Abstract: FR-PO798

Numerous Colon-Derived Solutes Are Efficiently Cleared by the Kidney

Session Information

Category: Dialysis

  • 601 Standard Hemodialysis for ESRD

Authors

  • Mair, Robert, Stanford , Palo Alto, California, United States
  • Sirich, Tammy L., Stanford , Palo Alto, California, United States
  • Plummer, Natalie, Stanford , Palo Alto, California, United States
  • Meyer, Timothy W., Stanford , Palo Alto, California, United States
Background

Previous studies have identified solutes derived from colon microbes that are normally excreted in the urine. The current study employed metabolomic analysis to identify additional solutes in this class and profile their renal clearance.

Methods

Samples from patients with total colectomies (n=12) and age matched controls (n=17) were analyzed using an established metabolomic platform. Solutes were considered colon-derived if they met both of the following criteria: 1) mean excretion rate was greater than four-fold higher in individuals with colons than without colons 2) the difference in excretion between the groups was assigned significance with a false discovery rate (q value) < 0.05.

Results

91 urinary solutes were identified as colon-derived. Of these, 46 were named compounds with known structure and 45 were unnamed compounds without confirmed chemical structure. Only 11 of the 46 named compounds identified as colon-derived in the current study had previously been shown to be be colon-derived. Binding to plasma proteins allowed a urinary clearance expressed in terms of the free, unbound solute concentration. Plasma levels in normal subjects were sufficient to estimate clearance values for 53 of the 91 colon-derived solutes. As shown in the figure, the estimated urinary clearance exceeded the creatinine clearance for the great majority of these solutes, consistent with tubular secretion.

Conclusion

Comparison of patients with and without colons identified 35 novel colon-derived solutes which are normally excreted by the kidneys and revealed the presence of additional colon-derived solutes for which chemical structures remain to be determined. Efficient renal clearance for many of these compounds, which are presumably of microbial origin, is achieved by tubular secretion. The large number of colon-derived solutes complicates the problem of identifying their potential toxicity.

Funding

  • NIDDK Support