Urinary excretion of Tamm-Horsfall protein in normotensive, normo-albuminuric type 1 diabetic patients.

Abstract

The excretion rate of a marker of distal tubular function, Tamm-Horsfall protein (THP), has been measured in urine (micrograms/min) overnight, during orthostasis and during a glycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 41 normotensive, normo-albuminuric type 1 diabetic patients. Eleven healthy subjects who were not clamped served as controls. A further 4 normo-albuminuric type 1 diabetic patients were rendered euglycaemic without a waterload. The excretion rate of THP overnight was similar in type 1 diabetic patients and normal subjects (26.1 vs. 23.5 micrograms/ml, p = NS). During the waterloaded euglycaemic clamp, THP increased significantly both in type 1 diabetic patients and control subjects (p < 0.001), but the increase was slightly greater in type 1 diabetic patients (67.2 vs. 38.4 micrograms/min, p = 0.05). Orthostasis did not increase the excretion rate of THP in either type 1 diabetic patients or in control subjects. In the 4 type 1 diabetic patients who were only clamped, the THP excretion rate increased less compared to the clamp plus waterload experiment (means: overnight 11.3 micrograms/min; clamp 22.5 micrograms/min). In Type 1 diabetes, overnight THP excretion was inversely correlated both with fasting blood glucose, HbA1 and sodium-lithium counter-transport activity (SLC). A direct relationship was present between urinary flow and the excretion rate of THP. In conclusion, this study shows that normotensive, normo-albuminuric type 1 diabetic patients present similar overnight excretion rates of THP compared to healthy controls and that the excretion rate of THP is unaffected by posture and increased during acute euglycaemia and waterload. The association between SLC and THP might suggest some relation between this putative marker of nephropathy and distal tubular function, but this finding needs confirmation and further study.