Acute Kidney Injury in Critically Ill Patients with Cancer

Abstract

Advances in cancer therapy have significantly improved overall patient survival; however, AKI remains a common complication in patients with cancer, occurring in anywhere from 11% to 22% of patients, depending on patient-related or cancer-specific factors. Critically ill patients with cancer as well as patients with certain malignancies (e.g., leukemias, lymphomas, multiple myeloma, and renal cell carcinoma) are at highest risk of developing AKI. AKI may be a consequence of the underlying malignancy itself or from the wide array of therapies used to treat it. Cancer-associated AKI can affect virtually every compartment of the nephron and can present as subclinical AKI or as overt acute tubular injury, tubulointerstitial nephritis, or thrombotic microangiopathy, among others. AKI can have major repercussions for patients with cancer, potentially jeopardizing further eligibility for therapy and leading to greater morbidity and mortality. This review highlights the epidemiology of AKI in critically ill patients with cancer, risk factors for AKI, and common pathologies associated with certain cancer therapies, as well as the management of AKI in different clinical scenarios. It highlights gaps in our knowledge of AKI in patients with cancer, including the lack of validated biomarkers, as well as evidence-based therapies to prevent AKI and its deleterious consequences.

Keywords: AKI; acute kidney injury; cancer; critical care nephrology and acute kidney injury series; drug nephrotoxicity; onconephrology.

Figure 1.

The spectrum of AKI is broad in patients with cancer. Ca⁺, hypercalcemia; HSCT, hematopoietic stem cell transplant; ICU, intensive care unit; NSAID, nonsteroidal anti-inflammatory agent; RAASi, renin-angiotensin-aldosterone system inhibitor; TLS, tumor lysis syndrome; TMA, thrombotic microangiopathy. Adapted from ref. , with permission.

Figure 2.

Causes of AKI in monoclonal gammopathies are classified based on histopathology. C3 GN, complement 3–related GN; GBM, glomerular basement membrane; HCDD, heavy chain deposition disease; k>l, κ-light chain>λ-light chain; LCDD, light chain deposition disease; L&HCDD, light and heavy chain deposition disease; MIDD, monoclonal immunoglobulin deposition disease; PGNMID: proliferative GN with monoclonal Ig deposits. Adapted from Bijol and Rennke (Kidney Week 2021 presentation), with permission.

Figure 3.

Obstructive nephropathy may be extrinsic or intrinsic to the genitourinary system. CT, computed tomography; GI, gastrointestinal; KUB, kidney, ureter, bladder; MRI, magnetic resonance imaging.

Figure 4.

Cisplatin-AKI is mediated by apoptosis, inflammation, DNA damage, and mitochondrial injury. Reactive oxygen species (ROS) are markers of oxidative stress and lead to DNA damage and mitochondrial injury. TNF-α is a proinflammatory cytokine. OCT, organic cation transporter.

Figure 5.

The pathophysiology of AKI from HSCT is variable. AmphoB, amphotericin B; CNI, calcineurin inhibitor; GVHD, graft-versus-host disease. Adapted from ref. , with permission.

Figure 6.

Pathophysiology of AKI in the setting of TLS and therapeutic targets. Allopurinol inhibits xanthine oxidase, an enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Rasburicase is a recombinant urate oxidase that converts uric acid into a more soluble metabolite, allantoin. Ca×P, calcium phosphate product; K, potassium.