UACR, eGFR Associated with Hospitalizations, Other Adverse Outcomes

Morgan Grams, MD, PhD

Credit: Johns Hopkins Bloomberg School of Public Health

Decreased estimated glomerular filtration rate (eGFR) and greater albuminuria were associated with multiple adverse outcomes, including kidney outcomes, cardiovascular diseases, and hospitalizations in a recent meta-analysis.

Findings revealed a stronger association for eGFR based on creatinine and cystatin C compared to creatine alone, highlighting the importance of cystatin C use in clinical practice.¹

“Both lower eGFR values and more severe albuminuria have been associated with higher rates of kidney failure with replacement therapy, acute kidney injury, all-cause mortality, and cardiovascular mortality,” wrote investigators.¹

According to the US Centers for Disease Control and Prevention, kidney diseases are the leading cause of death in the US. An estimated 37 million US adults are estimated to have chronic kidney disease, and most are undiagnosed. Although chronic kidney disease (CKD) tends to get worse over time and can progress to kidney failure, it can be treated if caught early.² Urine albumin-to-creatinine ratio (UACR) tests, blood tests for creatinine, and glomerular filtration rates are commonly used to diagnose kidney disease.³

To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse outcomes, Morgan Grams, MD, PhD, adjunct professor at the School of Medicine at Johns Hopkins Bloomberg School of Public Health, and a team of investigators in the CKD Prognosis Consortium measured the risk of 10 adverse outcomes among more than 27 million participants across 114 global cohorts.¹

Investigators in the CKD Prognosis Consortium were invited to participate in the meta-analysis if their represented cohorts included individuals with both eGFR and albuminuria as well as having 50 events or more for ≥1 of the selected outcomes, including kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The data sources included 37 observational studies or clinical trials of individuals identified from the general population, 49 electronic health record databases, and 28 observational studies or clinical trials of adults with CKD. In total, 27,503,140 individuals from 114 global cohorts had measurements for eGFR based on creatinine alone, 720,736 individuals from 20 cohorts had measurements for eGFR based on creatinine and cystatin C, and 9,067,753 individuals from 114 cohorts had measurements for albuminuria.¹

Investigators used Cox proportional hazards models to relate kidney measurements to adverse outcomes separately in each cohort. Random-effects models were used for the meta-analysis of the hazard ratios, and log hazard ratios were compared within each combined category of eGFR and albuminuria, measured as UACR, across populations or subgroups of populations using matched-pair Wilcoxon signed rank tests.¹

Among the population with eGFR based on creatinine alone, the mean age was 54 (standard deviation [SD], 17) years, 51% were female, the mean follow-up time was 4.8 (SD, 3.3) years, and the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2). Investigators noted the rates of adverse outcomes were lowest for peripheral artery disease (median rate among 62 cohorts, 1.4 events per 1000 person-years) and kidney failure with replacement therapy (median rate among 83 cohorts, 1.3 events per 1000 person-years), and highest for hospitalizations (median rate among 52 cohorts, 94 events per 1000 person-years). Compared with the reference category of 90 to 104 mL/min/1.73 m2, eGFR ≤ 60 mL/min/ 1.73 m2 was significantly associated with higher risk for each outcome.¹

Measures of albuminuria were available for 33.0% of the eGFR based on creatinine alone group and had a median UACR of 11 mg/g (interquartile range [IQR], 8-16 mg/g). Among participants with a UACR ≤10 mg/g, investigators pointed out an eGFR of 45 to 59 mL/min/1.73 m2 was associated with significantly higher hospitalization rates compared with an eGFR of 90 to104 mL/min/1.73 m2 (adjusted hazard ratio (aHR), 1.3; 95% confidence interval [CI], 1.2-1.3).¹

In the eGFR based on creatinine and cystatin C group, the mean age was 59 (SD, 12) years, 53% were female, and the mean follow-up time was 10.8 (SD, 4.1) years, and the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2). Compared with the reference category of 90 to 104 mL/min/1.73 m2, the eGFR categories ≤60 mL/min/ 1.73 m2 were significantly associated with higher risk for each outcome. Albuminuria measures were available for 44.4% of this group with a median UACR of 9 mg/g (IQR, 6-18 mg/g).¹

Whether based on creatinine alone or based on creatinine and cystatin C, decreased eGFR and greater UACR were each significantly associated with higher risk for each of the 10 adverse outcomes. For eGFR <15 mL/min/1.73 m2 and UACR ≥1000 mg/g, the highest rates of adverse outcomes were for hospitalizations (562 per 1000 person-years), kidney failure with replacement therapy (325 per 1000 person-years), and mortality (148 per 1000 person-years).¹

“The current study adds to the literature by providing strong evidence for the classification and risk stratification of CKD using the most up-to-date estimates of GFR, more categories of albuminuria, and additional cardiovascular outcomes,” concluded investigators.¹

References:

1. Writing Group for the CKD Prognosis Consortium. Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes. An Individual-Participant Data Meta-Analysis. JAMA. doi:10.1001/jama.2023.17002.
2. Centers for Disease Control and Prevention. Chronic Kidney Disease Basics. Chronic Kidney Disease Initiative. February 28, 2022. Accessed October 2, 2023. https://www.cdc.gov/kidneydisease/basics.html
3. National Kidney Foundation. Chronic Kidney Disease (CKD). Accessed October 2, 2023. https://www.kidney.org/atoz/content/about-chronic-kidney-disease