Claudio Ponticelli, MD, FRCP

Onconephrology is a new subspecialty of clinical nephrology that encompasses a large spectrum of renal complications related to cancer or its treatment. Acute kidney injury (AKI), tumor lysis syndrome, chronic kidney disease, fluid and electrolyte disorders are the most frequent renal complications of anti-cancer treatment, particularly in aged patients. Most of these complications may be prevented or attenuated by adequate preventive measures. AKI represents an important cause of morbidity and mortality in cancer patients. It may have multifactorial causes, the most frequent being diabetes, antibiotics, intravenous contrast, hyponatremia, and chemotherapy. Nephrologists may adopt measures that can reduce the incidence and severity of AKI in cancer patients. Just to give some examples, many nephrotoxic agents may be replaced by safer drugs, the risk of intravenous contrast may be reduced by appropriate hydration and forced diuresis, hyponatremia, and other electrolyte or acid-base unbalances can be easily corrected. Renal physicians can also help reduce the risk of renal disorders after chemotherapy, by assisting in the proper dosing of cytotoxic drugs in patients with decreased glomerular filtration rate (GFR), regulating intravenous hydration, and maintaining water and electrolyte balance. These measures should be integrated with appropriate treatment of hypertension, diabetes mellitus, and other comorbidities in patients with an established chronic kidney disease (CKD).

The use of novel anticancer agents—such as VEGF (vascular endothelial growth factor), tyrosine kinase inhibitors, mTOR inhibitors, etc—is a primary issue for oncologists. These drugs can exert important renal and systemic side effects which are probably related to dosage. However, little is known about the timing and dosing of these drugs in patients with reduced GFR, hypoalbuminemia or retention of uremic toxins, anyone of which not only is associated with poor physical performance and frailty but can also markedly alter the pharmacokinetic and pharmacodynamic properties of many drugs. The complexity of the problem is further amplified in patients on dialysis. A renal physician expert in handling “difficult” drugs in “difficult” patients can be of help in facing these problematic situations. Ideally, however, the nephrologist should be asked to investigate kidney function and to assess the need for dose adjustments before anticancer therapy is administered.

Another important issue is late diagnosis of renal events. Sometimes, the development of glomerular, tubulointerstitial, or vascular renal diseases represents the first clinical manifestation of an underlying solid cancer or hematopoietic malignancy. An early recognition of these cases can favor a prompt treatment of cancer and avoid useless and even dangerous treatment with glucocorticoids or immunosuppressive drugs. Patients on regular dialysis treatment and those exposed to prolonged immunosuppression, i.e., transplant recipients, and are at higher risk of cancer. A skillful nephrologist should frequently visit these patients and should not neglect signs or symptoms that may be the first manifestation of malignancy. In particular instances, early diagnosis and timely treatment of renal diseases can rescue the kidney function. Some renal complications caused by cancer or its treatment—such as thrombotic microangiopathy, small-vessel vasculitis, interstitial nephritis or extra-capillary glomerulonephritis—have a rapidly progressive course. In these cases, late diagnosis and treatment cannot arrest the development of irreversible end-stage renal disease. Although, few patients with dialysis dependent AKI recover renal function, the premorbid creatinine can be a prognostic clue. Usually, the higher the serum creatinine is at presentation the worse the outcome. Conversely, when treatment is initiated early, complete or partial remission of these complications is possible. However, nephrologists are often called too late, when renal failure already fully developed.

In summary, there are few doubts that a strict collaboration between oncologists and nephrologists can decrease the number and severity of renal events, reduce the length of hospitalization, and improve the life expectancy of cancer patients. Yet, there has been little interexchange between these specialists up to now. On the other hand, if many nephrologists can manage some trivial cases of dehydration or AKI, only few of them are familiar with the many issues an oncologic patient may present and even fewer nephrologists possess the wide stock of knowledge necessary to handle new anti-cancer drugs with narrow therapeutic range. This implies that nephrologists called for consultancy by a cancer unit should have a thorough knowledge of the renal safety profile of anticancer drugs, their metabolism, and their pharmacokinetic and pharmacodynamic properties. In the last decades clinical nephrology has had a terrific expansion and originated a number of subspecialties, including dialysis, transplantation, pediatric nephrology etc. The advent of onconephrology as a further subspecialty may open new perspectives for better life expectancy and quality of life in patients with cancer and renal disease.

Claudio Ponticelli, MD, FRCP
Senior consultant, Humanitas Clinical and Research Center, Rozzano (Milano)

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