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Article ; Online: Cisplatin nephrotoxicity: a review of the literature.

Manohar, Sandhya / Leung, Nelson

2017 Volume 31, Issue 1, Page(s) 15–25

Abstract: ... in the nephrotoxicity. Better understanding of these interactions could one day help devise better renoprotection ... Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978 ... It remains an important and effective therapy in many forms of cancer today. Cisplatin mediates ...

Abstract	Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. It remains an important and effective therapy in many forms of cancer today. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Although it is best known for DNA damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic reticulum and mitochondria. It also activates apoptotic pathways and inflicts cellular damage via oxidative stress and inflammation. One of its dose limiting toxicities is its effects on the kidney. This includes acute kidney injury as well as tubular injury resulting in electrolyte wasting. Extensive research has found that cisplatin entry into a cell is facilitated by a number of cellular transporters including human copper transport protein 1 (Ctr1) and the organic cation transporter 2 (OCT2) which are expressed on renal tubular cells. The interactions between the mechanisms of cytotoxicity and cellular transport play an important role in the nephrotoxicity. Better understanding of these interactions could one day help devise better renoprotection that would not reduce its anti-tumor effects.
MeSH term(s)	Acute Kidney Injury/chemically induced ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Acute Kidney Injury/therapy ; Animals ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/metabolism ; Apoptosis/drug effects ; Biological Transport ; Cation Transport Proteins/metabolism ; Cisplatin/adverse effects ; Cisplatin/metabolism ; Copper Transporter 1 ; DNA Damage ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney/pathology ; Nephritis, Interstitial/chemically induced ; Nephritis, Interstitial/metabolism ; Nephritis, Interstitial/pathology ; Nephritis, Interstitial/therapy ; Organic Cation Transporter 2/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; Cation Transport Proteins ; Copper Transporter 1 ; Organic Cation Transporter 2 ; SLC22A2 protein, human ; SLC31A1 protein, human ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2017-04-05
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	1093991-x
ISSN	1724-6059 ; 1120-3625 ; 1121-8428
ISSN (online)	1724-6059
ISSN	1120-3625 ; 1121-8428
DOI	10.1007/s40620-017-0392-z
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Zs.A 3369: Show issues

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Article: The Renin-Angiotensin System Involvement in Cisplatin-Induced Nephrotoxicity: An Overview of Physiological and Pathological Mechanisms-A Systematic Review.

Vakilian, Aryan / Mohammadi, Sina / Shokri, Fatemeh / Maleki, Maryam / Kheiry, Maryam / Kheiri, Amin

International journal of nephrology

2024 Volume 2024, Page(s) 1511216

Abstract: ... nephrotoxicity. This systematic review (SR) sought to identify the link between CDDP-induced nephrotoxicity and ... Cisplatin (CDDP) is a highly potent chemotherapy drug. But its nephrotoxicity poses a significant ... the involvement of the RAS in the CDDP-induced nephrotoxicity model, along with the activation ...

Abstract	Cisplatin (CDDP) is a highly potent chemotherapy drug. But its nephrotoxicity poses a significant limitation to its use. The renin-angiotensin system (RAS) has been proposed to play a role in drug-induced nephrotoxicity. This systematic review (SR) sought to identify the link between CDDP-induced nephrotoxicity and the RAS pathway. In this SR, relevant keywords were employed to explore databases such as PubMed (MEDLINE), Scopus (Elsevier), and Institute for Scientific Information (ISI) Web of Science up to October 2023. Nine studies were selected based on predefined inclusion/exclusion criteria. The findings support the involvement of the RAS in the CDDP-induced nephrotoxicity model, along with the activation of inflammatory mediators, lipid peroxidation, and changes in markers of kidney tissue damage. Furthermore, physiology and pathology of RAS-related interventions in CDDP-induced nephrotoxicity models have involved the factors such as human organic cation transporter 2 (hOCT2), organic anion transporting polypeptides 1B1 (OATP1B1) and 1B3, kallikrein-kinin system, and bradykinin receptors. CDDP-induced nephrotoxicity has been found to be substantially influenced by both classic and nonclassic RAS axes. Angiotensin II exacerbates renal damage induced by CDDP. Conversely, inhibiting the pressor arm of RAS in males mitigates this damage. However, activation of the renal vasodepressor arm of RAS exacerbates CDDP-induced nephrotoxicity in females. These findings underscore gender differences in renal function and response to RAS-related interventions in the presence of CDDP. This SR provides insights into both beneficial and adverse interventions associated with RAS in the CDDP-induced nephrotoxicity, offering valuable considerations for researchers and clinicians.
Language	English
Publishing date	2024-05-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573904-9
ISSN	2090-2158 ; 2090-214X
ISSN (online)	2090-2158
ISSN	2090-214X
DOI	10.1155/2024/1511216
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Article ; Online: Molecular mechanisms underlying cisplatin-induced nephrotoxicity and the potential ameliorative effects of essential oils: A comprehensive review.

Patel, Saraswati / Sathyanathan, V / Salaman, Samsi D

Tissue & cell

2024 Volume 88, Page(s) 102377

Abstract: ... to protect against cisplatin-mediated nephrotoxicity. These EO have shown the ability to counteract ... use is hampered by several side effects, notably nephrotoxicity and acute kidney injury, which arise ... protection. In this review, we have made an effort to summarize the molecular mechanisms and exploring new ...

Abstract	Since the Middle Ages, essential oils (EO) have been widely used for bactericidal, virucidal, fungicidal, insecticidal, medicinal and cosmetic applications, nowadays in pharmaceutical, agricultural and food industries. Recently, EO have emerged as promising adjuvant therapies to mitigate the toxicities induced by anti - cancerous drugs; among them cisplatin induced renal damage amelioration remain remarkable. Cisplatin (cis-diaminedichloroplatinum II, CDDP) is renowned as one of the most effective anti-neoplastic agents, widely used as a broad-spectrum anti-tumor agent for various solid tumors. However, its clinical use is hampered by several side effects, notably nephrotoxicity and acute kidney injury, which arise from the accumulation of CDDP in the proximal tubular epithelial cells (PTECs). To better understand and analyze the molecular mechanisms of CDDP-induced renal damage, it is crucial to investigate potential interventions to protect against cisplatin-mediated nephrotoxicity. These EO have shown the ability to counteract oxidative stress, reduce inflammation, prevent apoptosis, and exert estrogenic effects, all contributing to renal protection. In this review, we have made an effort to summarize the molecular mechanisms and exploring new interventions by which we can pave the way for safer and more effective cancer management in the future.
Language	English
Publishing date	2024-04-06
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	204424-9
ISSN	1532-3072 ; 0040-8166
ISSN (online)	1532-3072
ISSN	0040-8166
DOI	10.1016/j.tice.2024.102377
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Zs.A 1016: Show issues

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Article: Cisplatin nephrotoxicity: a review.

Yao, Xin / Panichpisal, Kessarin / Kurtzman, Neil / Nugent, Kenneth

The American journal of the medical sciences

2007 Volume 334, Issue 2, Page(s) 115–124

Abstract: ... on cisplatin nephrotoxicity to identify new information on the mechanism of injury and potential approaches ... Background: Cisplatin is a major antineoplastic drug for the treatment of solid tumors, but it has ... to prevention and/or treatment.: Results: Unbound cisplatin is freely filtered at the glomerulus and taken up ...

Abstract	Background: Cisplatin is a major antineoplastic drug for the treatment of solid tumors, but it has dose-dependent renal toxicity. Methods: We reviewed clinical and experimental literature on cisplatin nephrotoxicity to identify new information on the mechanism of injury and potential approaches to prevention and/or treatment. Results: Unbound cisplatin is freely filtered at the glomerulus and taken up into renal tubular cells mainly by a transport-mediated process. The drug is at least partially metabolized into toxic species. Cisplatin has multiple intracellular effects, including regulating genes, causing direct cytotoxicity with reactive oxygen species, activating mitogen-activated protein kinases, inducing apoptosis, and stimulating inflammation and fibrogenesis. These events cause tubular damage and tubular dysfunction with sodium, potassium, and magnesium wasting. Most patients have a reversible decrease in glomerular filtration, but some have an irreversible decrease in glomerular filtration. Volume expansion and saline diuresis remain the most effective preventive strategies. Conclusions: Understanding the mechanisms of injury has led to multiple approaches to prevention. Furthermore, the experimental approaches in these studies with cisplatin are potentially applicable to other drugs causing renal dysfunction.
MeSH term(s)	Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/toxicity ; Cisplatin/pharmacokinetics ; Cisplatin/toxicity ; Humans ; Kidney/drug effects ; Kidney/pathology ; Kidney/physiopathology ; Renal Insufficiency/chemically induced ; Renal Insufficiency/pathology ; Renal Insufficiency/prevention & control
Chemical Substances	Antineoplastic Agents ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2007-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1097/MAJ.0b013e31812dfe1e
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Article ; Online: Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis.

Schofield, Jessica / Harcus, Matthew / Pizer, Barry / Jorgensen, Andrea / McWilliam, Stephen

Pediatric nephrology (Berlin, Germany)

2023 Volume 39, Issue 3, Page(s) 699–710

Abstract: ... to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment ... of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing ... solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced ...

Abstract	Background: Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors. Objectives: This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer. Study eligibility criteria: Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed. Results: Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m Limitations: A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability. Conclusions: Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.
MeSH term(s)	Child ; Humans ; Antineoplastic Agents/adverse effects ; Cisplatin/adverse effects ; Glomerular Filtration Rate ; Magnesium/analysis ; Neoplasms/drug therapy ; Renal Insufficiency/chemically induced
Chemical Substances	Antineoplastic Agents ; Cisplatin (Q20Q21Q62J) ; Magnesium (I38ZP9992A)
Language	English
Publishing date	2023-09-20
Publishing country	Germany
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-023-06149-9
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Zs.A 2196: Show issues

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Article ; Online: A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation.

Li, Juanjuan / Wu, Yu / Chen, Cheng / Zhang, Wanfen / Yue, Lili / Liu, Tongqiang

Clinical and experimental nephrology

2023 Volume 28, Issue 1, Page(s) 1–12

Abstract: Background: Nephrotoxicity remains the most serious side effect of cisplatin therapy. Cisplatin ... induced nephrotoxicity (CIN) limits the use of this drug and affects up to 20% of patients ... Several possible interventions such as magnesium supplementation may prevent CIN. This study aimed to review ...

Abstract	Background: Nephrotoxicity remains the most serious side effect of cisplatin therapy. Cisplatin-induced nephrotoxicity (CIN) limits the use of this drug and affects up to 20% of patients. Several possible interventions such as magnesium supplementation may prevent CIN. This study aimed to review different types of hydration protocols and we conducted a meta-analysis of magnesium supplementation to understand its effect in protecting against CIN. Methods: A search of the PubMed, Embase, and Cochrane databases was performed. Trials were eligible if they enrolled patients who received cisplatin and different hydration protocols to prevent CIN. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the efficacy of different protocols. Results: We initially identified 1113 different studies and included 33 of them which met the selection criteria. A meta-analysis of 11 retrospective studies that examined magnesium supplementation during hydration showed that this treatment provided significant protection against CIN (OR = 0.22, 95% CI = 0.14 to 0.35). Conclusion: There has been uncertainty regarding the best method to prevent CIN. Our results highlight the potentially protective effect of magnesium supplementation during hydration. This study is registered in PROSPERO, CRD42020212682.
MeSH term(s)	Humans ; Cisplatin/adverse effects ; Magnesium Hydroxide ; Magnesium/therapeutic use ; Retrospective Studies ; Renal Insufficiency/chemically induced ; Dietary Supplements ; Systematic Reviews as Topic ; Meta-Analysis as Topic
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Magnesium Hydroxide (NBZ3QY004S) ; Magnesium (I38ZP9992A)
Language	English
Publishing date	2023-08-02
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-023-02386-2
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Zs.A 4922: Show issues

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Article ; Online: Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011-2022 review.

Davoudi, Maryam / Jadidi, Yasaman / Moayedi, Kiana / Farrokhi, Vida / Afrisham, Reza

Journal of nanobiotechnology

2022 Volume 20, Issue 1, Page(s) 504

Abstract: ... cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011-2022 review study was conducted ... nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria ... mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting ...

Abstract	Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011-2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1-3 trials.
MeSH term(s)	Cisplatin/toxicity ; Metal Nanoparticles ; Polymers ; Reactive Oxygen Species ; Silver
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Polymers ; Reactive Oxygen Species ; Silver (3M4G523W1G)
Language	English
Publishing date	2022-12-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-022-01718-w
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Article: Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review.

Zazuli, Zulfan / Vijverberg, Susanne / Slob, Elise / Liu, Geoffrey / Carleton, Bruce / Veltman, Joris / Baas, Paul / Masereeuw, Rosalinde / Maitland-van der Zee, Anke-Hilse

Frontiers in pharmacology

2018 Volume 9, Page(s) 1111

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2018-09-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2018.01111
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Article: Protective Effect of Mannitol on Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-Analysis.

Li, Songtao / He, Xiuyun / Ruan, Linjie / Ye, Ting / Wen, Yulong / Song, Zhihua / Hu, Siying / Chen, Yu / Peng, Bo / Li, Shijie

Frontiers in oncology

2021 Volume 11, Page(s) 804685

Abstract: ... malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting ... factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity ... containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis.: Methods: Potential ...

Abstract	Introduction: Cisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis. Methods: Potential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad's and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. Results: Four RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45-0.97], Conclusion: Current evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was ≥ 25 g in total or cisplatin was < 75 mg/m Systematic review registration: crd. york. ac. uk/PROSPERO, CRD 42021253990.
Language	English
Publishing date	2021-12-16
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.804685
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Article ; Online: Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review.

de Godoy Torso, Nadine / Pereira, João Kleber Novais / Visacri, Marília Berlofa / Vasconcelos, Pedro Eduardo Nascimento Silva / Loren, Pía / Saavedra, Kathleen / Saavedra, Nicolás / Salazar, Luis A / Moriel, Patricia

International journal of molecular sciences

2021 Volume 22, Issue 23

Abstract: ... nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis ... nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a ... The purpose of this systematic review was to map out and summarize scientific evidence ...

Abstract	The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.
MeSH term(s)	Animals ; Antineoplastic Agents/adverse effects ; Biomarkers/analysis ; Cisplatin/adverse effects ; Humans ; Kidney Diseases/diagnosis ; Kidney Diseases/genetics ; Kidney Diseases/therapy ; MicroRNAs/administration & dosage ; MicroRNAs/genetics ; Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents ; Biomarkers ; MicroRNAs ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2021-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222312765
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