目的 探讨25-羟维生素D3[25(OH)D3]在维持性血液透析(maintenance hemodialysis,MHD)和腹膜透析(peritoneal dialysis,PD)患者中与慢性肾脏病相关性瘙痒(chronic kidney disease-associated pruritus,CKD-aP)的关系及25(OH)D3水平对透析患者CKD-aP的预测价值。 方法 采用单中心横断面研究方法，选取2022年1月1日—12月31日在东南大学附属中大医院接受MHD、PD治疗的患者为研究对象，依据有无CKD-aP分为无瘙痒组、瘙痒组，比较2组患者临床资料和25(OH)D3水平，根据瘙痒评分进一步将瘙痒组分为轻度瘙痒组和中重度瘙痒组。总人群、MHD、PD患者以瘙痒程度分组比较25(OH)D3水平，通过多因素Logistic回归分析MHD、PD患者发生CKD-aP的影响因素。采用ROC曲线分析25(OH)D3在预测透析患者发生CKD-aP中的临床价值。 结果 共纳入331例患者，其中MHD患者238例，PD患者93例。CKD-aP患病率分别为56.5%、58.4%、51.6%。MHD及PD患者瘙痒组25(OH)D3均低于无瘙痒组(MHD：Z=-3.538，P＜0.001；PD：Z=-3.075，P=0.002)。无瘙痒组、轻度瘙痒组、中重度瘙痒组3组25(OH)D3比较存在统计学差异(总人群：H=28.823，P＜0.001；MHD：H=25.137，P＜0.001；PD：H=12.228，P=0.002)。多因素Logistic回归分析结果显示白细胞计数(OR=1.257，95% CI：1.033～1.529，P=0.022)、血磷 (OR =2.277，95% CI：1.215～4.268，P=0.010)、甲状旁腺激素(OR=1.002，95% CI：1.000～1.003， P=0.018)、β2-微球蛋白(OR =1.039，95% CI：1.007～1.073，P=0.017)是MHD患者发生CKD-aP的危险因素，血磷(OR=4.613，95% CI：1.354～15.719，P=0.015)、超敏C反应蛋白(OR=1.192，95% CI：1.019～1.395，P=0.028)是PD患者发生CKD-aP的危险因素，25(OH)D3是MHD和PD患者发生CKD-aP的保护因素(MHD：OR=0.937，95% CI：0.901～0.975，P=0.001；PD：OR=0.909，95% CI：0.830～0.995，P=0.038)。ROC曲线显示：当MHD患者25(OH)D3＜18.835 ng/ml时，预测患者发生CKD-aP的AUC为0.635；PD患者25(OH)D3＜10.545 ng/ml时，预测患者发生CKD-aP的AUC为0.685。 结论 较低的25(OH)D3在透析患者CKD-aP中起重要作用， 25(OH)D3水平在预测透析患者发生CKD-aP中具有一定的临床价值。
Objective To investigate the association between 25-hydroxyvitamin D3 [25(OH)D3] and chronic kidney disease-associated pruritus (CKD-aP) in patients on maintenance hemodialysis (MHD) or peritoneal dialysis (PD), and the predictive value of 25(OH)D3 level for CKD-aP in dialysis patients. Methods In this single-center, cross-sectional study, patients with MHD, or PD treatment from 1 January 2022 to 31 December 2022 in the Zhongda Hospital, affiliated with Southeast University were selected as subjects. Based on the absence of CKD-aP, the patients were divided into the non-pruritus and pruritus groups, then compare the clinical data and 25(OH)D3 level between the two groups. The pruritus group further divided into mild and moderate-to-severe pruritus based on the pruritus score. Then we compared the 25(OH)D3 levels in the general population, MHD, and PD patients in different itching severity groups. The ROC curve was used to analyze the clinical value of 25(OH)D3 in predicting the occurrence of CKD-aP in dialysis patients. Results A total of 331 dialysis patients were included, including 238 patients with MHD and 93 patients with PD. The prevalence of CKD-aP was 56.5%, 58.4% and 51.6%, respectively. The 25(OH)D3 in the pruritus group of MHD and PD patients was lower than that in the non-pruritus group (MHD: 13.490 (10.140, 17.980) vs. 18.900 (10.910, 24.630), Z=-3.538, P<0.001; PD: 7.215 (4.843, 11.875) vs. 12.090 (6.630, 15.240), Z=-3.075, P=0.002). Further analysis showed that There were statistically differences in 25(OH)D3 among no pruritus group, mild pruritus group, and moderate to severe pruritus group (total population: H=28.823 P<0.001; MHD: H=25.137 P<0.001; PD: H=12.228 P=0.002). 25(OH)D3 decreased with the increase of pruritus in the total population and MHD patients (P<0.05). The 25(OH)D3 in the non-pruritus group was higher than that in the mild pruritus group (P=0.015) and the moderate-to-severe pruritus group (P=0.003), and there was no significant difference in 25(OH)D3 between the mild pruritus group and the moderate-to-severe pruritus group (P=0.081). The results of multivariate logistic regression analysis showed that white blood cell count (OR=1.257, 95% CI: 1.033～1.529, P=0.022), serum phosphorus (OR=2.277, 95% CI: 1.215～4.268, P=0.010), parathyroid hormone (OR=1.002, 95% CI: 1.000～1.003, P=0.018), β2-microglobulin (OR=1.039, 95% CI: 1.007～1.073, P=0.017) were risk factors for CKD-aP in MHD patients, and serum phosphorus (OR=4.613, 95% CI: 1.354～15.719,P=0.015) and hypersensitive C-reactive protein (OR=1.192, 95% CI: 1.019～1.395, P=0.028) were risk factors for CKD-aP in PD patients. 25(OH)D3 was a protective factor for CKD-aP in patients with MHD and PD (MHD: OR=0.937, 95% CI: 0.901～0.975, P=0.001. PD: OR=0.909, 95% CI: 0.830～0.995, P=0.038). The ROC curve showed that the predicted AUC was 0.635 when the 25(OH)D3<18.835 ng/ml in MHD patients and 0.685 when the 25(OH)D3<10.545 ng/ml in PD patients. Conclusions Lower 25(OH)D3 may play an important role in CKD-aP in dialysis patients. Moreover, 25(OH)D3 level has certain clinical value in predicting the occurrence of CKD-aP in dialysis patients.
[1]. Yang, M., et al., Complications of progression of CKD. Adv Chronic Kidney Dis, 2011. 18(6): p. 400-5.
[2]. Kim, D. and C. Pollock, Epidemiology and burden of chronic kidney disease-associated pruritus. Clin Kidney J, 2021. 14(Suppl 3): p. i1-i7.
[3]. Molina, P., et al., Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together. Nefrologia (Engl Ed), 2023. 43(1): p. 48-62.
[4]. Bikle, D.D., Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol, 2014. 21(3): p. 319-29.
[5]. Jung, K.E., et al., Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study. J Dermatol, 2015. 42(8): p. 800-3.
[6]. Wu, H.Y., et al., A Comparison of Uremic Pruritus in Patients Receiving Peritoneal Dialysis and Hemodialysis. Medicine (Baltimore), 2016. 95(9): p. e2935.
[7]. Dilek Gokustun, A.Z.B.S., 25-Hydroxy Vitamin D Deficiency May Be the Secret Actor in the Pathogenesis of Uremic Pruritus in Hemodialysis Patients. Journal of Clinical Nephrology and Research, 2016.
[8]. 孙达等, 慢性肾脏病患者25-羟维生素D3水平的改变及其影响因素分析. 临床肾脏病杂志, 2016. 16(05): 第265-270页.
[9]. Verduzco, H.A. and S. Shirazian, CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management. Kidney Int Rep, 2020. 5(9): p. 1387-1402.
[10]. Nochaiwong, S., et al., Clinical interpretation of the Uremic Pruritus in Dialysis Patients (UP-Dial) scale: a novel instrument for the assessment of uremic pruritus. J Eur Acad Dermatol Venereol, 2018. 32(7): p. 1188-1194.
[11]. Abdallah, A.M., S.M. Elsheikh and R.A. ElBarbary, Prevalence and determinants of severity of uremic pruritus in hemodialysis patients: a multicentric study. J Investig Med, 2023. 71(1): p. 42-46.
[12]. Fallahzadeh, M.K., et al., Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications. Nephrol Dial Transplant, 2011. 26(10): p. 3338-44.
[13]. Keshari, S., et al., IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus. FASEB J, 2019. 33(11): p. 12036-12046.
[14]. Ruzicka, T., et al., Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N Engl J Med, 2017. 376(9): p. 826-835.
[15]. Silverberg, J.I., et al., Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allergy Clin Immunol, 2020. 145(1): p. 173-182.
[16]. Molina, P., et al., The effect of high-volume online haemodiafiltration on nutritional status and body composition: the ProtEin Stores prEservaTion (PESET) study. Nephrol Dial Transplant, 2018. 33(7): p. 1223-1235.
[17]. Obi, Y., et al., Vitamin D Receptor Activator Use and Cause-specific Death among dialysis Patients: a Nationwide Cohort Study using Coarsened Exact Matching. Sci Rep, 2017. 7: p. 41170.
[18]. Momose, A., et al., Calcium ions are abnormally distributed in the skin of haemodialysis patients with uraemic pruritus. Nephrol Dial Transplant, 2004. 19(8): p. 2061-6.
[19]. Sadeghi, K., et al., Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol, 2006. 36(2): p. 361-70.
[20]. Penna, G. and L. Adorini, 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol, 2000. 164(5): p. 2405-11.
[21]. Lang, C.L., et al., Vitamin D and the Immune System from the Nephrologist's Viewpoint. ISRN Endocrinol, 2014. 2014: p. 105456.
[22]. Brozyna, A.A., et al., Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy. Int J Mol Sci, 2022. 23(15).
[23]. Goetz, D.W., Vitamin D treatment of idiopathic itch, rash, and urticaria/angioedema. Allergy Asthma Proc, 2010. 31(2): p. 158-60.
[24]. Malekmakan, L., et al., Role of vitamin D in oxidative stress modulation in end-stage renal disease patients: A double-blind randomized clinical trial. Hemodial Int, 2020. 24(3): p. 367-373.
[25]. Kimmel, M., et al., The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients. Nephrol Dial Transplant, 2006. 21(3): p. 749-55.
[26]. 王颖与毕慧欣, 维持性血液透析患者皮肤瘙痒相关机制的研究进展. 中国血液净化, 2021. 20(01): 第43-46页.
[27]. Kemeny, L.V., et al., Vitamin D deficiency exacerbates UV/endorphin and opioid addiction. Sci Adv, 2021. 7(24).
[28]. Wimalawansa, S.J., Controlling Chronic Diseases and Acute Infections with Vitamin D Sufficiency. Nutrients, 2023. 15(16).
[29]. Andoh, T., et al., beta2-Microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 1. Eur J Pharmacol, 2017. 810: p. 134-140
