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Sepsis-associated acute kidney injury (SA-AKI) results in significant morbidity and mortality, and ferroptosis may play a role in its pathogenesis. Our aim was to examine the effect of exogenous H2S (GYY4137) on ferroptosis and AKI in in vivo and in vitro models of sepsis and explore the possible mechanism involved. Sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice, which were randomly divided into the sham, CLP, and CLP + GYY4137 group. The indicators of SA-AKI were most prominent at 24 h after CLP, and analysis of the protein expression of ferroptosis indicators showed that ferroptosis was also exacerbated at 24 h after CLP. Moreover, the level of the endogenous H2S synthase CSE (Cystathionine-γ-lyase) and endogenous H2S significantly decreased after CLP. Treatment with GYY4137 reversed or attenuated all these changes. In the in vitro experiments, LPS was used to simulate SA-AKI in mouse renal glomerular endothelial cells (MRGECs). Measurement of ferroptosis-related markers and products of mitochondrial oxidative stress showed that GYY4137 could attenuate ferroptosis and regulate mitochondrial oxidative stress. These findings imply that GYY4137 alleviates SA-AKI by inhibiting ferroptosis triggered by excessive mitochondrial oxidative stress. Thus, GYY4137 may be an effective drug for the clinical treatment of SA-AKI. [ABSTRACT FROM AUTHOR]

Background: The pharmaceutical services based on therapeutic care pathway for kidney transplantation from infants and young children (age <3 years, weight <15 kg) to pediatric recipients can detect and resolve medication-related problems. In this paper, we report our experience on pharmaceutical services based on therapeutic care pathway to evaluate the therapeutic effects and assess the feasibility of perioperative treatment protocols., Methods: We performed a retrospective study of 12 recipients who received their graft from infants and young children, between September 2011 and December 2013 at our institution. As providers of pharmaceutical services, the clinical pharmacists collected and reviewed the clinical data from all patients, including the clinical characteristics, outcome indices, and follow-up dates. A three-step-protocol of pharmaceutical services including clinician's application, pharmacist consultation, and ongoing direct pharmaceutical care and follow-up was used through the entire length of patient's admission, hospitalization, and discharge. This protocol was developed and refined based on the guidelines for transplant perioperative treatment and experiences of the clinical pharmacists to standardize the workflow, and improve the medical treatment and quality of life of patients., Results: There was no acute rejection, graft loss, or death in 10 recipients after transplantation, and another 2 received nephrectomy due to dysfunction. Postoperative follow-up of the patients who received the pharmaceutical services from the clinical pharmacist showed an effectiveness in managing medication-related complications, patient-related factors, and an improvement of the outcomes., Conclusions: The three-step protocol of pharmaceutical services for pharmaceutical care and individual dosing regimen sponsored by pharmacists facilitated access to personalized therapies for children undergoing kidney transplantation in our hospital., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-21-515/coif). The authors have no conflicts of interest to declare., (2022 Translational Pediatrics. All rights reserved.)

Objective: To analyze the epidemiographic features of urological malignancy in renal allograft recipients (RAR) in a single center, Methods: A retrospective analysis was made on 3150 patients who received renal allografts from June 1978 until the autumn of 2006 and anti-rejection treatment for at least 3 months., Results: Of the 3150 recipients, 33 (1.05%) developed malignancies, including 12 patients (0.38%; eight males and four females) with urological tumors and 21 patients with skin carcinoma, right liver lobular cystic adenocarcinoma, hepatocellular carcinoma, gastric cancer, colorectal carcinoma, ileocecal adenoma, lip cancer, nasopharyngeal carcinoma, Kaposi's Sarcoma, pulmonary lymphoma, and breast cancer. The 12 cases of urological malignancies included one case of renal cell carcinoma, one case of transplanted kidney carcinoma, two cases of bilateral pelvic transitional cell carcinoma (TCC), three cases of unilateral pelvic TCC, one case of bilateral ureter TCC, one case of unilateral ureter TCC, and three cases of bladder TCC. The age at which the diagnosis was made ranged from 48 to 66 years with a mean of 58.3 +/- 4.6 years, and the mean course of immunosuppressive therapy ranged from 26 to 120 months with a mean of 62 +/- 18 months. Of the 12 patients who developed urological malignancies, six had been on a Oyclosporine A + Azaithioprine + Prednisone (OsA + Aza + Pred) protocol; five on a Oyclosporine A + Mycophenolate Mofetil + Prednisone (OsA + MMF + Pred) protocol; and one on a Tacrolimus + Mycophenolate Mofetil + Prednisone (FK506 + MMF + Pred) protocol. One of the 12 patients died soon after the diagnosis was made, and the remaining 11 patients received surgical resection. Of them, 10 patients survived well, and the other one died from cerebral hemorrhage soon after operation., Conclusion: Urological malignancies, especially TCC, are an important complication in renal transplanatation found in this center. The incidence of urological malignancy in renal allograft recipients (RAR) is about 10 times that found in the general population of Shanghai versus two times for other malignancies. The occurrence of the malignancies in PAR seems to be closely related to the use of immunosuppressive agents. lmmunosuppression results in the weakening of immnuologic surveillance function, leading to mutation, aberration, and carcinogenesis. The immunological status of patients after renal transplantation should be assessed regularly. Painless macroscopic hematuria should be considered a significant sign in assessing the potential occurrence of urological malignancy in RAR. Treatment includes early diagnosis, timely surgical resection, and reduction of immunosuppressive agents.