Onconephrology: The intersections between the kidney and cancer

Rosner, Mitchell H.; Jhaveri, Kenar D.; McMahon, Blaithin A.; Perazella, Mark A.

doi:10.3322/caac.21636

Cited by 94 publications

(86 citation statements)

References 220 publications

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“…In a typical onconephrology clinic, the wide spectrum of diseases seen spans the breadth of the entire field of nephrology. 2 An onconephrologist needs a broad understanding of renal pathology and outstanding skills in the identification and triage of a wide range of glomerular, tubulointerstitial, and renal vascular diseases. Due to the broad spectrum of kidney diseases occurring in patients with cancer, onconephrology has a much more diffuse expertise that relies heavily on the diagnostic skills of a well-trained general nephrologist.…”

Section: Reason Number 1: An Onconephrologist Deploys the Wide-ranging Skills Of A General Nephrologistmentioning

confidence: 99%

“…Though there has been tremendous growth of interest, one cannot forget that the field of onconephrology is still extremely young. In 2011, the American Society of Nephrology (ASN) initially created the first forum dedicated to the field of onconephrology to improve medical care in cancer patients with kidney diseases 2 . As a result, few of the pioneers in this young field were able to publish two onconephrology curriculums in 2015.…”

Section: Reason Number 2: the Field Of Onconephrology Is Too Young To Warrant A Full Year Of Extra Trainingmentioning

confidence: 99%

See 1 more Smart Citation

An extra year of onco-nephrology fellowship training is not required for the subspecialty

Anand

Bassil

Sise

2020

Journal of Onco-Nephrology

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Section: Reason Number 1: An Onconephrologist Deploys the Wide-ranging Skills Of A General Nephrologistmentioning

confidence: 99%

Section: Reason Number 2: the Field Of Onconephrology Is Too Young To Warrant A Full Year Of Extra Trainingmentioning

confidence: 99%

An extra year of onco-nephrology fellowship training is not required for the subspecialty

Anand

Bassil

Sise

2020

Journal of Onco-Nephrology

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“…Along with chemotherapeutics, targeted antibodies 8 and small-molecule inhibitors 9 are also associated with renal impairment. Thus, one of the challenges in the emerging field of onconephrology [10][11][12][13] is to determine the mechanisms associated with these toxicities in order to develop mitigating strategies.…”

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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“…Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. 1 With the advent of novel chemotherapeutic agents, targeted therapies and immunotherapy, we are beginning to see even more kidney-related complications that require close collaboration with our oncology colleagues. [2][3][4] Likewise, the presence of preexisting chronic kidney disease (CKD) may limit the use of certain anti-cancer agents that could have superior outcomes.…”

mentioning

confidence: 99%

“…5 Genitourinary cancer related care, pre and post nephrectomy nephrology evaluation is also an evolving area for both clinical care and research. 1,6 Secondary to the increased number and complexity of onconephrology consultations spanning nephrology and oncology, there is a need to expand and focus clinical training in this area. It is imperative to have collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer.…”

mentioning

confidence: 99%

Onconephrology, an extra year of training: Where do we stand?

Jhaveri

Agarwal²

2020

Journal of Onco-Nephrology

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Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. As novel anti cancers are being used to treat patients, we are beginning to see even more kidney-related complications that require close collaboration with hematology and oncology colleagues. Secondary to the increased number and complexity of onconephrology consultations spanning nephrology and oncology, there is a need to expand and focus clinical training in this area. Some authors propose an extra year of fellowship in onconephrology and others propose against extra year of fellowship. An “area of concentration” during the second year of fellowship with 6–9 months of dedicated time might be a solution for a trainee interested in onconephrology. To train the next generation of fellows, all centers should consider at least a local expert in onconephrology and specialty clinics to teach the necessary skills. The large stand-alone cancer centers can then enhance those skills for a specific group of fellows interested by offering an extra year of fellowship. In this editorial, we discuss the pros and cons of having an extra year of training in onconephrology.

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Onconephrology: The intersections between the kidney and cancer

Cited by 94 publications

References 220 publications

An extra year of onco-nephrology fellowship training is not required for the subspecialty

An extra year of onco-nephrology fellowship training is not required for the subspecialty

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

Onconephrology, an extra year of training: Where do we stand?

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