Stimulation of tubular secretion of creatinine in health and in conditions associated with reduced nephron mass. Evidence for a tubular functional reserve

BACKGROUND: The increment in glomerular filtration rate (GFR) after a protein load has been taken to reflect the renal reserve capacity; however, this response is preserved in end-stage kidney disease. Tubular secretion of creatinine is increased in relation to the GFR in renal failure, but little is known about the tubular functional response to stimulation despite the fact that tubulointerstitial lesions are always pre-eminent in chronic renal damage. Therefore we decided to compare the urinary creatinine excretion (UcrV) and tubular secretion of creatinine (TScr) induced by a test meat meal in normal individuals and in individuals with reduced nephron mass. METHODS: We studied 12 normal subjects, seven healthy uninephrectomized (kidney donors) and eight patients with chronic renal disease (serum creatinine ranging from 212.2 to 486 micromol/l). They had been on a standard diet for 5 days before the studies. The test meal provided 80 g of animal protein. Three baseline and four stimulated (post-meal) 30-min simultaneous inulin and creatinine clearances were carried out. RESULTS: We found that normals increased more than twice the UcrV (post-meal=329.5 +/-SEM 13.1 nmol/min/kg) and 3.4 times the TScr (114.4+/-12.7 nmol/min/kg) after the test meal. In contrast, patients were unable to raise their baseline values (P<0.001), despite a normal increment in GFR. The data in kidney donors fell between normals and patients. Strong correlation existed between the stimulated (but not the baseline) TScr (P=0.003) and GFR and between UcrV post-meal/pre-meal ratio and GFR (P<0.0001). CONCLUSION: The increment in TScr resulting from a protein meal is related to the functioning nephron mass. Evaluation of this increment could have potential clinical relevance.