Advertisement

Urinary Creatinine-splitting Bacteria after Ileal-loop Diversion Causing Underestimate of Glomerular Filtration Rate

  • Julian L. Seifter
    Correspondence
    Requests for reprints should be addressed to Julian L. Seifter, MD, Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
    Affiliations
    Renal Division, Brigham and Women's Hospital, Boston, Massachusetts
    Search for articles by this author
      To the Editor:
      Use of ileal intestinal segments for urinary diversion following cystectomy is common practice.
      Although creatininase and creatinine deaminase are enzymes produced by gut flora, especially in patients with chronic renal failure,
      • Jones J.D.
      • Burnett P.C.
      Creatinine metabolism in humans with decreased renal function: creatinine deficit.
      • Dunn S.R.
      • Gabuzda G.M.
      • Superdock K.R.
      • Kolecki R.S.
      • Schaedler R.W.
      • Simenhoff M.L.
      Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.
      • Jones J.D.
      • Burnett P.C.
      Implication of creatinine and gut flora in the uremic syndrome: induction of “creatininase” in colon contents of the rat by dietary creatinine.
      they have not been isolated from urine. We report a patient with an ileal loop, bacteriuria, and marked underestimation of glomerular filtration rate (GFR) due to urinary creatininase.

      Case Report

      A 50-year-old man (weight 80.0 kg, height 1.98 m) with chronic kidney disease had suffered a traumatic spinal cord injury 20 years earlier, resulting in quadriplegia, leading to neurogenic bladder, urinary tract infections, and calculi requiring cystectomy and ileal conduit. The patient's serum creatinine level was 3.0 mg/dL. The serum sodium was 140 mEq/L, potassium 6 mEq/L, bicarbonate 15 mEq/L, and chloride 110 mEq/L.
      Due to concern that the serum creatinine might overestimate his true GFR because of the quadriplegia, renal clearance measurements were performed. Twenty-four-hour urine studies, collected from the loop, revealed a volume >6 L, protein excretion 5 g/day, urea clearance 3 mL/min, and a creatinine clearance of 4 mL/min, a value less than his urinary flow rate. Urine pH was 9 and a culture grew diphtheroids, Staphylococcus, and Streptococcus. Institution of hemodialysis was recommended.
      The creatinine excretion rate of 175 mg per day seemed low even for his decreased muscle mass, so an inulin clearance test was performed and gave a result of 21 mL/min. Urine frozen immediately upon collection and later tested yielded a creatinine clearance of 24 mL/min and a urea clearance of 15 mL/min. Dialysis was deferred. A rectal biopsy revealed amyloidosis.
      The patient's urine mixed with 1000 mg creatinine at 20°C was sampled at 0, 6, 12, and 24 hours, and showed a time-dependent decline in creatinine levels (Figure).
      Figure thumbnail gr1
      FigureDisappearance of creatinine added to patient’s urine in vitro.

      Discussion

      Creatinine-consuming bacteria in soil and bowel are known. Colonization of the gastrointestinal tract with creatininase would cause increased extrarenal clearance and overestimations of GFR based on serum creatinine alone but would not alter urinary clearance. Urine also provides an ideal environment for creatinine-degrading bacteria. The creatinine clearance calculated from a 24-hour urine collection was 5-fold less than the real value. Creatininase in the patient's urine was demonstrated in vitro. The results of the inulin test and use of creatinine assays on frozen urine support this finding. As creatininase was first discovered in soil Corynebacterium,
      • Dubos R.
      • Miller B.F.
      The production of bacterial enzymes capable of decomposing creatinine.
      this diphtheroid may have been the source of the patient's creatinine degradation. Urease, also present in the patient's urine, artifactually decreased urea clearance.
      A falsely low creatinine clearance may negatively impact medical decision-making. In patients with urinary diversions and bacteriuria, it is advised to freeze freshly collected urine samples before assay or to perform a true GFR by iothalamate or inulin clearance.

      Acknowledgements

      The author wishes to acknowledge Drs. John Goffinet and Andrew Fuller for valuable discussions.

      References

        • Jones J.D.
        • Burnett P.C.
        Creatinine metabolism in humans with decreased renal function: creatinine deficit.
        Clin Chem. 1974; 20: 1204-1212
        • Dunn S.R.
        • Gabuzda G.M.
        • Superdock K.R.
        • Kolecki R.S.
        • Schaedler R.W.
        • Simenhoff M.L.
        Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.
        Am J Kidney Dis. 1997; 29: 72-77
        • Jones J.D.
        • Burnett P.C.
        Implication of creatinine and gut flora in the uremic syndrome: induction of “creatininase” in colon contents of the rat by dietary creatinine.
        Clin Chem. 1972; 18: 280-284
        • Dubos R.
        • Miller B.F.
        The production of bacterial enzymes capable of decomposing creatinine.
        J Biol Chem. 1937; 121: 429-445