Remission of nephrotic range proteinuria in type I diabetes

Abstract

The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (≥ 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be ≤ 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 ± 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 ± 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients). For those who achieved remission (Remission group), the mean baseline versus final proteinuria was 5.0 ±: 2.0 versus 0.9 ± 0.7 g/24 hr (P < 0.01), and the mean baseline versus final serum creatinine was 1.5 ± 0.5 versus 1.6 ± 0.5 mg/dl (P = NS). For those who did not achieve remission (No remission group), the mean baseline versus final proteinuria was 6.2 ± 2.6 versus 5.1 ± 3.0 g/24 hr (P < 0.01), and baseline versus final serum creatinine was 1.5 ± 0.4 versus 3.2 ± 2.2 mg/dl (P < 0.001). Glomerular filtration rate (GFR) assessed by urinary iothalamate clearance was stable within the Remission group but declined significantly within the No remission group. During the Captopril Study, the Remission group did not differ from the No remission group with respect to diastolic blood pressure, glycohemoglobin level, oricholesterol level. However, mean systolic blood pressure during the Captopril Study was lower in the Remission group compared to the No remission group (126 ± 8 vs. 140 ± 13 mm Hg, P = 0.002). We conclude that long-term remission of nephrotic-range proteinuria with stable or nearly stable serum creatinine level is a realistic goal in Type I diabetes. Remission is significantly associated with captopril therapy and with achieving a lower systolic blood pressure.