GLUCOSE-INDUCED CHANGES IN RENAL HEMODYNAMICS IN PROTEINURIC TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS - INHIBITION BY ACETYLSALICYLIC-ACID INFUSION

The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic res ponse to an acute plasma glucose rise from sustained euglycaemia to su stained hyperglycaemia in eight persistently proteinuric Type 1 (insul in-dependent) diabetic patients. Studies were performed in a double-bl ind cross-over manner after i. v. injection of 450 mg lysine acetylsal icilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9 % NaCl (isotonic saline). In the isotonic saline experiments hype rglycaemia produced a significant rise, by approximately 35 %, in glom erular filtration rate in all patients from 41.5 +/- 5.2 to 55 +/- 6 m l . min-1 . 1.73 m-2 (p < 0.005) and an increase in sodium paraminohip purate clearance from 178 +/- 22.7 to 220 +/- 20.0 ml . min-1 . 1.73 m -2 (p < 0.05). These changes took place within the first 30 min of glu cose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine a cetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5 +/- 5.2 vs 30.0 +/- 5.7 ml . mi n-1 . 1.73 m-2; p < 0,05) and significantly blunted the rise in glomer ular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6 +/- 2.8 vs 5.3 +/- 1.8 ml . min-1 . 1.73 m-2; p < 0.005). The effects on renal plasma fl ow were similarly blunted. In five additional patients, time- and volu me-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodiu m paraminohippurate clearance. In Type 1 diabetic patients with advanc ed renal failure, acute hyperglycaemia induces a significant elevation in glomerular filtration rate and renal plasma flow which is likely t o be mediated by renal prostaglandin production.