UH Seidman Cancer Center Leads the Way in Growing Specialty of Onco-Nephrology

June 27, 2022

By UH

Arash Rashidi, MD, is founding member of new national organization promoting research and patient care

Innovations in Cancer | Summer 2022

University Hospitals Seidman Cancer Center is providing national leadership in the young but growing field of onco-nephrology, conducting needed research and helping to develop guidelines for managing the effects on the kidneys of newer cancer therapies like immune checkpoint inhibitors and CAR T-cells.

UH Seidman Cancer Center was among the first cancer centers to establish an inpatient onco-nephrology consult service in 2019. In addition, UH Seidman onco-nephrologist Arash Rashidi, MD, is one of the founding members of the newly formed American Society of Onco-Nephrology (ASON). He currently serves as treasurer of the society and will become the society president in January 2023, which was founded in December 2021.

“Last year we started discussing with other colleagues and other centers about the possibility of forming the American Society of Onco-Nephrology, to share knowledge in a very young field,” Dr. Rashidi says. “Onco-nephrology is growing very quickly, and there is a lot of interest across the country and world, so we needed an organization to put all these talents and energy together to edify and support the clinical, educational, and research needs at the intersection of both oncology and nephrology. The resulting society is a culmination of the hard work of scores of academic and practicing onco-nephrologists across the world, and will serve as an organized platform to foster research and education in onco-nephrology.”

There is a pressing clinical need for expert onco-nephrologists and onco-nephrology research, Dr. Rashidi says. It has been documented that cancer patients can sustain acute kidney injury (AKI) in the setting of conventional chemotherapies and hematopoietic stem cell transplant (HSCT) – which is only becoming more common. In addition, onco-nephrologists have noted hypertension among patients taking VEGF inhibitors, among other medications. Plus, with cancer patients living longer, many are developing chronic kidney disease, hypertension and electrolyte abnormalities unrelated to their cancer treatment – but still necessitating a nuanced, onco-nephrology approach to care.

Today’s emergence of tyrosine kinase inhibitors, immune checkpoint inhibitors and CAR T therapies have only added to the complicated picture for cancer patients when it comes to their kidneys, Dr. Rashidi says.

“Immune checkpoint inhibitors, for example, unleash our immune system against cancer, but they cause problems in different organs because of this,” he says. “The kidney is no exception and can be affected in form of acute kidney injury. Some of these targeted therapies can cause high blood pressure and sometimes kidney failure. They can also cause other types of kidney disease, such as proteinuria and nephrotic syndrome.”

Dr. Rashidi, in fact, was recently part of a large international study on acute kidney injury in patients treated with immune checkpoint inhibitors, published in the Journal for ImmunoTherapy of Cancer. This research was also selected by the journal for the 2022 Best Clinical/Translational Cancer Immunotherapy Paper Award. Researchers from 30 sites in 10 countries collected data on 429 patients with immune checkpoint inhibitor-induced AKI and 429 control patients who did not develop the complication, with the goal of identifying predictors of AKI in these patients – and predictors of recovery.

Results show that immune checkpoint inhibitor-induced AKI was not an uncommon problem in these patients, Dr. Rashidi says, sometimes even occurring many months after the last dose. What’s more, the research team found that patients taking proton pump inhibitors (PPIs) were at higher risk of AKI.

“The majority of these patients are being put on PPIs routinely,” Dr. Rashidi says. “But this is one of the instances where people actually should not be on PPIs because they are at much higher risk to get kidney problems.”

Dr. Rashidi has also published a case series in the journal Kidney 360, outlining the important role of kidney biopsy in managing acute kidney injury in cancer patients taking immune checkpoint inhibitors.

“We present a case series of patients with high clinical suspicion of immune checkpoint inhibitor-induced AKI, in which a kidney biopsy revealed acute tubular injury/necrosis (ATI), as opposed to the expectant acute interstitial nephritis (AIN),” he says. “Accurate diagnosis guided by biopsy findings allows for the continuation of immunotherapy and avoids potentially toxic use of high-dose corticosteroids.”

Beyond this work, Dr. Rashidi has published a study on renal outcomes after CAR T therapy among patients at UH Seidman Cancer Center, looking specifically at cancer patients with pre-existing chronic kidney disease (CKD). This study was published in the journal Nephrology Dialysis Transplantation.

“There are limited data regarding renal outcomes of patients treated with CAR T-cells, but there is no information about outcomes after CAR T-cell therapy in patients with underlying CKD,” he says. “Do they get more acute kidney injury? Does it affect their CAR T outcome? We showed that these patients are not different than non-CKD patients. They can get CAR T and their outcomes are not different. Of course, this was a small study at just one center, and more studies need to be done. But it is somewhat encouraging. You're not wanting to exclude these patients because of their underlying chronic kidney disease, because it seems they get the same benefit as other patients.”

Dr. Rashidi says he hopes these and other ongoing research efforts under the aegis of ASON will continue to inform clinical guidelines for patient care. There is room for improvement in that regard, he says.

“There is a need for onco-nephrology,” he says. “With most of the guidelines out there in regards to targeted therapies and immune checkpoint inhibitors, there is no nephrology collaboration. We are experts in the field of nephrology, so we know how to approach these patients, how to deal with these patients. Because of the activity of American Society of Onco-Nephrology, there are going to be lots of larger studies, putting all the energy and activity under one umbrella to produce more reliable results for patients. There are going to be lots of changes in this field, because of the data which are being produced and will be produced.”