Common Renal Medications for CKD Patients

Common Renal Medications for CKD Patients

Renal medications are an essential component of treating and preventing secondary complications in patients with chronic kidney disease (CKD). Patients with CKD are educated to follow a kidney disease diet to optimize health status, however, lifestyle changes alone may not be enough to maintain treatment goals as kidney disease progresses. Common renal medications include but are not limited to phosphate binders, erythropoietin-stimulating agents (ESA), intravenous (IV) iron agents, B complex vitamins, and immunosuppressants. The appropriate use of these medications is crucial to improving the quality of life, longevity, and clinical outcomes for CKD patients.

Chronic kidney disease–mineral bone disorder (CKD-MBD) describes a clinical set of symptoms encompassed by mineral, bone, and calcific cardiovascular abnormalities that develop in patients due to chronic renal impairment. Electrolyte disturbance begins in CKD stage 3 when dietary intake of phosphate exceeds urinary phosphate excretion, leading to elevated serum phosphate levels, or hyperphosphatemia. Hyperphosphatemia is an important risk factor for other abnormalities found in CKD-MBD and is associated with poor outcomes such as increased mortality in CKD stage 5 patients on chronic dialysis. To correct hyperphosphatemia, dietary phosphate restriction in combination with a phosphate-binding agent such as Velphoro (sucroferric oxyhydroxide), Renvela (sevelamer), and Phoslyra (calcium acetate) is recommended. When taken with food, these medications bind dietary phosphorus in the gastrointestinal (GI) tract, decreasing systemic absorption and reducing serum phosphorus levels. Common adverse effects are GI-related, including nausea, vomiting, diarrhea, constipation, and flatulence.1 Hypercalcemia is a potential adverse effect of calcium-based binders and recent evidence suggests calcium-based binders should be restricted due to mortality risks associated with oral calcium exposure.2 Medication selection should be individualized based on pill burden, side effect profile, phosphate binding capacity, cost, patient preference, and other patient-specific factors.1

Anemia due to CKD is common and can be characterized by reduced erythropoietin production by the kidneys, causing erythropoietin deficiency. Additional factors leading to anemia and/or iron deficiency in CKD dialysis and non-dialysis patients include frequent blood sampling, blood loss from surgical procedures, reduced iron absorption due to inflammation and drug interactions, and repeated blood loss due to retention of blood in the dialyzer and blood lines in hemodialysis. Patients may suffer anemia-related symptoms such as low energy, fatigue, and decreased physical function. Erythropoiesis-stimulating agents, used to treat chronic anemia in CKD, reduce the need for red blood cell transfusions by increasing hemoglobin concentrations and improving anemia-related symptoms.3 ESAs are erythropoietin receptor activators that trigger erythropoiesis by interacting with erythroid progenitor cells to increase red blood cell production. The potential benefits of use should be weighed against the risks related to ESA treatment. A black box warning is associated with all ESAs noting an increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access with use of this medication. ESAs have also been associated with shortened overall survival and/or increased risk of time to tumor progression or recurrence in studies with breast, cervical, head and neck, lymphoid, and non-small cell lung cancer patients. To mitigate these major risks, lower hemoglobin targets are advised with ESA therapy since studies show that adverse events are associated with elevated hemoglobin targets.3,4

Iron is essential for red blood cell production and support of ongoing erythropoiesis. As previously described, iron loss due to impaired GI absorption and other factors is common in CKD and, therefore, supplementation is often required to treat iron deficiency and maintain effective ESA treatment. Intravenous iron infusions are generally the preferred route of administration in patients on chronic hemodialysis due to concerns for inconsistent GI absorption, intolerance, and non-adherence associated with oral iron formulations.3 Examples of IV iron preparations include Venofer (iron sucrose), Feraheme (ferumoxytol), and Injectafer (ferric carboxymaltose). IV iron has been associated with infrequent but severe adverse effects and its benefits must be weighed against potential toxicities. All IV iron products contain a warning about anaphylactic and anaphylactoid reactions due to rare and fatal reported cases of hypersensitivity reactions. Patients should be monitored post-administration, and appropriately trained staff should be available to respond in case of serious adverse events. Adherence to the recommended rate of infusion is important to avoid infusion-related adverse reactions such as hypotension, nausea, vomiting, cramps, and chest pain.3,5 The role of iron administration in worsening an active infection is widely discussed, however, convincing clinical data on harm or benefit is lacking. This should prompt careful consideration for withholding or continuing iron in the setting of infection.3

Patients with CKD are susceptible to water-soluble vitamin deficiencies due to poor nutritional status, dietary limitations due to renal diet, medication-related malabsorption, and removal through dialysis. Therefore, renal vitamins containing appropriate amounts of water-soluble vitamins such as B complex and vitamin C should be used for most patients on dialysis. Fat-soluble vitamins A and K are typically excluded from renal vitamins due to potential accumulation in patients with renal dysfunction. Side effects and signs of toxicity of water-soluble vitamins are rarely reported, however, headache, GI symptoms, neuropathy, flushing, and myopathy are symptoms that have been associated with various B vitamins.6,7  

Vasculitis is a condition commonly found in patients with end stage renal disease (ESRD). The term vasculitis is used to describe a large group of diseases characterized by leukocyte infiltration of the blood vessels, often with necrosis that destroys affected tissues. There are many forms of vasculitis, each potentially involving a single or a multitude of organ systems.8 The kidney is a commonly affected organ, typically manifesting as a type of glomerulonephritis, a diverse category of kidney diseases that represent the third-leading cause of ESRD, following diabetes and hypertension.9 The management of some types of glomerulonephritis may involve glucocorticoids such as prednisone and other immunosuppressive agents such as azathioprine, used in combination or alone. Choice of therapy varies and depends on the specific classification of glomerular disease. Side effects of glucocorticoids include hypertension, hyperglycemia, peptic ulcer, weight gain, hypoadrenalism, cardiovascular disease, osteoporosis, cataracts, slow wound healing, and infection. Despite unfavorable side effects, these medications can be crucial to the therapeutic management of glomerular disease. Undesired consequences of glucocorticoid use may be minimized through employing preventive measures such as decreasing frequency of administration, utilizing short-acting glucocorticoids, promoting physical exercise, and slowly withdrawing therapy over weeks to months upon discontinuation.8,10

Renal medications are common in patients with CKD and appropriate use is essential to optimizing health-related outcomes in this patient population. Each agent has known risks and benefits associated with use that should be evaluated on an individual basis to ensure safe and effective use.

References

1. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009 Aug;113:S1-130. doi:10.1038/ki.2009.188
2. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2017;7(1):1-59. doi:10.1016/j.kisu.2017.04.001
3. Drüeke TB, Parfrey PS. Summary of the KDIGO guideline on anemia and comment: reading between the (guide)line(s). Kidney Int 2012 Nov;82(9):952-60.
4. Mircera (methoxy polyethylene glycol-epoetin beta) [prescribing information]. South San Francisco, CA: Hoffmann-La Roche Inc; June 2018.
5. Venofer (iron sucrose) [prescribing information]. Shirley, NY: American Regent Inc; December 2018.
6. Tucker BM, Safadi S, Friedman AN. Is Routine Multivitamin Supplementation Necessary in US Chronic Adult Hemodialysis Patients? A Systematic Review. J Renal Nutr 2015;25(3):257-64. doi:10.1053/j.jrn.2014.09.003
7. Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review. Semin Dial 2013;26(5):546-567.
8. Merkel PA, Matteson PL, Ramirez Curtis M. Overview of and approach to the vasculitides in adults. In: Post TW, ed. UpToDate, Waltham, MA.
9. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States. Natioal Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2018.
10. Ponticelli C, Locatelli F. Glucocorticoids in the Treatment of Glomerular Diseases: Pitfalls and Pearls. Clin J Am Soc Nephrol 2018;13(5):815-22. doi:10.2215/CJN.12991117.