Risk Factors for the Development of Albuminuria and Renal Impairment in Type 2 Diabetes

Three thousand and six hundred sixty-seven patients with T2D aged 30–74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m² according to MDRD) were followed up for 5 years (2002–2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR less than 60 mL/min/1.73 m² by MDRD or eCrCl > 60 mL/min by Cockgroft–Gault (C–G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes.

Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6–7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C–G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD).

In conclusion, distinct sets of modifiable risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in type 2 diabetes. Obesity and elevated serum triglycerides are semi-novel risk factors for development of renal dysfunction, and interestingly, glycaemic control only predicted the development of albuminuria but not development of renal impairment. To our surprise, the effects of BMI also accounted for a substantial proportion of the increased risk for both development of albuminuria and renal impairment. In a subset of type 2 diabetic patients, albuminuria does precede development of renal impairment, and non-albuminuric renal impairment was found in 6–7% of this study population. In these patients, screening for microalbuminuria may not be optimal to detect risk of developing renal impairment, and thus, other markers, such as reliable estimates of glomerular filtration rate, are therefore needed to monitor renal function. In population-based studies, the different equations currently used to estimate renal function may have an impact on interpretation of data, and renal function and MDRD should be preferred when analyzing the association with BMI.