Acute kidney disease (AKD) is increasingly recognized as a state that requires medical attention to avoid adverse outcomes. AKD reflects nonrecovery from acute kidney injury (AKI) persisting for 7-90 days or enduring subclinical alterations in kidney function without an AKI diagnosis, according to the Acute Disease Quality Initiative (ADQI). Recent studies on patients hospitalized with heart failure, cirrhosis, and critical illness find that AKD often leads to major adverse kidney events (MAKEs) and death.

Heart Failure

In Kidney International Reports, investigators reported outcomes from 7519 patients admitted for acute decompensated heart failure (ADHF), of whom AKI and AKD occurred in 9% and 21.2%, respectively. Within the AKI group, 39.4% of patients progressed to AKD as defined by ADQI criteria. In the group without prior AKI, AKD developed in 19.4% of patients.

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AKD was significantly associated with 32%, 30%, and 20% increased risks for all-cause death, MAKEs, and heart failure hospitalization, respectively, during 5 years of follow-up, corresponding author Chih-Hsiang Chang, MD, of Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taipei, Taiwan, and colleagues reported. MAKEs included end-stage kidney disease requiring long-term renal replacement therapy (RRT), new-onset chronic kidney disease (CKD), and death.

Dr Chang’s team developed prediction models that identified patients at high risk of any-stage AKD and stage 3 AKD or mortality, with AUROCs of 0.73 and 0.81, respectively. According to the investigators, it’s an easy-to-use tool that can effectively predict the risk of AKD after ADHF and aid in early AKD diagnosis and intervention. The scoring system requires additional validation.

“Our scoring system is an easy-to-use tool that can effectively predict the risk of AKD after ADHF and thus aid in early AKD diagnosis and intervention,” the authors wrote.

Identified risk factors for any AKD included female sex, AKI, AKI severity, diabetes, CKD, laboratory values including creatinine, hemoglobin, albumin, and B-type natriuretic peptide, and cumulative dosage of inotropes and intravenous loop diuretics. Age, blood urea nitrogen, and outpatient loop diuretic prescription were additional predictors for stage 3 AKD (defined as a serum creatinine level 3.0 times baseline, an absolute serum creatinine increase of 4.0 mg/dL or more, or RRT after 7 days and within 90 days). 

“Until evidence-based quality metrics are established, we should stick with a repertoire of common sense strategies for high-risk patients after ADHF: careful volume status and laboratory assessments, vigilant medication reconciliation, dietary counseling, careful titration of heart failure medications, and removal of aggravating (true) nephrotoxic factors,” Dr Chang and colleagues wrote. “Nephrologists should also assume an expert role in managing potential metabolic derangements from heart failure therapies (e.g., hyper/hypokalemia and dysnatremias), along with offering reassurance to patients and team members when small changes in [serum creatinine] are detected after therapy titrations.”


In the Journal of Hepatology, another team of investigators reported that AKD (also defined by ADQI criteria) developed in 32% of 6250 patients hospitalized with cirrhosis who had AKI. The risk for mortality at both 90 and 180 days was a significant 1.4-fold higher for patients with vs without AKD.

“Importantly, patients with AKD (and AKD non-recovery) are at a significantly higher risk for short- and longer-term mortality compared to patients without AKD…” Kavish R. Patidar, DO, of Indiana University School of Medicine, Indianapolis, Indiana, and colleagues wrote. “In addition, AKD remained significantly associated with mortality after adjusting for [model for end-stage liver disease sodium] and AKI stage, suggesting that the effect is independent of underlying liver disease severity and AKI severity.”

De novo CKD occurred in a significantly higher proportion of the AKD vs no AKD group: 64.0% vs 30.7%. The investigators found that AKD was independently associated with a 2.5-fold increased risk for de-novo CKD.

Dr Patidar’s team identified several independent risk factors for AKD. AKI stage 2 or 3 and community-acquired AKI were significantly associated with 9.4- and 1.6-fold increased odds for AKD, respectively. Pre-existing CKD and elevated serum albumin at the time of AKI were significantly associated with 3.1- and 1.4-fold increased odds of AKD, respectively. For every 1 mm Hg decrease in mean arterial pressure at the time of AKI, the odds of AKD significantly increased 1%. Ascites and obesity were significantly associated with 1.6- and 1.5-fold increased odds of AKD. Etiology of cirrhosis, presence of diabetes or hypertension, and vasopressor use within 7 days of AKI onset were not associated with AKD.

For cirrhosis patients with AKI, the investigators urged early nephrology consultation with follow-up and frequent lab monitoring and medication adjustments based on kidney function during and after hospitalization to help prevent AKD.

Critical Illness

In eClinicalMedicine, a product of The Lancet Discovery Science, researchers examined MAKEs and mortality outcomes among 5334 patients in intensive care (ICU), of whom 1620 (30.4%) had de novo AKI. AKD—defined as AKI persisting for longer than 7 days— occurred in 403 patients (24.9%).

Mark Andonovic, MD, of the University of Glasgow, Glasgow, UK, and colleagues observed significantly higher mortality rates in the ICU (16.1% vs 6.2%) and in the hospital (26.1% vs 11.6%) among patients with AKD compared with AKI that recovered. Long-term survival did not differ significantly between groups.

MAKEs occurred in a significantly higher proportion of the AKD group (54.2%) than the AKI group (41.9%). By component, a decline in estimated glomerular filtration rate (eGFR) of more than 30% from baseline (50.4% vs 41.9%), a doubling in serum creatinine (26.4% vs 18.8%), and initiation of long-term RRT (2.8% vs 0.6%) occurred in significantly more of the AKD group. AKD was significantly associated with 1.3-fold increased odds for MAKEs, the investigators found.

With respect to AKD risk factors, baseline eGFR of 30-60 or less than 30 mL/min/1.73 m2 was significantly associated with 1.4- and 2.0-fold increased odds for progression to AKD, respectively, the investigators reported. Male sex and admission due to sepsis were significantly associated with 1.3- and 1.4-fold increased odds for AKD, respectively.

“Further research is needed into this novel area to explore this potential association in long-term survival and whether AKD patients should be targeted for long-term nephrology follow up, given the strong association with future MAKEs,” Dr Andonovic’s team concluded.

Risk-stratification tools to predict AKD and its clinical course are needed to improve management and to test interventions.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of authors’ disclosures.


Chawla LS, Bellomo R, Bihorac A, et al; on behalf of the Acute Disease Quality Initiative Workgroup 16. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol 13:241–257.

KDIGO clinical practice guideline for acute kidney injury. March 2012. Accessed March 2, 2022.

Chen JJ, Lee TH, Kuo G, et al. Acute kidney disease after acute decompensated heart failure. Kidney Int Rep. Published online January 3, 2022. doi:10.1016/j.ekir.2021.12.033

Kwong YD, Liu KD, Hsu RK. Kidney dysfunction after acute heart failure: Is acute kidney disease the new acute kidney injury? Kidney Int Rep. Published online January 3, 2022. doi:10.1016/j.ekir.2021.12.034

Patidar KR, Naved MA, Grama A, et al. Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury. J Hepatol. Published online February 22, 2022. doi:10.1016/j.jhep.2022.02.009

Andonovica M, Traynorb JP, Shawa M, Simac MAB, Mark PB, Puxtyae KA. Short- and long-term outcomes of intensive care patients with acute kidney disease. eClinicalMedicine. Published online February 11, 2022. doi:0.1016/j.jhep.2022.02.009