Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer

A Population-Based Cohort Study

Abhijat Kitchlu; Eric McArthur; Eitan Amir; Christopher M. Booth; Rinku Sutradhar; Habeeb Majeed; Danielle M. Nash; Samuel A. Silver; Amit X. Garg; Christopher T. Chan; S. Joseph Kim; Ron Wald

Disclosures

J Natl Cancer Inst. 2019;111(7):727-736. 

In This Article

Abstract and Introduction

Abstract

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment.

Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007–2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.

Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.

Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.

Introduction

Cancer patients receiving treatment are known to have elevated risk for acute kidney injury (AKI).[1–4] Chemotherapy-associated nephrotoxicity, hypercalcemia, tumor lysis syndrome, paraneoplastic glomerulonephritis, and obstructive nephropathy are among the multiple causes of AKI inherent to patients with cancer.[5–7] These patients are also subject to increased risks of noncancer-specific causes of AKI, such as volume depletion, nephrotoxic medications (eg, nonsteroidal anti-inflammatory drugs, diuretics, renin-angiotensin system blockade) and contrast-induced nephropathy. AKI is of particular concern in this population, as a reduction in kidney function may delay or even preclude appropriate cancer therapies. Single-center studies have estimated that, short-term (ie, <6 months) mortality ranges from 51% to 87% after an episode of severe AKI for which dialysis was administered (AKI-D).[8–12]

Despite myriad risks to kidney function and its important prognostic implications, there is a paucity of data characterizing the burden of AKI in cancer patients, particularly in the contemporary era of cancer treatment. A 2006 study estimated that 12% of admissions to a comprehensive cancer center were complicated by AKI.[13] A Danish study using data from 1999 to 2006 estimated that the 1-year incidence of more severe forms of AKI (eg, RIFLE criteria categories of "injury" or "failure," which are more likely to require hospitalization or dialysis)[14] was 13%.[15]

However, considerable advances in the treatment of many cancer types have been made in the last decade, including in multiple myeloma[16,17] and kidney cancers (including kidney-preserving approaches, such as partial nephrectomy).[18,19] Also, targeted and immunotherapies have changed both outcomes in many cancers, as well as the potential adverse kidney sequelae.[20–23] As such, a reassessment of AKI incidence across various cancer types in the current era of cancer treatment is warranted.

We conducted a population-based cohort study of patients undergoing systemic treatment for cancer in Ontario, Canada. Our objectives were to assess the incidence of clinically relevant AKI (including hospitalizations for AKI or receipt of dialysis) and to identify patient-level risk factors. We also evaluated temporal trends in AKI and AKI-D incidence in this high-risk population.

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