trk-820 and Kidney-Failure--Chronic

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

Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.. This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch.. Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation.. Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.

Topics: Aged; Double-Blind Method; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Morphinans; Patient Satisfaction; Prospective Studies; Pruritus; Receptors, Opioid, kappa; Renal Dialysis; Spiro Compounds; Surveys and Questionnaires; Treatment Outcome

In this study, we investigated the severity and frequency of uremic pruritus and itch-associated insomnia in patients with end-stage renal disease (ESRD) or chronic kidney disease (CKD).. This questionnaire-based study included outpatients with ESRD or CKD who were attending Tokorozawa Renal Clinic in Saitama Prefecture or Musashi Ranzan Hospital and were stable on treatment. The questionnaire was completed by patients on hemodialysis (HD) before a dialysis session and by patients on peritoneal dialysis (PD) or conservative treatment at the time of an outpatient hospital visit.. Itching was reported by 61.6% of patients on HD, 61.5% on PD, and 43.2% on conservative CKD management. There was no statistically significant difference in the severity or frequency of itch according to whether patients were on HD for ESRD, PD for ESRD, or receiving conservative treatment for CKD. However, insomnia was significantly more common in the PD group than in the HD and conservative CKD groups.. Better skin management is needed for itch in patients with ESRD or CKD. Moisturizing and lifestyle factors are important. Topical or oral medications may also be used. Nalfurafine, a κ receptor agonist, is now available in Japan for the treatment of uremic pruritus in these patients.

Topics: Aged; Aged, 80 and over; Female; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Morphinans; Peritoneal Dialysis; Prevalence; Pruritus; Renal Dialysis; Sleep Initiation and Maintenance Disorders; Spiro Compounds

Topics: Humans; Kidney Failure, Chronic; Morphinans; Pruritus; Renal Dialysis; Spiro Compounds; Uremia