Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis

Abstract

Background: Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown.

Methods: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes.

Findings: We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts.

Interpretation: Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.

Funding: US National Kidney Foundation.

Figure 1. Hazard ratios for all-cause and cardiovascular mortality in the combined general and high-risk populations according to eGFR in individuals with and without diabetes

(A, B) All-cause mortality. (C, D) Cardiovascular mortality. Panels A and C use one reference point (diamond, eGFR of 95 mL/min per 1·73 m² in the no diabetes group) for both individuals with and without diabetes to show the main effect of diabetes on risk. Panels B and D use separate references (diamonds) in the diabetes and no diabetes groups to assess interaction with diabetes specifically. Hazard ratios were adjusted for age, sex, race, smoking, history of cardiovascular disease, serum total cholesterol concentration, body-mass index, and albuminuria (log albumin-to-creatinine ratio, log protein-to-creatinine, or categorical dipstick proteinuria [negative, trace, 1+, ≥2+]). Blue and red circles denote p<0·05 as compared with the reference (diamond). Significant interaction between diabetes and eGFR is shown by x signs. eGFR=estimated glomerular filtration rate.

Figure 2. Hazard ratios for all-cause and cardiovascular mortality in the combined general and high-risk populations according to ACR in participants with and without diabetes

(A, B) All-cause mortality. (C, D) Cardiovascular mortality. Panels A and C use one reference point (diamond, ACR of 5 mg/g in the no diabetes group), for both individuals with and without hypertension to show the main effect of diabetes on risk. Panels B and D use separate references (diamonds) in the diabetes and no diabetes groups to assess interaction with diabetes specifically. Hazard ratios were adjusted for age, sex, race, smoking, history of cardiovascular disease, serum total cholesterol concentration, body-mass index, and estimated glomerular filtration rate. Blue and red circles denote p<0·05 as compared with the reference (diamond). Significant interaction between diabetes and ACR is shown by x signs. ACR=albumin-to-creatinine ratio.

Figure 3. Hazard ratios for end-stage renal disease in the chronic kidney disease populations according to eGFR and ACR in participants with and without diabetes

(A, B) eGFR. (C, D) ACR. Panels A and C use eGFR of 50 mL/min per 1·73 m² (A) and ACR of 20 mg/g (C) in individuals without diabetes as the reference point (diamond) for both individuals with and without diabetes. Panels B and D use eGFR of 50 mL/min per 1·73 m² (B) and ACR of 20 mg/g (D) as the reference points (diamond) in diabetic and non-diabetic groups. Blue and red circles denote p<0·05 as compared with the reference (diamond). Hazard ratios were adjusted for age, sex, race, smoking, history of cardiovascular disease, serum total cholesterol concentration, body-mass index, and albuminuria (log albumin-to-creatinine ratio, log protein-to-creatinine, or categorical dipstick proteinuria [negative/ trace, 1+, 2+, ≥3+]) or eGFR. eGFR=estimated glomerular filtration rate. ACR=albumin-to-creatinine ratio.

Figure 4. Hazard ratios for all-cause mortality according to eGFR in participants with and without diabetes in individuals with and without hypertension from the general population and high-risk cohorts

(A, B) Individuals with hypertension. (C, D) Individuals without hypertension. Blue and red circles denote p<0·05 as compared with the reference (diamond). Significant interaction between diabetes and eGFR is shown by x signs. Hazard ratios were adjusted for age, sex, race, smoking, history of cardiovascular disease, serum total cholesterol concentration, body-mass index, and albuminuria (log albumin-to-creatinine ratio, log protein-to-creatinine, or categorical dipstick proteinuria [negative, trace, 1+, ≥2+])