Tenofovir Disoproksil Fumarat Tedavisi Alan Kronik Hepatit B Hastalarında Renal Toksisitenin Değerlendirilmesi

Öz

ÖZ Amaç Hepatit B virüsü (HBV) enfeksiyonu, önemli bir küresel sağlık sorunudur. İlk basamak antiviral tedavi olarak kullanılan tenofovir disoproksil fumarat (TDF), böbrek ve mineral metabolizması üzerinde olumsuz etkilerle ilişkilendirilmiştir. TDF’nin nefrotoksik potansiyeli literatürde tanımlanmış olsa da, Türkiye’den uzun dönemli gerçek yaşam verileri sınırlıdır. Bu çalışmada, TDF ile en az 36 ay süreyle tedavi edilen kronik HBV hastalarında böbrek fonksiyonlarını ve mineral parametrelerini değerlendirerek, klinik uygulamada takip stratejilerinin optimizasyonuna katkıda bulunmayı amaçladık. Gereç ve Yöntemler Toplam 58 kronik HBV hastası (ortalama yaş 50,7 ± 13,7 yıl, %60 erkek) retrospektif olarak incelendi. Serum kreatinin, tahmini glomerüler filtrasyon hızı (eGFR, CKD-EPI), kan üre azotu (BUN), kalsiyum ve fosfor düzeylerindeki seri değişiklikler; başlangıçta, 1. ay, 6. ay, 1. yıl ve sonrasında yıllık kontrollerde değerlendirildi. Tekrarlayan ölçümlerde ANOVA ve Bonferroni düzeltmesi kullanıldı; p < 0,05 istatistiksel anlamlılık sınırı olarak kabul edildi. Bulgular Otuz altı aylık takip süresince serum kreatinin ve eGFR düzeylerinde anlamlı bir uzun dönem değişiklik saptanmadı (p = 0,20 ve p = 0,07). Ancak, 1. ayda eGFR’de başlangıca kıyasla geçici bir düşüş eğilimi gözlendi (p = 0,045). BUN düzeyleri zaman içinde anlamlı olarak arttı (p < 0,01); bu artış hipertansif hastalarda daha belirgindi (p = 0,020). Serum kalsiyum düzeyleri değişmedi (p = 0,40), buna karşılık fosfor düzeylerinde zamanla anlamlı bir azalma görüldü (p < 0,01) ve hastaların %11,7’sinde hipofosfatemi saptandı. Sonuç TDF, 36 aylık takip süresince serum kreatinin veya eGFR düzeylerinde anlamlı bir bozulma olmaksızın genel olarak iyi tolere edildi. Bununla birlikte, tüm kohortta serum fosfor düzeylerinde anlamlı bir azalma gözlenirken, BUN düzeylerindeki artışın özellikle hipertansif hastalarda daha belirgin olduğu gözlendi. Çalışmamız, yüksek riskli gruplarda böbrek ve mineral parametrelerinin yakın takibinin gerekliliğini ortaya koyan, Türkiye kohortundan elde edilmiş gerçek yaşam verilerini sunmaktadır.

Anahtar Kelimeler

• Kronik hepatit B
• Tenofovir disporoksil fumarat
• Renal toksisite
• Glomerüler filtrasyon hızı
• Hipofosfatemi

Destekleyen Kurum

Yazarlar, bu çalışmanın herhangi bir finansal destek almadığını beyan etmişlerdir.

Etik Beyan

Bu araştırma, ilgili ulusal düzenlemeler ve kurumsal politikalar ile uyumludur ve Helsinki Bildirgesi ilkelerine uygun olarak yürütülmüştür. Çalışma, Akdeniz Üniversitesi Tıp Fakültesi Etik Kurulu tarafından onaylanmıştır (Onay numarası: 531-12/06/2019).

Evaluation of Renal Toxicity in Chronic Hepatitis B Patients Treated with Tenofovir Disoproxil Fumarate

Öz

ABSTRACT Objective Hepatitis B virus (HBV) infection remains a major global health concern. Tenofovir disoproxil fumarate (TDF), a widely used first line antiviral therapy, is associated with renal and mineral metabolism abnormalities. Although its nephrotoxic potential has been documented, real world data on long term outcomes remain limited in Turkey. This retrospective study aimed to evaluate renal function and mineral parameters in chronic HBV patients treated with TDF for at least 36 months and to provide evidence to optimize follow up strategies in clinical practice. Material and Methods We retrospectively analyzed 58 chronic HBV patients (mean age 50.7 ± 13.7 years, 60% male) treated with TDF for ≥36 months. Serial changes in serum creatinine, estimated glomerular filtration rate (eGFR, CKD-EPI), blood urea nitrogen (BUN), calcium, and phosphorus were assessed at baseline, month 1, month 6, year 1, and annually thereafter. Repeated measures ANOVA with Bonferroni correction was performed; statistical significance was defined as p < 0.05. Results No significant long term changes in serum creatinine or eGFR were observed over 36 months (p = 0.20 and p = 0.07, respectively). However, a transient decrease in eGFR was observed at month 1 compared with baseline (p = 0.045). BUN levels significantly increased over time (p < 0.01), with greater elevation in hypertensive patients (p = 0.020). Serum calcium remained stable (p = 0.40), whereas phosphorus levels showed a significant time dependent decline (p < 0.01), with hypophosphatemia detected in 11.7% of the patients. Conclusion TDF was generally well tolerated without significant deterioration in serum creatinine or eGFR during 36 months of follow up. However, a significant decline in serum phosphorus was observed in the overall cohort, while BUN levels increased more prominently among hypertensive patients, highlighting the importance of regular monitoring. Our study provides real world data from a Turkish cohort, emphasizing the need for close surveillance of renal and mineral parameters in high risk groups.

Anahtar Kelimeler

• Chronic hepatitis B
• Tenofovir disoproxil fumarate
• Renal toxicity
• Glomerular filtration rate
• Hypophosphatemia

Destekleyen Kurum

The authors declared that this study has received no financial support.

Etik Beyan

This research complies with all the relevant national regulations, institutional policies and is in accordance the tenets of the Helsinki Declaration and has been approved by the Akdeniz University Faculty of Medicine Ethics Committee (Approval number: 531-12/06/2019).

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