The Relationship Between Microalbuminuria and Glomerular Filtration Rate in Young Type 1 Diabetic Subjects: The Oxford Regional Prospective Study

Background: The purpose of this study was to examine the relationship between glomerular filtration rate (GFR) measured at 5 years' diabetes duration and annual urine albumin excretion in a prospective cohort of children with type 1 diabetes (T1DM).

Methods: Three hundred and eight children were followed from diagnosis of T1DM [aged 9.8 years (range 0.4-15.9) for a median duration of 10.9 years (6.0-17.8) with annual assessments comprising measurement of HbA1(c) and 3 urine samples for albumin:creatinine ratio (ACR). GFR was measured in all children at 5 years' diabetes duration.

Results: Two hundred forty-three (78.8%) subjects were normoalbuminuric (MA-) for the duration of the study. At 5 years: 35 (11.4%) subjects had MA (MA+) and 30 (9.7%) subjects were normoalbuminuric but developed MA during subsequent follow-up annual assessments (future MA+). In the future MA+ group compared to the MA+ and MA- groups; GFR was higher (167 vs. 134 vs. 139 mL/min/1.73 m(2), P < 0.002); the prevalence of hyperfiltration (GFR >125 mL/min/1.73 m(2)) was greater (97 vs. 57 vs. 64%, P= 0.006) and HbA1c levels were higher (11.4 vs. 10.8 vs. 9.7%, P < 0.001). The probability (Cox Model) of having hyperfiltration at 5 years' duration was related to puberty (a 1.7-fold increased risk with puberty onset) and poor glycemic control (a 10% increased risk for a 1% increase in HbA1c). Comparing subjects with and without hyperfiltration, prior to the first GFR measurement no difference in ACR levels existed; however, after this time median ACR levels were significantly greater [1.2 (0.1-86.4) vs. 0.9 (0.1-71.6) mg/mmol, P= 0.003], independent of age and HbA1c levels. The probability of developing MA between 5 and 10 years' duration was associated with poor glycemic control (a 30% increased risk for a 1% increase in HbA1c) and higher GFR at 5 years (22% increased risk for a 10 mL/min/1.73 m(2) rise in GFR).

Conclusion: Glomerular hyperfiltration is associated with puberty and increasing ACR levels and is predictive of MA independent of HbA1c. This suggests that factors other than poor glycemic control may be involved in the pathogenesis of early diabetic nephropathy and early intervention with medical therapy to reduce GFR may be beneficial even before onset of MA.