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Abstract: PO0447

Tubular Secretion of Creatinine and Risk of Kidney Failure: The Modification of Diet in Renal Disease Trial

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
  • Tighiouart, Hocine, Tufts Medical Center, Boston, Massachusetts, United States
  • Levey, Andrew S., Tufts Medical Center, Boston, Massachusetts, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
Background

Whether tubular secretion is associated with clinical outcomes beyond glomerular filtrate rate (GFR) or proteinuria is unknown. By using measured GFR and creatinine clearance, we evaluate the association of tubular secretion of creatinine with long-term kidney and mortality outcomes.

Methods

The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This prospective analysis included 838 participants with baseline measures of iothalamate glomerular filtration rate (mGFR) and 24-hour urine creatinine clearance (CrCl). Tubular secretion of creatinine (TScr) was calculated as the difference between CrCl and mGFR. The primary outcome was incident end-stage kidney disease (ESKD) and secondary outcomes were cardiovascular disease (CVD) related and all-cause mortality.

Results

At baseline, mean mGFR was 33 ml/min/1.73 m2 and the mean CrCl was 42 ml/min/1.73 m2. Over 21 years of follow up there were 626 ESKD, 202 CVD-related mortality, and 444 all-cause mortality events. Each 10 ml higher TScr was associated with a lower risk of ESKD (HR 0.74, 95% CI 0.66-0.84)) after adjustments for mGFR, proteinuria, and other potential confounding factors [Image]. Higher TScr was associated with lower risk of CVD related mortality (HR 0.78, 95% CI 0.65, 0.95) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.97) in unadjusted models but these associations were no longer statistically significant after adjusting for confounders (HR 0.82, 95% CI 0.66, 1.02 and HR 0.92, 95% CI 0.79, 1.06 respectively).

Conclusion

Higher TScr is associated with lower risk of ESKD, independent of mGFR, proteinuria, and other kidney disease factors. Tubular secretion provides prognostic information above and beyond GFR and proteinuria.

Funding

  • NIDDK Support