Kiera Liblik, MSc Candidate (Translational Medicine)
Dr. Sarah Moran and Dr. Samuel Silver presented Grand Rounds for the Departments of Medicine and Oncology. They discussed onconephrology, the field which aims to “help cancer teams identify, treat, and, if possible, prevent kidney problems”(1).
Onconephrology specifically explores how cancer-therapy/specific-factors, patient-specific factors, acute kidney injury (AKI), monoclonal gammopathy of renal significance, hematopoietic stem cell transplantation, electrolyte disorders, and pain management intersect to contribute to the development of chronic kidney disease (CKD)(1). As cancer survival improves, oncology patients are living long enough to develop CKD and require complex nephrology care. Oncology patients with declining renal function also have lower rates of initiation of chemotherapy, radiation, and palliative care(2-4). It follows that inpatient chemotherapy and active cancer are independent predictors of 1-year mortality following AKI(4). Despite the increased need for intervention in the onconephrology population, these patients are often subject to ‘renalism’ or underutilization of interventions and exclusion from clinical research due to concern of adverse events. Consequently, these patients are unable to properly benefit from clinical practice guidelines which have not been tested in their population(5).
Dr. Moran and Dr. Silver presented clinical cases to demonstrate the beneficial role of onconephrology in practice. The first case demonstrated clinical predictors of finding monoclonal gammopathy of renal significance on biopsy, including proteinuria ≥1.5g/day, hematuria, and an abnormal free light chain ratio(6). Next, they discussed intravenous contrast, pemetrexed, and pembrolizumab as possible causative agents of AKI in a patient with adenocarcinoma. The risk of contrast-associated AKI is low and it is important to consider the diagnostic benefit of its use(7). If the immune checkpoint inhibitor (ICI) is the suspected cause, a few factors can help guide clinicians as to whether therapy should be resumed. If the patient fully recovers, acute interstitial nephritis (AIN) is seen on biopsy, other causes of AIN can be discontinued, and/or the patient has an ICI sensitive tumor, rechallenge may be considered. Conversely, continued renal dysfunction, severe multi-organ involvement, previous completion of extended ICI therapy, and/or glomerulonephritis reduce the likelihood of benefitting from rechallenge(8, 9). The final case comprised a discussion on kidney biopsies as well as ICI-associated minimal change disease, which is treated with high-dose steroids. It is important to weigh the complications of biopsy, such as hematomas, bleeding, pain, macroscopic hematuria, and 0.06% risk of death (10).
Overall, oncology patients who are suspected to have AKI or electrolyte disturbances secondary to cancer therapy, have acute decline in renal function, an eGFR <30mL/min/1.732, and/or albumin-to-creatinine ratio >60mg/mmol should be referred to onconephrology. This collaboration not only benefits patients, but their healthcare team and the broader healthcare system.
Following Grand Rounds, Dr. Moran and Dr. Silver generously engaged in a discussion with Translational Medicine students. First, they discussed barriers to developing an onconephrology program. Clinically, it may be challenging to optimize renal function in patients who are at increased risk for CKD and AKI but need to continue on potentially renal-toxic therapeutics to manage their cancer. Additionally, patient beneficence must be balanced with clinical efficiency and resource stewardship in the context of a healthcare system with finite physicians and funding. Regardless, we must prioritize taking the time for knowledge translation in order to help patients make informed decisions. This is particularly important as the public understanding of kidney disease is limited by complex terminology, low health literacy, and that it is a ‘silent disease’ in early stages. Those in the patient’s care team must venture to understand their priorities throughout their disease course. To facilitate effective care, it is also important that we utilize markers of renal function that are reliable across demographic groups, such as cystatin C(11).
Dr. Moran and Dr. Silver’s closed by sharing their career journeys, which began an ocean apart. Dr. Moran went to medical school in Ireland, completing her Internal Medicine and Nephrology training followed by fellowships in Glomerulonephritis and Obstetric Nephrology at the University of Toronto. She reflected that she was drawn to nephrology as it is akin to ‘detective work’ and allows for long-term patient care with a focus on increasing not just lifespan, but quality of life. Dr. Silver also trained at the University of Toronto, where he completed his training in Internal Medicine and Nephrology before he was a research fellow at Stanford. His interest in nephrology similarly stems from an interest in longitudinal care, as well as the multi-system nature of care in this population. Both Dr. Moran and Dr. Silver are interested in quality improvement and system-based change, which is demonstrated by the success of the onconephrology program.
The students of the Translational Medicine program would like to thank Dr. Moran and Dr. Silver for their time as well as their incredible contributions to patient care.
References
1. Rosner MH, Jhaveri KD, McMahon BA, Perazella MA. Onconephrology: The intersections between the kidney and cancer. CA Cancer J Clin. 2021;71(1):47-77.
2. Kitchlu A, McArthur E, Amir E, Booth CM, Sutradhar R, Majeed H, et al. Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study. J Natl Cancer Inst. 2019;111(7):727-36.
3. Kitchlu A, Chan CT, Leung N, Chen S, Latcha S, Tam P. Perspectives From an Onconephrology Interest Group: Conference Report. Can J Kidney Health Dis. 2020;7:2054358120962589.
4. Silver SA, Harel Z, McArthur E, Nash DM, Acedillo R, Kitchlu A, et al. Causes of Death after a Hospitalization with AKI. J Am Soc Nephrol. 2018;29(3):1001-10.
5. Kitchlu A, Shapiro J, Amir E, Garg AX, Kim SJ, Wald R, et al. Representation of Patients With Chronic Kidney Disease in Trials of Cancer Therapy. JAMA. 2018;319(23):2437-9.
6. Klomjit N, Leung N, Fervenza F, Sethi S, Zand L. Rate and Predictors of Finding Monoclonal Gammopathy of Renal Significance (MGRS) Lesions on Kidney Biopsy in Patients with Monoclonal Gammopathy. J Am Soc Nephrol. 2020;31(10):2400-11.
7. Weisbord SD, Palevsky PM, Kaufman JS, Wu H, Androsenko M, Ferguson RE, et al. Contrast-Associated Acute Kidney Injury and Serious Adverse Outcomes Following Angiography. J Am Coll Cardiol. 2020;75(11):1311-20.
8. Johnson DB, Jakubovic BD, Sibaud V, Sise ME. Balancing Cancer Immunotherapy Efficacy and Toxicity. J Allergy Clin Immunol Pract. 2020;8(9):2898-906.
9. Seethapathy H, Herrmann SM, Sise ME. Immune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management. Kidney Medicine. 2021.
10. Poggio ED, McClelland RL, Blank KN, Hansen S, Bansal S, Bomback AS, et al. Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications. Clin J Am Soc Nephrol. 2020;15(11):1595-602.
11. Helmersson-Karlqvist J, Lipcsey M, Arnlov J, Bell M, Ravn B, Dardashti A, et al. Cystatin C predicts long term mortality better than creatinine in a nationwide study of intensive care patients. Sci Rep. 2021;11(1):5882.