Editorial: Women in onconephrology: 2022

With the advancement in cancer therapy there has been a dramatic improvement of the survival in cancer patients with nonetheless increased complexity regarding their care. Cancer therapeutics continues to be innovative by evolving from the use of traditional chemotherapies to that of targeted therapies based on gene mutations in the tumor and immunotherapies where we harness the immune system against tumors; all of which are associated with potentially significant renal toxicities. In addition, with the high dependence on adequate kidney function to be eligible for newer available therapies and clinical trials it has been realized that a vast aspect of Nephrology including electrolytes abnormalities, acute kidney injury (AKI) and chronic kidney disease (CKD) among others, occurring in an oncology patient represent important aspects of cancer patient's care. With the appreciation of the intersecting paths of both cancer medicine and nephrology, the term "Onconephrology" was coined. Several initiatives followed the birth of this specialized term such as an American society of nephrology (ASN) forum in 2011 under the leadership of Dr. Abdulla Salahudeen 1 2 , dedicated journal issues, onconephrology symposiums locally and internationally, an ASN onconephrology pre-course as part of kidney week and numerous onconephrology curriculums. Today a dedicated fellowship with at least four programs in the U.S and one program in Canada offer the opportunity to train in the field. Moreover, there is a journal solely dedicated to the specialty , and a Kidney disease improving global outcome (KDIGO) Onconephrology controversies meeting recently occurred 3 . Furthermore, with this immense recognition of Onconephrology as a specialty and rising numbers of onconephrologists, the American society of Onconephrology was first formed in 2021 under the leadership of Drs. Shruti Gupta and Kenar Jhaveri. It is nonetheless worth to mention that long before this formal recognition, the kidney complications within and from cancer, were already a matter of great concern among the scientific community, with concerning reports published since the 1950's as the first case of contrast associated AKI in a patient with myelomatosis in 1954 4 and the recognition of the associated nephrotoxicity of cisplatin 5 . This special issue of "Women in Onconephrology" aims to highlight the great contributions that prominent female nephrologists have made to the specialty nationally and internationally, pushing the field further and branching new interests such as transplant onconephrology [6][7][8][9][10][11][12][13][14][15][16] , with likely the first example being Thelma B. Dunn, the first woman elected as president of the American Association for Cancer Research. Many of her scientific contributions could be filed today under" Onconephrology" 17 18 . In this edition, 4 articles written by women pioneers are gathered and investigate forefront topics related to cancer and nephrology, and most notably immune checkpoint inhibitor (ICI) uses and associated renal toxicity.In a review by Miao et al, the authors present an overview of the incidence and risk factors for ICI nephrotoxicity, pathophysiological mechanisms, pathologies, and therapeutic options. They also discuss the controversies surrounding the re-challenge of a patient affected with AKI with ICI and the use of novel biomarkers for the non-invasive diagnosis of ICI induced kidney injury. They notably point out that while a single biomarker might neither be sensitive nor specific for the diagnosis of acute interstitial nephritis (AIN) induced by ICI, the use of multi-positive biomarkers could certainly be more sensitive and guide the decision of performing a kidney biopsy, a modality that Fenoglio et al advocate to use in their article where they review the findings of kidney biopsies done in a cohort of 30 patients to diagnose toxicities associated with targeted therapies and ICI. The authors demonstrated that histological findings were useful to initiate a more effective and targeted treatment rather than to empirically default to steroids and/or hold their cancer treatments in the presence of AKI. Also, in this issue, the sensitive topic of using ICI in kidney transplant recipients is thoroughly approached. This population has an increased risk of developing cancers especially non-melanoma skin cancers. The use of ICI to treat kidney transplant patients with skin cancers has been a challenge with an increased risk of rejection which has been noted to be as high as 42% at a median time of 24 days post ICI 19 . Meerhaeghe et al present a promising case series of 7 kidney transplant patients with advanced cutaneous squamous cell carcinoma (cSCC) in Belgium treated with cemiplimab (a human monoclonal IgG4 antibody against anti-PD-1). The study concluded that the overall response rate was 42.8% and only that one patient had biopsy-proven acute renal allograft rejection with nonetheless complete tumor response. Finally, this issue presents a case report by Qureshi et al where the authors present a patient with advanced non-small cell lung cancer and pre-existing antineutrophil cytoplasmic (anti-PR3) antibodies who later develops multi-organ vasculitis after ICI exposure, successfully treated with rituximab, with continued cancer remission for 3 years. The paper evaluates the rare incidence of autoimmune induction in the kidney after ICI exposure and the use of rituximab which has been proven to be effective in other published cases.In conclusion, this special issue of "Women in Onconephrology" by vibrant women researchers, presents interesting new perspectives in the field most notably related to better understanding of the use of ICI in patients with cancer and kidney disease but also highlights the numerous gaps that remain to be filled. It also illustrates the role of immunological triggers for the onset of glomerular diseases through the example of immunotherapy. Although not addressed in this issue, it would be also important to address in the future the differences between women and men in terms of risk, disease presentation and treatment effects in "onconephrology", an important feature of "Women in Onconephrology".

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