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A brief history in nephrology pharmacotherapy.

Article Excerpt
The kidneys play a vital role in maintaining homeostasis. Regulating body water, electrolytes, acid-base balance, and excretory regulation, in addition to metabolic (endocrine) processes, are some of the functions that the kidneys perform. Chronic kidney disease (CKD) results from progressive and irreversible destruction of the nephron mass. Virtually every organ system is affected in the setting of CKD.

As kidney function progressively declines, anemia develops due to decreased erythropoietin production. Erythropoiesis-stimulating agents (ESAs) can be given to increase red blood cell production. Intravenous iron is given to most patients with CKD to help manage iron deficiency anemia and to enable adequate erythropoiesis in response to ESA therapy.

Disturbances in mineral and bone metabolism leading to renal osteodystrophy are common consequences of hyperphosphatemia and hyperparathyroidism. Treatment and prevention include the use of oral phosphate binders, vitamin D analogs, and calcimimetics.

Kidney transplantation has emerged as a treatment option for patients with CKD. Successful kidney transplant is associated with improved quality of life (QOL), freedom from renal replacement therapy, and fewer dietary restrictions. Life-long immunosuppressive drugs are required to prevent graft rejection, some of which can be nephrotoxic.

Over the past 40 years, our understanding into the mechanisms of disease has vasty increased. During this same time period, many new and novel drugs have been developed to mitigate disease. Table 1 is a chronologic list of some nephrology-related medications and the year each was approved by the United States Food and Drug Administration (FDA). There has been significant advances in drugs used to treat diabetes and hypertension, two disease states that contribute significantly to the development of CKD. For brevity, this article will focus on how the management of anemia and renal osteodystrophy has evolved, and how immunosuppressive drugs transformed the field of transplantation.

Anemia

Anemia is a common complication of CKD, and it has negative effects on exercise capacity, cardiovascular disease, and QOL Anemia can result in significant morbidity and mortality. Throughout the 1970s and 1980s, androgens (such as testosterone and nandrolone) and transfusions were the mainstay for the management of anemia of CKD (DeGowin, Lavender, Forland, Charleston, & Gottschalk, 1970). In addition to treating anemia, the androgenic effects also had positive effects on nutritional parameters in malnourished patients. However, anabolic steroids were associated with significant adverse effects, such as virilization, increased libido, and liver toxicity (DeGowin et al., 1970). Anemia of CKD develops as a result of erythropoietin deficiency. The introduction of recombinant human erythropoietin (epoetin alfa, Epogen[R], and Procrit[R]--Amgen, Inc.) in 1989 led to improvements in exercise tolerance, and a decrease in transfusion requirements and use of androgens (Eschbach et al., 1989). Darbepoetin (Aranesp[R]--Amgen, Inc.) is a glycosylated recombinant human erythropoietin that has been modified to increase the time that the drug stays in the body. The increased half-life allows for once-a-week administration.

While the treatment of anemia with these ESAs has...

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