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IMN is a disease with a comparatively good prognosis in Japan even when it is associated with nephrotic syndrome. Steroid therapy, which has not been recommended for IMN in most review articles, seems to be useful at least for Japanese patients. In particular, a remission from heavy proteinuria likely results in a favorable outcome.

A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.

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