Glomerular Hyperfiltration in the Prediction of Nephropathy in IDDM: A 10-Year Follow-Up Study

Abstract

Glomerular hyperfiltration has been proposed as an independent risk factor for the development of diabetic nephropathy in patients with IDDM. In a case-controlled prospective study of IDDM patients without albuminuria, serial glomerular filtration rate (GFR) measurements were performed over an observation period of 10 years. A group of 25 IDDM patients (20 men, 5 women; initial age, 29 [17–49] years) with glomerular hyperfiltration (GFR >135 ml · min⁻¹ · 1.73 m⁻²) were matched for age, sex, and duration of diabetes with 25 IDDM patients (20 men, 5 women; initial age, 30 [17–48] years) with glomerular normofiltration (GFR 83–135 ml · min⁻¹ · 1.73 m⁻²). GFR, urinary albumin excretion rate (AER), blood pressure, and glycated hemoglobin were measured at baseline and at 5, 8, and 10 years. The two groups had similar entry levels of blood pressure, AER, and glycated hemoglobin. Metabolic control was similar in the two groups during follow-up. The final GFR remained higher in the group with hyperfiltration (122 [109–135] vs. 103 [95–111] ml · min⁻¹ · 1.73 m⁻²; P = 0.02) despite a nonsignificantly faster rate of fall of GFR compared with that of the control group (2.54 [1.20–3.88] vs. 1.50 [1.01–1.99] ml · min⁻¹ · year⁻¹; P = 0.14). A similar number of patients in each group progressed to either microalbuminuria or macroalbuminuria (n = 4 vs. n = 3) or developed hypertension (blood pressure, >160/95 mmHg; n = 3 vs. n = 4). End-of-study AER was, however, higher in the group with hyperfiltration (geometric mean [95% CI]: 18.9 [11.3–31.6] vs. 11.0 [8.1–15.0]; P = 0.05), and baseline glomerular hyperfiltration was an independent determinant of end-of-study blood pressure (P = 0.04). The strongest predictors of end-of-study AER and blood pressure were their baseline values (P < 0.04 and P < 0.01, respectively). In conclusion, levels of AER and blood pressure are the main risk factors for renal outcome, while glomerular hyperfiltration appears to play a lesser role.