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Organ function changes require regular monitoring, counseling
Chronic kidney disease (CKD) is a spectrum of conditions characterized by a progressive loss of kidney function. Thirty million Americans have some form of CKD, and millions more run the risk of developing it. Protecting and preserving kidney function can be an undertaking, as many medications are either cleared by the kidneys or alter kidney function. In dialysis patients, some drugs may dialyze out if administered prior to dialysis. But successfully managing this patient population transcends the intricacies of patient individuality and pharmacokinetics and must acknowledge that patients lack of awareness regarding the full spectrum of the condition.
“Kidney disease is very common, and often people who have it don’t necessarily know they have it because they don’t have symptoms until it’s quite advanced. In fact, many people don’t feel bad until they approach end-stage kidney disease,” says Kevin Erickson, MD, assistant professor medicine at Baylor College of Medicine.
Impaired kidney function affects other areas of the body, making monitoring exceedingly important. The kidneys play an important role in maintaining homeostasis in the body by regulating the extracellular fluid volume, one of the body’s natural buffering systems, and the body’s internal pH; governing ion concentrations; equilibrating the body’s osmolarity; excreting waste and other unwanted substances; and producing and activating hormones, including renin and erythropoietin. Anything that impairs kidney function can compromise the kidney’s ability to execute these critical tasks.
Choosing Medications and Doses
Different stages of kidney damage are defined by the rate at which the glomeruli of the kidney filter blood, the glomerular filtration rate (GFR). A GFR of 90 ml/min is classified as a stage 1 kidney disease with normal function while lower GFR values correspond to worsening kidney function. The most severe form of kidney disease-kidney failure-results in severe or near-complete loss of kidney function. According to Erickson, kidney function changes over time, so medications-especially those cleared by the kidneys-may require adjustments if taken for long periods.
From a pharmacological standpoint, the kidneys are one of the mechanisms by which the body clear drugs, so as kidney function declines, some drugs will accumulate within the body. Dose adjustments may involve decreasing the dose and dosing frequency for medications that are cleared renally. For example, an antibiotic typically dosed twice a day might need to be administered at half the dose and only once a day in a patient with reduced kidney function. Additionally, certain medications can cause additional kidney damage in some patients who are already renally compromised.
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Vicky Lewis, RPh, BCOP, a clinical pharmacy specialist in kidney transplantation at Texas Health Harris Methodist Hospital in Fort Worth says that patients with CKD should have their kidney function monitored for creatinine levels and creatinine clearance/estimated GFR (eGFR). Medication doses should be adjusted based on altered pharmacokinetics, and considering the effects of drug removal by dialysis. Additionally, certain medications should be used with caution or are contraindicated in CKD patients, she says.
Another crucial component of patient monitoring includes monitoring lab values for hyperphosphatemia, hypocalcemia, vitamin D deficiency, and secondary hyperparathyroidism-all of which may occur with CKD.
Because declining function hinders the kidneys’ ability to produce red blood cells, anemia can be common in CKD patients. Iron deficiency also contributes to the problem, but Lewis cautions that oral iron supplementation is rarely effective in CKD patients. Patients may need nutritional supplementation with a multivitamin specially formulated for CKD patients.
“Many standard multivitamins contain higher than recommended quantities of vitamins A and C,” Lewis says. Standard multivitamins may also have electrolytes that may be restricted in CKD patients, such as potassium and phosphorus.
Dialysis and Transplant
Some medications are dialyzed out and must be administered after the patient receives dialysis. “We have to think about whether dialysis removes the medications,” Erickson says. “Some medications need to be given as supplements, and generally, these are smaller molecules that aren’t protein-bound.”
Patients with advanced kidney disease typically receive erythropoietin stimulating agent and activated vitamin D. While some kidney patients may receive oral vitamin D, dialysis patients typically receive vitamin D injections.
Kidney transplant recipients have an additional layer of complexity to consider. A transplanted kidney typically responds similarly to a healthy native kidney, but Brenna Kane, PharmD, BCPS, a clinical pharmacy specialist in organ transplantation at the University of Chicago Medicine, stresses the importance of including kidney function when prescribing, dosing, and administering medications for these patients.
Dietary restrictions for patients with limited function and for some transplant recipients must also be considered. Kane says these dietary modifications vary per individual and largely depend on the individual’s kidney function and electrolyte balance. In such cases, CKD may not be the only factor that can disrupt electrolyte levels.
“Phosphorus is an interesting example [of electrolyte imbalance], as some patients with normal kidney function after transplant and persistent
secondary hyperparathyroidism may have hypophosphatemia or low blood levels requiring increased dietary phosphorus intake,” says Joseph Vassalotti, MD, chief medical officer for the National Kidney Foundation. Conversely, transplant recipients with low levels of kidney function, generally below an eGFR of 30 ml/1.73 m2, may develop hyperphosphatemia. These patients must restrict dietary phosphorus.
Certain medications, such as ACE inhibitors and calcineurin inhibitors used in CKD, can spike potassium levels, mandating a low-potassium diet. Additionally, calcineurin’s significant drug interactions can further complicate a patient’s medication regimen, creating an additional opportunity for pharmacist intervention.
“The intensity of drug interactions may lead us to avoid certain medications, if able, and pick medications with lower interaction potential,” Kane says. “We are generally careful with medications that have nephrotoxic potential following kidney transplant, but use them with close monitoring if the benefit outweighs the risks.”
Kane cites her preference for an integrase inhibitor-based antiretroviral regimen for an HIV transplant patient over a protease-based inhibitor regimen as an example. She also recommends avoiding NSAIDs in transplant patients to avoid the potential for hemodynamic kidney injury. Pharmacists working with CKD patients post-transplantation must use care when combining the patient’s post-transplant medication regimen with other medications that may exhibit myelosuppressive effects because of additive toxicities.
“Ensuring patients are compliant with their phosphate binders, calcium supplementation, vitamin D supplementation, and calcimimetics is critical for prevention of renal bone disease,” Lewis says.
Motivating patients to adopt dietary restriction of phosphorus is also important. Lewis says patient adherence to phosphate binder and a phosphate-restrictive diet is low, which she attributes to patients not understanding the consequences of too much phosphorus.
Managing CKD-regardless of the stage-is a challenge, but Kane says ensuring optimal outcomes includes managing much more than the CKD itself.
“I think the most challenging issue is the complexity of the CKD patient population,” she states, pointing out the prevalence of comorbidities and complicated drug regimens among CKD patients. “Pharmacists can help the team holistically address these comorbidities, provide patient education, and remove barriers to adherence.”
While the pharmacist’s role in CKD management may not be the complete solution for CKD patients, incorporating pharmacists in their care is definitely a step in the right direction.