Iron metabolism-related indicators as predictors of the incidence of acute kidney injury after cardiac surgery: a meta-analysis

Figures & data

Table 1. The detail NOS score of studies included.

Study	Selection				Comparability Control for important factor	Exposure			Scores
	Adequate definition of cases	Represent-ativeness of the cases	Selection of controls	Definition of controls		Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-responserate
Davis, CL 1999 [22]	★	★		★	★★	★	★	★	8
Tuttle, KR  2003 [21]	★	★		★	★★	★	★		7
Haase-Fielitz, A 2011 [24]	★	★		★	★	★	★	★	7
Ho, J 2011 [27]	★	★		★	★★	★	★	★	8
Prowle, J.R 2012 [23]	★	★		★	★★	★	★	★	8
Haase-Fielitz, A 2013 [25]	★	★		★	★	★	★	★	7
Choi, N 2018 [26]	★	★		★	★★	★	★	★	8
Choi, N 2019 [16]	★	★		★	★★	★	★	★	8
Albert, C  2020 [15]	★	★		★	★★	★	★	★	8

★: points (★: 1 point; ★★: 2 points). 

Table 2. The basic information table of studies included.

Study	Country	Age AKI/ No-AKI	Male (%) AKI/ No-AKI	number of included patients	Iron metabolism related indexes	outcomes	patient types	study types	sample	Specimen sampling time	NOS score
Davis, CL 1999 [22]	United States of America	58.1 ± 12.3/ 61.6 ± 10.2	9 (75)/ 10 (55.6)	12/18	SF	AKI	Patients undergoing  cardiac surgery	Prospective study	Serum	Before surgery	8
Tuttle, KR  2003 [21]	United States of America	65 ± 11/ 65 ± 11	36 (70.6)/ 56 (81.2)	51/69	SF	AKI	Patients undergoing  cardiac surgery	Retrospective study	Serum	Before surgery	7
Haase-Fielitz, A 2011 [24]	Germany	74 (70-77)/ 67 (56-73)	7 (77.78)/ 60 (65.9)	9/91	Plasma hepcidin, uHEPC,uHEPC/urine creatinine, FE of HEPC	AKI	Patients undergoing  cardiac surgery	Prospective study	Plasma,  urine	Before CPB, six hours after the start of CPB, and twenty-four hours after CPB	7
Ho, J 2011 [27]	Canada	66 ± 8/ 63 ± 10	24 (85.7)/ 242 (78.1)	28/310	uHEPC,uHEPC/urine creatinine	AKI	Patients undergoing  cardiac surgery	Prospective study	Urine	At 24 h after CPB	8
Prowle, J.R 2012 [23]	Germany	72 (67-78)/ 70 (61-75)	17 (68)/ 48 (70.59)	25/68	Plasma hepcidin, uHEPC, uHEPC/urine creatinine, FE of HEPC	AKI	Patients undergoing  cardiac surgery	Prospective study	Plasma,  urine	Pre-operatively, on return to ICU(mean time of 4.50 h; 3.58-9.13 h after CPB),at 24 h after CPB	8
Haase-Fielitz, A 2013 [25]	Germany	74 (70-77)/ 67 (56-73)	7 (77.78)/ 60 (65.9)	9/91	uHEPC	AKI	Patients undergoing  cardiac surgery	Prospective study	Urine	Before CPB	7
Choi, N 2018 [26]	Canada	70 (64-75)/ 66 (59-71)	27 (66)/ 204 (77)	41/265	uHEPC, uHEPC/urine creatinine	AKI	Patients undergoing  cardiac surgery	Prospective study	Urine	At 24 h after CPB	8
Choi, N 2019 [16]	Canada	70 (63-75) /66 (60-7)	27 (68)/ 198 (76)	40/261	Serum iron SF, uHEP, TRF saturation	AKI	Patients undergoing  cardiac surgery	Prospective study	Serum, urine	At the start of CPB, postoperative day 1	8
Albert, C  2020 [15]	Germany	74 (70-74)/ 67 (56-73)	7 (77.78)/ 60 (65.9)	9/91	uHEPC	AKI	Patients undergoing  cardiac surgery	Prospective study	Urine	6 hours after the commencement of CPB	8

Continuous variables with are presented as mean ± standard deviation or medians (interquartile range), for categorical variables number (percentages) are shown. SF: Serum ferritin; TRF: saturation; transferrin saturation; uHEPC: Urine hepcidin; FE of HEPC: fractional excretion of hepcidin; ICU: intensive care unit; CPB: cardio-pulmonary bypass.

Figure 1. Flowchart of study selection.

Figure 2. Forest plot of the incidence of acute kidney injury after cardiac surgery and serum ferritin. Forest plot revealing that patients who developed AKI after cardiac surgery had lower baseline serum ferritin levels than those who did not develop AKI (p = 0.010). 95% CI, 95% confidence interval.

Figure 3. Forest plot of the incidence of acute kidney injury after cardiac surgery and plasma hepcidin. Forest plot indicating no significant difference in plasma hepcidin levels between patients undergoing cardiac surgery who developed AKI and those who did not (p = 0.416; p = 0.539). 95% CI, 95% confidence interval.

Figure 4. Forest plot of the incidence of acute kidney injury after cardiac surgery and urinary hepcidin. Forest plot showing that after cardiac surgery, the level of 24-h postoperative urinary hepcidin in patients who developed AKI was lower than that in patients who did not develop AKI (p = 0.000); however, preoperative and 6-h postoperative urinary hepcidin levels were not significantly different between patients who developed AKI and those who did not develop AKI (p = 0.254; p = 0.542). 95% CI, 95% confidence interval.

Figure 5. Forest plot of the incidence of acute kidney injury after cardiac surgery and urinary hepcidin/urine creatinine ratio. Forest plot indicating that patients who developed AKI after cardiac surgery had a lower 24-h postoperative urinary hepcidin/urine creatinine ratio than those who did not develop AKI after cardiac surgery (p = 0.000); however, there was no significant difference in the 6-h postoperative urinary hepcidin/urine creatinine ratio between patients who developed AKI and those who did not develop AKI (p = 0.377). 95% CI, 95% confidence interval.

Figure 6. Forest plot of the incidence of acute kidney injury after cardiac surgery and urinary FE of hepcidin. Forest plot displaying that the levels of preoperative and 6-h postoperative urine FE of hepcidin (p = 0.038; p = 0.012) in patients who developed AKI after cardiac surgery were lower than those in patients who did not develop AKI after cardiac surgery; however, there was no significant difference in the levels of 24-h postoperative FE of hepcidin between patients who developed AKI after cardiac surgery and those who did not develop AKI after cardiac surgery (p = 0.726). 95% CI, 95% confidence interval.

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Choi N, Rigatto C, Zappitelli M, et al. Urinary hepcidin-25 is elevated in patients that avoid acute kidney injury following cardiac surgery. Can J Kidney Health Dis. 2018;5:2054358117744224.

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Choi N, Whitlock R, Klassen J, et al. Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery. J Thorac Cardiovasc Surg. 2019;157(1):287–297.e282.

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Albert C, Haase M, Albert A, et al. Urinary biomarkers may complement the cleveland score for prediction of adverse kidney events after cardiac surgery: a pilot study. Ann Lab Med. 2020;40(2):131–141.

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Data availability statement

All data analyzed during this study are available in the public domain.