THE ROLE OF RISING BLOOD-PRESSURE AND OF HUMAN ATRIAL-NATRIURETIC-PEPTIDE IN THE PATHOGENESIS OF DIABETIC NEPHROPATHY IN PATIENTS WITH TYPE-I DIABETES-MELLITUS

To answer the question how rising blood pressure and plasma levels of human atrial natriuretic peptide (hANP) may be related to the early pa thogenesis of diabetic nephropathy in type-I-diabetic patients, we dec ided to examine potential changes of urinary albumin excretion (UAE), urinary excretion of alpha1-microglobulin (A-1-M), mean arterial blood pressure (MAP), hANP levels, creatinine clearance and Hb(A1) in the c ourse of a prospective one-year study in 19 patients (13 females, 6 ma les, age, 29 +/- 2 years). All patients had intensified insulin treatm ent. 7 patients at increased risk for eventually developing nephropath y were retrospectively identified (group 1) by having repeatedly exhib ited elevated UAE (> 30 mg/24 h). The other patients served as control s (group 2). In the first half of the study (month 0-6), patients in g roup 1 differed from those in group 2 in increased average (+/- SD) UA E (21.4 +/- 5.9 vs. 9.4 +/- 1.8 mg/24 h, p < 0.01) and A-1-M (8.0 +/- 1.2 vs. 6.2 +/- 1.2 mg/l, p < 0.05). In the second half of the study ( month 7-12), patients in group 1 exhibited increases in MAP from 94.7 +/- 2.1 to 99.5 +/- 2.1 mmHg (p < 0.01), in hANP from 14.7 +/- 3.8 to 23.0 +/- 5.7 (p < 0.05) and in Hb(A1) from 8.9 +/- 0.2 to 9.5 +/- 0.2% (p < 0.01). Average UAE rose further to 27.2 +/- 5.0 mg/24 h. In pati ents in group 2, UAE, MAP, hANP and HbA, did not change. There were no differences in creatinine clearance between both groups throughout th e study. Elevated hANP levels in plasma in type-I-diabetic patients ar e due to increases in blood pressure which follow the elevation of UAE . Thus, they are no essential prerequisite for the early pathogenesis of nephropathy but may be part of the disease mechanisms which precipi tate the progression of diabetic kidney disease. Insufficient glycemic control, however, may add substantially to the risk of eventually dev eloping nephropathy. Increased A-1-M may serve as valid early marker.