Treating Pain in Patients With Chronic Kidney Disease: A Review of the Literature
Patients with chronic kidney disease (CKD) often suffer from chronic pain. It may be difficult to select appropriate analgesic therapy in this population because many patients require complex medication management for the comorbidities that accompany renal disease. A reduced glomerular filtration rate (GFR) alters the normal pharmacokinetics of analgesic medications and increases the potential for toxicity, undesirable side effects, and drug interactions. Appropriate analgesic selection, dose titration, and monitoring are critical for the successful management of this population.
More than 20 million people in the United States have CKD, including approximately 33% of adults with diabetes and 20% of adults with high blood pressure.1,2 In a recent study, 70% of CKD patients reported pain.3 Pain has been reported to be the most common symptom experienced by CKD patients, and often it is undertreated.4,5 The presence of pain in patients with moderate to severe CKD was found to be associated with lower quality of life (QOL) scores compared to the general population.3 Reduced QOL restrict patients’ functional capacity and impairs their social abilities.6 Reduced QOL may have negative effects on body mass index, blood pressure, pain levels, and medication use.7
Determining the cause of pain in patients with CKD is necessary for appropriate treatment. Aside from common causes of pain in the general population, patients with CKD have multifactorial (ischemic, neuropathic, bone, and musculoskeletal) pain conditions associated with their disease.8 They may experience pain caused by primary disease (polycystic kidney disease), bone disease (osteitis fibrosa cystica, osteomalacia, and 2-microglobulin amyloidosis), renal failure (uremic neuropathy and calciphylaxis), and comorbid conditions (cardiovascular disease, ischemic or diabetic neuropathy, and peripheral vascular disease).
Effective pain management in this population is hampered because primary care providers and nephrologists receive limited training in the assessment and treatment of chronic pain. Many physicians fail to consider the altered pharmacokinetics and adverse effects of medications in the setting of renal disease.8
The World Health Organization (WHO) established a 3-step ladder for cancer pain management in 1986 (Table 1). Although there are no specific guidelines for the management of pain in patients with renal disease, the WHO model has been used as a guideline for the management of cancer and noncancer pain.9 The first step of pharmacologic intervention for mild pain usually employs the use of non-opioid analgesics such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs). For moderate levels of pain, the second step includes the addition of schedule II opioids such as codeine and hydrocodone. Tramadol may be introduced at this step. In cases where pain persists despite the use of lower-potency opioids, or if the pain is severe, the third step involves the addition of morphine, oxycodone (OxyContin, Roxicodone, others), hydromorphone (Dilaudid, Exalgo, others), methadone (Dolophine, Methadose, others), or fentanyl (Duragesic, Subsys, others).10,11
Adjuvant analgesics may be added at any step of the WHO ladder based upon the nature and etiology of the pain. In general, adjuvant agents include antidepressants for chronic pain conditions, corticosteroids for inflammatory diseases, anticonvulsants for neuropathic pain, muscle relaxants for pain associated with muscle spasm, and bisphosphonates for bone pain that is associated with metastatic disease.10,12
The selection of analgesics should involve consideration for the type of pain, severity, anticipated duration of treatment, side effects, and interactions with other medications. The ability to recognize the nature of pain is necessary for tailoring effective analgesic therapy. Somatic pain, which is characterized as achy and localizable, often responds well to NSAIDs and opioids. Visceral pain, which is usually deep and poorly localized, may respond to opioids, but in some instances opioids may exacerbate an underlying problem, such as a bowel obstruction. Neuropathic pain, which is characterized as burning or lancinating in nature, is frequently associated with tingling, numbness, and sensory deficits. Neuropathic pain is less responsive to opioids and more responsive to anticonvulsant and antidepressant agents.13
Acetaminophen (Tylenol, others) is one of the most commonly prescribed medications. It is well known for its analgesic and antipyretic properties. It is recognized as a peripherally acting analgesic, although its true mechanism of action remains unclear.13 Acetaminophen has minimal anti-
inflammatory effects. It is associated with weak inhibition of cyclooxygenase (COX) enzyme isoforms COX-1 and 2.14
Since 1996, the National Kidney Foundation has supported the use of acetaminophen as the non-narcotic agent of choice for episodic treatment of mild to moderate pain in patients with CKD.7 Acetaminophen is a good analgesic for patients with advanced CKD and end-stage renal disease (ESRD), because it does not result in platelet inhibition or gastrointestinal irritation.13
It has been reported that acetaminophen may be safe to use in patients with advanced CKD, stages 4–5, without increasing the disease progression rates.15 Acetaminophen is metabolized by the liver and does not require dose adjustment in the presence of CKD. It is important to recognize that acetaminophen frequently is combined with low-potency narcotics and is found in many over-the-counter medications. The concurrent use of multiple acetaminophen-containing medications may place patients with CKD at risk for liver failure.16 Table 2 provides the recommended acetaminophen dosage reduction for patients with reduced glomerular filtration rate (GFR).17