Proteinuria Levels Predict Future Kidney Function Loss

Chi-yuan Hsu, MD

Proteinuria levels following an acute kidney injury (AKI) could help predict the future risk of the loss of renal function.

A team from several different institutions, led by Chi-yuan Hsu, MD, Division of Nephrology, University of California School of Medicine, San Francisco, found that more widespread quantification of proteinuria after a hospitalized acute kidney injury should be considered to better evaluate the risk of future kidney disease progression.

In a matched cohort study involving 1538 patients, half of which have an acute kidney injury during hospitalization, the investigators found higher urine albumin-to-creatinine ratio (ACR) quantified 3 months following hospitalization discharge with an AKI was linked to an increased risk of kidney disease progression and served as a risk discriminator.

The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective study at 4 clinical centers in North America between December 2009 and February 2015.

The investigators defined kidney disease progression as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease. They also defined an acute kidney injury based on a relative increase of at least 50% or .3 mg/dl or more in inpatient serum creatinine (SCr) concentration above the nearest outpatient, non-emergency department SCr concentration obtained 7-365 days prior to index hospitalization.

The mean age of participants was 65 years old, with a median eGFR of 68 mL/min/1.73m² and a median urine ACR of 15mg/g. A baseline study visit took place at a mean time period of 91 days following discharge.

Following a median follow-up of 4.7 years, a total of 138 (9%) of patients had kidney disease progression.

Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (HR, 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, .82).

The investigators also found the performance of urine ACR was stronger for patients who had AKI than in those who had not (C statistic, .70).

A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics), including ACR provided better discrimination for predicting kidney disease progression following hospital discharge among those who had AKI (C statistic, .85) compared to those who had not (C statistic, .76).

In the entire cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months following discharge, AKI (HR, 1.46; 95% CI, .51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, .50-4.72 for AKI stage 1 vs non-AKI; HR, .56; 95% CI, .07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, .33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression.

“Proteinuria level is a valuable risk-stratification tool in the post-AKI period,” the authors wrote. “These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.”

A single episode of AKI is strongly linked to more rapid subsequent loss of kidney function, highlighting the need to improve risk predictions to identify patients at the highest risk for kidney disease progression for appropriate follow-up.

The study, “Post—Acute Kidney Injury Proteinuria and Subsequent Kidney Disease Progression,” was published online in JAMA Internal Medicine.