PERMISSIVE ROLE OF HYPERTENSION IN THE DEVELOPMENT OF PROTEINURIA ANDPROGRESSION OF RENAL-DISEASE IN INSULIN-DEPENDENT DIABETIC-PATIENTS

Background In insulin-dependent diabetic subjects, heritable factors r elated to hypertension and cardiovascular disease are associated with nephropathy. Objective To determine the relationship of blood pressure , glycaemic control, family history of cardiovascular disease and sodi um-lithium countertransport activity to the onset of proteinuria and d ecline in glomerular filtration. Design A retrospective analysis of th e rate of onset of proteinuria and a longitudinal study of the progres sion of established renal disease. Setting Guy's Hospital Diabetes Ren al Clinic, a secondary referral centre. Patients Fifty-four insulin-de pendent diabetic patients with nephropathy, persistent total protein e xcretion rate > 500 mg/24 h, enrolled between 1978 and 1992. Main outc ome measures Rate of decline in glomerular filtration rate. Duration o f diabetes at onset of nephropathy (time to proteinuria). Blood pressu re and glycosylated haemoglobin at the time of diagnosis of nephropath y (baseline). Family history of cardiovascular disease and hypertensio n. Erythrocyte sodium-lithium countertransport activity in a subset of patients (n = 41) not being administered renal replacement therapy in 1992. Results The estimated (95% confidence interval) time to protein uria was shortened in relation to increments in diastolic blood pressu re at baseline and to a family history of cardiovascular disease in bo th parents [1.9 (0.2-3.2) years/10 mmHg, P < 0.05 and 6.7 (-0.3-13.7) years, P < 0.07, respectively]. During follow-up 15% (n = 8) of the pa tients who did not require antihypertensive therapy had slower rates o f decline in glomerular filtration and lower rates of sodium-lithium c ountertransport activity than did those who had been administered trea tment [median (range): 2.88 (0.2 to -11.28) versus 7.8 (0.1 to -20.4) ml/min per 1.73 m(2)/year, P < 0.05 and 0.28 (0.14-0.54) versus 0.43 ( 0.18-0.88) mmol/l per erythrocyte/h, P < 0.03, respectively]. In this group there was an inverse relationship between the time to proteinuri a and glycosylated haemoglobin (r = -0.79, P = 0.018). For the whole g roup a multivariate analysis showed hypertension and initial glomerula r filtration rate to be related independently to the rate of decline i n renal function; glycaemic control just failed to attain statistical significance (P < 0.06). Conclusion Elevation of blood pressure accele rates the onset of nephropathy and its progression; its absence, a red uced familial predisposition to cardiovascular disease, low sodium-lit hium countertransport activity and good blood glucose control favour a more benign prognosis. (C) Rapid Science Publishers.