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Kidney Week

Abstract: PO1793

Markers of Kidney Tubular Secretion and Risk of Adverse Events in Persons with CKD in SPRINT

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Ascher, Simon, Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, United States
  • Scherzer, Rebecca, Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, United States
  • Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Hallan, Stein I., Norges teknisk-naturvitenskapelige universitet, Trondheim, Norway
  • Jotwani, Vasantha, Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, United States
  • Malhotra, Rakesh, University of California San Diego, La Jolla, California, United States
  • Estrella, Michelle M., Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, United States
  • Seegmiller, Jesse C., University of Minnesota Academic Health Center, Minneapolis, Minnesota, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
  • Shlipak, Michael, Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, United States
  • Bullen, Alexander, University of California San Diego, La Jolla, California, United States
Background

Tubular secretion is an essential mechanism for the elimination of many drugs, metabolites, and toxins. Impaired tubular secretion may contribute to the high burden of adverse events (AEs) in persons with CKD. Whether novel measures of tubular secretion have prognostic value for AEs during hypertension treatment is unknown.

Methods

In 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR <60 ml/min/1.73m2, we created a summary secretion score from 10 tubular secretion biomarkers by averaging across their urine-to-plasma ratios. Multivariable Cox proportional hazards models were used to evaluate associations between secretion scores and risk of a composite of pre-specified serious AEs (hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, and injurious falls) and two outpatient AEs (hyperkalemia and hypokalemia).

Results

Mean age was 73 ±9 years and mean eGFR was 46 ±11 ml/min/1.73m2. Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. The association between secretion score and composite AE risk followed a curvilinear pattern. Compared to the lowest secretion score quartile, the highest quartile was associated with reduced risk of the composite AE in analyses adjusting for demographics and clinical characteristics (hazard ratio [HR]: 0.63; 95% CI: 0.44, 0.91) (Table). After additionally adjusting for baseline eGFR and albuminuria, the association attenuated and was no longer significant (HR: 1.01, 95% CI: 0.67, 1.50). In multivariable analyses of the individual AEs, higher secretion was independently associated with higher risk of syncope or hypotension (HR per 1-SD higher secretion score: 1.30, 95% CI: 1.10, 1.54) and lower risk of ambulatory hyperkalemia (HR: 0.71, 95% CI: 0.54, 0.95).

Conclusion

Among SPRINT participants with CKD, higher tubular secretion was associated with lower AE risk, but this association was not independent of eGFR and albuminuria.

Funding

  • NIDDK Support