Clinical Pearls & Morning Reports
Published May 3, 2017
Patients with cancer are at risk for acute kidney injury that is caused by sepsis, direct kidney injury due to the primary cancer, metabolic disturbances, the nephrotoxic effects of anticancer therapies, or hematopoietic stem-cell transplantation. Read the new Review Article on this topic.
Q. Is tumor-cell infiltration of the kidneys a common cause of acute kidney injury in patients with leukemia and lymphoma?
A. The kidney is the most common extrareticular site of leukemic and lymphomatous infiltration, and tumor-cell infiltrates in the kidney are seen in up to 30% of patients with lymphoma and up to 60% of patients on autopsy. However, renal infiltration causes acute kidney injury in only 1% of patients with acute leukemia and in even fewer patients with lymphoma or chronic leukemia.
Q. What are some of the causes of acute kidney injury in patients with multiple myeloma?
A. Acute kidney injury complicates multiple myeloma in, depending on the definition used, 20 to 50% of patients. Nephrotoxic effects often develop from overproduction of monoclonal immunoglobulins and free light chains, leading to cast nephropathy (the most common cause of acute kidney injury), light-chain–related proximal tubular injury, and various glomerulopathies such as light-chain deposition disease and amyloid light-chain (AL) amyloidosis. Furthermore, metabolic disturbances (e.g., hypercalcemia and hyperuricemia), sepsis, and nephrotoxin exposure may lead to acute kidney injury and may exacerbate paraprotein-related kidney injury.
A: The tumor lysis syndrome results from the release of intracellular electrolytes and nucleic acids from malignant cells that were lysed by anticancer therapies or, in rare circumstances, spontaneously. The tumor lysis syndrome is characterized by increases in serum levels of uric acid, potassium, and phosphorus and can be accompanied by hypocalcemia. Within the kidney, cytokine release associated with acute tubular injury, acute uric acid nephropathy, and acute nephrocalcinosis may contribute to the development of acute kidney injury. Uric acid nephropathy results when purine nucleotides released from cancer cells are metabolized by xanthine oxidase into insoluble uric acid. Very high levels of uric acid in the glomerular filtrate may precipitate in the renal tubules, leading to micro-obstruction and vasoconstriction, as well as renal ischemia and up-regulation of inflammatory cytokines, and resulting in an abrupt decrease in the glomerular filtration rate. Calcium phosphate precipitation in the renal tubules may also contribute to acute kidney injury in patients with severe hyperphosphatemia from the tumor lysis syndrome, especially if the urine is alkaline.
A: Targeted agents, defined as drugs designed to target specific gene mutations in malignant tissue, inhibit oncogenic signaling cascades associated with tumor growth. These agents, which are effective in the treatment of several cancers, have become a prominent cause of acute kidney injury. As with chemotherapeutic drugs, targeted agents cause injury in all nephron segments. Acute kidney injury, low-grade and nephrotic proteinuria, hypertension, and electrolyte disturbances are observed with many of these drugs. Vascular injury and glomerular injury occur with antiangiogenesis drugs targeting vascular endothelial growth factor. Although a number of lesions have been described in association with these drugs, thrombotic microangiopathy (associated with agents targeting vascular endothelial growth factor) and focal segmental glomerulosclerosis (associated with tyrosine kinase inhibitors) are the most common and are frequently associated with acute kidney injury. The checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab activate host T cells to enhance tumor killing by preventing tumor ligand binding to cytotoxic T-lymphocyte antigen 4 and programmed death 1 receptors, which deactivate T cells. However, this effect causes loss of self-tolerance (and perhaps tolerance to other drugs), leading to various forms of autoimmune injury, including acute interstitial nephritis, which is associated with moderate-to-advanced-stage acute kidney injury.