Abstract and Introduction
Abstract
The management of hematological malignancies (HM) in renally impaired patients may be a difficult task. Indeed, the kidney represents a major elimination pathway for many chemotherapeutic agents and their metabolites, whose serum levels are not usually measured in daily clinical practice. In addition, many antineoplastic drugs have a narrow therapeutic index for which they require dose adjustment when administered to patients with renal failure. Only limited data regarding the use of chemotherapy in patients with renal impairment and in those on dialysis are available. Indeed, renal patients with HM are often excluded from most clinical trials. Thus far, in order to provide recommendations, we have reviewed the pertinent literature, gathering information from published guidelines regarding chemotherapy in patients with kidney dysfunction and from articles describing the use of individual agents in renal patients with HM.
Introduction
The presence of renal impairment (RI) may represent an important concern in the management of hematological malignancies (HMs). Indeed, renal function represents one of the most important factors influencing patient susceptibility to adverse effects of antineoplastic treatments. Several forms of kidney dysfunctions owing to different causes and pathogenetic mechanisms may be observed in patients with HM (Table 1). Disease-related RI may occur in the form of acute kidney injury (AKI) or chronic renal failure (CRF). Therapy-related RI is another important issue in the management of HM. In this regard, traditional antineoplastic compounds, newer cytotoxic drugs or nonchemotherapeutic agents can induce several forms of kidney damage. Obviously, the administration of these nephrotoxic drugs in patients affected by a pre-existing RI may induce, through mechanisms presented in Table 2, additional kidney damage and further reduction of the residual renal function. Again, AKI and long-term renal dysfunctions, sustained by different underlying kidney diseases and complications, may occur in the late course of hematopoietic stem cell transplantation (HSCT). All of the aforementioned forms of kidney dysfunction observed in patients with HM may result in the delay of treatment and in the reduction of the dose intensity, thus negatively influencing the clinical outcome and the chances of cure. On the other hand, the relationship between the occurrences of HM in patients with a pre-existing CRF or end-stage renal disease (ESRD) deserves special attention. Indeed, a greater risk of developing malignant tumors, including HM, in renal patients compared with the general population has been reported. In this regard, the uremia-related chronic oxidative stress and immunosuppressant effects, the radiation exposure associated with repeated diagnostic procedures, and the prolonged lifespan of CRF/ESRD patients are all likely to be involved. Moreover, in patients who have undergone renal transplantation, the incidence of malignancies is markedly high compared with that of the general population; in this setting, lymphomas represent one of the most common types of neoplasia. Again, the majority of HM occurs in the elderly concomitantly with the higher incidence of most common causes of CRF, such as diabetes and hypertension. Therefore, several degrees of RI may be diagnosed in a significant number of patients with HM at the disease onset. However, very few data on the incidence of RI in HM patients and on the pharmacological behavior of chemotherapeutic agents in this setting are available owing to the exclusion of neoplastic patients with any significant degree of renal dysfunction from most clinical trials. Moreover, dose reduction is often based on limited data and empiric criteria. Again, the lack of uniformity in evaluating RI makes it difficult to compare the few reported data. However, some information can be derived from the setting of solid tumors. Recently, the Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study reported a prevalence of RI as high as 64% among 1218 cancer patients. Moreover, in a French national survey on 4684 patients with solid tumors, the reported prevalence of RI was 52.9%; most treated patients received potentially nephrotoxic drugs. In addition, a further analysis from this study focusing on elderly cancer patients (≥65 years of age) demonstrated a prevalence of RI as high as 65.2%; in particular, among those aged from 65 to 74 years, a 74.7% prevalence of RI was found. Thus far, in daily clinical practice RI represents an important concern, potentially compromising the effective management of most HM and requiring a close collaboration between hematologists, nephrologists and pharmacists. In this article, we have summarized the current knowledge and provided recommendations on the use of antineoplastic treatments in renal patients with HM.