Nephrotoxicity From Chemotherapeutic Agents: Clinical Manifestations, Pathobiology, and Prevention/Therapy

Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Seminars in Nephrology (Impact Factor: 3.48). 11/2010; 30(6):570-81. DOI: 10.1016/j.semnephrol.2010.09.005
Source: PubMed


Nephrotoxicity remains a vexing complication of chemotherapeutic agents. A number of kidney lesions can result from these drugs, including primarily tubular-limited dysfunction, glomerular injury with proteinuria, full-blown acute kidney injury, and long-term chronic kidney injury. In most cases, these kidney lesions develop from innate toxicity of these medications, but underlying host risk factors and the renal handling of these drugs clearly increase the likelihood of nephrotoxicity. This article reviews some of the classic nephrotoxic chemotherapeutic agents and focuses on examples of the clinical and histopathologic kidney lesions they cause as well as measures that may prevent or treat drug-induced nephrotoxicity.

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Available from: Gilbert W Moeckel, Jul 28, 2015
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    • "According to our previous study [8], animals that received 5 mg/kg cisplatin had evidence of renal damage and a lower mortality rate than animals that received 7 mg/kg during 1 year. The pattern of lesions observed in the 5-mg/kg cisplatin-induced CKD monkey model appeared to better mimic human stable CKD and fibrosis [15]. "
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    ABSTRACT: Chronic kidney disease (CKD) attributed to cisplatin is well documented. Mesenchymal stromal cells (MSCs) are proven to be renotropic. Although they have been shown to improve function in CKD and reduce fibrosis in different experimental rodent models, their efficiency in primates is unknown. The present study aimed to evaluate the prevention of CKD and reduction of fibrosis in monkeys treated with MSCs after cisplatin nephrotoxicity. We induced CKD in adult rhesus Macaca mulatta monkeys by means of intravenous administration of cisplatin. Autologous MSCs were transplanted by means of intrarenal arterial injections to assess the adverse effects of cisplatin in two CKD models: preventative and stable. Preventative CKD monkeys (n = 3) underwent cell transplantation 4 days after the cisplatin injection. The stable CKD monkeys (n = 2) underwent cell transplantation 6 months after the cisplatin injection. Non-treated (n = 4) and normal saline-injected animals (n = 3) comprised the control and vehicle groups, respectively. We followed the animals for survival rate, serum biochemistry, urine analysis and histopathological indices. In the preventive CKD model, MSC transplantation tended to improve some renal functions but significantly reduced the histopathologic score compared with the vehicle and control groups. In the stable CKD model, MSCs did not ameliorate renal function or pathological score. These results suggest that MSCs tend to delay progression of CKD and fibrosis but do not reduce established interstitial fibrosis in this unique primate model of cisplatin-induced nephrotoxicity. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Sep 2015 · Cytotherapy
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    • "Cisplatin (CDDP) is a chemotherapeutic drug to be used in several standard regimens for a variety of malignant tumors, such as non-small cell lung cancer, bladder, cervical, ovarian cancer, testicular cancer et al12. Although CDDP has been a mainstay for chemotherapy, its usefulness is often restricted by the following side-effects, especially the dose-dependent nephrotoxicity, which negatively affects patients' quality of life345. Although the hydration therapy has been proved as an effective renal-protective strategy, a certain percentage of patients still suffers from CDDP-induced nephrotoxicity5. "
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    ABSTRACT: The clinical use of cisplatin was severely limited by its associated nephrotoxicity. In this study, we investigated whether the pseudoginsenoside F11 had protective effects against cisplatin-induced nephrotoxicity. To clarify it, one in vivo model of cisplatin-induced acute renal failure was performed. The results showed that pretreatment with F11 reduced cisplatin-elevated blood urea nitrogen and creatinine levels, as well as ameliorated the histophathological damage. Further studies showed that F11 could suppress P53 activation, inverse the ratio of Bax/Bcl2 and the anti-oxidative and free radical levels induced by cisplatin, which in turn inhibited tubular cell apoptosis. Importantly, F11 enhanced rather than inhibited the anti-tumor activity of cispaltin in murine melanoma and Lewis lung cancer xenograft tumor models. Our findings suggested that administering F11 with cisplatin might alleviate the associated nephrotoxicity without compromising its therapeutic efficiency. This finding provides a novel potential strategy in the clinical treatment of cancer.
    Full-text · Article · May 2014 · Scientific Reports
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    • "The present study demonstrated that a high rate of malignancy was associated with the urokinase gene 3′-UTR C/C genotype in MN, but the relationship needs further clarification before definitive conclusions can be made. Our 13 MN patients received strong immunosuppressive agents for several years to counteract the poor response of proteinuria; thus, most of their cancers were those associated with known or suspected viral causes, such as lymphoma, cervical cancer, and skin cancer [37]. The results were similar to the results for organ transplant recipients, which suggest that immunity was oversuppressed in our strategy to manage resistant MN. "
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    ABSTRACT: Idiopathic membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults, and 25% of MN patients proceed to ESRD. Urokinase plasminogen activator (uPA) may play an important role in reducing renal fibrosis. This study was conducted to clarify the relationship between uPA gene polymorphisms and clinical manifestations of MN. We recruited 91 biopsy-diagnosed MN patients and 105 healthy subjects. Genotyping of uPA gene 3'-UTR T/C polymorphism was performed by polymerase chain reaction methods. The genotype distribution had no effect on the development of MN. Thirteen patients (15.9%; P = 0.008) acquired malignancies and seventeen (20.7%; P = 0.006) patients progressed to ESRD with the C/C genotype, but no patients with the T/C genotype did. In conclusion, we demonstrated that the presence of the uPA gene 3'-UTR C/C genotype was associated with ESRD as well as acquired malignancies in MN patients. These findings should prompt specific considerations for the treatment of MN patients to maintain a balance between treating disease entities and protecting the immune system from cancers.
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