For hospitalized patients with acute kidney injury (AKI), postdischarge measurement of albuminuria may improve the ability to identify patients at higher subsequent risk of progressive kidney disease, according to a prospective, multicenter cohort study reported in the March issue of JAMA Internal Medicine.
Patients with an episode of AKI are at high risk of rapidly declining kidney function. New approaches are needed to identify those patients at highest risk of kidney disease progression.
Doubling of the urine albumin-to-creatine ratio (UACR) after hospital discharge is associated with a 1.5-fold increase in the odds of kidney disease progression, according to the report by the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) investigators. The lead author is Chi-yuan Hsu, MD, MSc, chief of the division of nephrology at the University of California, San Francisco.
“Proteinuria level is a valuable risk-stratification tool in the post-AKI period,” Hsu and coauthors write. “These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.”
The researchers analyzed data on 1,538 hospitalized adults from the ASSESS-AKI Study. Patients were enrolled 3 months after discharge from four North American clinical centers, representing a range of hospital settings. During their hospital stay, 769 patients had an episode of AKI, defined as a relative increase of at least 50%, or 0.3 mg/dL in serum creatinine (SCr), compared to the most recent outpatient measurement (7 days to 1 year before admission). The patients were 519 men and 250 women, mean age 63.7 years; 15.2% were black. Median duration of the AKI episode was 2 days.
Patients in the AKI cohort were matched to 769 adults without AKI at index hospitalization. Both groups made an outpatient research study visit 3 months after hospital discharge. At this visit, mean estimated glomerular filtration rate (eGFR) was 65.7 mL/min/1.73 m2 in the AKI group, compared to 72.7 mL/min/1.73 m2 in patients without AKI. For AKI patients, the mean peak SCr value was 2.46 mg/mL.
At the study visit, patients also underwent random urine UACR measurement, with median values of 21 mg/g in the AKI group and 11 mg/g in patients without AKI. Patients with an episode of AKI were more likely to have UACR values between 30 and 300 mg/g (microalbuminuria), 27.4% versus 19.4%; as well as over 300 mg/g (macroalbuminuria), 15.5% versus 6.5%.
Data analysis focused on potential predictors of subsequent kidney disease progression, including proteinuria, eGFR, and a range of clinical and demographic variables. Progressive kidney disease was defined as halving of estimated eGFR or diagnosis of kidney failure.
Higher UACR linked to increased odds of kidney disease progression
Median follow-up was 4.7 years. During this time, kidney disease progression occurred in 138 patients: a rate of 9.0%. Fifty-eight of the patients with progressive disease were diagnosed with kidney failure. Of the 138 patients, 97 were in the AKI group.
Patients with higher UACR at the 3-month postdischarge visit were significantly more likely to have kidney disease progression: hazard ratio 1.53 for each doubling of UACR.
“The performance of postdischarge UACR was better in patients who experienced AKI than in patients discharged without AKI,” Hsu and coauthors write. C statistics were 0.82 versus 0.70, respectively.
Post-AKI eGFR was also a predictor of kidney disease progression: HR 1.50 per each decrease of 10 mL/min/1.73 m2. However, the C statistic of 0.77 was lower than the corresponding C statistic for post-AKI UACR (again 0.82). In a comprehensive model incorporating clinical risk factors, discrimination for predicting kidney disease progression was greater in patients who had AKI than in those who did not: C statistic 0.85 versus 0.76.
Patients with higher UACR at the 3-month postdischarge visit were significantly more likely to have kidney disease progression.
Call for more routine quantification of proteinuria after hospitalized AKI
Two recent reports have reported increases in proteinuria after AKI, “potentially reflecting residual renal parenchymal injury,” according to Hsu and coauthors. In a VA study, Parr et al. (2018) found that AKI patients were more likely to have 1+ or greater proteinuria in the year after discharge, compared to matched controls without AKI. Another report by Hsu and colleagues (2019), based on analysis of the prospective ASSESS-AKI and CRIC cohorts, concluded that “an episode of hospitalized AKI was independently associated with a 9% increase in the urine protein-to-creatinine ratio.”
The new results provide evidence that measuring proteinuria after AKI can help predict subsequent loss of kidney function—even more strongly than post-AKI eGFR. “[O]nce post-AKI proteinuria, post-AKI eGFR, and other known CKD risk factors are taken into account, patients who experience AKI during hospitalization have similar renal prognoses compared with hospitalized patients who did not experience AKI,” Hsu and colleagues write. The authors note some important strengths of their prospective cohort study, including rigorous measurement of proteinuria about 90 days after hospital discharge. They note that their findings are consistent with Healthy People 2020 objectives to increase the proportion of hospitalized patients with AKI who undergo follow-up renal assessment within 6 months after discharge.
Previous studies of renal outcomes have focused on SCr, but proteinuria is not commonly assessed. “Our findings demonstrate that proteinuria after AKI carries important prognostic information not conveyed by serum creatinine alone and that clinicians should not be falsely reassured by the latter,” Hsu and colleagues write.
Because proteinuria is itself a potentially modifiable risk factor, treatments to reduce proteinuria—including blood pressure control and angiotensin converting enzyme inhibitors or angiotensin receptor blockers—might lower the risk of adverse outcomes after AKI. Several recent studies have suggested benefits of ACE-I or ARB therapy for patients with AKI, many of whom also have other indications, although these medications “appear to be underutilized” after AKI, according to the authors.
Overall, the findings add evidence that “increased proteinuria (and decreased eGFR) [are] potentially key steps in the causal pathway linking AKI to CKD.” The ASSESS-AKI investigators conclude: “Our results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI, perhaps similar to how patients with diabetes mellitus undergo screening for proteinuria.”
The paper discussed in this article is:
Hsu CY, et al. Post-acute kidney injury proteinuria and subsequent kidney disease progression: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study. JAMA Intern Med 2020; 180:402–410.
Other papers mentioned:
- 1.
James MT, et al. Derivation and external validation of prediction models for advanced chronic kidney disease following acute kidney injury. JAMA 2017; 318:1787–1797.
- 2.
Parr SK, et al. Acute kidney injury is a risk factor for subsequent proteinuria. Kidney Int 2018; 93:460–469.
- 3.
Hsu CY, et al. Impact of acute kidney injury on urinary protein excretion: analysis of two prospective cohorts (ASSESS-AKI and CRIC). J Am Soc Nephrol 2019; 30:1271–1281.
