Acute Kidney Injury in Critically Ill Patients with Cancer
Section snippets
Definition and early identification of acute kidney injury
A major limitation to the correct interpretation of data on the epidemiology of AKI is the use of different definitions for AKI. At least 35 different definitions for AKI are used in the medical literature,45, 46 ranging from minor derangement of kidney function to severe AKI, such as AKI defined by the need for treatment with RRT. Comparison of incidence and outcome data of studies on AKI are hampered by this abundance of definitions. The RIFLE classification (Risk of renal dysfunction, Injury
Epidemiology of acute kidney injury in critically ill cancer patients
The incidence and hospital mortality associated with RRT in the general critically ill cancer population and the most important subgroups are depicted in detail in Tables 1 and 2, respectively. These tables include studies from 1990 onwards, focusing exclusively on cancer patients admitted to the ICU with life-threatening complications and for whom sufficient data were available.5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,
Causes of acute renal failure in critically ill cancer patients
AKI usually results from a combination of nephrotoxic insults in critically ill cancer patients, although a main insult is often identifiable in daily practice.6, 12, 13, 15 AKI may occur as a direct or indirect consequence of the cancer itself, its treatment, or associated complications. The most common causes of acute renal failure in cancer patients admitted to the ICU are listed in Table 3.6, 12, 13, 14, 15 Sepsis was the most common cause of AKI followed by nephrotoxic drugs. Dependent on
Sepsis
As in general ICU patients,49, 51, 52, 55 sepsis and, more particularly, severe sepsis and septic shock, is the most common main contributing factor to the development of AKI in critically ill cancer patients. Patients with hematologic malignancies, who often experience longer duration of neutropenia compared with solid tumor patients, are at particularly high risk of bacterial and, less frequently, fungal sepsis.2, 19, 20, 21, 25, 32, 37, 60 In a multicenter study comparing outcomes of cancer
Antimicrobial Drugs
Several antimicrobial drugs commonly used in the supportive care of febrile cancer patients and to those with severe sepsis and septic shock may induce AKI.14, 24
Aminoglycosides (gentamicin, tobramycin, amikacin) are commonly used in daily practice in cancer patients, although current guidelines no longer strictly recommend the use of aminoglycosides in combination with a β-lactam in febrile neutropenic patients.68 Also, 2 large meta-analyses, one performed in immunocompetent sepsis patients69
Tumor lysis syndrome
TLS is a metabolic disorder that results from the massive destruction of malignant cells and the subsequent abrupt release of intracellular anions (phosphate), cations (potassium), metabolic products of proteins, and nucleic acids (uric acid) into the extracellular space and the bloodstream.90, 91, 92 This rapid release may overwhelm the body's homeostatic mechanism to process and excrete these materials and result in the life-threatening clinical spectrum of TLS, which is characterized by AKI,
Diffuse Intravascular Coagulation
DIC is observed relatively frequently in cancer patients outside the setting of sepsis.93 The reported incidence is approximately 7% in solid tumor patients,94 increasing up to 10% to 15% in case of metastatic disease,93 to 15% to 20% in patients presenting with acute lymphoblastic leukemia, and to more than 90% in those with acute promyelocytic leukemia.93, 94 Darmon and colleagues14 reported that DIC was present in 26% of the cancer patients admitted to the ICU with AKI. Cancer-related DIC
Acute kidney injury secondary to ureteral obstruction
Ureteral obstruction is the fifth most common main or concomitant cause of AKI in cancer patients admitted to the ICU.14, 15 Ureteral obstruction carries an ominous prognosis, as it is usually observed in the context of extensive metastatic solid tumors often poorly responsive to chemotherapy. Median survival is only 3 to 7 months.118, 119, 120 Ureteral obstruction may result from a direct intrinsic or extrinsic compression of the ureters by a pelvic (bladder, prostate, cervix, ovaries) or
Multiple myeloma kidney
AKI is a common feature of multiple myeloma and often provides a clue to the diagnosis of this disease, particularly in the presence of a high serum total protein concentration in routine laboratory investigations. Only 52% of the multiple myeloma patients have normal renal function on presentation121, 122 and, depending on the definition, about 20% to 46% of de novo multiple myeloma patients present with AKI.122, 123, 124 Multiple myeloma represents about 3% of cancer patients30 and 10% to 21%
Who should benefit from advanced life-supportive therapy, including renal replacement therapy?
From the aforementioned data it should be clear that the presence of an underlying cancer alone can no longer be considered a contraindication to initiate RRT in critically ill patients. Moreover, long-term survival is no longer exceptional even in multiple organ failure cancer patients requiring RRT, at least in the context of septic shock outside the allogeneic hematopoietic transplant setting.12, 27 However, these relatively good results should not be used to warrant unrealistic therapeutic
Summary
Critically ill cancer patients have a higher incidence of AKI treated with RRT than critically ill patients without cancer. AKI may occur as a direct or indirect consequence of the cancer itself, its treatment, or associated complications. The presence of an underlying cancer alone can no longer be considered a contraindication to initiate RRT in critically ill patients. Moreover, recent studies have shown that long-term survival is no longer exceptional in multiple organ failure cancer
Acknowledgments
The authors would like to thank Pieter Depuydt, MD, PhD and Jean-Patrick Harvey, MD, respectively staff member and resident in training at the Department of Intensive Care of Ghent University Hospital Medical Unit, for reviewing the manuscript and for their useful comments.
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