Log in to MyACC
Markers of Kidney Tubule Function and Risk of CVD Events
Study Questions:
Are biomarkers of kidney tubular function associated with cardiovascular disease (CVD) outcomes in nondiabetics with chronic kidney disease (CKD)?
Methods:
The authors measured alpha-1 microglobulin (α1m), beta-2 microglobulin (β2m), and uromodulin in 2,377 nondiabetic patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 enrolled in the SPRINT (Systolic Blood Pressure Intervention Trial), and examined their association with a combined primary endpoint of acute coronary syndrome, stroke, acute heart failure, or death from cardiovascular cause. Secondary endpoints included all-cause mortality and the individual endpoints composing the primary outcome. Median follow-up time was 3.8 years.
Results:
The studied cohort included 40% women, 26% were black, and mean age was 73 years. Patients with higher α1m or β2m levels were more likely men and had a higher prevalence of CVD risk factors. In contrast, those with higher uromodulin had lower prevalence of CVD risk factors. There were a total of 305 composite CVD events, including 233 deaths. After multivariable adjustment, patients in the highest quartile of α1m (>25 mg/L), had an 80% higher risk of CVD events, compared to the lowest quartile (<7.09 mg/L). Neither β2m nor uromodulin were associated with the primary outcome in multivariable analyses. None of the markers were independently associated with all-cause death. Incorporating α1m to a risk prediction model incorporating CV risk factors only slightly improved the C-statistic by 0.009.
Conclusions:
Urinary α1m levels are associated with a composite of CVD events in nondiabetics with CKD and hypertension.
Perspective:
The authors depict kidney tubular markers as strong predictors of outcomes; however, α1m only weakly improved risk discrimination for the combined outcome. α1m was not associated with all-cause death, usually a red flag when evaluating biomarkers for risk. Neither uromodulin nor β2m were independently associated with outcomes when examined as quartiles. The authors claim that the association of α1m with outcomes was stronger than that of eGFR or albuminuria by comparing hazard ratios. An alternate approach would have been to compare the change in C-statistic afforded by the addition of each of these markers separately to a model. Last, these markers do not seem to have any potential usefulness in altering our management of patients. Until shown to be more effective in risk stratification than well-established biomarkers of risk such as high-sensitivity troponin, C-reactive protein, and B-type natriuretic peptide, α1m is likely to join the slew of other biomarkers with limited clinical value.
Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Prevention, ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension
Keywords: Acute Coronary Syndrome, Albuminuria, beta 2-Microglobulin, Biomarkers, Glomerular Filtration Rate, Heart Failure, Hypertension, Kidney Diseases, Kidney Tubules, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Stroke, Uromodulin
< Back to Listings
