International Urology and Nephrology

, Volume 49, Issue 2, pp 295–302 | Cite as

Hypoalbuminemia: a risk factor for acute kidney injury development and progression to chronic kidney disease in critically ill patients

  • Min Shao
  • Shengyu Wang
  • Praveen Kolumam Parameswaran
Nephrology - Original Paper



The increased likelihood of poor outcomes in critically ill patients with hypoalbuminemia is well recognized. However, hypoalbuminemia remains poorly defined as an independent predictor of acute kidney injury (AKI) and stage 4 chronic kidney diseases (CKD4). The aim of this study was to assess the role of hypoalbuminemia as an independent risk factor for AKI and CKD4 in critically ill patients.


A retrospective cohort study.


General intensive care unit (ICU) at Anhui Provincial Hospital, PR China.



Measurements and main results

We screened patients admitted to the ICU at Anhui Provincial Hospital between January 1, 2008, and October 31, 2011, and included those aged >18 years with available records of serum albumin (SA), baseline serum creatinine, and outcome data. The exclusion criteria were: (1) patients with known AKI and CKD stage 4, 5 before ICU admission; (2) patients lost to follow-up; and (3) patients without research authorization. A total of 588 patients with available data were enrolled in the study, and 62 patients with preexisting CKD stage 4 and CKD stage 5 and 115 with preexisting AKI were excluded. Thirty patients were lost to follow-up. Ultimately, 381 patients were analyzed, 233 (61.2%) of whom developed AKI. Patients with low SA were significantly more likely than those with normal SA (p = 0.0003) to develop AKI, and to progress from AKI to CKD4 (p = 0.0229). More patients in the AKI group than in the non-AKI group had risk factors such as hypotension, mechanical ventilation (MV), proteinuria, sepsis, nephrotoxin exposure, and high-risk surgery (p < 0.01). The difference in duration of MV, ICU days, ICU mortality, hospital days, and hospital mortality between the AKI and non-AKI groups was also significant (p < 0.01). Logistic regression showed that hypoalbuminemia was significantly associated with AKI and CKD4 [odds ratio (OR) 1.810, 95% confidence interval (CI) 1.102–2.992, and OR 2.494, 95% CI 1.231–5.295, respectively]. After 4 years of follow-up, Kaplan–Meier analysis showed that survival in hypoalbuminemia patients was significantly shorter than in patients with normal SA (p = 0.0393). In the Cox proportional hazard model, hypoalbuminemia was an independent predictor of long-term mortality (hazard ratio 1.5, 95% CI 1.042–2.183, p = 0.0291).


Hypoalbuminemia in critically ill patients is independently associated with an increased risk of development of AKI and AKI progressing to CKD4.


Acute kidney injury Chronic kidney disease (stage 4) Hypoalbuminemia Predictor Survival time Serum albumin 


Authors’ contributions

MS participated in the design and drafted the paper. SYW contributed equally with MS to the paper. PKP participated in critical review of the manuscript. MS played a principal role in the design, analysis, and preparation of the manuscript.


The present study was supported by the Natural Science Foundation of Anhui Province (grant no.1408085MH170) and the medical research projects of Anhui provincial health department (grant no.13zc024).

Compliance with ethical standards

Conflict of interest

There are no conflicts in our manuscript file.

Supplementary material

11255_2016_1453_MOESM1_ESM.doc (38 kb)
Supplementary material 1 (DOC 38 kb)


  1. 1.
    Uchino S, Kellum JA, Bellomo R et al (2005) Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294(7):813–818CrossRefPubMedGoogle Scholar
  2. 2.
    Waikar SS, Liu KD, Chertow GM (2008) Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol 3(3):844–861CrossRefPubMedGoogle Scholar
  3. 3.
    Bellomo R, Kellum JA, Ronco C (2012) Acute kidney injury. Lancet 380(9843):756–766CrossRefPubMedGoogle Scholar
  4. 4.
    Ali T, Khan I, Simpson W et al (2007) Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol 18(4):1292–1298CrossRefPubMedGoogle Scholar
  5. 5.
    Joannidis M, Metnitz B, Bauer P et al (2009) Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 35(10):1692–1702CrossRefPubMedGoogle Scholar
  6. 6.
    Metnitz PG, Krenn CG, Steltzer H et al (2002) Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med 30(9):2051–2058CrossRefPubMedGoogle Scholar
  7. 7.
    Joannidis M, Metnitz PG (2005) Epidemiology and natural history of acute renal failure in the ICU. Crit Care Clin 21(2):239–249CrossRefPubMedGoogle Scholar
  8. 8.
    Rothschild MA, Oratz M, Schreiber SS (1988) Serum albumin. Hepatology 8(2):385–401CrossRefPubMedGoogle Scholar
  9. 9.
    Herrmann FR, Safran C, Levkoff SE et al (1992) Serum albumin level on admission as a predictor of death, length of stay, and readmission. Arch Intern Med 152(1):125–130CrossRefPubMedGoogle Scholar
  10. 10.
    McCluskey A, Thomas AN, Bowles BJ et al (1996) The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit. Anaesthesia 51(8):724–727CrossRefPubMedGoogle Scholar
  11. 11.
    Margarson MP, Soni N (1998) Serum albumin: touchstone or totem? Anaesthesia 53(8):789–803CrossRefPubMedGoogle Scholar
  12. 12.
    Amdur RL, Chawla LS, Amodeo S et al (2009) Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis. Kidney Int 76(10):1089–1097CrossRefPubMedGoogle Scholar
  13. 13.
    Wald R, Quinn RR, Luo J et al (2009) Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA 302(11):1179–1185CrossRefPubMedGoogle Scholar
  14. 14.
    Mehta RL, Kellum JA, Shah SV et al (2007) Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11(2):R31CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kasiske BL, Wheeler DC (2014) Kidney disease: improving global outcomes—an update. Nephrol Dial Transpl 29(4):763–769CrossRefGoogle Scholar
  16. 16.
    Wiedermann CJ, Wiedermann W, Joannidis M (2010) Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies. Intensive Care Med 36(10):1657–1665CrossRefPubMedGoogle Scholar
  17. 17.
    Kheterpal S, Tremper KK, Heung M et al (2009) Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology 110(3):505–515CrossRefPubMedGoogle Scholar
  18. 18.
    Matheny ME, Miller RA, Ikizler TA et al (2010) Development of inpatient risk stratification models of acute kidney injury for use in electronic health records. Med Decis Making 30(6):639–650CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Basu RK, Zappitelli M, Brunner L et al (2014) Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int 85(3):659–667CrossRefPubMedGoogle Scholar
  20. 20.
    Cruz DN, Ferrer-Nadal A, Piccinni P et al (2014) Utilization of small changes in serum creatinine with clinical risk factors to assess the risk of AKI in critically lll adults. Clin J Am Soc Nephrol 9(4):663–672CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Contreras AM, Ramirez M, Cueva L et al (1994) Low serum albumin and the increased risk of amikacin nephrotoxicity. Rev Invest Clin 46(1):37–43PubMedGoogle Scholar
  22. 22.
    Levine JS, Koh JS, Triaca V et al (1997) Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells. Am J Physiol 273(4 Pt 2):F575–F585PubMedGoogle Scholar
  23. 23.
    Iglesias J, Abernethy VE, Wang Z et al (1999) Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS. Am J Physiol 277(5 Pt 2):F711–F722PubMedGoogle Scholar
  24. 24.
    Kaufmann MA, Castelli I, Pargger H et al (1995) Nitric oxide dose-response study in the isolated perfused rat kidney after inhibition of endothelium-derived relaxing factor synthesis: the role of serum albumin. J Pharmacol Exp Ther 273(2):855–862PubMedGoogle Scholar
  25. 25.
    Lee YJ, Han HJ (2008) Albumin-stimulated DNA synthesis is mediated by Ca2+/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-kappaB signal pathways in renal proximal tubule cells. Am J Physiol Renal Physiol 294(3):F534–F541CrossRefPubMedGoogle Scholar
  26. 26.
    Dixon R, Brunskill NJ (1999) Activation of mitogenic pathways by albumin in kidney proximal tubule epithelial cells: implications for the pathophysiology of proteinuric states. J Am Soc Nephrol 10(7):1487–1497PubMedGoogle Scholar
  27. 27.
    Gariballa SE, Parker SG, Taub N et al (1998) Influence of nutritional status on clinical outcome after acute stroke. Am J Clin Nutr 68(2):275–281PubMedGoogle Scholar
  28. 28.
    Knaus WA, Wagner DP, Draper EA et al (1991) The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100(6):1619–1636CrossRefPubMedGoogle Scholar
  29. 29.
    Caironi P, Tognoni G, Masson S et al (2014) Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 370(15):1412–1421CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Min Shao
    • 1
  • Shengyu Wang
    • 2
  • Praveen Kolumam Parameswaran
    • 3
  1. 1.Department of Critical Care MedicineAnhui Provincial Hospital Affiliated to Anhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Department of Pulmonary and Critical Care MedicineFirst Affiliated Hospital of Xi’an Medical UniversityXi’anPeople’s Republic of China
  3. 3.Department of Internal MedicineCoimbatore Medical College HospitalCoimbatoreIndia

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