Endogenous Opioid Imbalance as a Potential Factor Involved in the Pathogenesis of Chronic Kidney Disease-Associated Pruritus in Dialysis Patients

Abstract

Chronic pruritus is one of the most common symptoms of dermatological diseases. It may occur in the course of other disorders, such as kidney disease. Chronic kidney disease-associated pruritus (CKD-aP) most often affects people with end-stage renal disease. The etiology of this condition is still not fully understood, but researchers are currently focusing on a thorough analysis of the association between disturbed opioid balance and increased neuronal signaling leading to pruritus. The aim of this study is to assess the concentration of endogenous opioids in dialysis patients with and without pruritus and in the control group, and to determine the correlation between the concentration of these substances and the occurrence and severity of itching. The study involved 126 dialysis patients and 50 healthy controls. Patients were divided into groups with pruritus (n = 62) and without pruritus (n = 64). The severity of pruritus was assessed using the NRS scale. The concentration of endogenous opioids was determined using the ELISA. The concentration of met-enkephalin was higher in the group of patients with pruritus compared to the control group. Moreover, significantly lower levels of β-endorphin and dynorphin A were observed in the group of dialysis patients compared to the control group. In addition, a statistically significant difference was seen between the β-endorphin concentration in the group of dialysis patients with pruritus compared to the group without pruritus. The ratio of β-endorphin/dynorphin A concentrations was significantly lower in the group of patients with pruritus compared to patients without pruritus and the control group. No correlations were found between serum level of studied opioids and the severity of pruritus. The concentrations of the studied opioids did not correlate with the severity of pruritus. Observed opioid imbalance may affect the occurrence of CKD-aP in dialysis patients, but a thorough understanding of the mechanism of action of these substances in the sensation of pruritus is necessary to assess the possibility of finding a new therapeutic target.

Proenkephalin Levels and Its Determinants in Patients with End-Stage Kidney Disease Treated with Hemodialysis and Peritoneal Dialysis

“…In contrast, leu-enkephalin concentration was significantly lower in patients with ESKD as compared with healthy control and was not affected by dialysis [22]. Similar results were obtained by Wala-Zieli ńska et al [23] who investigated the correlation of CKD-associated pruritus with concentrations of endogenous opioids. In this study, the concentration of met-enkephalin was higher in the group of dialysis patients with pruritus compared to the healthy control group, whereas no significant differences in leu-enkephalin serum levels were found between the study groups.…”

“…In a study that evaluated the utility of PENK A in stable ambulatory patients with HF, higher levels of PENK A were associated with lower eGFR and decreased EF [17]. In another cohort of patients with new onset or worsening heart failure, higher PENK A levels were found in patients with more severe HF (reflected by a higher NYHA score and higher natriuretic peptides) and with poorer kidney function (higher creatine and urea levels, lower eGFR) [23]. Importantly, in all of the studies investigating PENK A in patients with HF, PENK A levels were strongly associated with eGFR [17,18,25].…”

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus

“…Researchers from our center focused on recent studies on serum levels of interleukin (IL)-31 and neurotrophin-4 in patients with CKD-aP requiring HD, proving that their concentrations are significantly higher in this particular group [ 12 , 13 ]. Moreover, a recent study demonstrated that disturbance in the balance between the concentrations of the individual components of the opioid system might lead to the development of pruritus or modulate it in patients requiring HD [ 14 ].…”