OGG1 aggravates renal ischemia-reperfusion injury by repressing PINK1-mediated mitophagy.

Renal ischemia-reperfusion injury (IRI) is mainly responsible for acute kidney injury for which there is no effective therapy. Accumulating evidence has indicated the important role of mitophagy in mitochondrial homeostasis under stress. OGG1 (8-oxoguanine DNA glycosylase) is known for functions in excision repair of nuclear and mitochondrial DNA. However, the role of OGG1 in renal IRI remains unclear. Herein, we identified OGG1, induced during IRI, as a key factor mediating hypoxia-reoxygenation-induced apoptosis in vitro and renal tissue damage in a renal IRI model. We demonstrated that OGG1 expression during IRI negatively regulates mitophagy by suppressing the PINK1/Parkin pathway, thereby aggravating renal ischemic injury. OGG1 knockout and pharmacological inhibition attenuated renal IRI, in part by activating mitophagy. Our results elucidated the damaging role of OGG1 activation in renal IRI, which is associated with the regulatory role of the PINK1/Parkin pathway in mitophagy.

MiR-20a-5p alleviates kidney ischemia/reperfusion injury by targeting ACSL4-dependent ferroptosis.

Ischemia/reperfusion injury (IRI) is prone to occur after kidney transplantation, leading to delayed graft function (DGF). MicroRNAs play a crucial role in the pathogenesis of ischemia/reperfusion-induced acute kidney injury, and miR-20a-5p was found to be the most significantly upregulated gene in a DGF patient cohort. However, the roles of microRNAs in transplanted kidneys remain largely unknown. In this study, we found that miR-20a-5p was upregulated in the kidneys of acute kidney injury mice and in patients with DGF. We identified early growth response-1 as a critical upstream target and verified the binding of early growth response-1 to a predicted sequence in the promoter region of the miR-20a-5p gene. Functionally, the miR-20a-5p mimic attenuated IRI and postischemic renal fibrosis, whereas the miR-20a-5p inhibitor delivery aggravated IRI and fibrosis. Importantly, delivery of the miR-20a-5p mimic or inhibitor in the donor kidneys attenuated or aggravated renal loss and structural damage in cold storage transplantation injury. Furthermore, our study identified miR-20a-5p as a negative regulator of acyl-CoA synthetase long-chain family member 4 (ACSL4) by targeting the 3' untranslated region of ACSL4 mRNA, thereby inhibiting ACSL4-dependent ferroptosis. Our results suggest a potential therapeutic application of miR-20a-5p in kidney transplantation through the inhibition of ACSL4-dependent ferroptosis.

Application progress in classification of puncture biopsy after kidney transplantation / 器官移植

Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

Transplant of Kidneys From Hepatitis C Virus-Positive Donors To Hepatitis C Virus-Negative Recipients: A Retrospective Study and Systematic Review.

OBJECTIVES: Kidneys from hepatitis C virus-positive donors were often discarded due to the lack of an effective treatment for hepatitis C virus. However, the advent of direct-acting antivirals has facilitated great progress for treatment of hepatitis C virus, providing additional opportunities for patients waiting for kidney transplant. We explored the feasibility and safety of kidney transplant from hepatitis C virus- positive donors to hepatitis C virus-negative recipients in combination with direct-acting antiviral therapy. MATERIALS AND METHODS: This was a single-center retrospective study of 7 recipients of hepatitis C virus- positive kidneys from June 2018 to June 2021. All recipients were treated with sofosbuvir/velpatasvir for 12 weeks after kidney transplant. The primary recipients' outcome was achievement of sustained viral eradication at 12 weeks after treatment, and follow-up secondary outcomes were kidney function recovery, liver function, and adverse drug reactions. We reviewed previous studies, from 2017 to 2022, to analyze achievement of sustained viral eradication at 12 weeks after treatment, recipient and graft survival, and adverse event of kidney transplant from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient. RESULTS: Median follow-up time was 71 weeks (range, 56-183 weeks). All recipients achieved sustained viral eradication at 12 weeks after treatment, and their kidney function recovered without severe liver damage or adverse drug reactions. Previous studies suggested that transplant of hepatitis C virus-positive donor kidneys is safe and feasible when combined with direct-acting antiviral therapy. However, details regarding optimal duration of treatment and directacting antiviral regimen remain undetermined, so prospective randomized studies are warranted. CONCLUSIONS: Our study further confirms that kidney transplant from hepatitis C virus-positive donors to hepatitis C virus-negative recipients is safe and feasible with direct-acting antiviral treatment. Grafts from hepatitis C virus-infected donors may be effective to resolve the problem of kidney shortage.