Non-invasive biomarkers of acute rejection in pediatric kidney transplantation: New targets and strategies.

Kidney transplantation is the preferred treatment for pediatric end-stage renal disease. However, pediatric recipients face unique challenges due to their prolonged need for kidney function to accommodate growth and development. The continual changes in the immune microenvironment during childhood development and the heightened risk of complications from long-term use of immunosuppressive drugs. The overwhelming majority of children may require more than one kidney transplant in their lifetime. Acute rejection (AR) stands as the primary cause of kidney transplant failure in children. While pathologic biopsy remains the "gold standard" for diagnosing renal rejection, its invasive nature raises concerns regarding potential functional impairment and the psychological impact on children due to repeated procedures. In this review, we outline the current research status of novel biomarkers associated with AR in urine and blood after pediatric kidney transplantation. These biomarkers exhibit superior diagnostic and prognostic performance compared to conventional ones, with the added advantages of being less invasive and highly reproducible for long-term graft monitoring. We also integrate the limitations of these novel biomarkers and propose a refined monitoring model to optimize the management of AR in pediatric kidney transplantation.

The Protective Effect of Ursolic Acid on Unilateral Ureteral Obstruction in Rats by Activating the Nrf2/HO-1 Antioxidant Signaling Pathway.

Renal interstitial fibrosis is a common pathological feature of a variety of kidney diseases that progress to end-stage renal disease. The excessive deposition of extracellular matrix (ECM) is a typical pathological change of renal interstitial fibrosis. The production of reactive oxygen species in renal tubules is an important factor leading to the development of renal interstitial fibrosis. Ursolic acid (UA) is a natural pentacyclic triterpene carboxylic acid compound widely found in plants. It has anti-inflammatory, antioxidant, and antitumor cell proliferation effects. It can reduce the development of fibrosis by inhibiting the oxidative stress response of the liver; there is currently no relevant research on whether UA can protect the renal interstitial fibrosis by resisting oxidative stress in the kidneys. In this study, our purpose is to investigate the effect of ursolic acid on renal interstitial fibrosis after unilateral ureteral obstruction (UUO) in rats and its related mechanisms. We established a UUO model by surgically ligating the right ureter of the rat and instilling UA preparation (40 mg/kg/d) through the stomach after the operation, once a day for 7 days. We found that UUO caused impaired renal function, increased pathological damage, increased renal interstitial fibrosis, increased apoptosis, increased oxidative stress damage, and decreased antioxidants. However, after UA preparations were given, the abovementioned damage was significantly improved. At the same time, we also found that UA preparations can significantly increase the relative expression of Nrf2/HO-1 signaling pathway in kidney tissue after UUO. In order to further verify whether the Nrf2/HO-1 signaling pathway is involved in the development of renal interstitial fibrosis, we injected zinc protoporphyrin (ZnPP, 45 umol/kg), a specific blocker of the Nrf2/HO-1 signaling pathway, into the intraperitoneal cavity after UUO in rats and before the gastric perfusion of ursolic acid preparations. Subsequently, we observed that the protective effect of UA on renal interstitial fibrosis after UUO in rats was reversed. Combining all the research results, we proved that UA has a protective effect on renal interstitial fibrosis after UUO in rats, which may be achieved by activating the Nrf2/HO-1 signaling pathway.

Retrospective Analysis of the Efficacy of Da Vinci Robot-Assisted Pyeloplasty in the Treatment of Ureteropelvic Junction Obstruction in Children.

Ureteropelvic junction obstruction (UPJO) is one of the common causes of hydronephrosis in children, and the purpose of this study was to observe the application effect of da Vinci robot-assisted laparoscopic treatment of UPJO and to investigate the safety, feasibility, and advantages of da Vinci robot-assisted laparoscopic surgery. 13 patients who underwent robot-assisted pyeloplasty (RAP) for UPJO admitted from May 2020 to March 2021 were retrospectively analyzed in our study. The clinical data among them revealed the intraoperative and postoperative indicators and complications as follows. UPJO was found on the left side in 9 patients and on the right side in 4 patients. The average operative time, blood loss, and hospital stay were 227.3 (175-310) min, 9.2 (5-30) mL, and 9.2 (6-14) days, respectively. Two cases of gross hematuria and two cases of minor urinary tract infection occurred after surgery, and the rest had no perioperative complications. The clinical treatment efficiency at postoperative follow-up was 100%. Our initial analysis showed that da Vinci robot-assisted laparoscopic surgery is a highly effective and safe option for the treatment of UPJO in children.

Super-Mini Percutaneous Nephrolithotomy Reduces the Incidence of Postoperative Adverse Events in Pediatric Patients: A Retrospective Cohort Study.

OBJECTIVE: To assess the safety of the super-mini percutaneous nephrolithotomy (SMP) versus the minimally invasive percutaneous nephrolithotomy (MPCNL) in the treatment of pediatric renal calculus. METHODS: We retrospectively reviewed the electronic records of pediatric patients who underwent treatment for renal stones by either SMP or MPCNL from May 2015 to May 2016. We compared the safety of the 2 surgical procedures in the treatment of renal calculus in children by using the generalized estimating equation (GEE) multivariate regression analysis, in which the exposures are the surgical procedures and postoperative adverse events (postoperative complications, fever, and WBC counts) are set as outcome variables. RESULTS: The study included 39 patients (26 boys and 13 girls), of which 22 underwent MPCNL and 17 underwent SMP, with a mean age of 110.05 ± 45.01 and 93.18 ± 41.72 months, respectively. In the univariate logistic regression model, the surgical procedures showed no significant association with postoperative complications (95% CI 0.0-1.5), fever (95% CI 0.1-2.1), postoperative peripheral WBC (95% CI 0.1-2.2). In the multiple logistic regression analysis, there was an insignificant association between surgical methods and postoperative complications (95% CI 0.28-1.1), fever (95% CI 0.1-1.2), and postoperative peripheral WBC (95% CI 0.03-1.8). While using GEE with multiple dependent variables and MPCNL as a reference, the OR of adverse events was 0.15 and the 95% CI were 0.04-0.55. CONCLUSIONS: Compared to MPCNL, SMP has a lower incidence of postoperative complications and appears to be a safer treatment for children with kidney stones.

Involvement of Activation of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Proliferation of Urethral Plate Fibroblasts in Finasteride-Induced Rat Hypospadias.

BACKGROUND We investigated the role of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in finasteride-induced hypospadias rats and explored the mechanisms involved. MATERIAL AND METHODS The hypospadias model was established by intragastric administration of finasteride and confirmed by hematoxylin and eosin (HE) staining. The urethral plate fibroblasts (UPF) were obtained from normal and modeled rats and identified based upon vimentin expression. Thereafter, UPF were divided into a normal control group, a model group, a model + MAPK inhibitor group, and a model + ERK inhibitor group. Cell proliferation, apoptosis, and cell cycling of UPF were assessed. Quantitative real-time PCR and Western blot analysis were used to evaluate expression of the MAPK signaling pathway and apoptosis-related genes. RESULTS HE staining confirmed that 10 mg/kg finasteride caused severe hypospadias in rats. UPFs obtained from the 10 mg/kg finasteride group showed higher proliferation and cell cycling and lower apoptosis compared with those obtained from the normal control group (P<0.05). Interestingly, a MAPK inhibitor or an ERK inhibitor could attenuate the abnormalities of cell proliferation, cycling, and apoptosis of UPF induced by finasteride. Compared with controls, the relative expression of p-MEK1/MEK1, caspase 3, and P53 in the UPF of the model group were reduced, while the relative expression of p-MAPK14/MAPK14 was increased in the cells of the model group. By contrast, a MAPK inhibitor or an ERK inhibitor could alleviate the abnormalities of MAPK/ERK signaling pathway and apoptosis-related gene expression induced by finasteride. CONCLUSIONS Our study reveals that the MAPK/ERK signaling pathway is involved in the regulation of proliferation, apoptosis, and cell cycling of UPFs in finasteride-induced hypospadias.

A high-fat diet impairs reproduction by decreasing the IL1ß level in mice treated at immature stage.

Obesity causes low-grade inflammation that is involved in male infertility. Interleukin 1 beta (IL1ß) plays an important role in this process. A high-fat diet (HFD) is the most common cause of obesity. However, the effect of a HFD on IL1ß and its consequence in reproduction remain unclear. We established a HFD model in mice treated at immature stage (mice-TIS) and mice treated at mature stage (mice-TMS). Surprisingly, we found that a HFD decreased IL1ß levels and was accompanied by an increase in testosterone in mice-TIS, while the reverse results were observed in mice-TMS. In addition, a HFD caused a reduction in testis macrophages and in the expression of inflammasome-related genes and proteins in mice-TIS. Furthermore, we found that IL1ß inhibited testosterone secretion through down-regulating the gene expression of P450SCC and P450c17. However, the influence on mice-TIS that were induced by a HFD was recovered by stopping the HFD. In this study, we are the first to report that a HFD impairs the reproductive system by decreasing IL1ß and enhancing testosterone levels in mice-TIS, which are different from the effects in mice-TMS. This provides new ideas for the treatment of obesity-induced infertility.

Transumbilical Single-Site Multiport Laparoscopic Pyeloplasty for Children with Ureteropelvic Junction Obstruction in China: A Multicenter Study.

BACKGROUND: Transumbilical single-site multiport laparoscopic pyeloplasty (TSMLP) for children with ureteropelvic junction obstruction (UPJO) has become feasible and popular recently. The purpose of this study was to evaluate the safety and efficacy of TSMLP for pediatric UPJO in a large multicenter series. MATERIALS AND METHODS: Medical records of consecutive patients who underwent TSMLP for pediatric UPJO in six academic institutions between June 2010 and May 2015 were retrospectively analyzed. The data of ultrasound, magnetic resonance urography, and diuretic renogram using 99Tc-diethylene triamine pentaacetic acid scan were collected during preoperative and postoperative periods. RESULTS: A total of 704 patients (750 kidneys) with UPJO who underwent TSMLP were recruited for this study. Of these patients, there were no significant differences in demographics and clinical presentation of the patients among the six centers. The operative time of all patients decreased significantly with time. The earlier the beginning of the operation, such as cohort A, B, and C, the longer the learning curve has been. Of these 704 patients, there were 60 (8.11%) postoperative minor complications during the postoperative hospitalization period, and all minor postoperative complications were cured by observation or drugs. There were 14 (1.99%) major postoperative complications, and all major complications were cured by minimally invasive surgery. No additional complications were encountered during the follow-up of 2.1 years (mean, ranged 1 year to 4 years). Success rate of TSMLP are more than 95% among six centers. CONCLUSIONS: We reported a multi-institutional series of TSMLP in children with UPJO. Our findings suggest that TSMLP represents a feasible treatment option for UPJO by offering reliable outcomes, low postoperative complications and high success rates.