A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. Chemotherapeutic agents can affect the glomerulus, tubules, interstitium or the renal microvasculature, with clinical manifestations that range from an asymptomatic elevation of serum creatinine to acute renal failure requiring dialysis.
The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Renal impairment can result in delayed drug excretion and metabolism of chemotherapeutic agents, resulting in increased systemic toxicity. Many drugs require dose adjustment when administered in the setting of renal insufficiency (table 1). Minimizing nonrenal systemic toxicity may be a particular problem in patients on chronic hemodialysis, especially when the details of drug elimination and metabolism are not fully known .
The nephrotoxicity of different chemotherapy agents, preventive strategies, and recommended dose modifications in patients with renal insufficiency will be reviewed here. An overview of renal diseases associated with various cancers (including paraneoplastic syndromes), and the renal complications of tumor lysis syndrome and hematopoietic cell transplantation are discussed elsewhere. (See "Overview of renal disease associated with malignancy" and "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors" and "Kidney disease following hematopoietic cell transplantation".)
ESTIMATION OF GFR FOR POSSIBLE DOSE ADJUSTMENT
There are two principal pathways for drug excretion by the kidney: glomerular filtration and tubular secretion. Glomerular filtration plays a major role with non-protein-bound small molecules (ie, of a size that can pass through the glomerular capillary wall). Such molecules cannot be filtered if they are protein-bound in the circulation; these drugs, if they are renally excreted, enter the urine by secretion in the proximal tubule.
For those drugs in which renal excretion is an important determinant of elimination of the intact drug or an active metabolite, dose adjustment is often required if renal function is impaired. Although the prevalence of an elevated serum creatinine is low in cancer patients (<10 percent), the prevalence of a reduced GFR is relatively high (50 to 53 percent in two cohort studies [2,3]).