Consensus Report from Oncology Advisory Board Meeting

8 • Strategies for Prevention and Management of CI-AKI and the Role of Contrast in Oncology CT Settings of cardiac output), which ensures high levels of toxicant delivery. High tubular re-absorptive capacity of kidneys can lead to high intracellular tubular cell concentrations of any drug. In addition, kidneys can concentrate toxins to high levels within the medullary interstitium; an important site for xenobiotic metabolism and may transform relatively harmless parent compounds into toxic metabolites. Kidneys also have a high metabolic rate and the workload to renal cells results in increased sensitivity to toxicants and a high sensitivity to vasoactive agents. As kidneys are major elimination pathway for many antineoplastic drugs and their metabolites, any impairment in renal functions can result in delayed drug excretion and metabolism of chemotherapeutic agents, resulting in increased systemic toxicity. Understandably, many drugs require dose adjustment when administered in the setting of renal insufficiency. In general, oncology patients are at heightened risk of nephropathy owing to the disease per se, its treatment or its follow-up. The various types of clinical settings where the risk of nephropathy in oncology patients is increased are: y y Tumor lysis syndrome (TLS); y y Hypercalcemia; y y Cancers, such as multiple myeloma where light chain are excreted via kidneys and cause renal failure; y y Pelvic tumors – hydronephrosis; y y Dehydration – vomiting, diarrhoea, and poor intake; y y Liver dysfunction due to metastases; y y Nephrotoxic chemotherapy drugs; y y Supportive care drugs – NSAIDs and zoledronic acid; y y Infections – sepsis and septic shock; y y Comorbidities – diabetes and metastatic involvement; y y Tumor or treatment-related microangiopathy; y y Tumor or treatment-related nephritic syndrome; and y y Contrast-induced acute kidney injury (CI-AKI). Potentially, most of the anti-cancer drugs are nephrotoxic. But, few of them are more notorious for causing nephrotoxicity. These include methotrexate, cisplatin, ifosfamide, epirubicin, gemcitabine, carboplatin, doxorubicin, paclitaxel, oxaliplatin, irinotecan, bevacizumab, and trastuzumab. Cisplatin merits further elaboration, as it can cause acute tubular necrosis (ATN), interstitial damage, and AKI due to dehydration-related hypovolemia (Tables 1–3). Table 1. Drugs associated with tubular toxicity. Drugs Pathological findings Clinical syndromes Cisplatin y y Acute tubular necrosis y y Chronic interstitial fibrosis and cyst formation y y Acute kidney injury y y Hypomagnesemia y y Renal sodium wasting y y Chronic kidney disease Ifosfamide y y Acute tubular necrosis y y Fanconi syndrome (partial/complete) y y Acute kidney injury y y End stage renal disease Methotrexate y y Crystal nephropathy y y Nonoliguric acute kidney injury Pemetrexed y y Acute tubular necrosis y y Acute interstitial nephritis y y Tubular atrophy and interstitial fibrosis y y Acute kidney injury y y Chronic kidney disease y y Nephrogenic diabetes insipidus Ipilimumab y y Acute interstitial nephritis y y Acute kidney injury American Society of Nephrology; Onco-Nephrology Curriculum; 2016. Table 2. Drugs associated with glomerular toxicity. Drugs Pathological findings Clinical syndromes Gemcitabine  y y Thrombotic microangiopathy y y Acute kidney injury y y Microangiopathic hemolytic anemia y y Hypertension Mitomycin y y Thrombotic microangiopathy y y Dose dependent: Acute kidney injury, microangiopathic hemolytic anemia y y Hypertension Bevacizumab y y Thrombotic microangiopathy y y Proteinuria y y Hypertension y y Less common: Nephrotic syndrome, acute kidney injury, microangiopathic hemolytic anemia Vascular endothelial growth factor multitarget tyrosine kinase inhibitors (VEGFR mTKI) Sunitinib Sorafenib Axitinib Pazopanib y y Thrombotic microangiopathy y y MCD/cFSGS (minimal change disease and/or collapsing-like focal segmental glomerulosclerosis) y y Proteinuria y y Hypertension y y Less common: Nephrotic syndrome y y Acute kidney injury, microangiopathic hemolytic anemia American Society of Nephrology; Onco-Nephrology Curriculum; 2016.