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Abstract: TH-PO635

Gut-Derived Uremic Retention Solutes in Patients with CKD and Healthy Adults

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Wiese, Gretchen, Purdue University, West Lafayette, Indiana, United States
  • Biruete, Annabel, Indiana University School of Medicine, Muncie, Indiana, United States
  • Stremke, Elizabeth, Purdue University, West Lafayette, Indiana, United States
  • Jannasch, Amber, Purdue University, West Lafayette, Indiana, United States
  • Thakkar, Riya, Purdue University, West Lafayette, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Muncie, Indiana, United States
  • Lindemann, Stephen R., Purdue University, West Lafayette, Indiana, United States
  • Moorthi, Ranjani N., Indiana University School of Medicine, Muncie, Indiana, United States
  • Hill Gallant, Kathleen M., Purdue University, West Lafayette, Indiana, United States
Background

Elevated serum levels of the uremic retention solutes (URS), indoxyl sulfate (IS), p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO), have been observed in patients with late stage CKD/dialysis and have been associated with poor health outcomes. Diet is known to impact the production of these URS, yet no study to date has compared patients with mild/moderate CKD vs healthy adults on a controlled diet.

Methods

This secondary analysis aimed to determined serum and urine URS (sURS and uURS) in patients with mild/moderate CKD vs controls participating in a controlled feeding study. Patients with CKD (N=7, eGFR=29-55 mL/min/1.73m2) were studied vs controls (N=7) matched for sex, age, and race. Subjects ate a diet controlled for macronutrients (protein 0.8g/kg/d), fiber (25g/d), P (1500mg/d), Ca (1400mg/d), K (3500mg/d), and Na (2400mg/d) content for 1 week. Fasting serum and urine were collected at the end of the study and IS, PCS, and TMAO were measured by LC/MS-MS. Differences between CKD and control were determined by paired comparisons, and associations were made by Pearson’s correlations.

Results

Fasting sURS were higher in CKD vs controls (p<0.02). Fasting uURS (ratio to urine Cr) tended to be higher in CKD vs control, but only uIS reached significance (p<0.05). eGFR was inversely related to each sURS and uURS (r=-0.54 to -0.71, p=0.01-0.07). When correlations of eGFR with each sURS and uURS were evaluated by group (CKD or control), the inverse correlations persisted in CKD for sURS (r=-0.69 to -0.77, p=0.04-0.09), uTMAO (r=-0.79, p=0.03) and uIS (r=-0.77,p=0.04), but no associations remained in controls (p>0.30). There were strong correlations among the three sURS (r=0.82-0.95,p<0.001), which were strongest within CKD but still evident in controls. There were also strong correlations between the sURS and corresponding uURS (r=0.62-0.91,p<0.02), and these persisted within CKD and control groups.

Conclusion

These results show that URS are elevated in serum and urine in CKD vs matched healthy adults on a controlled diet. In the CKD patients, lower eGFR corresponded to higher serum and urine URS. Further studies are needed comparing different diets in patients with CKD to reduce the adverse health outcomes associated with URS production and retention.

Funding

  • NIDDK Support