Download Treatment with erythropoiesis-stimulating agents in chronic kidney

B-CRF: other complications
B-CRF: Hematological complications
H-07: cancer-associated kidney diseases
Treatment with erythropoiesis-stimulating agents in chronic kidney
disease patients with cancer
Azzour D Hazzan1, Hitesh H Shah1, Susana Hong1, Vipulbhai Sakhiya1, Rimda Wanchoo1
and Steven Fishbane1
Kidney International (2014) 86, 34–39
1
Division of Kidney Diseases and Hypertension, Department of Medicine, North Shore
University Hospital, Long Island Jewish Medical Center Hofstra, North Shore-LlJ School of
Medicine, Great Neck, New York, USA
Correspondence: Steven Fishbane, Division of Kidney Diseases and Hypertension,
Department of Medicine, North Shore University Hospital, Long Island Jewish Medical Center
Hofstra, North Shore-LIJ School of Medicine, 100 Community Drive, 2nd Floor, Great Neck,
New York 11021, USA. E-mail: [email protected]
ABSTRACT
Treatment of anemia remains an important component in the care of patients with
nondialysis chronic kidney disease (CKD) and end-stage renal disease (ESRD).
Erythropoietin-stimulating agents (ESAs) remains a key anemia treatment strategy in this
patient population. However, anemia management in this group can become more
complicated by prior or current history of malignancy. There has been a great deal of work
both scientifically and in clinical trials in oncology that have revealed certain concerns and
risks of ESA use in patients with cancer. In this review, we will bring together knowledge from
nephrology and oncology literature to help nephrologists understand the implications for ESA
treatment when CKD/ESRD is complicated by cancer. We also suggest an approach to the
management of anemia in this patient group with active or previous malignancy.
Keywords:
anemia; chronic kidney disease; cancer; erythropoietin
COMMENTS
Anemia remains an important complication of chronic kidney disease (CKD). Although
several factors may have a contributing role in the development of anemia in CKD, the most
important cause is an inappropriately low secretion of erythropoietin from the diseased
kidneys.
Erythropoiesis-stimulating agents (ESAs) continue to have an important role in the treatment
of anemia in patients with CKD. ESA use in this group of patients has been shown to raise
hemoglobin (Hgb) levels, decrease blood transfusion requirements, and improve the quality
of life and symptoms related to anemia. However, normalization of Hgb levels in CKD
patients has been associated with increased thromboembolic (cardiovascular and
cerebrovascular) events. Studies reported in the oncology literature have also raised
concerns regarding ESA safety, including an increased possible risk of cancer progression
leading to poorer outcomes including increased mortality
The binding of Epo to some cancer cells having a receptor for this molecule can suppress
NF-κB activation and proinflammatory genes, resulting in an immunosuppressive effect.
ESAs have been used in cancer patients because of pervasive anemia, for the most part in
an effort to reduce fatigue and related symptoms and to reduce transfusion dependence. In
addition, some trials, especially in head and neck cancer, had used ESAs to increase tumor
cell oxygenation for what was hypothesized to provide more effective radiotherapy.
The most recent Cochrane Database analysis published in December 2012 reviewed 91
randomized controlled trials including 20,102 patients. Strong evidence was found that ESAs
increased mortality during the active study periods (death occurring up to 30 days after active
study protocol) (hazard ratio 1.17; 95% CI 1.06–1.29), and borderline evidence that ESAs
decreased overall survival (hazard ratio 1.05; 95% CI 1.00–1.11). It should be noted that the
increase in mortality risk was attributed to studies of patients with baseline Hgb, before ESA
treatment, over 12 g/d
What is presently documented:
(1) there is an increase in mortality risk with ESA treatment in cancer;
(2) although the increased risk appears to be at higher levels of Hgb, safety cannot be
assured for more conservative Hgb initiation points or goals;
(3) risk clearly appears to be greater when ESAs are used outside of the setting of
concurrent chemotherapy; and (4) although it is likely that the risk may depend on the type of
cancer, there is insufficient evidence at present to delineate risk profiles in a way that would
influence treatment.
In addition to mortality risk, a substantial increased risk for thromboembolic complications
was found using ESA treatment in cancer (RR 1.52, 95% CI 1.34–1.74).
Pr. Jacques CHANARD
Professor of Nephrology