gamma-linolenic-acid and Pruritus

Uremic itch is a frequent and sometimes very tormenting symptom in patients with advanced or end-stage renal failure, with a strong negative impact on the quality of life. According to a representative study, the point prevalence of chronic itch is 25% in hemodialysis patients but may reach more than 50% in single cohorts depending on the country and dialysis efficacy. Not much is known regarding the pathogenesis of uremic itch. Besides parathyroid hormone, histamine, tryptase, and alteration of the calcium-phosphate metabolism have been suspected. More recently, derangements in the opioid system and an inflammatory condition have been investigated as suspected players in the pathogenesis of uremic itch, but remain unproven so far. Treatment of chronic itch in dialysis patients remains difficult. Besides topical application of rehydrating or immunomodulating compounds, such as γ-linolenic acid or tacrolimus treatment with nalfurafine may be helpful. Apart from that, gabapentin and pregabalin are promising drugs to alleviate uremic itch. In many cases, UVB phototherapy is effective in reducing the intensity of itch. When treating patients, one should take into account that most of the drugs available are not licensed for the treatment of itch. Therefore, a deliberate use of therapeutic options aiming for a good risk-benefit relation should be adopted. In very severe and refractory cases, patients suitable for renal transplantation might be switched to 'high urgency' status, as successful renal transplantation cures uremic pruritus in most of the cases.

Topics: Acupuncture Therapy; Amines; Analgesics, Opioid; Anticonvulsants; Calcineurin Inhibitors; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; gamma-Linolenic Acid; Humans; Kidney Failure, Chronic; Morphinans; Narcotic Antagonists; Pregabalin; Pruritus; Receptors, Opioid, kappa; Receptors, Opioid, mu; Renal Dialysis; Spiro Compounds; Tacrolimus; Ultraviolet Therapy; Uremia

Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP.

Topics: Acupuncture Therapy; Amines; Anti-Inflammatory Agents; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; gamma-Linolenic Acid; Humans; Morphinans; Naltrexone; Narcotic Antagonists; Pentoxifylline; Phototherapy; Pregabalin; Pruritus; Receptors, Opioid, kappa; Renal Insufficiency, Chronic; Spiro Compounds; Tacrolimus; Thalidomide; Uremia

Pruritus is a predominant and serious phenomenon of various skin diseases. As mediators of pruritus, histamine, serotonin (hydroxytryptamine), eicosanoids, neuropeptides, cytokines and proteases are known. The symptomatic treatment of pruritus is variable. Glucocorticoids are well known antipruritic drugs. H1-antihistaminics are used frequently. But the efficacy of these drugs is questionable in dogs. Additionally, mast cell stabilisators, unsaturated fatty acids (i. e. primrose oil, fish oil) and other antipruritic agents (local anesthetics) are used.

Topics: Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipruritics; Cytokines; Eicosanoids; Endopeptidases; Fatty Acids, Essential; Fish Oils; gamma-Linolenic Acid; Glucocorticoids; Histamine Release; Linoleic Acids; Neuropeptides; Oenothera biennis; Plant Oils; Pruritus; Serotonin; Skin Diseases

Pruritus is a bothersome symptom affecting up to 80% of dialysis patients. Lymphocyte and cytokine interaction has an important role in the pathogenesis of uremic pruritus. Gamma-linolenic acid (GLA) is associated with immune modulation of T lymphocytes and lymphokines. The aim of this study is to determine whether topical GLA can attenuate uremic pruritus.. Seventeen dialysis patients with refractory uremic pruritus who passed the screening criteria entered a prospective, randomized, double-blind, placebo-controlled, crossover study. They stopped all antipruritic therapy at least 2 weeks before the study and were randomly assigned to treatment with either GLA 2.2% cream or placebo-based cream applied to the entire body after taking a bath once a day and to pruritic sites 3 times a day for 2 weeks, and then the reverse treatment after a 2-week washout period. Severity of pruritus was evaluated by using a traditional visual analogue scale (VAS) and a modified questionnaire method (pruritus score [PS]). Hemogram, aspartate and alanine aminotransferases, bilirubin, albumin, blood urea nitrogen, creatinine, calcium, phosphate, and intact parathyroid hormone were measured.. Sixteen patients completed the study; 1 patient was withdrawn because of an allergic skin reaction. There were no significant differences between groups except for sex distribution. Median VAS and PS values between groups did not differ significantly at baseline. There is a greater antipruritic effect of GLA based on evaluation with both the VAS and PS. There is persistence of a residual effect into the second treatment period after GLA treatment.. GLA-rich cream is better than placebo-based cream for alleviating uremic pruritus. It is a useful adjuvant in the management of refractory uremic pruritus.

Topics: Administration, Topical; Adult; Aged; Double-Blind Method; Drug Resistance; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Placebos; Pruritus; Renal Dialysis; Treatment Outcome; Uremia

Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n-6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either gamma-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.

Topics: Administration, Oral; Adult; Aged; Cholesterol; Dermatologic Agents; Double-Blind Method; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Kidney Failure, Chronic; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Phospholipids; Plant Oils; Pruritus; Renal Dialysis; Skin Diseases; Triglycerides; Uremia

Topics: Double-Blind Method; gamma-Linolenic Acid; Humans; Pruritus; Renal Dialysis; Skin; Uremia

A randomised double-blind parallel study lasting eight weeks was used to assess the effects of olive oil in a group of atopic dogs whose clinical signs were well controlled by dietary supplementation with a combination of evening primrose oil and fish oil. Nine of the 11 dogs which continued to receive this combination were considered unchanged at the conclusion of the study, whereas eight of the 10 dogs switched to olive oil had deteriorated. The mean plasma concentration of dihomogammalinolenic acid, a precursor of potentially antiinflammatory mediators, was significantly reduced (P < 0.05) in the olive oil-treated group at the end of the study. There were no significant differences between the mean plasma linoleic, eicosapentaenoic and arachidonic acid concentrations in the two groups. These findings suggest that olive oil is not an effective therapeutic agent in the control of canine atopy.

Topics: Animal Feed; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dietary Fats, Unsaturated; Dog Diseases; Dogs; Double-Blind Method; Drug Combinations; Erythema; Fatty Acids, Essential; Female; Fish Oils; gamma-Linolenic Acid; Hypersensitivity, Immediate; Linoleic Acids; Male; Oenothera biennis; Olive Oil; Plant Oils; Pruritus; Treatment Outcome

Twenty dogs with atopy or idiopathic pruritus were treated in a double-blinded clinical trial with computer-randomized and computer-generated sequences of 4 fatty acid-containing products: evening primrose oil, cold water marine fish oil, DVM Derm Caps, and EfaVet. Each dog received each product for a 2-week period. Five of 20 dogs (25%) had a good-to-excellent reduction in their level of pruritus with at least 1 of the products: evening primrose oil (2 dogs), DVM Derm Caps (1), EfaVet (1), DVM Derm Caps and cold water marine fish oil (1). Only 1 dog experienced a side effect (loose stools). Clinical response to fatty acid supplements appeared to be quite individualized, and independent of age, breed, sex, weight, duration of disease, specific diagnosis, or number of positive intradermal test reactions.

Topics: Animals; Dermatologic Agents; Dog Diseases; Dogs; Fatty Acids, Essential; Female; Fish Oils; gamma-Linolenic Acid; Hypersensitivity; Linoleic Acids; Male; Oenothera biennis; Plant Oils; Pruritus