Five-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 (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients.


METHODS
A longitudinal study of 32 normoalbuminuric (AER < 20 micrograms/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml.min-1 x 1.73 m-2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months.


RESULTS
There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline 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); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 micrograms/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria.


CONCLUSIONS
The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).
Silveiro
S P
SP
Endocrinology Division, Hospital de Clínicas de Porto Alegre, Brazil.
Friedman
R
R
de Azevedo
M J
MJ
Canani
L H
LH
Gross
J L
JL
D000328:Adult; D000368:Aged; D000419:Albuminuria; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003925:Diabetic Angiopathies / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000652:urine; D003929:Diabetic Neuropathies / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D013997:Time Factors
D015415:Biomarkers