Renal clearance of N-1-methylnicotinamide: A sensitive marker of the severity of liver dysfunction in cirrhosis

Background/Aims: Data have appeared suggesting that an impairment of renal tubular secretion is present in liver cirrhosis, even in the absence of a c linically evident renal dysfunction. To address this question, we evaluated the renal clearance of N-1-methylnicotinamide (NMN), a marker of the renal secretory function, in healthy subjects and patients with liver cirrhosis of increasing severity, but with a normal glomerular filtration rate. Metho ds: The renal clearances of endogenous NMN, inulin, and creatinine were mea sured in 14 normal subjects and in two groups of age-matched cirrhotic pati ents (10 Child A and 10 Child C). In 6 subjects, 2 per group, the concentra tion dependence of the NMN clearance was also studied, following an oral ni cotinamide load. Results:Contrary to expectations, the renal NMN clearance increased in cirrhotic patients, in relation to the severity of liver disea se (r = 0.83 with Pugh's score; p < 0.001). The NMN-to-inulin clearance rat io increased from a control value of 2.2 +/- (SD) 0.4 to 3.1 +/- 0.2 and 5. 2 +/- 0.9 in Child A and Child C cirrhotics, respectively (p < 0.001 for al l comparisons), indicating that NMN was completely cleared from plas- ma in the latter patients. Consistently, the analysis of the concentration depen dence of the renal NMN clearance revealed the presence of a carrier-mediate d reabsorption which apparently was no longer operating in the decompensate d patients. Discriminant: analysis showed that renal NMN clearance, and NMN -to-creatinine and NMN-to-inulin clearance ratios could all distinguish bet ween the three study groups, with sensitivities and specificities equal or greater than 90%. Conclusions: Contrary to previous proposals, NMN is not a probe of general validity for renal tubular secretion. In particular, due to an imbalance between secretion and reabsorption, its renal clearance in liver cirrhosis cannot be used to determine the degree of tubular secretion of which an individual is capable. However, renal NMN clearance appears to be a very sensitive marker of the severity of liver dysfunction in cirrhos is. The potentialities of this renal parameter as a diagnostic and prognost ic test: in liver cirrhosis deserve further study. Copyright (C) 2000 S. Ka rger AG, Basel.