ABSTRACT: Using a community-based cohort we studied the association between changes in the estimated glomerular filtration rate (eGFR) over time and the risk of all-cause mortality. We identified 529,312 adults who had at least three outpatient eGFR measurements over a 4-year period from a provincial laboratory repository in Alberta, Canada. Two indices of change in eGFR were evaluated: the absolute annual rate of change (in ml/min per 1.73 m(2) per year) and the annual percentage change (percent/year). The adjusted mortality risk associated with each category of change in eGFR was assessed, using stable eGFR (no change) as the reference. Over a median follow-up of 2.5 years there were 32,372 deaths. Compared to the reference participants, those with the greatest absolute annual decline less than or equal to 5 ml/min per 1.73 m(2) per year had significantly increased mortality (hazard ratio of 1.52) adjusted for covariates and kidney function at baseline (last eGFR measurement). Participants with the greatest increase in eGFR of 5 ml/min per 1.73 m(2) per year or more also had significantly increased mortality (adjusted hazard ratio of 2.20). A similar pattern was found when change in eGFR was quantified as an annual percentage change. Thus, both declining and increasing eGFR were independently associated with mortality and underscore the importance of identifying change in eGFR over time to improve mortality risk prediction.Kidney International advance online publication, 23 January 2013; doi:10.1038/ki.2012.443.
Kidney International 01/2013; · 6.61 Impact Factor
It is unclear what degree of change in the eGFR over a 1-year period indicates clinically significant progression, and whether this change adds additional information beyond that obtained by a single eGFR measure alone.Methods
We included 598 397 adults who had at least two outpatient eGFR measurements (at least 6 months apart) during 1-year accrual period in Alberta, Canada. Change in kidney function (using the first and last eGFR) was defined by change in kidney function category with confirmation based on percent (%) change in eGFR [(last eGFR - first eGFR)/first eGFR × 100]. The groups for change in kidney function were thus defined as: 'certain drop' (drop in CKD category with ≥25% decrease in the eGFR); 'uncertain drop' (drop in CKD category with <25% decrease in the eGFR); 'stable' (no change in CKD category); 'uncertain rise' (rise in CKD category with <25% rise in the eGFR) and 'certain rise' (rise in CKD category with ≥25% increase in the eGFR). Adjusted end-stage renal disease (ESRD) rates (per 1000 person-years) for each group of change in kidney function were calculated using Poisson regression. Adjusted risks of ESRD associated with change in kidney function, in reference to stable kidney function, were estimated.ResultsAmong the 598 397 participants, 74.8% (n = 447 570) had stable (no change in CKD category), 3.3% (n = 19 591) had a certain drop and 3.7% (n = 22 171) had a certain rise in kidney function. Participants who experienced a certain change in kidney function (both drop and rise) were older, more likely to be female, and had a higher prevalence of comorbidities, in comparison with those with stable kidney function. There were 1966 (0.3%) ESRD events over a median follow-up of 3.5 years. Compared with participants with stable kidney function, after adjustment for covariates, and the first eGFR measurement, those with certain drop had 5-fold increased risk of ESRD (HR: 5.11; 95% CI: 4.56-5.71), whereas those with an uncertain drop had 2-fold increased risk (HR: 2.13; 95% CI: 1.84-2.47). After adjustment for the eGFR and covariates at the last visit, neither a certain nor uncertain drop in the eGFR was associated with an increased ESRD risk. The ESRD risk associated with the last eGFR level, adjusted for the slope over time, were 2.89 (95% CI: 2.35-3.55), 10.98 (95% CI: 8.69-13.87), 35.20 (95% CI: 27.95-44.32) and 147.96 (116.92-187.23) for categories 2, 3a, 3b and 4, respectively, in reference to category 1.ConclusionsA change in eGFR category accompanied by ≥25% decline (certain drop) is associated with increased ESRD risk. However, this elevated risk is captured by patient characteristics and eGFR at the last visit, suggesting that eGFR trajectories based on more than two serum creatinine measurements over a period longer than 1 year are required to determine ESRD risk and allow more reliable risk prediction.
Nephrology Dialysis Transplantation 07/2012; · 3.40 Impact Factor
ABSTRACT: Serum creatinine is routinely measured to estimate glomerular filtration rate (GFR). Long-term cohort studies report that death is a likelier outcome than progression to kidney failure. However, it is unclear how short-term changes in estimated GFR (eGFR) over a 1-year period relate to subsequent mortality risk.
Using a provincial laboratory registry from Alberta, Canada, we identified 598,397 adults who had ≥2 outpatient eGFR measurements at least 6 months apart during a 1-year accrual period. Change in kidney function was categorized by both changes in eGFR category and percent change ≥25% into 5 groups: certain drop, uncertain drop, stable (no change in CKD category), uncertain rise, and certain rise. Cox proportional hazards models, adjusting for baseline covariates, kidney function, and proteinuria were used to estimate the risk of all-cause mortality associated with each group change in kidney function in reference to stable kidney function.
Among the study participants, 447,570 (74.8%) had stable kidney function, 19,591 (3.3%) had a certain drop, and 22,171 (3.7%) had a certain rise in kidney function. Participants with change in kidney function (both drop and rise) were older, more likely to be female, and had a higher prevalence of comorbidities in comparison to those with stable kidney function. There were 51,473 (8.6%) deaths during a median follow-up of 3.5 years. Compared to participants with stable kidney function, those with a certain drop had an almost twofold increased mortality risk (hazard ratio 1.89, 95% CI 1.83-1.95) adjusted for baseline eGFR, proteinuria, and covariates. Participants with a certain rise (3.7%) in kidney function also experienced an increased mortality risk (hazard ratio 1.51, 95% CI 1.46-1.56) compared to those with stable kidney function. Risk of death was similarly increased with adjustment for eGFR at the last visit.
Change in kidney function of ≥25% in any direction over a 1-year period is associated with a substantially increased risk of mortality.
American Journal of Nephrology 06/2012; 36(1):41-9. · 2.54 Impact Factor