Acute kidney injury after cardiac surgery remains one of the most important complications in perioperative cardiovascular care. Even small postoperative increases in serum creatinine can predict worse outcomes, and cardiac surgery–associated acute kidney injury is linked to longer hospital stays, greater resource use, and increased morbidity and mortality. Because cardiopulmonary bypass, hemodynamic instability, inflammation, hemodilution, and nephrotoxic exposures can all contribute to kidney injury, clinicians have long searched for fluid strategies that might protect renal function during and after surgery.
This systematic review and meta-analysis examined one specific and clinically relevant question: does hyperoncotic human albumin, usually given as 20%–25% albumin, influence the risk of acute kidney injury after adult on-pump cardiac surgery? Albumin is often used because it can expand plasma volume with less administered fluid than crystalloids. In theory, this could reduce tissue edema, support oncotic pressure, and improve hemodynamic stability. However, hyperoncotic albumin may also create renal stress by increasing intravascular oncotic pressure, lowering transglomerular filtration pressure, and exposing renal tubules to a concentrated protein load. These competing biological effects have made albumin use in cardiac surgery controversial.
The authors searched PubMed, Embase, and Cochrane CENTRAL for studies published from January 1, 1995, through July 17, 2025. Eligible studies included adult patients undergoing on-pump cardiac surgery, such as coronary artery bypass grafting, valve surgery, or aortic surgery with cardiopulmonary bypass. The intervention was 20%–25% human albumin administered either intraoperatively, such as during cardiopulmonary bypass priming or before separation from bypass, or postoperatively within 24 hours of surgery. Comparators included crystalloid-based strategies or iso-oncotic 4%–5% albumin. The primary outcome was any-stage acute kidney injury within seven days after surgery, using KDIGO criteria when available or comparable AKIN/RIFLE definitions.
Four studies met inclusion criteria, comprising 6,651 total patients. Two were randomized controlled trials and two were retrospective cohort studies. The randomized trials included 1,063 patients and evaluated postoperative 20% albumin compared with crystalloid-based or usual-care strategies. The two cohort studies focused on intraoperative albumin use, including one large propensity-matched Chinese study and one smaller Iranian historical cohort. Together, these studies provided a focused evidence base on whether higher-concentration albumin improves or worsens kidney outcomes in adult cardiac surgery.
The primary finding was clinically important: hyperoncotic albumin was associated with a statistically significant increase in postoperative acute kidney injury. In the pooled analysis, 20%–25% albumin increased AKI risk compared with crystalloids or 4%–5% albumin, with a risk ratio of 1.10 and a 95% confidence interval of 1.05–1.16. Heterogeneity was minimal, with an I² of 0%, meaning the direction of effect was consistent across the included studies. Although the increase in risk was modest, the consistency of the finding is notable because albumin is sometimes used with the expectation that it may be kidney protective.
When the authors restricted the analysis to randomized controlled trials, the result remained similar. The RCT-only estimate showed a risk ratio of 1.12, with a 95% confidence interval of 1.04–1.20. This supports the robustness of the main finding and reduces concern that the overall signal was driven only by observational confounding. The largest randomized trial, ALBICS-AKI, reported higher acute kidney injury rates in the albumin group, while the HAS FLAIR II secondary analysis showed a directionally similar but not statistically significant effect.
The timing of albumin administration did not appear to change the kidney risk. Intraoperative albumin was associated with a pooled risk ratio of 1.09, while postoperative albumin was associated with a pooled risk ratio of 1.12. The statistical test for interaction was not significant, suggesting that the increased AKI risk was not meaningfully different whether albumin was administered during surgery or shortly afterward in the ICU. This is important because it argues against the idea that simply changing the timing of hyperoncotic albumin can transform it into a renal-protective strategy.
The authors also examined acute kidney injury severity. Stage 1 AKI was increased with albumin, with an estimated risk ratio of approximately 1.11. This finding suggests that albumin did not merely fail to prevent minor creatinine changes; it was associated with more early kidney injury events. However, evidence regarding severe AKI, renal replacement therapy, and longer-term renal recovery was limited. These harder outcomes were inconsistently reported and too sparse for reliable meta-analysis. As a result, the study is strongest for any-stage AKI and less definitive for dialysis, severe AKI, or long-term kidney function.
Several limitations temper the findings. Only four studies were eligible, and only two were randomized controlled trials. The observational cohorts were subject to confounding by indication, since clinicians may preferentially give albumin to sicker patients, those with vasoplegia, capillary leak, hypotension, or greater perceived risk of renal hypoperfusion. Baseline kidney function, serum albumin concentration, cardiopulmonary bypass duration, operative complexity, and fluid co-interventions were not consistently reported across studies. These factors make it difficult to identify whether any specific subgroup might benefit from albumin, such as patients with severe hypoalbuminemia but preserved kidney function.
The trial sequential analysis also showed that randomized evidence has not yet reached the required information size. The authors estimated that approximately 1,914 randomized patients would be needed to detect a 20% relative change in acute kidney injury risk, while the available randomized evidence included 1,063 patients. The cumulative evidence approached but did not cross formal monitoring boundaries for harm, benefit, or futility. This means the signal of harm is credible but not absolutely conclusive, and larger multicenter randomized trials are still needed.
From a clinical perspective, the study supports a cautious approach to routine hyperoncotic albumin use in adult on-pump cardiac surgery. The evidence does not support 20%–25% albumin as a general strategy for preventing cardiac surgery–associated acute kidney injury. Instead, kidney-protective perioperative care should continue to focus on established principles: balanced crystalloid-based resuscitation, avoidance of nephrotoxins, careful hemodynamic optimization, prevention of venous congestion, and implementation of KDIGO-style AKI prevention bundles.
The findings do not mean albumin should never be used. Albumin may still have a role in selected patients, such as those with marked hypoalbuminemia, ongoing third spacing, or a need for smaller-volume plasma expansion when excessive crystalloid could worsen pulmonary edema or fluid overload. However, the study argues against routine or prophylactic use of hyperoncotic albumin simply to prevent kidney injury after cardiac surgery. Future trials should define albumin triggers, dosing strategies, baseline albumin levels, chronic kidney disease status, and patient-centered renal outcomes more clearly.
Overall, this meta-analysis adds important evidence to a practical perioperative question. Hyperoncotic albumin offers theoretical hemodynamic advantages, but in adult cardiac surgery, those advantages did not translate into reduced acute kidney injury. Instead, the available evidence suggests a small but consistent increase in AKI risk, independent of whether albumin is given intraoperatively or postoperatively. Until larger randomized trials clarify the balance of benefit and harm, routine perioperative administration of 20%–25% albumin should be approached with restraint.
