Onconephrologists focus on protecting kidneys from dangers of cancer treatment
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“This specialty is not just about kidney cancer; it is about any cancer and cancer-related treatment and its effect on the kidney,” Kenar Dinesh Jhaveri, MD, said about the emerging area of onconephrology.
“We are talking about two different areas,” Jhaveri, professor of medicine and associate chief in the division of kidney diseases and hypertension and co-director of onconephrology at Northwell Health and at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, told Healio | Nephrology News & Issues. “Oncologists and urologists have been treating renal cell carcinoma for decades by removing the tumor, consider a course of chemotherapy, doing a full or partial nephrectomy if needed and monitoring the patient to determine if dialysis may be required,” he said.
Source: Northwell Health
But onconephrology during the last decade has taken a different focus: the management of kidney health in the presence of aggressive therapies for treating cancer in other organs.
“That can involve drugs used to treat cancer, or the cancer itself,” Jhaveri said. “What we have seen in the last 10 years in the development of onconephrology is understanding how chemotherapy, novel targeted therapies and immunotherapies used to treat cancer impact the kidney.”
Small subspecialty
Clinicians interviewed for this Cover Story said onconephrology is still a young, emerging subspeciality with room for expansion.
“It is a new field that has evolved over the last decade,” Raad B. Chowdhury, MD, FASN, an onconephrologist in the division of renal medicine at Brigham and Women’s Dana Farber Cancer Institute, told Healio | Nephrology News & Issues. “There are only a handful of major cancer centers in the country that have a true onconephrology practice, and five or so fellowship positions in total.”
Chowdhury is a member of the planning staff and Jhaveri is a founding member of the American Society of OncoNephrology (ASON), which supports the annual OncoNephrology Symposium. This year the meeting is taking placeOct. 6-7 in Houston and is sponsored by the MD Anderson Cancer Center.
“The theme for this year’s symposium is ‘Interdisciplinary approaches in onconephrology,’ Biruh Tesfa Workeneh, MD, FASN, an associate professor in the department of emergency medicine in the division of internal medicineat the University of Texas MD Anderson Cancer Center, and this year’s program director, told Healio | Nephrology News & Issues. “We hope attendees will walk away with an understanding of the necessity of interdisciplinary cooperation in managing complex cases of patients suffering from both kidney disease and cancer,” Workeneh said.
Chowdhury, an instructor in medicine at Harvard Medical School, and Jhaveri see the symposium as an opportunity to expand interest in onconephrology. Other resources are available to help the subspecialty grow, Jhaveri said. These include:
- Onco-Nephrology Core Curriculum(https://www.asn-online.org/education/distancelearning/curricula/onco/) was released in 2023 by the American Society of Nephrology. “The recent proliferation in new cancer therapies has significantly improved survival and at the same time introduced brand new challenges for nephrologists,” according to the ASN website.
- Onconephrotoxin Library Collaboration (OLIC; https://www.olic-app.info/) offers a database of more than 50 onconephrotoxins deemed harmful to the kidney, An example includesCDK 4/6 inhibitors, linked to acute tubular necrosis, acute tubulointerstitial nephritis, water/electrolyte disturbances, an increase in serum creatinine and an increased incidence of urinary tract infections.
“The information in the OLIC database is gathered via collaboration with a world-renowned team of onconephrologists, pharmacists and pathologists,” Paul Hannah, MD, MSc, creator of the registry, told Healio | Nephrology News & Issues. “We aspire to provide a comprehensive overview of evidence-based medicine but will occasionally include expert opinions, considering much of the adverse effects of new cancer therapies is in uncharted territory.”
New program
Vanderbilt University Medical Center nephrologist Hunter K. Huston, MD, FASN, shares his background with Chowdhury. They met at the University of Pittsburgh Medical Center (UPMC), and Huston re-joined Vanderbilt recently after leaving UPMC Hillman Cancer Center to start the Nashville-based health care system’s new onconephrology program.
In an interview with Healio | Nephrology News & Issues, Huston said the profession is still evolving.
“Onconephrology started out with treating myelomas and amyloids, so years ago we had a lot of multiple myeloma patients who had kidney manifestations in one way, shape or form,” Huston said. “That and the treatment of myeloma and their success evolved into a greater appreciation and overlap of bone marrow into the liquid oncology, diseases and their kidney manifestations. I think fast forwarding to just the last few years, the overlap has become a greater enterprise.”
Huston said the expansion not only includes evaluating cancer of various types but the impact of the malignancy on kidney function. “When I say I am an onconephrologist, when I say that I treat cancer of the kidney, the first thought is kidney cancer and renal cell,” Huston said. “But that is an increasingly small piece of the overall pie.”
Disease management
Chowdhury likewise separates treatment therapies by the disease and its management.
“Bucket A has the treatment-related complications from [kidney] cancer, including renal complications of chemotherapy, stem cell transplant, nephrectomy due to renal carcinoma, immune therapy. Renal complications in this bucket can range from acute kidney injury, electrolyte disorders, thrombotic microangiopathy, tumor lysis, just to name a few,” Chowdhury said.
“Bucket B would be the cancer manifestations in the kidney itself. Since the mid-1800s, we have known that there are abnormal proteins in the urine of myeloma patients, which became known as an indicator called Bence-Jones Protein. Fast forward 150 years, and we are increasingly appreciative that blood disorders have various fascinating kidney manifestations. Additionally, we are also learning that solid tumors can cause immunogenic disease in the glomerulus of the kidney; kidney diseases, like membranous nephropathy or minimal change disease, can sometimes be triggered by cancer.
“Ultimately, cancer patients are living longer and their dialysis needs are changing. We are also evaluating how kidney transplant fits into this population. The management of these disorders in this patient population can be complex and often relies on a multidisciplinary approach and expert opinion. We often don’t have a full understanding of the pathophysiology of how these interactions work or have large-scale trials to guide our management,” Chowdhury said.
Jhaveri has focused some of his research on renal toxicities of novel oncological agents. “We are finding more about the toxicities associated with new chemotherapy and immunotherapy agents. The effects we see are increased cases of hypertension and proteinuria and novel electrolyte disorders,” Jhaveri said.
Cancer and kidney disease
While the focus of onconephrology has been on protecting the kidney from harmful toxicities, clinicians are also getting a better understanding of the risks of kidney cell carcinoma. Cases have increased in recent years, accountingfor about 4% of all adult malignancies; 270,000 new cases are diagnosed annually worldwide. In 2021, 76,080 new cases of renal cell carcinomawere diagnosed in the United States, according to a report in the Journal of Kidney Cancer.
In a paper titled, “Onconephrology: The intersections between the kidney and cancer,” Mitchell Rosner, MD, and colleagues outlined the risks that patients may face in developing chronic kidney disease after a cancer diagnosis.
“CKD may preexist in a substantial number of patients with cancer,” Rosner and colleagues wrote in the paper. “This is likely because of comorbid conditions, such as diabetes mellitus and hypertension, which are highly prevalent in the population. ... CKD may be associated with a higher risk for certain malignancies, especially those of the urinary tract,” the authors wrote.
Jhaveri, one of the co-authors on the paper, told Healio | Nephrology News & Issues that a decline of eGFR among patients with cancer should be monitored.
A recent paper published in the Journal of the National Comprehensive Cancer Network authored by Wendy J. Bottinor, MD, MSCI, a cardio-oncologist and member of the cancer prevention and control research program at Virginia Commonwealth University Massey Cancer Center, and colleagues, looked at the risk for hypertension among adolescents and young adults treated for kidney cancer. Nearly half of adolescents and young adults in the study who were treated with sorafenib (Nexavar, Bayer) and one-third of patients treated with sunitinib (Sutent, Pfizer) developed hypertension, the researchers wrote in the paper.
“The large number of [young adults] who had high blood pressure during treatment with sunitinib or sorafenib suggests that even individuals without identifiable preexisting factors – such as older age, obesity and male gender – are also at significant risk for hypertension from these drugs,” Bottinor and colleagues wrote.
Risk equation model
Researchers have also explored the risk of end-stage kidney disease once kidney cancer is detected. Oksana Harasemiw, MD, and colleagues from the Chronic Disease Innovation Center at the Seven Oaks General Hospital, Winnipeg, Canada, developed a risk equation model to predict whether patients who received a nephrectomy due to removal of a carcinoma would go on to kidney failure.
“Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer,” they wrote in the American Journal of Kidney Diseases. “However, surgery can potentially result in the loss of kidney function, or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long-term.”
The authors reviewed 1,026 adults from Manitoba, Canada, who were diagnosed with nonmetastatic kidney cancer between Jan. 1, 2004, and Dec. 31, 2016. Patients were treated with either a partial or radical nephrectomy and had at least one eGFR measurement pre- and post-nephrectomy. Researchers found 10.3% of patients in the cohort had kidney failure after nephrectomy.
“Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer,” the authors wrote.
Detecting kidney cancer – or identifying the risk of cancer therapies – make up a subspecialty that has room to grow, but a shortage of fellows in nephrology, Jhaveri said, may slow down development of new onconephrology programs. Huston said his program at Vanderbilt will proceed.
“Some institutions, particularly places like MD Anderson Cancer Center and Sloan-Kettering Cancer Center, have had well-defined oncology divisions and programs for a few years at this point. The field is growing in its academic presence. There is a lot of collaboration across institutions ... I think that [collaboration] is helping support the idea for us to get onboard and develop our program. “Onconephrology is here to stay,” Huston said.
- References:
- Alzubaidi A, et al. Jrnl of Kid Cancer. 2022;doi:10.15586/jkcvhl.v9i2.219.
- Harasemiw O, et al. Am Jrnl Kid Disease. 2023;doi:10.1053/j.ajkd.2023.06.002.
- https://www.healio.com/news/hematology-oncology/20230712/adolescent-young-adult-survivors-of-kidney-cancer-at-high-risk-for-cardiovascular-disease
- Rosner M, et al. CA Cancer J Clin. 2021;doi:10.3322/caac.21636.
- For more information:
- Raad B. Chowdhury, MD, FASN, can be reached at rbchowdhury@bwh.harvard.edu.
- Hunter K. Huston, MD, can be reached at hunter.k.huston@vumc.org.
- Kenar Dinesh Jhaveri, MD, can be reached at kjhaveri@northwell.edu.
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