title: Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.
abstract: Creatinine degradation was prospectively studied in four healthy subjects and 35 patients with varying degrees of chronic renal failure by measuring creatininase activity in stool isolates. Patients were subdivided into those with serum creatinine above and below 6 mg/dL. Creatinine degradation in the former group of patients who had not taken antibiotics in the previous 3 months was significantly greater than the latter (64% v 26%; P < 0.001), which was similar to healthy controls. This degradation was abolished when antibiotics were added directly to the patient's stool during incubation (P < 0.002). In a subset of five patients, duodenal intubation demonstrated small bowel bacterial overgrowth associated with high concentrations of toxic methylamines generated there from and increased stool creatinine consumption. We conclude that retained creatinine in advanced chronic renal failure induces bacterial creatininase activity throughout the bowel, causing creatinine degradation and subsequent potential loss of creatinine to the creatinine pool. The modifying effects of antibiotics on creatinine degradation has important clinical implications for the interpretation of serum creatinine measurements in renal failure.
authors.affiliation: Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Dunn
authors.forename: G M
authors.initials: GM
authors.lastname: Gabuzda
authors.forename: K R
authors.initials: KR
authors.lastname: Superdock
authors.forename: R S
authors.initials: RS
authors.lastname: Kolecki
authors.forename: R W
authors.initials: RW
authors.lastname: Schaedler
authors.forename: M L
authors.initials: ML
authors.lastname: Simenhoff
mesh_terms: D000581:Amidohydrolases / Q000096:biosynthesis* / Q000187:drug effects; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001420:Bacteria, Aerobic / Q000187:drug effects / Q000378:metabolism; D001421:Bacteria, Anaerobic / Q000187:drug effects / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism*; D004790:Enzyme Induction; D005243:Feces / Q000201:enzymology / Q000382:microbiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000382:microbiology; D008297:Male; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D000581:Amidohydrolases; C019946:creatininase