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Can urinary caspase-3 and cytochrome c levels be used as predictive biomarkers in the management of unilateral antenatal hydronephrosis?

  • Urology - Original Paper
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Abstract

Purpose

We aimed to investigate the urinary caspase-3 and cytochrome c levels in patients with unilateral antenatal hydronephrosis and to determine whether changes in urinary biomarker levels could be useful for both predicting the need for surgical intervention due to ureteropelvic junction obstruction (UPJO) and postoperative surgical success.

Methods

Sixty-five children with a history of unilateral antenatal hydronephrosis and postnatal anteroposterior diameter ≥ 10 mm were included in this prospective case–control study between January 2013 and December 2021. The obstruction group consisted of 33 patients (28 boys, 84.8%) who underwent open dismembered pyeloplasty due to UPJO. The non-obstructive dilatation (NOD) group consisted of 32 patients (27 boys, 84.4%) with stable or improving hydronephrosis and no significant reduction in ipsilateral split renal function during follow-up, whereas 34 healthy children were enrolled in the study as a control group. Urinary urinary caspase-3 and cytochrome c levels using ELISA were measured.

Results

The median preoperative urinary caspase-3 level was significantly higher in the obstruction group when compared to the NOD group (4.82 ng/mgCr vs. 2.61 ng/mgCr, p = 0.013) as well as the control group (4.82 ng/mgCr vs. 1.72 ng/mgCr, p = 0.002). In the postoperative period, urinary caspase-3 levels significantly decreased compared to preoperative measurements (4.82 ng/mgCr vs. 2.51 ng/mgCr, p = 0.006) and became similar to the control group (2.51 ng/mgCr vs. 1.72 ng/mgCr, p = 0.422). On the other hand, no significant differences were observed in urinary cytochrome c levels between the groups. All patients who underwent pyeloplasty achieved postoperative resolution in hydronephrosis and improved drainage on MAG-3, so none of the patients required re-do pyeloplasty. Postoperative decrease in caspase-3 level was found to be compatible with adequate urine drainage on MAG-3 scan. The cut-off value of urinary caspase-3 to predict patients requiring pyeloplasty was found to be 3.31 ng/mg creatinine with 63.6% sensitivity, 62.5% specificity (AUC = 0.679). In the multivariable analysis, urinary caspase-3 level (OR: 1.653, p = 0.019), anteroposterior pelvic diameter (OR: 1.401, p = 0.001), and split renal function on MAG-3 (OR: 1.277, p = 0.011) were found to be independent factors in determining patients who require surgery.

Conclusion

Based on our preliminary findings, urinary caspase-3 levels could be a useful biomarker not only for predicting the need for surgical intervention but also for determining the postoperative surgical success in children with UPJO.

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Data availability

Data are available from the corresponding author on reasonable request.

Abbreviations

APD:

Anteroposterior pelvic diameter

AUC:

Area under curve

ELISA:

Enzyme-linked immunosorbent assay

HSP70:

Heat shock protein 70

IQR:

Interquartile range

max:

Maximum

min:

Minimum

NOD:

Non-obstructive dilatation

ROC:

Receiver operating characteristic

SFU:

The Society of Fetal Urology

SRF:

Split renal function

UPJO:

Ureteropelvic junction obstruction

VCUG:

Voiding cystourethrography

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Health Sciences, Istanbul University, Istanbul, Turkey

    Seyide Görkem Zeybek

  2. Department of Urology, Division of Pediatric Urology, Istanbul Faculty of Medicine, Istanbul University, Çapa-Fatih, 34093, Istanbul, Turkey

    İsmail Selvi, Tayfun Oktar, M. İrfan Dönmez & Orhan Ziylan

  3. Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Şule Seçkin & Canan Küçükgergin

Authors
  1. Seyide Görkem Zeybek
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  2. İsmail Selvi
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  3. Tayfun Oktar
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  4. M. İrfan Dönmez
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  5. Orhan Ziylan
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  6. Şule Seçkin
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  7. Canan Küçükgergin
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Contributions

Zeybek SG: Conception and design, Acquisition of data, Analysis and Interpretation of data, Statistical analysis, Literature Search. Selvi I: Analysis and Interpretation of data, Statistical analysis, Literature Search, Drafting of the manuscript. Oktar T: Conception and design, Administrative, Critical revision of the manuscript for important intellectual content, Supervision. Dönmez Mİ: Conception and design, Administrative, Critical revision of the manuscript for important intellectual content. Ziylan O: Administrative, Critical revision of the manuscript for important intellectual content, Supervision. Seçkin Ş: Administrative, Critical revision of the manuscript for important intellectual content, Supervision. Küçükgergin C: Conception and design, Acquisition of data, Technical or material support, Critical revision of the manuscript for important intellectual content, Supervision.

Corresponding author

Correspondence to İsmail Selvi.

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Conflict of interest

The authors declare no conflicts of interest and has nothing to disclose.

Funding

This study was supported by the Research Fund of Istanbul University (No. TYL-2021-37576).

Ethical approval

The study received Institutional Review Board approval (Ethical IRB number: 29624016-050.99- 1854). All procedures performed in our study were in accordance with the ethical standards of the local research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Zeybek, S.G., Selvi, İ., Oktar, T. et al. Can urinary caspase-3 and cytochrome c levels be used as predictive biomarkers in the management of unilateral antenatal hydronephrosis?. Int Urol Nephrol (2024). https://doi.org/10.1007/s11255-024-04008-6

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  • DOI: https://doi.org/10.1007/s11255-024-04008-6

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