5-YEAR PROSPECTIVE-STUDY OF GLOMERULAR-FILTRATION RATE AND ALBUMIN EXCRETION RATE IN NORMOFILTERING AND HYPERFILTERING NORMOALBUMINURIC NIDDM PATIENTS

OBJECTIVE - To evaluate the evolution of glomerular filtration rate (G FR) and albumin excretion rate (AER) of normofiltering (NF) and hyperf iltering (HF) normoalbuminuric NIDDM patients. RESEARCH DESIGN AND MET HODS - A longitudinal study of 32 normoalbuminuric (AER <20 mu g/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals w as done. Subjects had their GFR (Cr-51-labeled EDTA single-injection m ethod) measured at entry and after 40 and 60 months. At entry, 13 NIDD M patients had GFR values above the upper limit of the normal range in our laboratory (>137 ml . min(-1). 1.73 m(-2)) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA(1c), urin ary urea, and mean arterial blood pressure (MBP) were analyzed at entr y and after 40 and 60 months. RESULTS - There was a significant declin e of GFR in NIDDM patients and normal subjects at 60 months. The decli ne was significantly greater in HF patients (-0.61 ml . min(-1). month (-1); P = 0.001) than in NF (-0, 18) and control subjects (-0, 14); th e rate of change in NF and control subjects was the same (P > 0.05). I n stepwise multiple regression analysis, with GFR decline as the depen dent variable and GFR and AER al baseline, age and change in MBP, chan ge in urinary urea, change in HbA(1c), and change in therapy as indepe ndent variables, only baseline GFR (R(2) = 0.19, P = 0.002) and age (R (2) = 0.31, P = 0.048) were significantly related to the outcome. At 6 0 months, AER raised >20 mu g/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although st ill in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of micro albuminuria. CONCLUSIONS - The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to b aseline GFR and age. HF NIDDM patients show a faster decline in GFR th an NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The developmen t of microalbuminuria is related to higher baseline AER and to increas es in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NID DM patients (P > 0.05).