CKD-aP is a cutaneous complication that affects many dialysis patients and is linked to poor outcomes. Patients with severe Pruritus have a worse prognosis, as severe Pruritus is associated with death independently of other co-morbidities (6). We found that about 38.8% of the patients had Pruritus, with a mean severity grade of 10 ± 4.2. Mostly being generalized or localized to the trunk, or to a lesser extent to the upper limbs, lower limbs, or the head with symmetrical distribution, 47.9% of patients implied having the symptoms at night. These findings are consistent with the literature, where the pooled prevalence of Pruritus is 55%. About 50% of these patients have generalized Pruritus, and in the remaining patients, CKD-aP seems to affect predominantly the back, face, and shunt arm with bilateral symmetry (1–3).
Many tried to explain what could be the cause behind CKD-aP, but the pathophysiology of this condition is still elusive. One of the most robust hypotheses is the immune-mediated hypothesis. Several studies show a central role of inflammation in the pathogenesis of Pruritus in dialysis patients (24). Furthermore, patients on dialysis have an alteration in their immune system, with 30–50% of them having a pro-inflammatory state(25).
In this study, we believe patients with pruritus experience inflammation more than patients without Pruritus, which is suggested by the significantly lower levels of albumin in those with Pruritus (p value < 0.05). Albumin is considered a negative inflammatory marker, and it's found that there is an association between lower levels of albumin and CKD-aP(26). In addition, patients with Pruritus had higher levels of ferritin and WBCs. However, they were not statistically significant, but it is well known that ferritin and WBCs levels are reliable inflammatory markers(26, 27). Unfortunately, CRP levels could not be obtained for those patients to provide evidence for the inflammatory state further.
In addition, we found a significant association between DM and CKD-aP (p value < 0.05). Therefore, it is suggested that DM causes neuropathy in peripheral nerves (c-fibres) in the skin that transmits the itching sensation and that glycemic control correlates with itch severity. However, the exact mechanism remains to be determined (5). On the other hand, inflammation is acknowledged as a key factor in the development and progression of CKD in diabetics (13), with evidence that diabetic patients experience a low-grade inflammatory state, with increased blood concentrations of inflammatory markers such as alpha-1 acid glycoprotein, serum amyloid A, CRP, cortisol, and the main cytokine mediator of the response, IL-6 (28), which supports the presence of an inflammatory state in people with Diabetes with Pruritus.
New evidence shows that IL-31, a member of the IL-6 family of cytokines, is associated with Pruritus in atopic dermatitis patients (29) and other autoimmune skin diseases, like Bullous pemphigoid (30). Ko MJ et al. show that there was indeed a significant association between IL-31 and CKD-aP in HD patients (21). In our study, we could not find one, the mean levels of IL-31 were higher in those with Pruritus than those without Pruritus (4936.6, 3919.2), respectively, but it was statistically insignificant (p value = 0.78). This difference could be related to racial differences. According to Hoffmann SC et al., ethnicity may play a role in expressing inflammatory cytokines (31). Alternatively, it could be related to the fact that their blood samples were collected after an overnight fast of more than 8 hours, whereas our samples were not.
In addition, we found a statistically significant negative correlation between phosphate levels and Pruritus (r= -269, p value < 0.05), which is opposite to what has been reported by Gatmiri. et al. (32). We believe this result was most likely because most patients took one form of phosphate-binding medications, e.g., calcium gluconate or sevelamer, which led to this unexpected negative correlation between pruritus severity and phosphate levels.
Up to our knowledge, this study was the first to address CKD-aP in the region. It offered a better understanding of the mechanism of Pruritus as it took into consideration a lot of variables and the association between them and Pruritus. Although the data gathered is comprehensive and covers a variety of laboratory testing and clinical evaluations, the study still has some possible limitations. First, as this is a cross-sectional study, we could not follow up the patients without Pruritus and with high levels of interleukin to see if they would have a possibility of developing Pruritus in the future. Secondly, C-reactive protein (CRP) and other inflammatory cytokines have not been used to support the pro-inflammatory state further. Thirdly, during the study, patients were on phosphate binders, which could affect the 12-item pruritus severity scale results.