The Impact of Persistent Severe Acute Kidney Injury on Outcomes in Critically Ill Patients

Background Introduction

Acute Kidney Injury (AKI) is a common complication among hospitalized and critically ill patients, causing over 10 million deaths globally each year and serving as a significant risk factor for the progression of Chronic Kidney Disease (CKD). Although most AKI cases resolve within 72 hours, a small subset of patients develop persistent severe AKI, which is associated with significantly worse outcomes. However, there is currently no unified understanding of the definition, epidemiology, risk factors, or impact on patient outcomes of persistent severe AKI. To better understand its clinical significance and provide a basis for future therapeutic interventions, Hernando Gómez and his team conducted this study.

Source of the Paper

The study was led by Hernando Gómez from the Critical Care Medicine Program at the University of Pittsburgh, in collaboration with scholars from the University of Pittsburgh, Straub Clinic and Hospital, Icahn School of Medicine at Mount Sinai, and University Hospital of Münster in Germany. It was published in Intensive Care Medicine in 2025 under the title “Persistent severe acute kidney injury is a major modifiable determinant of outcome during critical illness.”

Study Process and Results

Study Design and Methods

The study employed a retrospective cohort design, analyzing data from 190,550 adult critically ill patients admitted to 16 hospitals in Western Pennsylvania between January 2010 and June 2018. The primary focus was on patients who developed AKI during their hospital stay. Persistent severe AKI was defined as progressing to Kidney Disease: Improving Global Outcomes (KDIGO) stage 2-3 AKI and persisting at stage 3 for at least 72 hours.

The study used the Super Learner algorithm (combining Lasso logistic regression and XGBoost) along with multivariate logistic regression or Cox proportional hazards models to assess risk factors for persistent severe AKI and its association with patient outcomes. Primary outcomes included 90-day mortality, renal recovery (defined as serum creatinine returning to ≤150% of baseline without dialysis at discharge), readmission rates, and the risk of recurrent persistent severe AKI during subsequent admissions.

Key Results

1. Incidence of Persistent Severe AKI
   Among the 190,550 patients, 34.2% (65,119) developed KDIGO stage 2-3 AKI, of whom 12.4% (8,059) progressed to persistent severe AKI, representing 4.2% of the total cohort. After excluding patients who died within 24 hours of admission, the incidence of persistent severe AKI increased to 17.4%.

2. Risk Factor Analysis
   Important risk factors for persistent severe AKI included severe early community-acquired AKI, high fluid balance, multiple organ dysfunction, sepsis, and shock. Additionally, cumulative fluid input, total urine output, thrombocytopenia, and low arterial pH before AKI were independently associated with persistent severe AKI.

3. Association with 90-Day Mortality
   Patients with persistent severe AKI had a significantly higher 90-day mortality rate compared to those without persistent severe AKI (hazard ratio HR=1.5, 95% confidence interval CI: 1.4–1.6). This association remained significant after adjusting for other confounding factors.

4. Renal Recovery and Readmission Risk
   Patients with persistent severe AKI had a significantly lower probability of renal recovery (odds ratio OR=0.14, 95% CI: 0.13–0.15) and an increased risk of readmission (OR=2.0, 95% CI: 1.8–2.3).

Highlights of the Study

1. Clear Definition and Strict Classification
   The study was the first to adopt a strict definition of persistent severe AKI and compare it with other AKI subgroups (e.g., transient AKI and persistent mild-moderate AKI), providing an important reference framework for future research.

2. Multidimensional Data Analysis
   Advanced machine learning algorithms (Super Learner) and various statistical models were used to comprehensively evaluate AKI risk factors and their impact on outcomes, ensuring the reliability of the results.

3. Significant Clinical Implications
   The findings indicate that persistent severe AKI is a key modifiable determinant of outcomes in critically ill patients, offering a clear target for future clinical trials and therapeutic interventions.

Conclusions and Significance

This study provides the first systematic description of the incidence, risk factors, and impact of persistent severe AKI on outcomes in critically ill patients. The results demonstrate that persistent severe AKI is a critical pathophysiological event in the progression of renal injury, closely associated with reduced renal recovery, increased readmission risk, and higher mortality. These findings underscore the importance of early identification and intervention for persistent severe AKI in clinical practice and provide a scientific basis for future treatment strategies.

Value of the Study

1. Scientific Value
   The study fills gaps in the epidemiology and risk factors of persistent severe AKI, offering new insights into the pathophysiological mechanisms of AKI.

2. Clinical Application Value
   The results provide clinicians with tools to identify high-risk patients and lay the groundwork for developing treatment strategies targeting persistent severe AKI.

3. Future Research Directions
   The study highlights the importance of fluid management and inflammation control in the prevention and treatment of AKI, offering valuable references for designing future clinical trials.

This study not only deepens our understanding of AKI but also provides crucial scientific evidence for improving outcomes in critically ill patients.