Progression of renal insufficiency in type 2 diabetes with and without microalbuminuria: results of the Heart Outcomes and Prevention Evaluation (HOPE) randomized study.

BACKGROUND: In patients with type 2 diabetes with overt nephropathy, the risk for progressive renal failure is high. This risk is less well established for those with type 2 diabetes and microalbuminuria or normalbuminuria. We studied changes in serum creatinine levels during 3.5 to 5.5 years in a large cohort of people with diabetes at high cardiovascular risk with microalbuminuria or normalbuminuria.

METHODS: Retrospective analysis of serum creatinine levels at baseline and yearly thereafter was performed in the Microalbuminuria and Renal Outcomes in the Heart Outcomes and Prevention Evaluation study comparing ramipril's effects with placebo during 4.5 years in 3,577 participants with diabetes, including 1,139 participants with microalbuminuria and 333 participants with renal insufficiency. Participants with dipstick-positive proteinuria (>1+) or serum creatinine levels greater than 2.3 mg/dL (200 micromol/L) were excluded.

RESULTS: Serum creatinine levels did not increase significantly during the study if all participants with diabetes are considered or for subgroups with microalbuminuria and/or renal insufficiency at baseline. However, slopes of serum creatinine over time showed a significant trend for increasing values. There were no differences between the placebo and ramipril-treated groups. A serum creatinine level of 1.4 mg/dL (125 micromol/L) or greater newly developed in 474 of 3,238 people (243 patients, placebo; 231 patients, ramipril; P = 0.5033). A doubling of baseline serum creatinine level or end-stage renal disease developed in 8 of 333 participants with renal insufficiency at baseline.

CONCLUSION: In people with type 2 diabetes, but without overt nephropathy, who are at high risk for cardiovascular disease, progression of renal insufficiency is slow on the basis of changes in creatinine levels. On the basis of reaching threshold levels of renal function, progression rates are clinically meaningful, especially considering population life expectancy.