Onco-nephrology: AKI in the cancer patient

Abstract

AKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology.

Figure 1.

Lymphomatous infiltration of the kidney. (A) A 63-year-old man with a history of B cell chronic lymphocytic leukemia not on therapy developed AKI with a serum creatinine of 3.2 mg/dl and leukocytosis of 87,000. Renal biopsy disclosed diffuse lymphomatous infiltration of the kidney characterized by monomorphic cellular infiltrates throughout the interstitium visible on hematoxylin and eosin stain. (B) The cellular infiltrate was positive for CD20 (brown stain), confirming the B cell identity of the infiltrate and consistent with the patient’s B cell leukemia. (C) The patient was started on fludarabine + rituxan therapy, and serum creatinine improved to 1.8 mg/dl, where it has remained for 2 years. Fludar, fludarabine; ritux, rituxan. Images courtesy of Helmut Rennke.

Figure 2.

Cast nephropathy. Schematic diagram illustrating the pathophysiology of AKI in cast nephropathy. Free light chains filtered by the glomerulus are taken up by proximal tubular epithelial cells through the cubulin–megalin receptor complex and clathrin-dependent endocytosis, where they are metabolized in lysosomes. Excess free light chains overwhelm lysosomal capacity, leading to activation of redox pathways, increased NF-κB and mitogen-activated protein kinase expressions, and production of proinflammatory, profibrotic cytokines. Light chains bind to Tamm–Horsfall protein in the lumen of the distal tubule, where they precipitate and form casts. CCL2, C–C motif chemokine 2; MAPK, mitogen-activated protein kinase; THP, Tamm–Horsfall protein. Modified from ref. , with permission.

Figure 3.

Comparison of sieving coefficients between high cutoff (HCO) and high-flux membranes. Clearance of higher molecular weight molecules, including light chains, is greater with HCO dialyzers compared with conventional high-flux membranes. Reprinted from ref. , with permission.

Figure 4.

Thrombotic microangiopathy after hematopoietic cell transplantation. (A) A 25-year-old woman was diagnosed with high-risk acute myelogenous leukemia, underwent induction chemotherapy, and experienced a slow hematologic recovery. She subsequently underwent allogeneic double-cord blood hematopoietic cell transplantation; 6 months later, her serum creatinine rose from 1.2 to 2.4 mg/dl in association with new hypertension, thrombocytopenia, and evidence of microangiopathic hemolysis. Kidney biopsy revealed diffuse and severe endothelial damage with double contours and occlusion of capillary lumens (periodic acid–Schiff stain). (B) There is marked endothelial swelling (endotheliosis) with fragmented red blood cells visible in capillary lumens and the damaged mesangium (arrows, hematoxylin and eosin stain). (C) Electron microscopy of a single glomerular capillary loop reveals expansion of the subendothelial space by electron lucent debris (asterisks), narrowing of the capillary lumen, and loss of endothelial fenestrae. Images courtesy of Helmut Rennke.