EVALUATION OF GLOMERULAR-FILTRATION RATE IN NON-INSULIN-DEPENDENT DIABETES - IMPLICATIONS FOR A STUDY DESIGN IN PATIENTS WITH MICROALBUMINURIA AND HYPERTENSION DURING INTERVENTION TRIALS

In the present work total body clearance (TBC) and renal clearance (RC ) of Cr-51-EDTA were compared in 26 NIDDM patients with microalbuminur ia (>20, <200 mu g/min), serum creatinine lower than 220 mu mol/l and hypertension (BP>140/90 mmHg), Serial TBC were measured in two groups of NIDDM hypertensive microalbuminuric (H+M+) patients switched from c onventional treatment (target<160/95 mmHg) with beta-blockers and/or d iuretics to strict (target<140/85 mmHg) therapy either with angiotensi n converting enzyme (ACE) inhibitors (20 subjects) or with Ca2+ channe l blockers (6 subjects), A biexponential function was found to fulfil statistical and heuristic criteria for modelling analysis of TBC with 19 samples, following bolus intravenous Cr-51-EDTA injection. The anal ysis of variance for repeated measurements showed no difference betwee n mean TBC and RC, The sample size required in each group was calculat ed according the formula n=2 sigma(2) (z(1)+z(2))2/delta(2) and was a result of at least 37 patients, The repeatability coefficients were 16 .56 for the RC and 7.54 for the TBC method, showing that the latter is more reproducible, The coefficient of variation of TBC (CV-TBC: SD/Me an%) was 5.0+/-0.3% and that of RC (CV-RC) 12.1+/-1.3% (p<0.01). Durin g conventional therapy the rate of decline of GFR was 3.05+/-0.14 ml/m in/1.73 m(2) per year, A two-slope decline was observed during strict antihypertensive therapy with an abrupt, 3-4 fold steeper, GFR decay i n the first 3-6 months after therapy was begun, This was followed by a much slower decline during the remaining 24-36 months (2.23+/-0.16 ml /min/1.73 m(2) per year both on subjects on ACE or Ca2+ blockers), It would seem from these results that the first, steeper slope reflects t he modulation of renal haemodynamics due to abrupt lowering of blood p ressure levels and hormonal alterations, while the second, smoother sl ope is probably due to structural disturbances at the renal level seco ndary to pathological processes. (C) 1997, Editrice Kurtis.