Serum Cystatin C as a predictor of acute kidney injury in neonates: a meta-analysis

Yang, Hui; Lin, Chunlan; Zhuang, Chunyu; Chen, Jiacheng; Jia, Yanping; Shi, Huiling; Zhuang, Cong

doi:10.1016/j.jped.2021.08.005

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Sumário

REVIEW ARTICLE • J. Pediatr. (Rio J.) 98 (3) • May-Jun 2022 • https://doi.org/10.1016/j.jped.2021.08.005 copy

Serum Cystatin C as a predictor of acute kidney injury in neonates: a meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

The objective of this meta-analysis is to evaluate the diagnostic value of serum Cystatin C in acute kidney injury (AKI) in neonates

Sources:

PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang Database were searched to retrieve the literature related to the diagnostic value of Cystatin C for neonatal AKI from inception to May 10, 2021. Subsequently, the quality of included studies was determined using the QUADAS-2 tool. Stata 15.0 statistical software was used to calculate the combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Additionally, meta-regression analysis and subgroup analysis contributed to explore the sources of heterogeneity

Summary of the findings:

Twelve articles were included. The pooled sensitivity was 0.84 (95%CI: 0.74-0.91), the pooled specificity was 0.81 (95%CI: 0.75-0.86), the pooled PLR was 4.39 (95%CI: 3.23-5.97), the pooled NLR was 0.19 (95%CI: 0.11-0.34), and the DOR was 22.58 (95%CI: 10.44-48.83). The area under the receiver operating characteristic curve (AUC) was 0.88 (95%CI: 0.85-0.90). No significant publication bias was identified (p > 0.05).

KEYWORDS
Cystatin C (Cys-C); Neonates; Acute kidney injury (AKI); Diagnosis; Meta-analysis

First author	Year	Country	Gestational weeks	Detection time	Detection method	Case (control)	Cut-off value	Sensitivity	Specificity	TP	FP	FN	TN
Sarafidis¹⁶16. Sarafidis K, Tsepkentzi E, Agakidou E, Diamanti E, Taparkou A, Soubasi V, et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol. 2012;27:1575–82.	2012	Greece	≥ 36 W	24h	ELISA	8 (5)	2.87 mg/L	0.667	0.885	5	1	3	4
Elmas¹⁷17. Elmas AT, Tabel Y, Elmas ZNL. Serum cystatin C predicts acute kidney injury in preterm neonates with respiratory distress syndrome. Pediatr Nephrol. 2013;28:477–84.	2013	Turkey	Preterm neonates	72h	PENIA	6 (22)	1.62 mg/L	0.16	0.82	1	4	5	18
Treiber¹⁸18. Treiber M, Gorenjak M, Balon BP. Serum cystatin-C as a marker of acute kidney injury in the newborn after perinatal hypoxia/ asphyxia. Ther ApherDial. 2014;18:57–67.	2014	Slovenia	Full-term neonates	0h	PENIA	50 (50)	1.67 mg/L	0.84	0.9	42	5	8	45
Liu JX¹⁹19. Liu J, Wang H, Dai S, Liu H. Diagnostic value of serum cystatin c level on early renal impairment in newborns with asphyxia. Pract J Cardiac Cerebral Pneumal Vasc Dis. 2015;23:36–9.	2015	China	Full-term neonates	NA	LETIA	61 (26)	NR	0.9477	0.7667	54	7	3	23
Wang QX²⁰20. Wang Q, Chen Y, He J, Zheng X. Value of urinary Neutrophil Gelatinase Associated Lipocalin combined with serum Cystatin C on the early diagnosis of acute renal injury in newborns. Chin Gen Pract. 2015;18:4450–4.	2015	China	Preterm neonates	24h	NR	23 (233)	1.55 mg/L	0.82	0.87	19	31	4	202
Abdelaal²¹21. Abdelaal N, Shalaby S, Khashana A, Abdelwahab A. Serum cystatin C as an earlier predictor of acute kidney injury than serum creatinine in preterm neonates with respiratory distress syndrome. Saudi J Kidney Dis Transpl. 2017;28:1003–14.	2017	Egypt	Preterm neonates	72h	PENIA	24 (36)	1.28 mg/L	1	0.833	24	6	0	30
Qian L²²22. Qian L, Cheng R, Wang C, Chen Q, Zhang A. Clinical value of serum cystatin C in diagnosis of acute kidney injury associated with hyperbilirubinemia in full-term newborns. J Third Military Med Univ. 2018;40:165–8.	2018	China	Full-term neonates	1h	NR	46 (171)	2.17 mg/L	0.826	0.709	38	65	8	158
El-Gammacy²³23. El-Gammacy T, Shinkar D, Mohamed N, Al-Halag A. Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome. Scand J Clin Lab Invest. 2018;78:352–7.	2018	Egypt	Preterm neonates	72h	ELISA	13 (37)	1.3 mg/L	0.923	0.96	12	2	1	36
Zhang BB a²⁴24. Zhang B, Zhang F, Yin H, Gong Q, Xu J. Predictive value of serum cystatin C and retinol binding protein in neonatal acute kidney injury within 48 hours after birth. J Qiqihar Med Univ. 2019;40:665–9.	2019	China	Both	48h	NR	106 (152)	2.15 mg/L	0.968	0.717	103	43	3	109
Zhang BB b²⁴24. Zhang B, Zhang F, Yin H, Gong Q, Xu J. Predictive value of serum cystatin C and retinol binding protein in neonatal acute kidney injury within 48 hours after birth. J Qiqihar Med Univ. 2019;40:665–9.	2019	China	Full-term neonates	48h	NR	39 (58)	2.13 mg/L	0.754	0.833	29	10	10	48
Zhang BB c²⁴24. Zhang B, Zhang F, Yin H, Gong Q, Xu J. Predictive value of serum cystatin C and retinol binding protein in neonatal acute kidney injury within 48 hours after birth. J Qiqihar Med Univ. 2019;40:665–9.	2019	China	Preterm neonates	48h	NR	67 (94)	2.21 mg/L	0.817	0.715	55	27	12	67
Zhou R²⁵25. Zhou R, Sun M, Xu L. The correlation analysis of serum and urine neutrophil gelatinase associated lipocalin and cystatin in early clinical diagnosis of neonatal ischemic renal injury. Int J Urol Nephrol. 2020;40:282–5.	2020	China	Full-term neonates	24h	LETIA	70 (25)	1.6 mg/L	0.73	0.68	51	8	19	17
Zhang Y²⁶26. Zhang Y, Zhang B, Wang D, Shi W, Zheng A. Evaluation of novel biomarkers for early diagnosis of acute kidney injury in asphyxiated full-term newborns: a case-control study. Med Princ Pract. 2019;29:285–91.	2020	China	Full-term neonates	24h	LTIA	37 (73)	1.86 mg/L	0.615	0.693	23	22	15	51
Zheng BB²⁷27. Zheng B, Chen Q. The diagnostic value of serum cystatin C in acute renal injury of premature infants with respiratory distress syndrome. Chin J Woman Child Health Res. 2020;31: 603–8.	2020	China	Preterm neonates	72h	ELISA	10 (30)	1.33 mg/L	0.923	0.96	9	1	1	29

Parameter	Category	Number of studies	SEN	p value	SPE	p value	LRTchi	p value	I² (%)
Country	China	9	0.85 (95%CI:0.76-0.95)	0.73	0.77 (95%CI:0.72-0.83)	0.00	4.58	0.1	56 (95%CI:2-100)
	Other	5	0.81 (95%CI:0.64-0.99)		0.88 (95%CI:0.81-0.95)
Language	English	6	0.78 (95%CI:0.62-0.94)	0.07	0.84 (95%CI:0.77-0.92)	0.04	2.77	0.25	28 (95%CI:0-100)
	Chinese	8	0.88 (95%CI:0.79-0.96)		0.79(95%CI:0.72-0.85)
sample size	>96	7	0.84 (95%CI:0.72-0.95)	0.33	0.78 (95%CI:0.71-0.85)	0.00	1.71	0.43	0 (95%CI:0-100)
	<96	7	0.85 (95%CI:0.72-0.97)		0.85 (95%CI:0.78-0.92)
gestational weeks	Preterm neonates	7	0.89 (95%CI:0.80-0.98)	0.93	0.84 (95%CI:0.77-0.90)	0.04	2.75	0.25	27 (95%CI:0-100)
	Other	7	0.79 (95%CI:0.66-0.92)		0.77 (95%CI:0.69-0.85)
detection time	>24H	11	0.83 (95%CI:0.72-0.93)	0.72	0.81 (95%CI:0.75-0.87)	0.14	10.35	0.01	81 (95%CI:59-100)
	<24H	2	0.84 (95%CI:0.63-1.00)		0.80 (95%CI:0.67-0.94)
detection method	ELISA	3	0.86 (95%CI:0.65-1.00)	0.64	0.94 (95%CI:0.88-1)	0.56	77.69	0.00	97 (95%CI:96-99)
	Other	6	0.81 (95%CI:0.64-0.98)		0.79 (95%CI:0.72-0.85)
Cut-off value	>1.6	9	0.77 (95%CI:0.65-0.89)	0.02	0.75 (95%CI:0.69-0.80)	0.00	23.94	0.00	92 (95%CI:84-99)
	<1.6	4	0.93 (95%CI:0.85-1.00)		0.88 (95%CI:0.84-0.93)
Main cause	Asphyxiation	9	0.82 (95%CI:0.71-0.94)	0.18	0.84 (95%CI:0.77-0.90)	0.04	2.04	0.36	2 (95%CI:0-100)
	Other	5	0.87 (95%CI:0.75-0.98)		0.77 (95%CI:0.69-0.85)

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[1] 1
Hui Yang, Chunlan Lin contribute equally