REMISSION OF NEPHROTIC RANGE PROTEINURIA IN TYPE-I DIABETES

The present study assessed the extent to which remission of nephrotic- range proteinuria occurred in patients with Type I diabetes enrolled i n the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients rec ruited into the Captopril Study, 108 had nephrotic-range proteinuria ( greater than or equal to 3.5 g/24 hr) at entry in the Study (baseline) . This group was the subject of the present study. Remission of nephro tic-range proteinuria was defined as follows: (1) Onset of the remissi on was taken as the date when proteinuria was first noted to be less t han or equal to 1.0 g/24 hr. (2) The reduction in proteinuria had to b e sustained for a minimum of six months and until the end of the Capto pril Study. (3) During the remission, the average of all 24 hour prote inuria measurements could not exceed 1.5 g. (4) Decline in renal funct ion could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captop ril 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 y ears) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-u p 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs, placebo-treated patients). For those who achieved remission (Remis sion 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 = N S). 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 filtrati on rate (GFR) assessed by urinary iothalamate clearance was stable wit hin the Remission group but declined significantly within the No remis sion group. During the Captopril Study, the Remission group did not di ffer from the No remission group with respect to diastolic blood press ure, glycohemoglobin level, or cholesterol level. However, mean systol ic blood pressure during the Captopril Study was lower in the Remissio n group compared to the No remission group (126 +/- 8 vs. 140 +/- 13 m m Hg, P = 0.002). We conclude that long-term remission of nephrotic-ra nge proteinuria with stable or nearly stable serum creatinine level is a realistic goal in Type I diabetes. Remission is significantly assoc iated with captopril therapy and with achieving a lower systolic blood pressure.