Department of Biochemistry, Institute of Health Sciences, Istanbul University, Istanbul, Turkey.
Department of Urology, Division of Pediatric Urology, Istanbul Faculty of Medicine, Istanbul University, Çapa-Fatih, 34093, Istanbul, Turkey.
Int Urol Nephrol. 2024 Aug;56(8):2459-2466. doi: 10.1007/s11255-024-04008-6. Epub 2024 Mar 18.
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.
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.
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.
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.
本研究旨在探讨单侧产前肾积水患儿的尿半胱天冬酶-3 和细胞色素 c 水平，并确定尿生物标志物水平的变化是否可用于预测因肾盂输尿管连接部梗阻（UPJO）而需要手术干预的可能性，以及术后手术的成功与否。
本前瞻性病例对照研究纳入了 2013 年 1 月至 2021 年 12 月期间单侧产前肾积水且产后前后径≥10mm 的 65 例患儿。梗阻组由 33 例（28 名男孩，84.8%）因 UPJO 行开放离断式肾盂成形术的患儿组成。非梗阻性扩张（NOD）组由 32 例（27 名男孩，84.4%）患儿组成，这些患儿在随访期间肾积水稳定或改善，且对侧分肾功能无明显下降。34 名健康儿童作为对照组纳入研究。采用 ELISA 法检测尿胱天冬酶-3 和细胞色素 c 水平。
与 NOD 组（4.82ng/mgCr 比 2.61ng/mgCr，p=0.013）和对照组（4.82ng/mgCr 比 1.72ng/mgCr，p=0.002）相比，梗阻组术前尿胱天冬酶-3 水平明显更高。术后与术前相比，尿胱天冬酶-3 水平明显下降（4.82ng/mgCr 比 2.51ng/mgCr，p=0.006），且与对照组相似（2.51ng/mgCr 比 1.72ng/mgCr，p=0.422）。另一方面，各组间尿细胞色素 c 水平无显著差异。所有行肾盂成形术的患者术后肾积水均得到缓解，MAG-3 上引流改善，因此无患者需要再次行肾盂成形术。术后胱天冬酶-3 水平的降低与 MAG-3 扫描上的充分尿液引流相符。发现尿胱天冬酶-3 预测需要行肾盂成形术的截断值为 3.31ng/mg 肌酐，其敏感性为 63.6%，特异性为 62.5%（AUC=0.679）。在多变量分析中，尿胱天冬酶-3 水平（OR：1.653，p=0.019）、盆腔前后径（OR：1.401，p=0.001）和 MAG-3 上的分肾功能（OR：1.277，p=0.011）是决定患者是否需要手术的独立因素。
根据我们的初步发现，尿胱天冬酶-3 水平不仅可用于预测手术干预的必要性，还可用于确定 UPJO 患儿术后手术的成功与否。
