Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine

Akioka, Kiyokazu; Ishikawa, Tomohito; Osaka, Masafumi; Kadotani, Yayoi; Okugawa, K.; Nakano, K; Osaka, Yoshio; Tsuchiya, Ken; Sako, Hirotaka

doi:10.1016/j.transproceed.2016.11.015

Cited by 9 publications

(4 citation statements)

References 7 publications

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“…Our results revealed that administration with CP obviously attenuated the rise of UA levels in serum and liver. Besides, many studies have suggested that a high level of serum UA is closely related to renal dysfunction (Akioka et al, 2017). Serum BUN and Cre are the two most widely used indexes to assess renal function.…”

Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Cheng

et al. 2022

Front. Pharmacol.

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Hyperuricemia (HUA), a common metabolic disease, is treated as the second-largest metabolic disease after diabetes in China. Cortex Phellodendri (CP) is one of the most frequently used herbal medicines for treating gout or HUA. However, the mechanism underlying the anti-HUA effect of CP is still unrevealed. Hence, this study aimed to explore the pharmacological mechanism of CP against HUA using network pharmacology coupled with in vivo experimental validation. Active compounds and potential targets of CP, as well as the potential targets related to HUA, were retrieved from multiple open-source databases. The drug-disease overlapping targets were obtained by Venn diagram analysis and used to construct the herb-component-target (HCT), protein-protein-interaction (PPI), and component-target-pathway (CTP) networks. The functional enrichment analysis was also performed for further study. Furthermore, a HUA mouse model was induced by a combination of intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) and intragastric administration of hypoxanthine (HX, 300 mg/kg) daily for 10 days. Different dosages of CP (200, 400, and 800 mg/kg) were orally given to mice 1 h after modeling. The results showed that 12 bioactive compounds and 122 drug-disease overlapping targets were obtained by matching 415 CP-related targets and 679 HUA-related targets, and berberine was one of the most important compounds with the highest degree value. The core targets of CP for treating HUA were TP53, MAPK8, MAPK3, IL-6, c-Jun, AKT1, xanthine oxidase (XOD), and ATP-binding cassette subfamily G member 2 (ABCG2). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that the anti-HUA effect of CP mainly involved the pathways of inflammation and apoptosis, such as PI3K/Akt, TNF, MAPK, TLR, AMPK, NF-κB, and NLRP3 signaling pathways. In vivo animal experiment further confirmed the hypouricemic effect of CP in a HUA mouse model, as evidenced by significantly restored kidney histological deteriorations, and considerably decreased levels of serum uric acid (sUA), creatinine (Cre), blood urea nitrogen (BUN), and hepatic UA. Furthermore, the hypouricemic action of CP in vivo might be attributed to its suppression of XOD activity in the liver, rather than ABCG2 in the kidney. Real-time qPCR (RT-qPCR) and Western blot analysis also confirmed the key roles of the hub genes in CP against HUA. In conclusion, CP exhibited therapeutic effect against HUA via multi-compounds, multi-targets, and multi-pathways. It possessed anti-HUA and nephroprotective effects via suppressing XOD activity, and reversed the progression of renal injury by exerting anti-inflammatory and anti-apoptotic effects.

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Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Cheng

et al. 2022

Front. Pharmacol.

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“…Owing to the low incidence of adverse events such as bone marrow suppression, gastrointestinal discomfort, and viral infections, this drug is typically used as an alternative to mycophenolic acid (MPA) drugs. Previous studies have reported that mizoribine increases serum uric acid levels, with an incidence rate of approximately 32.0–87.5% [ 4 , 5 ]. Further, it competitively inhibits inosine monophosphate dehydrogenase (IMPDH), leading to an increase in purine alkaloids and subsequent production of more uric acid; this ultimately results in elevated serum uric acid levels [ 6 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Acute renal failure after kidney transplantation due to mizoribine-induced ureteral stones

Ding,

Zhao,

Zhu

2024

BMC Nephrol

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Introduction Mizoribine (MZR) is used to prevent rejection reactions after kidney transplantation and increase the risk of hyperuricemia. There is a lack of reports of MZR-induced ureteral stones after kidney transplantation. The surgery treatment of ureteral stones in transplanted kidney is a challenging clinical issue that should only be performed by experienced urologists at professional centers. It is very important to have a thorough understanding of the patient's medical history, analyze the causes of stone formation, and choose a reasonable treatment plan based on the characteristics of the stones. The case report is aim to emphasize the recognition of the possibility of mizoribine-induced ureteral uric acid stones in transplanted kidney and to avoid unnecessary surgery. Case presentation A patient after kidney transplantation was diagnosed with acute renal failure caused by ureteral stones. The medical history, CT images of the renal graft, the results of laboratory test and stone composition analysis were provided. Based on medical history and laboratory test results, it was determined that the ureteral stones of renal graft was induced by MZR. To our best knowledge, this is the first report of MZR-induced stones in transplanted kidney and ureters. It was completely cured by urinary alkalinization, avoiding surgery treatment. We summarize the characteristics, treatment and methods for preventing the formation of uric acid stones of patients with MZR. Conclusion By analyze our case report, it shows that acute renal failure with ureteral stones after kidney transplantation can caused by MZR. Urinary alkalinization for MZR induced uric acid stones is simple and effective.

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“…In contrast, caution is required in regard to hyperuricemia, which is a characteristic side-effect of MZR. 15,16 The mechanism should be associated with hypoxanthine-guanine phosphoribosyl transferase, which catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. 17 It plays a central role in the generation of purine nucleotides through the purine salvage pathway.…”

Section: Discussionmentioning

confidence: 99%

High‐dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study

et al. 2017

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Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine

Cited by 9 publications

References 7 publications

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice

Acute renal failure after kidney transplantation due to mizoribine-induced ureteral stones

High‐dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study

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