Recent research has shown that episodes of acute kidney injury (AKI) are strongly associated with more rapid subsequent loss of kidney function. “AKI is a common condition that is often first encountered in the hospital setting,” explains Chi-yuan Hsu, MD, MSc. “After patients are discharged following episodes of AKI, it is important to determine which patients are at highest risk for kidney disease progression so that these individuals are followed up and cared for appropriately.”

Several investigations have stressed the prognostic importance of post-AKI serum creatinine (SCr) and estimated glomerular filtration function (eGFR) levels. More recently, studies have suggested that proteinuria levels increase after episodes of AKI. This can potentially reflect the presence of a residual renal parenchymal injury. “It is possible that proteinuria levels after AKI are strongly associated with subsequent loss of kidney function,” Dr. Hsu says. “Known risk factors for future loss of kidney function—specifically proteinuria, eGFR, and other known risk factors for chronic kidney disease—may help further stratify risk after AKI episodes.”

Taking a Closer Look

Findings from the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) study were recently published in JAMA Internal Medicine. In this investigation, Dr. Hsu and colleagues analyzed data from more than 1,500 patients who were enrolled 3 months after hospital discharge, half of whom had an episode of AKI during their hospitalization. They defined kidney disease progression as halving of eGFR or end-stage renal disease. AKI episodes were defined based on a relative increase in inpatient SCr of at least 50% or 0.3 mg/dl or more above the nearest outpatient, non-emergency department SCr concentration obtained in the year prior to the index hospitalization.

At a median follow-up of 4.7 years, 9% of study patients had kidney disease progression. “We found that patients with a higher urine albumin-to-creatinine ratio (ACR), which was quantified at 3 months after post-AKI hospitalization discharge, was associated with an increased risk of kidney disease progression and served as a powerful risk discriminator,” says Dr. Hsu (Figure). A comprehensive model of clinical risk factors that included ACR, eGFR, blood pressure, and demographics provided better discrimination for predicting kidney disease progression after hospital discharge among patients with AKI when compared with those without AKI.

An Important Prognosticator

Findings from the ASSESS-AKI study highlight the prognostic importance of proteinuria after patients suffer episodes of AKI. “Our findings suggest that proteinuria after AKI is associated with subsequent loss of kidney function, perhaps more than post-AKI eGFR levels,” Dr. Hsu says. “Known risk factors for future kidney function loss that are readily available—including proteinuria and eGFR—can successfully distinguish risk in patients after episodes of AKI.”

According to Dr. Hsu, most patients who have mild to moderately severe episodes of AKI will be seen by primary care clinicians (PCPs), not nephrologists. “Many PCPs will check SCr and eGFR levels after patients have an AKI episode but will not check for proteinuria,” he says. “Our findings demonstrate that proteinuria after AKI carries important prognostic information that is often not conveyed by SCr alone. Clinicians should not be falsely reassured by SCr assessments alone. Instead, a more complete picture of kidney health is needed to ensure proper clinical decision making regarding the benefits and risks of any future interventions.”

In light of the findings, a greater emphasis should be placed on testing and evaluating ACR after AKI. “We need more widespread and routine quantification of albuminuria after patients are AKI, just like how patients with diabetes undergo screening for albuminuria,” says Dr. Hsu. “This would represent a substantial change from current clinical practice, but it is important to ensuring the most appropriate care for patients. Albuminuria is a modifiable risk factor that can be managed with antihypertension therapies and use of drugs like angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Therapies to reduce albuminuria may decrease the likelihood of adverse outcomes after episodes of AKI.”

References

Hsu CY, Chinchili VM, Coca S, et al; for the ASSESS-AKI Investigators. 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. 2017 Jan 27 [Epub ahead of print]. Available at: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2759742.

Hsu CY, Hsu RK, Liu KD, 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(7):1271-1281.

Hsu RK, Hsu CY. The role of acute kidney injury in chronic kidney disease.  Semin Nephrol. 2016;36(4):283-292.

Parr SK, Matheny ME, Abdel-Kader K, et al.  Acute kidney injury is a risk factor for subsequent proteinuria. Kidney Int. 2018;93(2):460-469.