end-stage renal disease (ESRD) in IgAN...

BACKGROUND: The effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy...

SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose lowering therapies, with additional benefits of weight loss and blood pressure reduction. Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality. Ongoing research using hard renal endpoints such as end stage kidney disease rather than surrogate markers might clarify the renoprotective benefits of both agents...

BACKGROUNDS: Recently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown. METHODS: We retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels...

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although most IgAN cases are sporadic, few show a familial aggregation. However, the prevalence and prognosis of IgAN individuals with positive familial history (FH) of renal disorders remains uncertain. To address these issues, we conducted a longitudinal observational study on a single-institution cohort of patients with biopsy-proven IgAN. METHODS: A total of 467 IgAN patients who underwent renal biopsy during 1994 to 2019 were ascertained to have positive- or negative-FH by history taking and were followed for an average of 8...

RATIONALE & OBJECTIVE: An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope...

BACKGROUND: The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression. METHODS: We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort...

BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d...

BACKGROUND: Plasma copeptin is a surrogate of arginine vasopressin (AVP) secretion and is associated with a risk of renal and cardiovascular disease. We investigated associations between copeptin and renal events, cardiovascular events and mortality in type 1 diabetes (T1D). METHODS: We conducted a prospective cohort study on 658 individuals with T1D from Steno Diabetes Center Copenhagen. Plasma copeptin concentrations and conventional risk factors were assessed at baseline...

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), hypertension is prevalent and cardiovascular events are the main cause of death. Thiazide diuretics are often prescribed as second-line antihypertensives, on top of renin-angiotensin-aldosterone system (RAAS) blockade. There is a concern, however, that diuretics may increase vasopressin concentration and RAAS activity, thereby worsening disease progression in ADPKD. We aimed to investigate the validity of these suggestions...

PURPOSE OF REVIEW: Chronic kidney disease is a global health problem with few effective therapies available that slow the progression to end-stage renal disease. The established clinical endpoints for renal trials; doubling of serum creatinine or end-stage renal disease, are late manifestations of CKD. This leads to large trials enrolling preferably patients with advanced stages of CKD. The use of valid surrogate biomarkers that substitute a clinical endpoint (surrogate endpoints), can lead to trials of shorter duration that can be performed at earlier stages of CKD...

Diabetic kidney disease (DKD) represents an enormous burden in patients with type 2 diabetes mellitus (T2DM). Preclinical studies using most glucose-lowering agents have suggested renal-protective effects, but the proposed mechanisms of renoprotection have yet to be defined, and the promising results from experimental studies remain to be translated into human clinical findings to improve the prognosis of patients at risk of DKD. Also, it is important to distinguish effects on surrogate endpoints, such as decreases in albuminuria and estimated glomerular filtration rate (eGFR), and hard clinical endpoints, such as progression to end-stage renal disease (ESRD) and death from renal causes...

BACKGROUND: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled...

BACKGROUND: There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease. METHODS: In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD. RESULTS: Low eGFR (<60 mL/min/1...