Causal relationship between hypoalbuminemia and acute kidney injury

  • Wiedermann CJ, Wiedermann W, Joannidis M.
  • World J Nephrol. 2017 July 6;6(4):176–187.

This review article explores the relationship between low albumin levels and acute kidney injury (AKI). It reviews 43 relevant studies in several settings. There is only one randomised trial, and most are retrospective. There is a clear association between low albumin levels and the likelihood of developing AKI – yet there is no hard evidence for causation. The authors remark that the randomised trial demonstrated reduced AKI incidence with albumin administration, but acknowledge that much more quality research is needed to define the relationship.

AKI is a rapid deterioration of renal function that occurs rapidly, over hours or days, it involves a rising serum creatinine and a decreasing urine output. It is an acute systemic disease, yet one that has potentially significant consequences for other organs. In the short-term, it is associated with fluid, electrolyte and acid/base abnormalities; featuring rising levels of uraemic toxins, cytokines and systemic inflammation. In the longer term, it is associated with myocardial infarction, chronic kidney disease (CKD), increased mortality, the need for renal replacement and potentially transplantation. It is a common disorder, one that may be provoked by infection, acute glomerular disease, underlying CKD, trauma and haemorrhage or a number of iatrogenic causes. Hypoalbuminaemia (defined in different settings as either ≤3.5 g/dL or <3.5–4.0 g/dL), is an established risk factor for increased morbidity and mortality, and was previously identified as a significant independent predictor of AKI and death following AKI by the authors of this report. The purpose of this review was to explore data that has come to light subsequently.

A literature search was performed on the PubMed database (September 2009–December 2016 inclusive), data were extracted on the clinical setting, population, study design and size, assessment of albumin levels, occurrence of AKI and mortality. They identified 43 research articles: 37 of which were retrospective, five were prospective observational studies and one was a randomised controlled trial.

Cardiac surgery and acute coronary interventions

AKI is a common complication following cardiac surgery, and carries morbidity, mortality and economic costs. This review identified eight studies in this setting comprising around 4,000 participants.

  • The only interventional study in the review was by Lee et al. with 220 patients; they found that the rate of post-operative AKI increased as post-operative serum albumin decreased. The interventional component of the study administered either albumin solution or saline intra-operatively; finding that the incidence of post-operative AKI was lower in patients given albumin (17.6% versus 31.7% with saline; p=0.031). Albumin administration also increased urine output during surgery (mean volume 550 ml versus 370 ml; p=0.006), although there were no significant differences in mortality, need for renal replacement therapy (RRT) or severe AKI.
  • An observational, retrospective review of data collected prospectively on 530 patients examined patients with normal renal function undergoing isolated coronary artery bypass graft (CABG) surgery, and sought to determine the effect of pre-operative albumin levels. The authors found that requirement for RRT and death within 30 days were more frequent in the group with pre-operative albumin <3.5 g/dL (p=0.018 and p=0.037, respectively). Several other observational studies in CABG have also identified pre-operative albumin levels as a risk factor for AKI. Although further research is needed to establish whether exogenous albumin administration counters this risk.
  • Another study (n=200) was carried out in the setting of left ventricular assist device implantation, finding that very low albumin levels increased the risk of AKI: <2 g/dL = 42.9% chance of developing AKI; 2.5–3.5 g/dL = 16.5% chance; >3.5 g/dL = 17.3% chance (p=0.05).
  • Two studies were explored in the context of acute coronary intervention; one prospective observational study (n=456) found no effect of albumin levels on clinical outcomes, while a separate retrospective study (n=890) found an inverse risk association between serum albumin and AKI incidence – suggesting that pre-intervention albumin level may be a useful risk stratification tool.

Infectious diseases

This review identified several studies covering infectious diseases:

  • In one prospective observational analysis in HIV positive patients (n=3540), low serum albumin was one variable significantly associated with death following AKI (mean albumin level at hospitalisation in patients who died 2.14 g/dL, mean level in survivors 3.20 g/dL; p<0.001).
  • In a study on AKI in malaria (n=915), hypoalbuminaemia was more common in malaria patients who developed AKI; AKI is a major contributory factor in morbidity and mortality. There was no causative link demonstrated.
  • Two retrospective trials explored scrub typhus infection and albumin levels, and found that a serum albumin of <3.0 g/dL was closely related to AKI occurrence and other adverse outcomes. Although no mortality difference was demonstrated in the first trial (n=246), the second (n=174) demonstrated an increased effect on mortality (mean albumin level in patients who died was 2.4 g/dL, mean albumin level in survivors was 2.9 g/dL; p<0.001).
  • Other studies included H1N1 pneumonia (n=22); positive correlation between hypoalbuminaemia and death (mean albumin level in deaths was 1.82 g/dL, mean level in survivors was 2.61 g/dL, p<0.01); and acute hepatitis A (n=391; OR 8.24 for death with albumin <3.0g/dL; 95% CI 2.53–26.86; p<0.0001).

Transplant surgery

Hypoalbuminaemia is common before and after transplantation – particularly in liver cirrhosis.

  • There was one prospective study (n=24) that found reduced pre-orthoptic liver transplant albumin was associated with AKI (p=0.02). They also noted that increased MELD score (model for end-stage liver disease) was associated with AKI, and suggested that albumin may be a component of the linkage mechanism of hepatorenal syndrome.
  • A larger, albeit retrospective, propensity matching study on 998 living donor liver transplant patients found that albumin levels of <3 g/dL within 48 hours of the operation was an independent risk factor for AKI (OR 0.42; 95% CI 0.28–0.64; p<0.001).
  • One study showed that hypoalbuminaemia in the 6 months prior to renal transplant is associated with increased 12-month mortality (n=2763; HR 1.71; 95% CI 1.18–2.49; p<0.001). Other studies have explored the relationship between serum albumin and the likelihood of graft failure – finding that the relative risk of failure was lowest in the group with the highest albumin levels pre-operatively.

Cancer

An association between hypoalbuminaemia and AKI-related morbidity and mortality has also been noted.

  • One prospective study (n=591) reviewed patients undergoing transarterial chemoembolisation (TACE). They noted that lower albumin was more common in hepatocellular carcinoma patients with ascites, and that hypoalbuminaemia occurred more often in ascetic patients who did develop AKI after TACE. They noted following a logistic regression analysis that hypoalbuminaemia was the only independent risk factor predictive for AKI.
  • A retrospective analysis of AKI (n=4718) following partial or total gastrectomy found that hypoalbuminaemia (alongside other factors) was a risk factor for postoperative AKI. Several smaller studies also demonstrated a similar effect.

Other

There were 15 other studies that explored albumin and AKI in other settings. The largest (n=37,142) noted that in total knee replacement, mortality was higher in patients with low serum albumin (OR 3.17; 95% CI 1.56–6.35; p=0.001) as was risk of AKI (OR 5.19; 95% CI 1.96–13.37; p=0.001).

This review article goes through the recent evidence on AKI and albumin. The only study that clearly demonstrates something new is the RCT – suggesting a potential benefit for albumin administration in the cardiac surgery setting, albeit from a relatively small-scale study. Hypoalbuminaemia is potentially reflective of many disease states, from reduced liver function through to malnutrition or severe infection, and AKI may result from many of these same processes. It is possible that albumin is the common factor, however, despite a clear association between the two, much careful research is needed to define causation.

Explore the Fluid Management Knowledge Centre to discover more about the role of fluid therapy in cardiac surgery, critically ill patients, liver cirrhosis, and more.

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