Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy

BACKGROUND: The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR is diminished in patients obtaining remission of nephrotic range albuminuria, but information is scarce concerning the impact of remission of nephrotic range albuminuria on the long-term prognosis.

METHODS: At the Steno Diabetes Center, we performed a prospective cohort study of all type 1 diabetic patients with nephrotic range albuminuria (N= 125), who had annual measurement of GFR [(51)chromium-ethylenediaminetetraacetic acid ((51)Cr-EDTA) plasma clearance] carried out for at least 3 years. Patients were followed from onset of nephrotic range albuminuria until death or the end of year 2003. Nephrotic range albuminuria was defined as persistent albuminuria above 2.5 g/24 hours, remission of nephrotic range albuminuria was defined as sustained albuminuria <0.6 g/24 hours for at least 1 year.

RESULTS: Nephrotic range albuminuria occurred in 90 men and 35 women, age [mean (SD)] 34 (8) years, duration of diabetes 22 (8) years, and follow-up time from onset of nephrotic range albuminuria [median (range)] 12.4 (3.0 to 24.9) years. Remission was induced in 32 patients (26%), 25 predominantly treated with angiotensin-converting enzyme (ACE) inhibitors, seven with non-ACE inhibitors. The remission lasted 5.5 (1.0 to 22.4) years. At the end of follow-up, 25% in the remission group and 74% in the no remission group had reached the composite end point of end-stage renal disease (ESRD) (dialysis, transplantation) or death. A Cox proportional hazard regression analysis with gender and age as fixed covariates and remission as time-dependent covariate revealed that obtaining remission was associated with a lower risk of dialysis, transplantation, or death, relative risk (95% CI) 0.28 (0.13 to 0.59), P= 0.001, whereas older age at onset of nephrotic range albuminuria (per 10-year increase) was associated with higher risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01.

CONCLUSION: Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression in diabetic nephropathy and a substantially improved survival.