Strong Associations Between Inflammation, Pruritus and Mental Health in Dialysis Patients

Abstract

Itch, impaired mental health and inflammation contribute to morbidity in dialysis patients. We therefore analysed laboratory results, intensity of itch and psychological tests in dialysis patients with pruritus, without and healthy people. The data was analysed by different statistical tests. This revealed 3 independent groups. One was mainly driven by itch, one by mental health and another by inflammatory parameters. Additionally, all 3 showed strong associations. This means inflammation, mental health and itch are some how interconnected in dialysis patients. Since all 3 comorbidities are associated with the risk of death, knowledge about the interdependence of these factors is important. Pruritus, impaired mental health and inflammation contribute to morbidity in end-stage renal disease. There are no studies on all 3 conditions. We therefore obtained inflammatory parameter data (C-reactive protein and interleukin-6), pruritus data and psychological test data (36-Item Short-Form Health Survey, "Allgemeine Depressionsskala" and Toronto Alexithymia Scale-20) for 19 dialysis patients with pruritus, 20 dialysis patients without pruritus and 15 healthy controls. Non-parametric hierarchical clustering revealed 3 clusters of parameters: one mainly driven by pruritus scores (chronic kidney disease-associated pruritus cluster), one by mental health scores (mental health cluster) and one by inflammatory parameters (inflammatory cluster). Factor analysis showed strong associations (mental health cluster/chronic kidney diseaseassociated pruritus cluster, r=-0.49; mental health cluster/inflammatory cluster, r=-0.52; inflammatory cluster/chronic kidney disease-associated pruritus cluster, r=0.48). For the first time, complete correlations between inflammation, mental health and pruritus in dialysis patients have been established. As all 3 conditions are associated with mortality, knowledge about their interdependence helps to understand endstage renal disease pathophysiology.

A Systematic Review of the Evidence on Inflammation in Depressive Illness and Symptoms, in Chronic and End Stage Kidney Disease

“…Only good quality cross sectional studies (21 analyses) reported significantly higher concentrations of IL-6 in depressed compared to non-depressed groups (see table 4b) 33, 36, 41, 46, 52-54, 56-59, 62-67, 80, 82, 87 . These results were not replicated in fair quality studies 32,47,49,61 ; both fair and good quality studies reported considerable heterogeneity (see table 5b).…”

“…All studies using the HAMD or Zung depression scale reported significantly higher CRP levels amongst those with DS 38, 40 44, 46 . Studies which used the ADS-L (>23) or the PHQ 9 (>10) also reported significant positive correlations between depression scores and CRP 45,49 .…”

“…There were 13 studies reporting significant associations between CRP and DS. [38][39][40][41][42][43][44][45][46][47][48][49][50] Eight of these were fit for purpose studies. Three were from East Asia and using a BDI cut of score of >14, they found elevated CRP levels in DS compared to the no DS group 39,40,47 .…”

“…Twenty studies present cross-sectional analysis on the association between depression and IL-6 32,33,36,41,47,49,[51][52][53][54][55][56][57][58][59][60][61][62][63][64] . Of these, the majority were fit for purpose (17/20, 85%).…”

Treatments for chronic pruritus outside of the box

“…In recent years, research into the pathophysiological mechanisms of pruritus has been intensified and the clinical significance of the symptom is now much more widely recognized in both skin and systemic diseases . While all of these efforts have so far not resulted in an approved anti‐itch drug, we now know a lot more about the potential targets for the treatment of itch.…”