Association Between Neuropathic Pain and Serum Interleukin-6 and C-Reactive Protein Levels in Patients with Stage 3 to 5 Chronic KidneyDisease

Abstract

Background: Chronic kidney disease (CKD) is commonly associated with peripheral neuropathy, yet its pathophysiology remains incompletely understood. Inflammatory markers, particularly interleukin-6 (IL-6) and C-reactive protein (CRP), are thought to play a role in the development and persistence of neuropathic pain. This study aimed to evaluate the relationship between neuropathic pain and serum IL-6 and CRP levels in patients with stage 3–5 CKD. Methods: This prospective single-center study included 80 patients: 40 with stage 3–4 CKD and 40 with stage 5 CKD on dialysis (5D). Neuropathic pain was assessed using the PainDETECT questionnaire. Serum IL-6 and CRP levels were measured, and their associations with neuropathic pain were analyzed using correlation analysis, ROC curves, and multivariate logistic regression. Results: Neuropathic pain was present in 44% of stage 3–4 and 73% of stage 5D patients. PainDETECT scores were significantly higher in stage 5D (p=0.009) and showed moderate positive correlations with IL-6 (r=0.642, p<0.001) and CRP (r=0.354, p=0.001). ROC analysis identified IL-6 as a strong predictor of neuropathic pain (AUC: 0.808, cut-off: 8.5 pg/mL), while CRP showed lower predictive ability (AUC: 0.658). IL-6 was the only independent predictor in multivariate analysis (OR: 1.155, p=0.005). Although HbA1c was not associated with neuropathic pain, diabetes duration showed a strong correlation with PainDETECT scores in diabetic patients. Conclusion: Elevated IL-6 is significantly associated with neuropathic pain in CKD, particularly in pre-dialysis patients. IL-6 may be a more reliable biomarker than CRP, highlighting the role of systemic inflammation in CKD-related neuropathy.

Keywords

• Neuropathic pain
• Chronic kidney disease
• interleukin-6
• C-reactive protein
• PainDETECT questionnaire

Evre 3-4 ve Evre 5 Kronik Böbrek Hastalığı Olan Hastalarda Nöropatik Ağrı ile Serum İnterlökin-6 ve C-Reaktif Protein Düzeyleri Arasındaki İlişki

Abstract

Giriş: Kronik böbrek hastalığı (KBH), sıklıkla periferik nöropati ile ilişkilidir; ancak altta yatan patofizyolojik mekanizmalar tam olarak açıklığa kavuşmamıştır. İnflamatuvar belirteçler, özellikle interlökin-6 (IL-6) ve C-reaktif protein (CRP), nöropatik ağrının gelişimi ve devamında rol oynayabilir. Bu çalışmanın amacı, evre 3–5 KBH hastalarında nöropatik ağrı ile serum IL-6 ve CRP düzeyleri arasındaki ilişkiyi değerlendirmektir. Yöntemler: Bu prospektif, tek merkezli çalışmaya evre 3–4 KBH’li 40 hasta ile diyalize giren evre 5 (5D) KBH’li 40 hasta olmak üzere toplam 80 hasta dahil edildi. Nöropatik ağrı değerlendirmesi PainDETECT anketi ile yapıldı. Serum IL-6 ve CRP düzeyleri ölçüldü; bu biyobelirteçlerin nöropatik ağrı ile ilişkileri korelasyon analizi, ROC eğrisi ve çok değişkenli lojistik regresyon yöntemleriyle analiz edildi. Bulgular: Nöropatik ağrı, evre 3–4 hastalarda %44, evre 5D hastalarda ise %73 oranında saptandı. PainDETECT skorları evre 5D hastalarda anlamlı olarak daha yüksekti (p=0,009) ve IL-6 (r=0,642, p<0,001) ile CRP (r=0,354, p=0,001) düzeyleriyle orta düzeyde pozitif korelasyon gösterdi. ROC analizinde IL-6, nöropatik ağrıyı öngörmede güçlü bir belirteç olarak tanımlandı (AUC: 0,808; cut-off: 8,5 pg/mL). CRP'nin öngörü gücü daha düşüktü (AUC: 0,658). Çok değişkenli analizde yalnızca IL-6 bağımsız bir prediktör olarak saptandı (OR: 1,155; p=0,005). HbA1c ile nöropatik ağrı arasında anlamlı ilişki bulunmazken, diyabet süresi ile PainDETECT skorları arasında güçlü bir korelasyon mevcuttu. Sonuç: Serum IL-6 düzeyindeki artış, özellikle diyaliz öncesi KBH hastalarında nöropatik ağrı ile anlamlı şekilde ilişkilidir. IL-6, CRP'ye kıyasla daha duyarlı ve özgül bir biyobelirteç olabilir. Bu bulgular, KBH’ye bağlı nöropatide sistemik inflamasyonun önemli rolünü ve IL-6'nın klinik bir belirteç olarak potansiyel değerini ortaya koymaktadır.

Keywords

• Nöropatik Ağrı
• Kronik Böbrek Hastalığı
• İnterlökin-6
• C-Reaktif Protein
• PainDETECT anketi

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