Kidney clearance of secretory solutes is associated with progression of CKD: The CRIC study

Yan Chen, Leila R. Zelnick, Ke Wang, Andrew N. Hoofnagle, Jessica O. Becker, Chi Yuan Hsu, Harold I. Feldman, Rupal C. Mehta, James P. Lash, Sushrut S. Waikar, Tariq Shafi, Stephen L. Seliger, Michael G. Shlipak, Mahboob Rahman, Bryan R. Kestenbaum

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. However, the clinical significance of the kidney's clearance of tubular secretory solutes is uncertain. Methods: In this prospective cohort study, we evaluated 3416 participants with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. We measured plasma and 24-hour urine concentrations of endogenous candidate secretory solutes at baseline, using targeted liquid chromatography-tandem mass spectrometry. The study defined CKD progression by a ≥50% decline in the eGFR, initiation of maintenance dialysis, or kidney transplantation. We used Cox proportional hazards regression to test associations of secretory-solute clearances with CKD progression andmortality, adjusting for eGFR, albuminuria, and other confounding characteristics. Results: Participants in this ancillary study had a mean age of 58 years and 41% were black; the median eGFR was 43 ml/min per 1.73m2. After adjustment, lower kidney clearances of six solutes-kynurenic acid, pyridoxic acid, indoxyl sulfate, xanthosine, isovalerylglycine, and cinnamoylglycine-were associated with significantly greater risks of CKD progression, with clearance of kynurenic acid, a highly protein-bound solute, having the strongest association. Lower clearances of isovalerylglycine, tiglylglycine, hippurate, and trimethyluric acid were significantly associated with all-cause mortality after adjustment. Conclusions: We found lower kidney clearances of endogenous secretory solutes to be associated with CKD progression and all-cause mortality, independent of eGFR and albuminuria. This suggests that tubular clearance of secretory solutes provides additional information about kidney health beyond measurements of glomerular function alone.

Original languageEnglish (US)
Pages (from-to)817-827
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number4
StatePublished - Apr 2020

ASJC Scopus subject areas

  • Nephrology


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