Fermented Ophiocordyceps sinensis mycelium products for preventing contrast-associated acute kidney injury: a systematic review of randomized controlled trials

Figures & data

Figure 1. PRISMA flowchart of literature screening and selection.

Table 1. Basic information of the included studies.

Study ID	Country	Contrast agent	Dose of contrast agent (mL)	N (T/C)	Mean age (SD)	Comparison	Treatment		Control				Maximum follow-up time	Outcomes
							Drug	Patterns of drug intake	Course of treatment	Drug	Patterns of drug intake	Course of treatment
Xu [49]	China	Low-osmolar nonionic contrast media	–	T: 30; C: 10	T: 47.57 ± 13.22; C: 48.60 ± 10.77	FOSM + control group vs. control group	Bailing capsule (1 g, tid)	Oral	7 d before till 7 d after injection of the contrast	Half-isotonic saline (1 mg/kg/h)	Injection	12 h before till 12 h after injection of the contrast	7 d	②④
Liao et al. [45]	China	–	–	T: 20; C: 20	T: 70.4 ± 5.4; C: 69.6 ± 6.1	FOSM vs. blank control	Jinshuibao capsule (1 g, tid)	Oral	7 d following the contrast injection	–	–	–	7 d	④⑤
Zhao et al. [39]	China	Low-osmolar nonionic contrast media	C: 248.9 ± 48.7; T: 246.8 ± 49.7	T: 52; C: 51	T: 62.58 ± 3.71; C: 63.9 ± 4.3	FOSM + control group vs. control group	Bailing capsule (3 g, tid)	Oral	3 d before till 3 d after injection of the contrast	Normal saline (1 mL/kg/h)	Injection	6 h before till 12 h after injection of the contrast	3 d	①④⑥⑦
Zhao et al. [40]	China	Iso-osmolar nonionic contrast media (iodixanol: 320 mg/mL)	C: 246.87 ± 49.76; Ts: 248.86 ± 48.68; Ti: 250.85 ± 50.73	Ts: 49; Ti: 50; C: 51	Ts: 63.95 ± 4.27; Ti: 65.13 ± 6.26; C: 64.59 ± 5.72	FOSM + control group vs. control group	Ts: Bailing capsule (2 g, tid); Ti: Bailing capsule (3 g, tid)	Oral	3 d before till 3 d after injection of the contrast	Half-isotonic saline (1 mg/kg/h)	Injection	12 h before till 12 h after injection of the contrast	3 d	①②③④⑥⑦⑧⑨
Shi [46]	China	Iodinated contrast	C: 107.2; T: 110.4	T: 40; C: 40	T: 65.1 ± 9.5; C: 66.2 ± 9.1	FOSM + control group vs. control group	Jinshuibao capsule (1 g, tid)	Oral	7 d following the contrast injection	Normal saline (1 mL/kg/h)	Injection	12 h before till 12 h after injection of the contrast	7 d	④⑤
Zhang et al. [50]	China	Iso-osmolar nonionic contrast media (iodixanol)	–	T: 30; C: 30	–	FOSM + control group vs. control group	Jinshuibao capsule (1 g, tid)	Oral	3 d before till 5 d after injection of the contrast	Normal saline (1 mL/kg/h)	Injection	2 h before till 12 h after contrast	2 d	③④⑤⑧⑨
Zhao et al. [38]	China	Low-osmolar nonionic contrast media (iopamidol)	C: 246.85 ± 49.74; Ts: 248.87 ± 48.69; Ti: 250.87 ± 50.72	Ts: 39; Ti: 40; C: 41	Ts: 63.94 ± 4.26; Ti: 65.12 ± 6.27; C: 64.58 ± 5.71	FOSM + control group vs. control group	Ts: Bailing capsule (2 g, tid); Ti: Bailing capsule (3 g, tid)	Oral	3 d before till 3 d after injection of the contrast	Normal saline (1 mL/kg/h)	Injection	6 h before till 12 h after injection of the contrast	3 d	①②③④⑥⑦⑧⑨
Liang et al. [44]	China	Low-osmolar nonionic contrast media (iopromide: 370 mg/mL)	The dosage was calculated according to the patient’s body mass index. The injection speed is 5–7 mL/min.	T: 40; C: 40	T: 62.5 ± 4.6; C: 64.5 ± 3.8	FOSM vs. control group	Jinshuibao capsule (1 g, tid)	Oral	2 d before till 3 d after injection of the contrast	Normal saline (350 mL)	Oral	30 min following the contrast injection	3 d	①
Cao et al. [41]	China	Low-osmolar nonionic contrast media (iohexol)	The dosage was calculated according to the patient’s body mass index. The injection speed is 5–6 mL/min.	T: 30; C: 30	–	FOSM + control group vs. control group	Jinshuibao capsule (1 g, tid)	Oral	2 d before till 3 d after injection of the contrast	Normal saline (1 mL/kg/h)	Injection	2 h before till 12 h after injection of the contrast	2 d	①③④⑤⑧⑨
Wang et al. [48]	China	Low-osmolar nonionic contrast media (iohexol)	C: 115.6 ± 28.1; T: 118.2 ± 23.2	T: 50; C: 50	T: 61.2 ± 10.5; C: 62.3 ± 9.3	FOSM + control group vs. control group	Jinshuibao capsule (1 g, tid)	Oral	1 d before till 4 d after injection of the contrast	Shenkang injection (40 mL, qd) + 5% glucose liquid (250 mL, qd)	Injection	1 d before till 4 d after injection of the contrast	3 d	①②③④⑤⑧
Song [47]	China	Iso-osmolar nonionic contrast media (iopromide)	C: 145.06 ± 10.38; T: 144.26 ± 10.21	T: 100; C: 100	T: 65.25 ± 12.34; C: 64.87 ± 12.51	FOSM + control group vs. control group	Jinshuibao capsule (1 g, tid)	Oral	12 h before till 4 d after injection of the contrast	Alprostadil (100–200 μg, qd)	Injection	12 h before till 4 d after injection of the contrast	4 d	①②③④⑤⑧⑨
Dong and Mao [42]	China	Low-osmolar nonionic contrast media (iohexol: 300 mg/mL)	C: 127.01 ± 14.84; T: 125.11 ± 13.08	T: 40; C: 40	T: 56.03 ± 5.17; C: 55.85 ± 4.83	FOSM + control group vs. control group	Bailing capsule (3 g, tid)	Oral	3 d before till 7 d after injection of the contrast	Alprostadil (10 μg, qd) + normal saline (100 mL, qd)	Injection	3 d before till 7 d after injection of the contrast	7 d	①②③④⑤⑧⑨
Li et al. [43]	China	Low-osmolar nonionic contrast media (iohexol: 300 mg/mL)	C: 127.01 ± 15.22; T: 127.11 ± 15.41	T: 51; C: 51	T: 61.03 ± 8.17; C: 60.91 ± 7.83	FOSM + control group vs. control group	Bailing capsule (3 g, tid)	Oral	1 d before till 3 d after injection of the contrast	Alprostadil (10 μg, qd) + normal saline (100 mL, qd)	Injection	1 d before till 3 d after injection of the contrast	3 d	①②③④⑤⑧⑨
Zhou [51]	China	Low-osmolar nonionic contrast media (iohexol: 350 mg/mL)	C: 100; T: 100	T: 27; C: 29	T: 65.56 ± 16.84; C: 71.45 ± 10.63	FOSM + control group vs. control group	Zhiling mycelium capsule (1 g, tid)	Oral	3 d before till 3 d after injection of the contrast	Baoshen tablet (9.68 g, tid)	Oral	3 d before till 3 d after injection of the contrast	1 m	①②③④⑤⑧⑨

T: trial group; C: control group; SD: standard deviation; FOSM: fermented O. sinensis mycelia; Ts: standard dosage of FOSM product; Ti: intensive dosage of FOSM product; ① the incidence of CA-AKI; ② eGFR (estimated glomerular filtration rate) level; ③ need for dialysis; ④ serum creatinine level; ⑤ blood urea nitrogen level; ⑥ interleukin 18 level; ⑦ kidney injury molecule-1 level; ⑧ adverse events; ⑨ other indicators.

Figure 2. Risk of bias of the included trials. (A) Risk of bias summary; (B) risk of bias graph.

Figure 3. Forest plot of incidence of contrast-associated acute kidney injury (A), serum creatinine level (B), and epidermal growth factor receptor level (C) for Fermented O. sinensis mycelia products plus routine preventive procedure versus routine preventive procedure.

Table 2. Subgroup analysis on the incidence of CA-AKI.

Subgroups	Number of trials	RD/MD	95% CI	p Value	Heterogeneity among trials
Incidence of CA-AKI
Type of FOSM products
BL	5	−0.06	−0.09 to −0.02	p = .001	p = .784; I^2 = 0.0%
ZL	1	−0.07	−0.21 to 0.07	p = .352	–
JSB	5	−0.07	−0.11 to −0.02	p = .007	p = .517; I^2 = 0.0%
The moment of intervention
Before injection of the contrast	10	−0.06	−0.09 to −0.03	p = .000	p = .672; I^2 = 0.0%
After injection of the contrast	1	−0.02	−0.10 to 0.06	p = .569	–

RD: risk difference; MD: mean difference; CI: confidence intervals; FOSM: fermented O. sinensis mycelia; BL: Bailing capsule; ZL: Zhiling capsule; JSB: Jinshuibao capsule; CA-AKI: contrast-associated acute kidney injury; Scr: serum creatinine.

Table 3. Adverse events reported in included studies.

Types of adverse events	Total events/total number		Risk ratio (95% CI)	p Value
	Intervention	Control
Acute heart failure	4/506	4/422	0.84 [0.21, 3.32]	.798
Death	2/506	4/422	0.42 [0.06, 2.28]	.314
Recurrent angina pectoris	3/506	7/422	0.36 [0.09, 1.39]	.138
Recurrent myocardial infarction	1/506	2/422	0.42 [0.04, 4.60]	.476
In total	10/506	17/422	0.50 [0.23, 1.08]	.078

CI: confidence intervals.

Figure 4. Publication bias of the included trials on the incidence of contrast-associated acute kidney injury.

Table 4. Evidence summary of CA-AKI: FOSM products + RPP versus RPP.

Certainty assessment							No. of patients		Effect		Certainty	Importance
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Treatment	Control	Relative (95% CI)	Absolute (95% CI)
Incidence of CA-AKI
11	Randomized controlled trial	Serious^a	Not serious	Serious^c	Not serious	Undetected	598	513	–	RD 0.06 lower (0.09 lower to 0.03 lower)	⨁⨁◯◯ Low certainty	Critical
Scr level
12	Randomized controlled trial	Serious^a	Serious^b	Serious^c	Not serious	Undetected	628	523	–	MD 10.19 μmol/L lower (17.05 lower to 3.33 lower)	⨁◯◯◯ Very low certainty	Important
eGFR level
8	Randomized controlled trial	Serious^a	Serious^b	Serious^c	Not serious	Undetected	476	372	–	MD 4.10 mL/min-1.73 m^2 higher (2.24 higher to 5.96 higher)	⨁◯◯◯ Very low certainty	Important

CA-AKI: contrast-associated acute kidney injury; FOSM: fermented Ophiocordyceps sinensis mycelia; RPP: routine preventive procedure; no.: number; RD: risk difference; MD: mean difference; CI: confidence interval; Scr: serum creatinine; eGFR: estimated glomerular filtration rate.

^a Selection of the reported result bias was assessed as some concerns.

^b I² value was large.

^c Indirectness of FOSM products intervention time (before and after injection of the contrast).

^d A small number of events of less than 300.

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Data availability statement

The original data and material are available in this article/supplementary material and further enquiries can be directed to the authors.