Proximal tubule reabsorptive dysfunction and risk of cardiovascular death among community-living adults: the HUNT-3 cohort.
Higher levels of urinary A1M and B2M are associated with an increased risk of cardiovascular death, but the clinical implications of these findings require further investigation.
Where it sits
this study against the rest of the thymosin alpha-1 corpusSummary and findings
This study evaluated the association between proximal tubule dysfunction and cardiovascular death in a general population. It involved 1246 participants, measuring urinary alpha-1 microglobulin (A1M) and beta-2 microglobulin (B2M). Over a median follow-up of 13 years, 166 cardiovascular deaths were recorded.
Abstract
<h4>Aims</h4>Proximal tubule dysfunction in the kidney is associated with cardiovascular disease (CVD) in populations with prevalent chronic kidney disease (CKD). We sought to evaluate the nature of this association in the general population.<h4>Methods and results</h4>We conducted a case-cohort study within the North Trøndelag Health Study (HUNT-3). We randomly sampled 1246 participants and all cases of cardiovascular death. Alpha-1 microglobulin (A1M) and beta-2 microglobulin (B2M) were measured in urine to assess proximal tubule reabsorptive dysfunction. Cardiovascular death was assessed using the Norwegian Cause of Death registry. We estimated the association of each biomarker with cardiovascular death after adjustment for baseline characteristics, including estimated glomerular filtration rate (eGFR) and albuminuria. Mean participant age was 51 years, 55% were female. Median urine albumin-to-creatinine ratio was 1.3 [interquartile range (IQR) 1.0-1.8] mg/mmol and mean eGFR was 98 (SD 17) mL/min/1.73 m<sup>2</sup>. Cardiovascular death occurred in 166 participants over a median follow-up of 13 years. The weighted incidence among those with low-normal, mid-normal, high-normal, and elevated A1M was 0.8 (0.6-1.1), 1.5 (1.0-2.0), 2.0 (1.3-2.6), and 4.5 (2.6-6.4) per cent, respectively. After adjustment for baseline characteristics, 1-SD higher urine A1M [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.12-1.58] and urine B2M (HR 1.28, 95% CI 1.10-1.48) were each associated with higher risk of cardiovascular death. We did not observe interaction across subgroups based on age, sex, albuminuria, or prevalent CVD.<h4>Conclusion</h4>In a population-based cohort of adults, proximal tubule reabsorptive dysfunction, as indicated by elevated levels of urinary A1M and B2M, was associated with higher risk of cardiovascular death independent of eGFR and albuminuria.