Renal clearance of uremic solutes may be connected to the development of CVD
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The “strong associations” of urine-to-plasma ratios with cardiovascular mortality implies a connection between renal clearance of uremic solutes and CVD pathogenesis, according to a speaker from ASN Kidney Week.
“In dialysis patients CVD mortality is 10 to 30 times higher than in general population, particularly for those with diabetes as the underlying cause of chronic kidney disease. Few biomarkers for CVD in the context of the diabetic kidney disease (DKD) have been identified, and fewer still have been validated by high-quality reproducible assays,” Hima Sapa, PhD, of Case Western Reserve University, said. “The goal of this study is to evaluate association of three specific uremic solutes: asymmetric dimethylarginine, symmetric dimethylarginine and trimethylamine-N-oxide in people with diabetes and CKD.”
Researchers took a random subcohort of 555 REasons for Geographic And Racial Differences in Stroke (REGARDS) Study participants with diabetes and eGFR less than 60 mL/min/1.73m2 at study entry, then used mass spectrometry to assay uremic solutes in plasma and urine. Plasma concentrations and urine-to-plasma ratios of each solute were tested for correlation with cardiovascular mortality, all-cause mortality and incident end-stage kidney disease.
Using Cox regression models, researchers predicted the hazard ratios per log2 increment, adjusted for demographic and CVD risk factors, baseline eGFR and urine albumin–creatinine ratio (UACR).
“The primary outcome was cardiovascular (CV) mortality. The secondary outcomes were all cause mortality and incidence ESKD,” Sapa said.
During the mean 6.2 years of follow-up, overall mortality occurred in 285 participants, CV death occurred in 120 and ESKD occurred in 89. Analyses revealed higher plasma asymmetric dimethylarginine and lower urine-to-plasma ratios of all three solutes correlated with increased CV mortality. Similarly, higher plasma concentrations and lower urine-to-plasma ratios were also “significantly associated” with all-cause mortality. However, higher plasma symmetric dimethylarginine was only associated with incident ESKD.
“We concluded the association of carefully assayed uremic solute biomarkers with CVD may identify patients with diabetic kidney disease who would benefit from established prophylactic cardiovascular disease interventions. The strong association of CV mortality with urine-to-plasma ratios and less consistent associations of plasma levels suggest a connection between renal clearance of uremic solutes CVD pathogenesis,” Sapa said.
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Sapa H, et al. Uremic solutes are associated with cardiovascular death in diabetic kidney disease. Presented at: ASN Kidney Week; Nov. 4-7, 2021 (virtual meeting).
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