Albuminuria shows a stronger association with kidney failure than proteinuria

1. In this individual-level meta-analysis, urinary albumin-creatinine ratio (UACR) had a stronger association with increased risk of kidney failure when compared with urinary protein-creatinine ratio (UPCR).

2. The association between UPCR and increased risk of cardiovascular death was stronger compared with UACR, although UPCR and UACR were similarly associated with increased risk of other cardiovascular events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The first manifestation of chronic kidney disease (CKD) is often increased urinary protein excretion, a marker of kidney damage that is associated with progressive worsening of kidney function. Protein in blood is usually determined by measuring either albumin concentration or dividing total protein by urine creatinine concentration, generating an urinary albumin-creatinine ratio (UACR) or urinary protein-creatinine ratio (UPCR), respectively. Although UPCR remains more accessible globally, UACR availability is increasing, with both ratios having their own benefits and uses. This study aimed to determine the associations of UACR and UPCR with clinical outcomes including kidney failure and cardiovascular events. An analysis of almost 10,000 kidney failure outcomes showed that both UACR and UPCR had log-linear associations with increased risk for kidney failure. The association with kidney failure was somewhat stronger with UACR than UPCR regardless of patient sex, age, BMI, or history of hypertension or diabetes. An analysis of slightly over 10,000 heart failure events showed that both UACR and UPCR had near log-linear associations with increased risk for heart failure, with these associations being similar in strength. Analyses of myocardial infarctions and strokes showed similar associations between UACR and UPCR and increased risk for these outcomes, while a slightly stronger association with increased risk for cardiovascular death was seen for UPCR than for UACR. The generalizability of this study is limited by potential variability in measurement of UACR and UPCR and the possibility that UACR and UPCR were not derived from the same urine sample. Nevertheless, this study suggests that UACR exhibits stronger associations with kidney failure than UPCR, indicating that it may be a better tool for diagnosing and risk-stratifying CKD.

Click to read this study in AIM

Relevant Reading: Comparison of Urinary Albumin and Urinary Total Protein as Predictors of Patient Outcomes in CKD

In-Depth [meta-analysis]: This study aimed to compare the associations between UACR and UPCR and clinical outcomes including kidney failure and cardiovascular events. Patients were obtained from cohorts that participated in the CKD Prognosis Consortium (CKD-PC), and they were eligible if they had data on age, sex, and estimated glomerular filtration rate (eGFR), had both UACR and UPCR measured on the same day, had not previously received long-term dialysis or kidney transplant, and had been followed-up for kidney failure, myocardial infarction, stroke, heart failure, or cardiovascular death. Each cohort needed to have at least 50 events of at least 1 of the outcomes. Outcomes were incident kidney failure with kidney replacement therapy, myocardial infarction, stroke, heart failure, and cardiovascular death. Patients were excluded from analyses for incident myocardial infarction, stroke, and heart failure if they had had a history of the event at baseline. The study included 38 cohorts with a total of 148,994 participants. The mean age was 63 years (standard deviation [SD], 16); 46% (n = 68,236) of participants were female, 43% (n = 65,529) had diabetes, 25% (n = 37,861) had cardiovascular disease, and 47% (n = 70,659) were taking renin-angiotensin system inhibitors (RASis). The mean eGFR was 63mL/min/1.73m² (SD, 30). The median UACR was 47 mg/g (interquartile range [IQR], 12 to 276 mg/g) and the median UPCR was 200 mg/g (IQR, 97 to 597 mg/g). Over a mean follow-up of 3.8 years (SD, 3.2), 9773 kidney failure outcomes were observed among 122,657 participants in 34 cohorts. Log-linear associations were seen between UACR and UPCR and increased risk of kidney failure. The HR for kidney failure associated with each increase in SD was 2.55 (95% CI, 2.36 to 2.74) for log-transformed UACR and 2.40 (95% CI, 2.28 to 2.53) for log-transformed UPCR. Stronger associations were seen between UACR and kidney failure than between UPCR and kidney failure (relative ratio for UACR vs. UPCR, 1.08 [95% CI, 1.04 to 1.11]). Subgroup analyses showed similar results among men and women, older and younger participants, participants with higher and lower BMI, and participants with and without hypertension, diabetes, or RAS inhibition. The study also observed 10,752 heart failure events among 34 cohorts. Near log-linear associations were seen between UACR and UPCR and increased risk of heart failure. The HR for heart failure associated with each increase in SD was 1.49 (95% CI, 1.43 to 1.55) for UACR and 1.52 (95% CI, 1.46 to 1.58) (p for difference = 0.024). Similar HRs were seen in most subgroups with the exception of high-risk patients with moderately to severely elevated UACR, where associations with heart failure were higher for UACR than UPCR (relative ratio in UACR ≥1000 mg/g, 1.22 [95% CI, 1.08 to 1.37]). A total of 6434, 4186, and 5064 myocardial infarctions, strokes, and cardiovascular deaths were observed in 33, 32, and 32 cohorts, respectively. The HRs associated with these events were similar for UACR and UPCR. The strength of the associations with myocardial infarction (relative ratio, 0.99 [95% CI, 0.98 to 1.01]) and stroke (relative ratio, 0.99 [95% CI, 0.97 to 1.01]) were similar for UACR and UPCR, but UPCR had a slightly stronger association with cardiovascular mortality compared with UACR (relative ratio, 0.97 [95% CI, 0.95 to 0.99]). Overall, this study suggests that UACR shows stronger associations with increased risk for kidney failure compared with UPCR.

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