Development and Progression of Renal Insufficiency With and Without Albuminuria in Adults With Type 1 Diabetes in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study

OBJECTIVE

This multicenter study examined the impact of albumin excretion rate (AER) on the course of estimated glomerular filtration rate (eGFR) and the incidence of sustained eGFR <60 ml/min/1.73 m² in type 1 diabetes up to year 14 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study (mean duration of 19 years in the Diabetes Control and Complications Trial [DCCT]/EDIC).

RESEARCH DESIGN AND METHODS

Urinary albumin measurements from 4-h urine collections were obtained from participants annually during the DCCT and every other year during the EDIC study, and serum creatinine was measured annually in both the DCCT and EDIC study. GFR was estimated from serum creatinine using the abbreviated Modification of Diet in Renal Disease equation.

RESULTS

A total of 89 of 1,439 subjects developed an eGFR <60 ml/min/1.73 m² (stage 3 chronic kidney disease on two or more successive occasions (sustained) during the DCCT/EDIC study (cumulative incidence 11.4%). Of these, 20 (24%) had AER <30 mg/24 h at all prior evaluations, 14 (16%) had developed microalbuminuria (AER 30–300 mg/24 h) before they reached stage 3 chronic kidney disease, and 54 (61%) had macroalbuminuria (AER >300 mg/24 h) before they reached stage 3 chronic kidney disease. Macroalbuminuria is associated with a markedly increased rate of fall in eGFR (5.7%/year vs. 1.2%/year with AER <30 mg/24 h, P < 0.0001) and risk of eGFR <60 ml/min/1.73 m² (adjusted hazard ratio 15.3, P < 0.0001), whereas microalbuminuria had weaker and less consistent effects on eGFR.

CONCLUSIONS

Macroalbuminuria was a strong predictor of eGFR loss and risk of developing sustained eGFR <60 ml/min/1.73 m². However, screening with AER alone would have missed 24% of cases of sustained impaired eGFR.It has generally been thought that increases in urine albumin excretion rate (AER) precede a fall in glomerular filtration rate (GFR) in patients developing diabetic chronic kidney disease (1). Some large studies in patients with type 2 diabetes (2–4) and a few smaller studies in individuals with type 1 diabetes (5–9), however, have demonstrated that a substantial proportion of diabetic individuals with decreased GFR levels do not have increased AER.In this article, we examine the effects of prior and current levels of AER on the rate of decline in estimated GFR (eGFR) and on the risk of decreased levels of eGFR (<60 ml/min/1.73 m²) in subjects with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT) and/or the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study.