Chronic Kidney Disease-Associated Pruritus: A Review.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP), also known as uraemic pruritus, is a disabling symptom for patients and a challenging condition for clinicians. Despite being common amongst end-stage kidney disease (ESKD) patients, it remains underestimated and underdiagnosed. The exact pathogenesis remains largely elusive, which hampers the synthesis of a definite treatment approach. SUMMARY: Chronic pruritus (lasting 6 weeks or more in duration) is a common and potentially disabling symptom in patients with advanced CKD. A unified hypothesis of pathogenesis has not yet been concluded. Studies have shown changes in the immunochemical milieu of the skin in patients with CKD-aP with several inciting stimuli identified. However, other unrecognized factors are likely to be involved. This article will review the current observations and understanding of the postulated pathogenesis of CKD-aP, as well as the evidence for current management strategies. Key Messages: CKD-aP is a common and troubling symptom amongst ESKD patients that is associated with decreased quality of life and poor prognosis. Its exact pathogenesis, at the time of writing, is not well-understood. A stepwise approach is recommended for management. Systematic reviews show the largest body of evidence was found for the effectiveness of gabapentin. Comparison is needed between newly emerging pharmacological agents such as kappa-opioid receptor agonists and more established agents, such as the gabapentinoids. Finally, renal transplantation should be considered in severe and refractory cases who are suitable transplant candidates as it has shown an excellent outcome in most cases.

Developmental neurotoxic effects of Malathion on 3D neurosphere system.

Developmental neurotoxicity (DNT) refers to the toxic effects induced by various chemicals on brain during the early childhood period. As human brains are vulnerable during this period, various chemicals would have significant effects on brains during early childhood. Some toxicants have been confirmed to induce developmental toxic effects on CNS; however, most of agents cannot be identified with certainty. This is because available animal models do not cover the whole spectrum of CNS developmental periods. A novel alternative method that can overcome most of the limitations of the conventional techniques is the use of 3D neurosphere system. This in-vitro system can recapitulate many of the changes during the period of brain development making it an ideal model for predicting developmental neurotoxic effects. In the present study we verified the possible DNT of Malathion, which is one of organophosphate pesticides with suggested possible neurotoxic effects on nursing children. Three doses of Malathion (0.25 µM, 1 µM and 10 µM) were used in cultured neurospheres for a period of 14 days. Malathion was found to affect proliferation, differentiation and viability of neurospheres, these effects were positively correlated to doses and time progress. This study confirms the DNT effects of Malathion on 3D neurosphere model. Further epidemiological studies will be needed to link these results to human exposure and effects data.