Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts

Abstract

Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.

Figure 1

Pooled hazard ratios (95% confidence intervals) for end-stage renal disease according to spline eGFR (upper panels) and albumin-to-creatinine ratio ( (lower panels), adjusted for each other and for age, sex and cardiovascular risk factors (continuous analyses). Reference categories are eGFR 95 mL/min/1.73 m² and albumin-to-creatinine ratio 5 mg/g or dipstick negative or trace. Left panels show results for general population cohorts, and right panels for high risk cohorts. Dots represent statistical significance, triangles represent non significance, and shaded areas are 95% confidence intervals. Abbreviations are: HR, hazard ratio; eGFR, estimated glomerular filtration rate; ACR, albumin-to-creatinine ratio; ESRD, end-stage renal disease; AKI, acute kidney injury; pCKD, progressive chronic kidney disease; GP cohorts, general population cohorts and HR cohorts, high risk cohorts.

Figure 2

Pooled adjusted hazard ratios or Odds Ratios (95% confidence intervals) for end-stage renal disease (upper panel), acute kidney injury (middle panel) and progressive chronic kidney disease (lower panel) according to eGFR and albuminuria based on continuous models with eGFR (splines), albuminuria (log-linear albumin-to-creatinine ratio or categorical dipstick) and their interaction terms. Hazard ratios are adjusted for age, sex and cardiovascular risk factors. Reference category is eGFR 95 mL/min/1.73 m² plus albumin-to-creatinine ratio 5 mg/g or dipstick negative or trace. Left panels shows results for general population cohorts, and right panels for high risk cohorts. Dots represent statistical significance, triangles represent non significance, and shaded areas are 95% confidence intervals. In this figure albuminuria is treated categorically. Black lines and blue shading represent an albumin-to-creatinine ratio < 30 mg/g or dipstick negative or trace, green lines and green shading an albumin-to-creatinine ratio 30–299 mg/g or dipstick 1+, and red lines and red shading an albumin-to-creatinine ratio ≥ 300 mg/g or dipstick ≥ 2+. Abbreviations are: HR, hazard ratio; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; AKI, acute kidney injury; pCKD, progressive chronic kidney disease; GP cohorts, general population cohorts and HR cohorts, high risk cohorts.