The link between kidney disease and cancer: complications and treatment

Małyszko, Jolanta; Tesařová, Petra; Capasso, Giovambattista; Capasso, Anna

doi:10.1016/s0140-6736(20)30540-7

Cited by 82 publications

(68 citation statements)

References 76 publications

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“…Suggestive reasons as to why patients with kidney impairment may have worse outcomes include the high prevalence in frailty in this population, which increases risk of death and other poor outcomes, the high inflammatory state in kidney disease, and unclear recommendations regarding use of therapeutics. 85,88 The kidney is one of the main determinants of drug exposure and pharmacokinetics, impairment in its function may lead to adjustments in drug dosing; however recommendations for such are limited. As most anticancer medications have a narrow therapeutic index, studies specifically regarding dosing in advanced kidney disease or in dialysis, would be helpful given the physiologic changes that occur related to drug handling in these conditions.…”

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

“…89 To further complicate matters, there is an additional lack of clarity as to how to best estimate of kidney function in the cancer population, as sarcopenia may contribute to an overestimation of function and lead to unintended consequences of drug dosing and side effects. 85 In essence, there is no consensus guideline on chemotherapy dose adjustments for patients with CKD and for patients with end stage kidney disease on dialysis, 87,92,93 which makes finding the balance between therapeutic effect and adverse reactions of these agents very difficult.…”

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

“…Though advances in cancer prevention and treatments are leading to earlier diagnosis, and improved survival, it comes with the effects of chronic illness, and the subsequent effects of these treatments on other organ systems, particularly the kidneys. 85 Alternatively, with advances in the treatment for CKD, patients may be living longer than previously with transplants and on dialysis, and therefore an increased prevalence of malignancy in these populations may be seen. AKI and CKD may be seen as an effect of cancer and its therapy, likely in part related to the metabolism of cancer related therapeutics, or effects of such therapeutics in complications such as tumor lysis syndrome.…”

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

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The intersection of oncology, nephrology, and palliative care

Corona

Koncicki

2021

Journal of Onco-Nephrology

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Onconephrology patients share a common feature: decreased survival. This is where Palliative Care finds a role in managing for these patients. However, during the course of illness and its treatment, providers often overlook the importance of assessing prognosis, predicting disease trajectory, and addressing goals of care discussions with patients and their family. Knowing which factors portend a poor outcome in this population helps bind together the subspecialties of Oncology, Nephrology and Palliative Care and frame interventions within patients’ treatment goals. As the life expectancies of patients suffering from cancer and kidney disease is short, knowledge of these foreboding factors helps initiate end of life planning which has shown to be beneficial for our patients’ quality of life.

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Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

Section: Cancer In the Chronic Kidney Disease Populationmentioning

confidence: 99%

See 2 more Smart Citations

The intersection of oncology, nephrology, and palliative care

Corona

Koncicki

2021

Journal of Onco-Nephrology

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“…A broad array of factors increase the risk of renal dysfunction in cancer patients [1][2][3] . While certain malignancies can directly affect kidney function 4 , cancer therapy can also trigger fluid and electrolyte disorders 5 , acute kidney injury (AKI) 6 , and chronic kidney disease (CKD) 7 .…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxicity of the BRAF-kinase inhibitor Vemurafenib is driven by off-target Ferrochelatase inhibition

Bai¹,

Kim²,

Jayne³

et al. 2021

Preprint

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A multitude of disease and therapy related factors drive the frequent development of renal disorders in cancer patients. Along with chemotherapy, the newer targeted therapeutics can also cause renal dysfunction through on and off-target mechanisms. Interestingly, among the small-molecule inhibitors approved for the treatment of cancers that harbor BRAF-kinase activating mutations, vemurafenib can trigger tubular damage and acute kidney injury (AKI). To investigate the underlying mechanisms, here, we have developed cell culture and mouse models of vemurafenib nephrotoxicity. Our studies show that at clinically relevant concentrations vemurafenib induces cell-death in transformed and primary murine and human renal tubular epithelial cells (RTEC). In mice, two weeks of daily vemurafenib treatment causes moderate AKI with histopathological characteristics of RTEC injury. Importantly, RTEC-specific BRAF gene deletion did not influence renal function under normal conditions or alter the severity of vemurafenib-associated renal impairment. Instead, we found that inhibition of ferrochelatase (FECH), an enzyme involved in heme biosynthesis contributes to vemurafenib nephrotoxicity. FECH overexpression protected RTECs and conversely FECH knockdown increased the sensitivity to vemurafenib nephrotoxicity. Collectively, these studies suggest that vemurafenib-associated RTEC dysfunction and nephrotoxicity is BRAF-independent and caused in part by off-target FECH inhibition.Translational StatementBRAF is the most frequently mutated protein kinase and a critical oncogenic driver in human cancers. In melanoma and other cancers with BRAF activating mutations, BRAF targeted small-molecule therapeutics such as vemurafenib, and dabrafenib have shown remarkable clinical benefits. However, recent clinical studies have shown that a significant number of patients that receive vemurafenib develop AKI through mechanisms that remain unknown. The present study describes the development of novel experimental models of vemurafenib nephrotoxicity and reveals the underlying off-target mechanisms that contribute to renal injury.

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Iron imbalance in cancer: Intersection of deficiency and overload

Basak

Kanwar

2022

Cancer Medicine

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Iron, an essential trace element, plays a complex role in tumour biology. While iron causes cancer clearance through toxic free radical generation, iron‐induced free radical flux also acts as a cancer promoter. These fates majorly guided through cellular response towards pro‐oxidant and antioxidant settings in a tumour microenvironment, designate iron‐induced oxidative stress as a common yet paradoxical factor in pro‐tumorigenesis as well as anti‐tumorigenesis, posing a challenge to laying down iron thresholds favouring tumour clearance. Additionally, complexity of iron's association with carcinogenesis has been extended to iron‐induced ROS's involvement in states of both iron deficiency and overload, conditions identified as comparable, inevitable and significant coexisting contributors as well as outcomes in chronic infections and tumorigenesis. Besides, iron overload may also develop as an unwanted outcome in certain cancer patients, as a result of symptomatic anaemia treatment owed to irrational iron‐restoration therapies without a prior knowledge of body's iron status with both conditions synergistically acting towards tumour aggravation. The co‐play of iron deficiency and overload along with iron's pro‐tumour and antitumour roles with intersecting mechanisms, thus presents an unpredictable regulatory response loop in a state of malignancy. The relevance of iron's thresholds beyond which it proves to be beneficial against tumorigenesis hence becomes questionable. These factors pose a challenge, over establishing if iron chelation or iron flooding acts as a better approach towards antitumour therapies. This review presents a critical picture of multiple contrasting features of iron's behaviour in cancer, leading towards two conditions lying at opposite ends of a spectrum: iron deficiency and overload in chronic disease conditions including cancer, hence, validating the critical significance of diagnosis of patients' iron status prior to opting for subsequent therapies.

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The link between kidney disease and cancer: complications and treatment

Cited by 82 publications

References 76 publications

The intersection of oncology, nephrology, and palliative care

The intersection of oncology, nephrology, and palliative care

Nephrotoxicity of the BRAF-kinase inhibitor Vemurafenib is driven by off-target Ferrochelatase inhibition

Iron imbalance in cancer: Intersection of deficiency and overload

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