Importance
The established chronic kidney disease (CKD) progression endpoint, end-stage renal disease (ESRD) or doubling of serum creatinine (corresponding to a change in estimated glomerular filtration rate (eGFR) of −57% or greater) is a late event, limiting feasibility of nephrology clinical trials.
Objective
To characterize the association of decline in eGFR with subsequent progression to ESRD, with implications for using lesser declines in eGFR as potential alternative endpoints for CKD progression. Since most people with CKD die before reaching ESRD, we also investigated mortality risk.
Data Sources
Individual meta-analysis of up to 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts.
Study Selection
Cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine over 1-3 years and outcome data.
Data Extraction and Synthesis
Transfer of individual participant data or standardized analysis of outputs for random effects meta-analysis took place between July 2012 and September 2013 with baseline eGFRs during 1975-2012.
Main Outcomes and Measures
ESRD (initiation of dialysis or transplantation) or all-cause mortality risk related to percent change in eGFR over 2 years adjusted for potential confounders and first eGFR.
Results
The adjusted hazard ratios (HR) of ESRD and mortality were exponentially higher with larger eGFR decline. Among participants with baseline eGFR <60 ml/min/1.73m2, the adjusted HRs for ESRD were 32.1 (95% CI 22.3-46.3) and 5.4 (4.5-6.4) for −57% and −30% eGFR changes, respectively. However, changes of −30% or greater were much more common than changes of −57% (6.9% (6.4-7.4%) vs. 0.79% (0.52-1.06%) in the whole consortium). This association was strong and consistent across length of baseline (1 or 3 years), baseline eGFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD for eGFR changes of −57%, −40%, −30% and 0% were 99% (95-100%), 83% (71-93%), 64% (52-77%), vs. 18% (15-22%) respectively at baseline eGFR of 35 ml/min/1.73m2. Corresponding mortality risks were 77% (71-82%), 60% (56-63%), 50% (47-52%), vs. 32% (31-33%), showing a similar but weaker pattern.
Conclusions and Relevance
Declines in eGFR smaller than doubling of serum creatinine occur more commonly and are strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in eGFR, such as 30% reduction over 2 years, as an alternative endpoint for CKD progression.
We found that CD14(++)CD16(+) monocytes were independently associated with CV events in non-dialysis CKD patients. Our results support the notion that CD16(+) monocytes rather than CD16(-) monocytes are involved in human atherosclerosis.
In patients with end-stage renal disease (ESRD) treated with haemodialysis or peritoneal dialysis, hypertension is common and often poorly controlled. Blood pressure (BP) recordings obtained before or after haemodialysis display a J- or U-shaped association with cardiovascular events and survival, but this most likely reflects the low accuracy of these measurements and the peculiar haemodynamic setting related to dialysis treatment. Elevated BP detected by home or ambulatory BP monitoring is clearly associated with shorter survival. Sodium and volume excess is the prominent mechanism of hypertension in dialysis patients, but other pathways, such as arterial stiffness, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, endothelial dysfunction, sleep apnoea and the use of erythropoietin-stimulating agents may also be involved. Non-pharmacologic interventions targeting sodium and volume excess are fundamental for hypertension control in this population. If BP remains elevated after appropriate treatment of sodium and volume excess, the use of antihypertensive agents is necessary. Drug treatment in the dialysis population should take into consideration the patient's comorbidities and specific characteristics of each agent, such as dialysability. This document is an overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research.
CD14++CD16+ monocytes independently predicted cardiovascular events in subjects referred for elective coronary angiography. Future studies will be needed to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies in atherosclerosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.