Sepsis is the most commonly identified risk factor for acute kidney injury (AKI), according to published research. “While we know that sepsis-associated acute kidney injury (SA-AKI) has significant short-term complications—including an increased mortality risk—the long-term follow up of patients with SA-AKI remains understudied,” says Alexander H. Flannery, PharmD, PhD.

It is well documented that AKI complicates the short-term management of patients with sepsis, but it also puts patients at risk for long-term complications, such as the development of chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), and short- and long-term mortality. “A significant number of patients with SA-AKI have persistent kidney dysfunction several days into their hospital course with SA-AKI,” Flannery says. “This is more formally defined as acute kidney disease (AKD), which is persistently reduced kidney function for at least 7 days but less than 90 days.”


Aiming to Stratify Risk

For a study published in Kidney Medicine, Flannery and colleagues assessed how well AKD staging criteria developed by the Acute Disease Quality Initiative (ADQI), applied either at hospital discharge or shortly after, stratified risk of long-term adverse kidney-related outcomes, including death, KFRT, or new/worsening CKD. “These AKD staging criteria are serum creatinine-based criteria that we classified by calculating the last observed serum creatinine at hospital discharge (or within 90 days following hospital discharge) and dividing by the baseline serum creatinine,” explains Flannery. “Based on this calculated ratio, we studied the long-term outcomes of groups with stage 0A AKD (ratio <1.1), stage 0C AKD (ratio ≥1.1 to <1.5), or stage ≥1 AKD (ratio ≥1.5).”

In total, the study evaluated data on 6,290 critically ill patients who were admitted to the ICU with severe sepsis or septic shock. Survivors who were alive and free of KFRT for up to 90 days following hospital discharge were assessed for their AKD status. The composite endpoint was time to developing incident CKD, progression of CKD, KFRT, or death.


Stage of AKD Matters

According to the findings, patients who survived an AKI associated with sepsis often failed to return to baseline kidney function by the time they were discharged. Nearly half (46.9%) of patients who survived SA-AKI had persistent elevations in serum creatinine at hospital discharge, or stages 0C and ≥1 AKD. Importantly, the stage of AKD was an important predictor of the composite endpoint (Table).

“With a median follow-up period of 14 months, we noted significant impairments in long-term outcomes for patients with SA-AKI,” says Flannery. “The degree to which patients experienced the composite outcome of death, KFRT, or new or worsening CKD was strongly related to their AKD stage at hospital discharge or shortly after. The risk of these poor outcomes increased in a graded manner depending on if patients were classified as stage 0A AKD, stage 0C AKD, or stage ≥1 AKD. This supports the notion that the ADQI AKD staging criteria, when assessed around the time of hospital discharge, appropriately risk-stratifies patients for long-term kidney-related complications of SA-AKI.”


Informing Strategies to Alter Trajectory

Results from the study can help clinicians better identify risks for long-term kidney complications in patients with SA-AKI and ensure that they receive the most appropriate attention and care after they are discharged from the hospital. “Assessing a patient’s AKD status at discharge may inform the trajectory of kidney health in patients with SA-AKI over the next 1 to 2 years and can help with prognostication,” Flannery says. “This may help with planning a patient’s follow-up for optimal kidney health following SA-AKI.”


Future Research Needs

According to Flannery, post-AKI care is increasingly recognized as an area that requires more research to minimize the progression of kidney disease and associated complications. “This not only includes studies of pharmacologic interventions, but also patterns of care,” he says. “While our research indicates that the ADQI AKD criteria appropriately risk-stratify, there may be biomarkers that better inform clinicians regarding risks of declining kidney health over the long term. By having optimal methods of risk-stratification in post-AKI care, the hope is that targeted interventions can be developed and studied for patients who may benefit the most.”