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Abstract: SA-OR29

Uremic Solutes Are Associated with Cardiovascular Death in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Author

  • Sapa, Hima, Case Western Reserve University, Cleveland, Ohio, United States

Group or Team Name

  • CKD Biomarkers Consortium (BioCon)
Background

Cardiovascular disease (CVD) is a major cause of mortality among people with diabetic kidney disease (DKD). The pathophysiology of CVD in DKD is not explained adequately by traditional CVD risk factors. Three small molecular weight, uncharged uremic solutes, asymmetric and symmetric dimethylarginine (ADMA, SDMA) and trimethylamine-N-oxide (TMAO) have been linked to CVD in ESKD. These solutes may be markers of CV mortality in non-ESKD DKD, as well as DKD progression to ESKD.

Methods

Uremic solutes in plasma and urine were assayed by mass spectrometry from a random subcohort of 555 REGARDS Study participants with diabetes and eGFR <60 ml/min/1.73m2 at study entry. Plasma concentrations and urine:plasma (U/P) ratios of each solute were tested for association with CV mortality (primary outcome), all-cause mortality and incident ESKD (secondary outcomes). Cox regression models estimated the hazard ratios (HR) per log2 increment, adjusted for demographic and CVD risk factors, baseline eGFR and urine albumin to creatinine ratio (UACR).

Results

Mean (SD) baseline eGFR was 44 ± 12 ml/min/1.73 m2, median (IQR) UACR was 32 (11, 203) mg/g. CV death, overall mortality and ESKD occurred in 120, 285 and 89 participants, respectively, during mean 6.2 years of follow-up. Higher plasma ADMA, and lower U/P ratios of all three solutes were associated with increased CV mortality (Table). Higher plasma concentrations and lower U/P ratios of all three solutes were significantly associated with all-cause mortality. Only higher plasma SDMA was associated with incident ESKD.

Conclusion

Higher plasma concentration and lower U/P ratio of ADMA were independently associated with CV and all-cause mortality in DKD. The strong associations of U/P ratios with CV mortality outcomes suggest a connection between renal clearance of uremic solutes and CVD pathogenesis.

Funding

  • NIDDK Support