Uremic Itch is a ---#Itch

Question

What agents are best for treating uremic pruritus?

Jenny A. Van Amburgh, PharmD, CDE
Assistant Dean of Academic Affairs; Associate Clinical Professor, School of Pharmacy, Northeastern University; Director, Clinical Pharmacy Team Director, Residency Program, Harbor Health Services, Inc., Boston, Massachusetts

Uremic pruritus, or more aptly called "chronic kidney disease-associated pruritus" (CKD-aP), is chronic itching that occurs in patients with advanced or end-stage renal disease. [1] It is known to affect about 20%-50% of patients with renal failure and often causes long-term pain and suffering. [2]

Several theories exist regarding the etiology of CKD-aP, including systemic inflammation, elevated levels of histamine, overactivation of mu-opioid receptors, and possibly increased levels of C-reactive protein. [1,3,4] Although many hypotheses have been postulated, the true pathophysiology of CKD-aP remains poorly understood. [1,4] As a result, high-quality clinical trials to support treatment modalities are lacking. [5]

Current management strategies are based on anecdotal case studies and a few small placebo-controlled trials. [1,6] Therapeutic options can be categorized as physical (dialysis-related), topical, or systemic. [3] The present treatment approach is centered on the response to therapy and the resolution of symptoms. Treatment strategies often begin with topical agents and gabapentin as first-line options, then proceed to other exploratory systemic treatments in refractory cases. [1]

Suboptimal dialysis is associated with pruritus; thus, initial treatment options should include modifying the patient's dialysis regimen to ensure adequate solute clearance. [2] The target Kt/V (amount of dialysis delivered: K = clearance of urea, t = time of dialysis, V = estimated total body water) should be 1.4 or greater. By simply increasing the dialysis dose, pruritic symptoms can be greatly improved. [2,7]

Topical agents may be particularly useful in patients with localized itching. [3] The use of topical emollients for approximately 4 weeks has shown benefit in reducing itch intensity. [4,8] High-water-content emollients are the preferred topical treatment, especially if the patient has visibly dry skin. [4]

Tacrolimus 0.03% and 0.1% ointments have been studied in several small trials and have shown significant reduction in the severity of CKD-aP, with no serious adverse reactions. [1,4] However, the sustained use of this topical agent is not advised, owing to the risk for skin cancers. [3,4] Gamma-linolenic acid ointment has also been suggested as an appropriate option to reduce the intensity of pruritus. [1] If symptoms persist despite appropriate use of emollients, a topical local analgesic agent, such as pramoxine, could be considered. [6]

Systemic treatments have been found to be safe and effective in refractory cases of CKD-aP. Oral antihistamines have historically been used when topical agents have failed or in cases of generalized pruritus. [4] Unfortunately, the benefits of these agents are limited in many patients; they are typically considered because they are widely available and relatively inexpensive. [3]

Recent studies suggest that gabapentin and pregabalin, agents used for neuropathic pain, may be particularly useful in the treatment of CKD-aP. [1,3,9] Clinical trials demonstrated that gabapentin 300 mg orally 3 times a week for 4 weeks or 100 mg orally 3 times a week was both beneficial and tolerable. [1] Pregabalin is also suggested as a viable treatment option if gabapentin is intolerable or has been tried with no response. [1] In a small study, pregabalin initiated at 25 mg 3 times weekly resulted in rapid reduction of itching in over one half of patients. Most patients responded best with 25 mg daily. [9]

There is evidence that systemic ultraviolet light (UV-B) treatment has been therapeutic in CKD-aP. [3-5] The use of UV-B therapy should be considered on a patient-specific basis because the risks may outweigh the benefits, particularly in patients with fair skin tones and those at an increased risk of developing cancer. [4]

This article is not intended to be an exhaustive review, but rather focuses on the most significant agents explored to date. Several other agents, including pentoxifylline, thalidomide, and naltrexone, have been explored, but there is limited evidence to confirm their effectiveness. [1,3,4]

Perhaps the only definitive cure for CKD-aP is kidney transplantation. However, this option is not feasible for all patients. [5] The consensus is that more research into the mechanism of CKD-aP is warranted so that definitive treatment options can be explored.

Acknowledgment: The author wishes to acknowledge the assistance of Clara C. Ofodile, PharmD; Tayla N. Thompson, PharmD; and Karrie E. Juengel, PharmD, PGY1 Residents at Northeastern University School of Pharmacy, in collaboration with Federally Qualified Health Centers & the Program of All-Inclusive Care for the Elderly, Boston, Massachusetts.