A new clinic specializing in onco-nephrology — an emerging medical subspecialty that strives to preserve kidney health in cancer patients — has been established under the leadership of David I. Ortiz-Melo, MD, a Duke nephrologist specializing in chronic kidney disease, acute kidney injury and kidney transplant care.
The Duke Onco-Nephrology Clinic provides nephrology subspecialty consultation for cancer survivors and patients undergoing therapy for cancer. This includes the management of acute kidney injury (AKI) and chronic kidney disease (CKD); CKD from total or partial nephrectomy for kidney cancer; CKD from paraproteinemias, multiple myeloma and amyloidosis; kidney injury due to chemotherapy, targeted therapy and immunotherapy; severe fluid and electrolyte abnormalities; and dosing and timing of chemotherapy in patients with AKI and CKD.
The clinic works by provider referral via telephone or email. Ortiz-Melo is able to fit cancer patients into his two-days-a-week General Nephrology clinic schedule at Duke South 2B.
With an increase in the number of patients living with cancer, malignancy-related and cancer treatment-related kidney disease, both acute and chronic, is on the rise. Cancer itself can directly cause kidney injury through tumor infiltration or production of nephrotoxic (kidney-toxic) substances. Patients can also suffer kidney injury and “nephrotoxicity” as a side effect of cancer treatment. In addition, cancer patients with underlying chronic kidney disease have limited options for cancer therapies due to their decreased renal function.
“Kidney disease is a growing concern in the cancer population,” Ortiz-Melo said. “Any specialty can get interested with cancer at some point, as multiple organs can be affected by cancer, but in the case of nephrology, there’s a bi-directional relationship. Cancer and cancer treatments affect the kidney and kidney disease actually raises the risk of getting cancer.”
A damaged kidney, he cautioned, can lead to interruptions of cancer therapy, including dose reduction or use of alternative, suboptimal regimens, said. Kidney injury can also result in increased length of stay in the hospital, increased cost and increased mortality, and it limits patient participation in clinical trials.
Sometimes you have to compromise your best therapies and settle for something not as good because it has to be kidney-friendly,” he said. “There are also ethical considerations around whether or not to withhold dialysis and when to use palliative dialysis.”
Ortiz-Melo recalled a patient with metastatic melanoma for whom medications are working perfectly from the cancer perspective, but they were “significantly compromising kidney function.”
“If you do not have any other therapies available for the cancer, the question to answer here is how much nephrotoxicity are we willing to tolerate, in order to help with the melanoma if no further therapeutic options are available?” he said.
While he’s not an oncologist, the relationship between cancer and nephrotoxicity and the disease’s effect on the kidney has interested Ortiz-Melo ever since he was a Duke nephrology fellow eight years ago.
“Every time I’ve gone to the 9th floor, where seriously ill cancer patients are treated, I’ve seen how complicated the kidney injuries are,” he said.
In a recent presentation for the Department of Medicine Grand Rounds, Ortiz-Melo cited a Danish population-based cohort study that found a 17.5 percent overall average risk of acute kidney injury in cancer patients in the first year following diagnosis and a 27 percent average risk in the first five years. That study team also found that overall and for most cancers, risks were higher among patients with distant metastases at cancer diagnosis. They observed the highest one-year risk of acute kidney injury in kidney cancer (44 percent), followed by multiple myeloma (31.8 percent), and liver cancer (33 percent).
The top risk factors for chronic kidney disease (also called chronic kidney failure) are diabetes, followed by high blood pressure. The third and fourth most common risk factors of chronic kidney disease are inflammation of the glomeruli (the kidney’s filtering units) and interstitial nephritis (inflammation of the spaces between the kidney tubules, the interstitium) — both of which can be caused by some cancers and cancer therapies.
Membranous nephropathy, a type of glomerular disease, is one of the most common causes of nephrotic syndrome in adults, which over time can lead to kidney failure. In lung cancer, breast cancer and other solid tumors, Ortiz-Melo explained, it can happen at any time starting with diagnosis and even before cancer is diagnosed.
Chronic lymphocytic leukemia (CLL), he said, can invade the kidney and cause infiltrative disease of the kidney, enlarged kidneys with poor function, and paraneoplastic glomerular disease.
Hodgkin lymphoma can sometimes cause Minimal Change Disease, another disease that damages the filtering units (glomeruli) of the kidney. This disease is the most common cause of nephrotic syndrome in children. (Melo-Ortiz notes that if a Hodgkin lymphoma survivor, even years later, is found to suddenly have protein in their urine, this could mean they’ll have a cancer relapse.)
Various types of nephrotoxicity have increased with development of new targeted therapeutic drugs and intensive chemotherapy regimens. A variety of conventional chemotherapies and targeted therapies, used across many cancers, Ortiz-Melo said, can cause, for example, tubulopathies (diseases of the renal tubules of the nephron), podocyte injury, thrombotic microangiopathy (TMA), and interstitial nephritis.
One of the newer challenges in onco-nephrology, Ortiz-Melo said, is assessing the impact that immunotherapies — PD-1 and CTL-4 checkpoint inhibitors specifically — have on the kidneys.
They can cause side-effects in the kidneys anywhere from immediately to months after the first dose, he said. Though there’s limited data — as they’ve been FDA-approved for less than a decade — Ortiz-Melo said some have been implicated in interstitial nephritis, one of the risk factors for chronic kidney disease. (He noted that endocrine and gastrointestinal side-effects are more prevalent than kidney side-effects)
Patients who’ve had parts or all of their kidney removed, due to kidney cancer, are also at high risk for chronic kidney disease. Ortiz-Melo works with DCI urologic cancer surgeons on preoperative evaluation, operative management, and postoperative management. They also collaborate on patient cases of bladder cancer and urethral carcinomas which can also damage the kidneys.
Kidney injury from radiation therapy — radiation nephritis — can also develop in some patients, he said.
Ready, Set, Go
Since informally announcing the establishment of the Duke Onco-Nephrology Clinic about six months ago, Ortiz-Melo’s had about five or six patient referrals a month from a handful of Duke Cancer Institute oncologists, including specialists in multiple myeloma, CLL, melanoma, and urologic oncology.
He considers them partners in comprehensive onco-nephrology care, a relatively new field that only emerged as a dedicated sub-specialty of nephrology over the past decade.
“The oncology model is moving so fast; there’s so many different agents and so many side-effects, that as a general nephrologist it’s a challenge to keep up with it,” he said. “It’s so much easier if you have a multidisciplinary team — for us and for the patient’s outcomes and peace of mind. If I’m there at the snap of a finger to see a cancer patient in my clinic or follow up with labs, we can minimize the side effects that cancer and cancer treatment has on their kidneys.”
In the future, Ortiz-Melo said he’d like to have access to examine the renal tissue that’s removed from all cancer patients who are at risk for CKD — especially patients who present with high blood pressure, diabetes, and protein in the urine — to see if they may already have kidney disease.
“This would give us some idea of how to approach these patients later on, especially as regards their kidney function,” he said. “Onco-nephrology represents multiple opportunities for expanding nephrology practice, training, and research collaborations.”
Ortiz-Melo rounds at Duke University Hospital every other month and, as the director of DaVita Bull City Dialysis in Durham, he sees dialysis patients every other month in Durham, as well as in Roxboro and Louisburg. For referrals and appointments for the Onco-Nephrology clinic, call 919.660.6860.
WATCH (only those with Duke ID): David Ortiz-Melo, MD, presents Grand Rounds -- Onco-nephrology: A closer look at the cancer-kidney connection