Influence of Urine Creatinine Concentrations on the Relation of Albumin-Creatinine Ratio With Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine is correlated with muscle mass, and low muscle mass is also associated with CVD. Whether low urine creatinine in the denominator of the ACR contributes to the association of ACR with CVD is uncertain. Study Design Prospective cohort study. Setting & Participants 6,770 community-living individuals without CVD. Predictors Spot urine albumin, the reciprocal of the urine creatinine concentration (1/UCr), and ACR. Outcome Incident CVD events. Results During a mean of 7.1 years’ follow-up, 281 CVD events occurred. Geometric means for spot urine creatinine, urine albumin and ACR were 95 ± 2 (SD) mg/dl, 0.7 ± 3.7 mg/dl and 7.0 ± 3.1 mg/g. Adjusted HRs per 2-fold higher increment in each urinary measures with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). Urine creatinine was lower in older, female, and low weight individuals. ACR ≥10 mg/g was more strongly associated with CVD events in individuals with low weight (HR for lowest vs. highest tertile: 4.34 vs. 1.97; p for interaction=0.006). Low weight also modified the association of urine albumin with CVD (p for interaction=0.06), but 1/urine creatinine did not (p for interaction=0.9). Limitations We lacked 24-hour urine data. Conclusions While ACR is more strongly associated with CVD events among persons with low body weight, this association is not driven by differences in spot urine creatinine. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin and less by urine creatinine.

The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury

“…Beyond marking urine tonicity, we previously found that urine creatinine concentrations indicate differences in muscle mass, 32 and 1/urine creatinine itself is associated with adverse clinical outcomes in ambulatory persons. 33 Because of these findings, we have preferred to adjust for urine creatinine as a separate covariate in models. Adjustment allows us to evaluate the association of the biomarker in the numerator (uKIM-1 in this instance) independent of these determinants on urine creatinine, while still accounting for urine tonicity at the time of specimen collection.…”

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

“…Albuminuria, which we defined as a urine albumin to creatinine ratio (UACR) ≥30 mg/g, was measured from a single morning urine sample. Urinary albumin was determined by nephelometry using the Array 360 CE Protein Analyzer (Beckman Instruments Inc), whereas urinary creatinine was determined by the rate Jaffe method using the Vitros 950IRC instrument (Johnson & Johnson Clinical Diagnostics, Inc) 47, 50. Glomerular filtration rate (GFR) was estimated at examinations 1, 3, 4, and 5, whereas UACR was measured at examinations 1, 2, 3, and 5.…”

Metabolic syndrome and incident peripheral artery disease – the Multi-Ethnic Study of Atherosclerosis

“…The urinary creatinine albumin ratio was measured using spot urine tests as previously described. 11,12 Intensity of physical activity and intentional exercise were measured by self-report as previously described. 13 …”