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.
Background
Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.
Study Design
Meta-analysis of cohort studies.
Setting & Population
8 general population (1,285,045 participants) and 5 CKD (79,519 participants) cohorts.
Selection Criteria for Studies
Cohorts participating in the CKD Prognosis Consortium.
Predictors
Diabetes and hypertension status, eGFR by the CKD Epidemiology Collaboration 2009 creatinine equation, urine ACR, and interactions.
Outcome
Hospitalization with AKI, using Cox proportional hazards models to estimate hazard ratios (HR) of AKI and random effects meta-analysis to pool results.
Results
Over a mean follow-up period of 4 years, there were 16,480 episodes of AKI in the general population and 2,087 episodes in the CKD cohorts. Low eGFR and high ACR were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR 80 mL/min/1.73m2 in non-diabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared to non-diabetic patients. The risk gradient for AKI with lower eGFR was greater in those without diabetes than with diabetes, but similar with higher ACR in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFR greater than 60 ml/min/1.73m2 than those without hypertension. However, the risk gradients for AKI with both lower eGFR and higher ACR were greater for those without than with hypertension.
Limitations
AKI identified by diagnostic code.
Conclusions
Lower eGFR and higher ACR are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
Background: There is strong biologic plausibility to support change in albuminuria as a surrogate endpoint for progression of chronic kidney disease (CKD), but empirical evidence to supports its validity in epidemiologic studies is lacking. Methods: We analyzed 28 cohorts including 693,816 individuals (80% with diabetes) and 7,461 end-stage kidney disease (ESKD) events, defined as initiation of kidney replacement therapy. Percent change in albuminuria was quantified during a baseline period of 1, 2 and 3 years using linear regression. Associations with subsequent ESKD were quantified using Cox regression in Coresh et al.
We examined the acceptability and effects of delivering doctors' visit notes electronically (via OpenNotes) to patients and care partners with authorized access to patients' electronic medical records. Adult patients and care partners at Geisinger Health System were surveyed at baseline and after 12 months of exposure to OpenNotes. Reporting on care partner access to OpenNotes, patients and care partners stated that they had better agreement about patient treatment plans and more productive discussions about their care. At follow-up, patients were more confident in their ability to manage their health, felt better prepared for office visits, and reported understanding their care better than at baseline. Care partners were more likely to access and use patient portal functionality and reported improved communication with patients' providers at follow-up. Our findings suggest that offering patients and care partners access to doctors' notes is acceptable and improves communication and patients' confidence in managing their care.
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