Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic individuals: the Japan Diabetes Complications Study (JDCS)

Abstract

Aims/hypothesis: The aim of the study was to determine the transition rate and factors associated with the progression of normo- and low microalbuminuria to diabetic nephropathy (overt proteinuria).

Methods: For 8 years we prospectively observed 1,558 Japanese patients with type 2 diabetes mellitus whose basal urinary albumin:creatinine ratio (UACR) had been measured as <17.0 mg/mmol at entry. The incidence of nephropathy (UACR >33.9 mg/mmol) was determined by measuring UACR twice a year.

Results: Progression to nephropathy occurred in 74 patients. The annual transition rate was 0.67%, and was substantially higher for the low-microalbuminuric group than for the normoalbuminuric group (1.85% and 0.23%, respectively; hazard ratio for the low-microalbuminuric group 8.45, p < 0.01). The hazard ratio for an HbA(1c) of 7-9% or ≥9% was 2.72 (p < 0.01) or 5.81 (p < 0.01) relative to HbA(1c) <7.0%, respectively. In comparison with individuals with a systolic blood pressure (SBP) of <120 mmHg, the hazard ratios for patients with an SBP of 120-140 mmHg or ≥140 mmHg were 2.31 (p = 0.06) and 3.54 (p < 0.01), respectively. Smoking also affected progression to proteinuria (hazard ratio 1.99, p < 0.01). In contrast, 30.3% of the low-microalbuminuric group returned to normoalbuminuria (i.e. were in remission).

Conclusions/interpretation: These results suggest that if patients with type 2 diabetes mellitus are receiving treatment from diabetologists for hyperglycaemia and hypertension when they are in the early stages of nephropathy (i.e. normo- or low microalbuminuria), their rate of transition to proteinuria is considerably lowered, and that differentiating patients with low microalbuminuria from those with high microalbuminuria might be clinically useful.

Trial registration: UMIN Clinical Trials Registry C000000222.

Fig. 1

Kaplan–Meier curves for progression to overt nephropathy according to: UACR (a), HbA_1c levels (b), SBP (c) and smoking status (d). a The hazard ratio for the low-microalbuminuric group (solid line) was 8.45 (95% CI 4.97–14.38, p < 0.01) relative to the normoalbuminuric group (dashed–dotted line). b The hazard ratio of HbA_1c for a range of 7–9% (solid line) and for ≥9% (dotted line) was 2.72 (95% CI 1.22–6.03, p < 0.01) and 5.81 (95% CI 2.49–13.55, p < 0.01), respectively, relative to an HbA_1c of <7% (dashed–dotted line). c The hazard ratio for an SBP of 120–140 mmHg (solid line) or ≥140 mmHg (dotted line) was 2.31 (95% CI 0.96–5.54, p < 0.06) and 3.54 (95% CI 1.50–8.40, p < 0.01), respectively, relative to an SBP of <120 mmHg (dashed–dotted line). d The hazard ratio for current smoking (solid line) was 1.99 (95% CI 1.24–3.18, p < 0.01) relative to past smoking or never smoked (dashed–dotted line)