Acute Kidney Injury after Cardiac Surgery Is Associated with Increased Iron Deficiency Anemia Risk

Introduction- An estimated 33% of acute kidney injuries (AKI) occur postoperatively. While studies have demonstrated that anemia is a predictor of AKI, few have looked at the inverse relationship or examined iron deficiency anemia (IDA). Further research is required to assess the impact of erythropoiesis-stimulating agents (ESAs) on anemia risk. Postoperative AKI is especially common among the 2 million patients undergoing cardiac surgery annually. We hypothesize that postoperative AKI may increase risk of red blood cell (RBC) transfusion, mortality, and other IDA-associated complications.

Methods- A US claims and electronic health record database (TriNetX Research Network) was queried from 2000-2023. Patients aged ≥18 years who underwent cardiac surgery (CPT 1006057) with cardiopulmonary bypass (ICD-10-PCS 5A1221Z) were eligible for inclusion. Exclusion criteria included diagnoses of acute kidney failure (ICD-10-CM N17), chronic kidney disease (N18), end stage renal disease (N18.6), renal dialysis (Z99.2), and hemoglobin ≤8 g/dL within 1-month preoperatively.

A propensity-matched cohort analysis was used to examine the relationship between 7-day postoperative AKI and 3-month, 6-month, and 12-month postoperative mortality, all cause anemia, iron deficiency anemia (D50), repeat cardiac surgery, RBC transfusion, acute myocardial infarction (MI) (I21), atrial fibrillation and flutter (I48), and recent hemoglobin (Hb) and hematocrit (Hct) levels within the outcome period.

Propensity score matching was performed for age, ethnicity, race, sex, preoperative diabetes mellitus (E08-E13), neoplasms (C00-D49), alcohol related disorders (F10), liver diseases (K70-K77), sepsis (A40-41), MI, cerebral infarction (I63), essential hypertension (I10), renal tubulo-interstitial diseases (N10-N16), acute and subacute endocarditis (I33), and preoperative hemoglobin level (9014) split into: 8-10 g/dL, 10-12 g/dL, and ≥12 g/dL.

A sub-analysis examined the effect of ESAs darbepoetin alfa (RxNorm 283838), epoetin alfa (105694), methyoxy polyethylene glycol-epoetin beta (729596), and peginesatide (1248798) on subsequent anemia risk, comparing cardiac surgery patients without 7-day postoperative AKI with cardiac surgery patients with 7-day postoperative AKI and ESA treatment within 3 months postoperatively.

Results- Of 114,777 patients undergoing cardiac surgery, 9,462 developed 7-day postoperative AKI while 105,315 did not. After matching, each cohort had 9,423 patients. At 3 months after surgery, 7-day postoperative AKI was associated with increased mortality (11.80% vs. 2.73%, risk ratio (RR) 4.33, 95% confidence interval [3.79-4.94]), all cause anemia (26.70% vs. 15.90%, RR 1.68 [1.59-1.78]), IDA (6.01% vs. 3.88%, RR 1.55 [1.36-1.76]), RBC transfusion (18.44% vs. 10.25%, RR 1.80 [1.67-1.94]), repeat cardiac surgery (17.37% vs. 9.07%, RR 1.92 [1.77-2.07]), acute MI (15.30% vs. 9.22%, RR 1.66 [1.53-1.80], atrial fibrillation or atrial flutter (43.98% vs. 30.36%, RR 1.45 [1.39-1.51]), and lower Hb (9.9 vs. 10.4 g/dL, adj. P=0.0001) and Hct (30.7 vs. 32.1, adj. P=0.0001). These trends persisted in the 6- and 12-month analyses.

In the ESA sub-analysis, 474 patients had 7-day postoperative AKI and received ESAs within 3-months postoperatively and 105,315 patients did not develop 7-day postoperative AKI. After matching, each cohort had 470 patients. At 12 months post-surgery, patients with ESAs and 7-day postoperative AKI still had increased risk of mortality (23.62% vs. 14.04%, RR 1.68 [1.28-2.22]), all cause anemia (52.34% vs. 41.28%, RR 1.27 [1.10-1.46]), and RBC transfusion (24.26% vs. 17.87%, RR 1.36 [1.06-1.75]). There was no difference in risk of IDA (16.81% vs. 17.45%, RR 0.96 [1.06-1.75]), acute MI (22.34% vs. 19.15%, RR 1.17 [0.91-1.50]), and atrial fibrillation or flutter (45.96% vs. 44.26%, RR 1.04 [0.90-1.20]). Patients treated with ESA had lower risk of repeat cardiac surgery (14.26% vs. 22.34%, RR 0.64 [0.48-0.84]).

Conclusions -Postoperative AKI was associated with increased risk of mortality, RBC transfusions, and IDA at all time points post-surgery. The increased 12-month risk of IDA and repeat cardiac surgery was mitigated with ESA treatment within 3 months with no increase in acute MI. Postoperative ESA use may protect against AKI-associated anemia without increased adverse events, representing an opportunity to improve health outcomes.

Hepner:Pharmacosmos: Consultancy, Research Funding; UpToDate: Consultancy, Patents & Royalties: Royalties for editorial work. Connors:Werfen: Honoraria; Perosphere: Honoraria; Bristol Myers Sqibb: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Anthos: Honoraria; Abbott: Honoraria.