Impact of AKI on Urinary Protein Excretion: Analysis of Two Prospective Cohorts
Authors: Hsu Chi-yuan , Hsu Raymond K. , Liu Kathleen D. , Yang Jingrong , Anderson Amanda , Chen Jing , Chinchilli Vernon M. , Feldman Harold I. , Garg Amit X. , Hamm Lee , Himmelfarb Jonathan , Kaufman James S. , Kusek John W. , Parikh Chirag R. , Ricardo Ana C. , Rosas Sylvia E. , Saab Georges , Sha Daohang , Siew Edward D. , Sondheimer James , Taliercio Jonathan J. , Yang Wei , Go Alan S. ,   on behalf of the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators and the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study
Published: June 2019

Significance Statement
Studies of the adverse renal consequences of AKI have almost exclusively focused on eGFR changes, whereas few studies have examined AKI’s effects on proteinuria. The authors analyzed data from two prospective cohort studies that assessed urine protein-to-creatinine ratio, BP, eGFR, medication use and other important covariates annually per research protocol and tracked interim episodes of hospitalization for AKI. They found that an episode of hospitalized AKI was independently and significantly associated with increased proteinuria. Further research is needed to examine worsening proteinuria as a potential mechanism by which AKI leads to accelerated loss of renal function. The authors’ findings also suggest that routine monitoring of proteinuria after AKI may be warranted, and highlight the need for research to determine how to best manage proteinuria post-AKI.

Background
Prior studies of adverse renal consequences of AKI have almost exclusively focused on eGFR changes. Less is known about potential effects of AKI on proteinuria, although proteinuria is perhaps the strongest risk factor for future loss of renal function.

Methods
We studied enrollees from the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) study and the subset of the Chronic Renal Insufficiency Cohort (CRIC) study enrollees recruited from Kaiser Permanente Northern California. Both prospective cohort studies included annual ascertainment of urine protein-to-creatinine ratio, eGFR, BP, and medication use. For hospitalized participants, we used inpatient serum creatinine measurements obtained as part of clinical care to define an episode of AKI (i.e., peak/nadir inpatient serum creatinine ≥1.5). We performed mixed effects regression to examine change in log-transformed urine protein-to-creatinine ratio after AKI, controlling for time-updated covariates.

Results
At cohort entry, median eGFR was 62.9 ml/min per 1.73 m2 (interquartile range [IQR], 46.9–84.6) among 2048 eligible participants, and median urine protein-to-creatinine ratio was 0.12 g/g (IQR, 0.07–0.25). After enrollment, 324 participants experienced at least one episode of hospitalized AKI during 9271 person-years of follow-up; 50.3% of first AKI episodes were Kidney Disease Improving Global Outcomes stage 1 in severity, 23.8% were stage 2, and 25.9% were stage 3. In multivariable analysis, an episode of hospitalized AKI was independently associated with a 9% increase in the urine protein-to-creatinine ratio.

Conclusions
Our analysis of data from two prospective cohort studies found that hospitalization for an AKI episode was independently associated with subsequent worsening of proteinuria.