title: Renal clearance of N(1)-methylnicotinamide: a sensitive marker of the severity of liver dysfunction in cirrhosis.
abstract: OBJECTIVE
  Data have appeared suggesting that an impairment of renal tubular secretion is present in liver cirrhosis, even in the absence of a clinically 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.
  
  
  METHODS
  The renal clearances of endogenous NMN, inulin, and creatinine were measured in 14 normal subjects and in two groups of age-matched cirrhotic patients (10 Child A and 10 Child C). In 6 subjects, 2 per group, the concentration dependence of the NMN clearance was also studied, following an oral nicotinamide load.
  
  
  RESULTS
  Contrary to expectations, the renal NMN clearance increased in cirrhotic patients, in relation to the severity of liver disease (r = 0.83 with Pugh's score; p < 0.001). The NMN-to-inulin clearance ratio 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 all comparisons), indicating that NMN was completely cleared from plasma in the latter patients. Consistently, the analysis of the concentration dependence of the renal NMN clearance revealed the presence of a carrier-mediated reabsorption which apparently was no longer operating in the decompensated patients. Discriminant analysis showed that renal NMN clearance, and NMN-to-creatinine and NMN-to-inulin clearance ratios could all distinguish between 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 cirrhosis. The potentialities of this renal parameter as a diagnostic and prognostic test in liver cirrhosis deserve further study.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Orlando
authors.forename: M
authors.initials: M
authors.lastname: Floreani
authors.forename: E
authors.initials: E
authors.lastname: Napoli
authors.forename: R
authors.initials: R
authors.lastname: Padrini
authors.forename: P
authors.initials: P
authors.lastname: Palatini
mesh_terms: D000328:Adult; D001693:Biological Transport, Active; D015415:Biomarkers; D016022:Case-Control Studies; D003404:Creatinine / Q000378:metabolism; D006801:Humans; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D015415:Biomarkers; D009536:Niacinamide; D007444:Inulin; D003404:Creatinine; C024058:N(1)-methylnicotinamide