Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n=6, albumin excretion rate (AER) mean (range) 4 (0-10) mu g/min] and microalbuminuric [group B, n=6, AER 88 (35-198) mu g/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta(2)-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P<0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with beta(2)-microglobulin in the diabetic subjects (r=0.665, P<0.05) and with the degree of microalbuminuria in group B patients (r=1, P<0.01). Urinary GH was also greater than 10 mu U, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of Cr-51-ethylene diamine tetra-acetic acid (EDTA) and T-125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbuminuric group compared with controls (P<0.05) and group B (P<0.05). Absolute proximal reabsorption of sodium and of water (APR(Na) and APR(H2O)) was significantly higher in group A patients (P<0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.