Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts

Abstract

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Figure 1

Crude incidence rate of mortality (per 1,000 person-years) by (A) category of estimated glomerular filtration rate and (B) category of albuminuria. Solid lines represent studies which assessed albuminuria using albumin:creatinine ratio (categories: <30, 30–299, 300–999, ≥1,000 mg/g). Dashed lines represent studies which assessed albuminuria using protein:creatinine ratio (categories: <50, 50–499, 500–1,499, ≥1,500 mg/g). Dotted lines represent studies which assessed albuminuria using dipstick protein (categories: −/±, +, ++, ≥+++). Points with ≤5 participants are excluded.

Figure 2

Forest plot of adjusted hazard ratio for mortality associated with (A) a 15 mL/min/1.73 m² lower estimated glomerular filtration rate (below an eGFR of 45 mL/min/1.73 m²) and (B) an 8-fold higher albumin:creatinine ratio or protein:creatinine ratio. The models are adjusted for age, sex, race, prior cardiovascular disease, smoking status, diabetes mellitus, systolic blood pressure, serum total cholesterol concentration and albuminuria (A) or eGFR splines (B).

Figure 3

Crude incidence rate of end-stage renal disease (per 1,000 person-years) by (A) category of estimated glomerular filtration rate and (B) category of albuminuria. Solid lines represent studies which assessed albuminuria using albumin:creatinine ratio (categories: <30, 30–299, 300–999, ≥1,000 mg/g). Dashed lines represent studies which assessed albuminuria using protein:creatinine ratio (categories: <50, 50–499, 500–1,499, ≥1,500 mg/g). Dotted lines represent studies which assessed albuminuria using dipstick protein (categories: −/±, +, ++, ≥+++). Points with ≤5 participants are excluded.

Figure 4

Forest plot of adjusted hazard ratio for end-stage renal disease associated with (A) a 15 mL/min/1.73 m² lower estimated glomerular filtration rate (below an eGFR of 45 mL/min/1.73 m²) and (B) an 8-fold higher albumin:creatinine ratio or protein:creatinine ratio. The models are adjusted for age, sex, race, prior cardiovascular disease, smoking status, diabetes mellitus, systolic blood pressure, serum total cholesterol concentration and albuminuria (A) or eGFR splines (B).