Causal relationship between hypoalbuminemia and acute kidney injury

Table 1 PubMed (MEDLINE) search strategy

1 Search: "acute kidney injury" OR AKI OR "acute renal failure" OR ARF

2 Search: mortality OR survival OR death

3 Search: "serum albumin" OR hypoalbuminemia* OR hypoalbuminaemia*

4 Filter: Publication date from 2009/09/01 to 2016/12/31

5 Search: #1 AND #2 AND #3 AND #4

The search was conducted without applying restrictions to language or publication type.

Table 2 Included studies on cardiac surgery and acute coronary interventions

Ref.	Population/setting	Study design	Overall study size	Albumin measurement	Hypoalbuminemia-related outcomes
					AKI/ARF	Mortality
Lee et al[13]	OPCAB surgery	Prospective RCT	220	Postoperative albumin 3.5-3.9 vs < 3.0 g/dL	Increased rate: 29.5% vs 41.7%. AKI rate lower with albumin vs control (13.7% vs 25.7%; P = 0.048)	ND
Grodin et al[20]	Acute heart failure	Prospective, observational	456	Admission albumin level (continuous and stratified by median ≥ 3.5 g/dL)	NS	NS
Moguel-González et al[16]	Cardiac surgery	Prospective, observational, longitudinal	164	Preoperative albumin < 4.0 g/dL	Increased risk: OR = 3.852 (95%CI: 1.101-13.473; P = 0.063)	ND
Lee et al[14]	OPCAB surgery	Retrospective, observational, propensity score matching	1182 (incl. 323 matched pairs)	Preoperative albumin < 4.0 g/dL	Increased risk: OR = 1.83 (95%CI: 1.27-2.64); P = 0.001; propensity analysis: OR = 1.62 (95%CI: 1.12-2.35); P = 0.011	ND
Murat et al[21]	ACS and PCI	Retrospective, observational	890	Albumin level at hospitalization	Low albumin (3.52 g/dL vs 3.94 g/dL) predictive of CI-AKI: OR = 0.177 (95%CI: 0.080-0.392; P < 0.001)	ND
Kim et al[17]	Thoracic aorta repair with CPB	Retrospective, observational, propensity score matching	702 (incl. 183 matched pairs)	Preoperative albumin < 4.0 g/dL	Increased risk: OR = 2.50 (95%CI: 1.39-4.50; P = 0.002)	ND
Findik et al[15]	CAB surgery	Retrospective, observational	530	Preoperative albumin < 3.5 g/dL	Increased rate: OR = 1.661 (95%CI: 1.037-2.661); P = 0.035	ND
Go et al[19]	LVAD implantation	Retrospective, observational	200	< 2.5 g/dL (low) vs 2.5-3.5 g/dL (mid-range) vs > 3.5 g/dL (normal)	Increased ARF: 42.9% vs 16.5% vs 17.3%; P = 0.05	NS

ACS: Acute coronary syndromes; AKI: Acute kidney injury; ARF: Acute renal failure; CI-AKI: Contrast-induced acute kidney injury; CPB: Cardiopulmonary bypass; LVAD: Left ventricular assist device; ND: Not disclosed; NS: Not significant; OPCAB: Off-pump coronary artery bypass; OR: Odds ratio; PCS: Percutaneous coronary intervention; RCT: Randomized, controlled trial.

Table 3 Included studies on infectious diseases

Ref.	Population/setting	Study design	Overall study size	Albumin measurement	Hypoalbuminemia-related outcomes
					AKI/ARF	Mortality
Prakash et al[22]	HIV	Prospective, observational	3540	Albumin level at hospitalization	ND	2.14 g/dL in patients who died vs 3.2 g/dL in survivors; P < 0.001
Vannaphan et al[34]	Severe falciparum malaria	Retrospective, observational	915	Albumin < 3.5 g/dL	Associated with ARF (P < 0.001)	ND
Lee et al[39]	Acute viral hepatitis A	Retrospective, observational	391	Albumin < 3.0 g/dL	OR = 8.24 (95%CI: 2.53-26.86; P < 0.0001)	ND
Lee et al[35]	Scrub typhus	Retrospective, observational	246	Admission albumin < 3.0 g/dL vs ≥ 3.0 g/dL	Increased rate of non-oliguric ARF (40.4% vs 11.1%; P < 0.001)	ND
Mehra et al[40]	Dengue fever	Retrospective, observational	223	Admission Albumin level	Lower albumin (2.65 g/dL) in patients with vs without AKI (3.09 g/dL; P < 0.001)	ND
Vikrant et al[36]	Scrub typhus	Retrospective, observational	174	Admission albumin level	ND	2.4 g/dL in patients who died vs 2.9 g/dL in survivors; P < 0.001
Ceylan et al[41]	Antibiotic therapy	Retrospective, observational	112	Albumin level at start of colistin therapy	Lower albumin (2.4 g/dL vs 2.7 g/dL) predicts colistin-induced AKI: OR = 0.643 (95%CI: 0.415-0.994; P = 0.047)	ND
Trimarchi et al[37]	H1N1 pneumonia	Retrospective, observational	22	Albumin level at study inclusion	NS	ARF in 10 of 12 deaths: 1.82 g/dL in patients who died vs 2.61 g/dL in survivors; P < 0.01

AKI: Acute kidney injury; ARF: Acute renal failure; ND: Not disclosed; OR: Odds ratio; NS: Not significant.

Table 4 Included studies on transplant surgery

Ref.	Population/setting	Study design	Overall study size	Albumin measurement	Hypoalbuminemia-related outcomes
					AKI/ARF	Mortality
Tinti et al[45]	Liver transplantation	Prospective, observational	24	Preoperative albumin level	Lower albumin (3.1 g/dL vs 3.7 g/dL) predictive of ARF (P = 0.02)	ND
Moore et al[48]	Renal transplantation	Retrospective, observational	2763	Albumin < 4.0 g/dL	Predictive of transplant failure: HR = 1.71 (95%CI: 1.18-2.49; P < 0.001)	ND
Sang et al[46]	LDLT	Retrospective, observational, propensity score matching	998 (incl. 249 matched pairs)	Albumin < 3.0 g/dL vs ≥ 3.0 g/dL before surgery	Albumin < 3.0 g/dL associated with increased AKI: OR = 0.42 (95%CI: 0.28-0.64; P < 0.001)	Survival rate lower with postoperative albumin < 3.0 g/dL (P = 0.02)
Park et al[47]	LDLT	Retrospective, observational	538	Preoperative albumin level	Albumin < 3.5 g/dL: OR = 1.76 (95%CI: 1.05-2.94; P = 0.032)	ND
Yang et al[49]	Renal transplantation	Retrospective, observational	375	Preoperative albumin < 3.5 g/dL vs 3.5-3.9 g/dL vs 4.0-4.4 g/dL vs ≥ 4.5 g/dL	Lowest risk of graft failure with ≥ 4.5 g/dL: HR = 0.536 (P = 0.029) vs < 3.5 g/dL	ND
Chen et al[44]	Liver transplantation	Retrospective, observational, matching	334 (incl. 118 matched pairs)	Preoperative albumin ≤ 3.5 g/dL	OR = 2.785 (95%CI: 1.427-5.434; P = 0.003); risk factor for posttransplantation AKI or ARF	ND

AKI: Acute kidney injury; ARF: Acute renal failure; HR: Hazard ratio; LDLT: Living donor liver transplantation; ND: Not disclosed; OR: Odds ratio.

Table 5 Included studies on cancer

Ref.	Population/setting	Study design	Overall study size	Albumin measurement	Hypoalbuminemia-related outcomes
					AKI/ARF	Mortality
Hsu et al[51]	HCC with ascites	Prospective, observational	591	Albumin < 3.3 g/dL	Independently associated with ARF: OR = 7.3 (95%CI: 1.47-35.7; P = 0.009)	ND
Kim et al[50]	Gastric cancer surgery	Retrospective, observational	4718	Preoperative albumin < 4.0 g/dL	Independent predictor of AKI: OR = 1.40 (95%CI: 1.11-1.77; P = 0.005)	ND
Mizuno et al[55]	Chemotherapy-induced hypotension	Retrospective, observational	972	Hypoalbuminemia defined as ≤ 3.5 g/dL	Associated with low BP: OR = 1.497 (95%CI: 1.070-2.095; P = 0.019). Low BP associated with AKI	ND
Lahoti et al[56]	AML or HR-MDS	Retrospective, observational	537	Albumin level at baseline (median 3.3 g/dL)	Hypoalbuminemia predictive of AKI: OR = 0.7 (95%CI: 0.5-0.99; P = 0.049)	ND
Haynes et al[57]	Multiple myeloma	Retrospective, observational	107	Albumin ≥ 3.5 g/dL vs < 3.5 g/dL	ND	Higher albumin predictive of survival: HR = 0.56 (95%CI: 0.35-0.91; P = 0.02)
Fischler et al[59]	Cancer	Retrospective, observational	103	Albumin level at start of CVVHDF	ND	Low albumin (median 2.5 g/dL vs 3.05 g/dL) associated with mortality: OR = 3.341 (95%CI: 1.229-9.077); P = 0.02

AKI: Acute kidney injury; AML: Acute myelogenous leukemia; ARF: Acute renal failure; BP: Blood pressure; CVVHDF: Continuous venovenous hemodiafiltration; HCC: Hepatocellular carcinoma; HR: Hazard ratio; HR-MDS: High-risk myelodysplastic syndrome; ND: Not disclosed; OR: Odds ratio.