Sistinozis Hastalarının Değerlendirilmesi ve Kronik Böbrek Hastalığı İlişkili Faktörler

Yıl 2023, Cilt: 6 Sayı: 2, 308 - 312, 31.08.2023

Begüm Avcı , Gönül Parmaksız

https://doi.org/10.36516/jocass.1335966

Öz

Giriş: Sistinozis, nadir görülen genetik bir lizozomal depo hastalığı olup, başta böbrekler olmak üzere diğer organları da etkiler. Prognozu belirleyen en önemli faktör, özellikle nefropatik sistinoziste böbrek tutulumudur. Bu çalışma, sistinozis hastalarının klinik, laboratuvar ve prognozlarının değerlendirilmesini ve kronik böbrek hastalığı (KBH) ile ilişkili faktörleri belirlemeyi amaçlamıştır.
Yöntemler: Onsekiz nefropatik sistinozis hastasının kayıtları retrospektif incelendi. Hastaların demografik ve klinik özellikleri, prognozları değerlendirildi. Hastalar, son vizitteki tahmini glomerüler filtrasyon oranına (eGFR) göre eGFR <60 ml/dak/1.73 m² ve eGFR >60 ml/dak/1.73 m² olarak sınıflandırıldı ve gruplar, KBH ile ilişkili faktörler açısından istatistiksel olarak karşılaştırıldı.
Bulgular: Ortalama tanı yaşı 46.61±50.42 aydı. En yaygın alel c.451A>G idi. Poliüri, polidipsi, kusma, büyüme geriliği ve renal osteodistrofi tipik klinik bulgulardı. Tanı anında ortalama eGFR 72.94±21.69 ml/dak/1.73 m² idi. Ortalama 68.28±60.18 ay takip süresinden sonra, ortalama eGFR 63.97±23.59 ml/dak/1.73 m² idi ve hastaların %44.4'ünde KBH gözlendi ve 5'i (%27.8) böbrek replasman tedavisi aldı. GFR<60 ml/dak/1.73 m² olan hastalarda, başlangıç sisteamin dozu düşük (p=0.03) istatistiksel anlamlı düşük saptanırken, akraba evliliği (p=0.04) ve aile öyküsü varlığı (p=0.01), tanıda renal osteodistrofi varlığı ve rikets gelişimi (p=0.02) istatistiksel olarak anlamlı derecede yüksekti.
Sonuç: Bu çalışma, erken tanı ve uygun doz sisteamin tedavisi ile iyi sistinozis yönetiminin; komplikasyonları, özellikle de ESKD'yi önlemede etkin olduğunu vurgulamaktadır. Akraba evliliği ve aile öyküsü, rikets varlığı, KBH ile ilişkili faktörler olarak ortaya çıkmıştır, bu da sistinoziste genetik danışmanlığın ve kemik sağlığı takibinin önemini vurgulamaktadır.

Anahtar Kelimeler

sistinozis, böbrek, çocuk

Destekleyen Kurum

Başkent Üniversitesi

Proje Numarası

KA23-253

Evaluation of Cystinosis Patients and Factors Associated with Chronic Kidney Disease

Öz

Introduction: Cystinosis is a rare genetic, lysosomal storage disorder, leading to kidney involvement and other organs. The most critical factor determining the prognosis is its impact on the kidneys especially nephropatic cystinosis. This study aimed to evaluate cystinosis patients and identify factors associated with chronic kidney disease (CKD).
Methods: The medical records of 18 nephropatic cystinosis patients were retrospectively reviewed. Demographic and clinical features, prognosis were evaluated. Patients were classified according to their estimated glomerular filtration rate (eGFR) at last visit as eGFR<60 ml/min/1.73 m2 and eGFR>60 ml/min/1.73 m2, and were compared for CKD related factors.
Results: The mean age at diagnosis was 46.61±50.42 months. The most common allel was c. 451A>G. Polyuria, polydipsia, vomiting, growth retardation, and renal osteodystrophy were typical presenting symptoms. At diagnosis, the mean eGFR was 72.94±21.69 ml/min/1.73 m². After an average follow-up of 68.28±60.18 months, the mean eGFR was 63.97±23.59 ml/min/1.73 m², and CKD was observed in 44.4% of patients, and 5 (27.8%) underwent kidney replacement theraphy (KRT). In patients with GFR<60 ml/min/1.73 m², the initial cysteamine dose was found to be significantly lower (p=0.03), while consanguinity (p=0.04) and family history presence (p=0.01), presence of renal osteodystrophy at diagnosis and the development of rickets (p=0.02), were statistically significantly higher.
Conclusion: This study highlights the importance of effective cystinosis management, focusing on early diagnosis and optimal cysteamine treatment to prevent complications especially ESKD. Consanguinity and family history, accompanying rikets emerged as notable risk factors for CKD, underscoring the significance of genetic counseling and bone health monitoring.

Anahtar Kelimeler

cystinosis, kidney, children

Proje Numarası

KA23-253

Kaynakça

• 1.Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013; 28(1): 51-9. https://doi.org/10.1007/s00467-012-2242-5
• 2.Emma F, Nesterova G, Langman C, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014; 29 Suppl 4(Suppl 4): iv87-94. https://doi.org/10.1093/ndt/gfu090
• 3.Topaloglu R. Nephropathic cystinosis: an update on genetic conditioning. Pediatr Nephrol. 2021; 36(6): 1347-52. https://doi.org/10.1007/s00467-020-04638-9
• 4.Topaloglu R, Gulhan B, İnözü M, et al; contributors of The Turkish Cystinosis Study Group. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin J Am Soc Nephrol. 2017; 6;12(10): 1634-41. https://doi.org/10.2215/CJN.00180117
• 5.Veys KR, Elmonem MA, Arcolino FO, et al. Nephropathic cystinosis: an update. Curr Opin Pediatr. 2017; 29(2): 168-178. https://doi.org/10.1097/MOP.0000000000000462
• 6.Wilmer MJ, Schoeber JP, van den Heuvel LP, et al. Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol. 2011; 26(2): 205-15. https://doi.org/10.1007/s00467-010-1627-6
• 7.Ames EG, Thoene JG. Programmed Cell Death in Cystinosis. Cells. 2022; 15;11(4): 670. https://doi.org/10.3390/cells11040670
• 8.Brodin-Sartorius A, Tête MJ, Niaudet P, et al. Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults. Kidney Int. 2012; 81(2): 179-89. https://doi.org/10.1038/ki.2011.277
• 9.Atmis B, K Bayazit A, Cevizli D, et al. More than tubular dysfunction: cystinosis and kidney outcomes. J Nephrol. 2022; 35(3): 831-40. https://doi.org/10.1007/s40620-021-01078-y
• 10.Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009; 20(3): 629-37. https://doi.org/10.1681/ASN.2008030287
• 11.Topaloglu R, Baskın E, Bahat E, et al. Hereditary renal tubular disorders in Turkey: demographic, clinical, and laboratory features. Clin Exp Nephrol. 2011; 15(1): 108-13. https://doi.org/10.1007/s10157-010-0367-z
• 12.Özlü SG, Yılmaz AÇ, Polat E, et al. Difficulties in the Diagnosis and Management of Nephropathic Cystinosis Nefropatik. Sistinozis Olgularında Tanı ve Tedavide Karşılaşılan. Türkiye Çocuk Hastalıkları Dergisi. 2016; 10(4): 244-8.
• 13.Greco M, Brugnara M, Zaffanello M, et al. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol. 2010;25(12):2459-67. https://doi.org/10.1007/s00467-010-1641-8
• 14.Bertholet-Thomas A, Berthiller J, Tasic V, et al. Worldwide view of nephropathic cystinosis: results from a survey from 30 countries. BMC Nephrol. 2017; 18(1): 210. https://doi.org/10.1186/s12882-017-0633-3
• 15.Önenli Mungan N, Kör D, Karabay Bayazıt A, et al. Genotypic and phenotypic features of the cystinosis patients from the Southeastern part of Turkey. Turk J Pediatr. 2016; 58(4): 362-70. https://doi.org/10.24953/turkjped.2016.04.003
• 16.Topaloglu R, Vilboux T, Coskun T, et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr Nephrol. 2012; 27(1): 115-21. https://doi.org/10.1007/s00467-011-1942-6
• 17.Doğan M, Bulan K, Kaba S, et al. Cystinosis in Eastern Turkey. J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):965-9. https://doi.org/10.1515/jpem-2014-0477
• 18.Caltik A, Akyüz SG, Erdogan O, et al. Rare presentation of cystinosis mimicking Bartter's syndrome: reports of two patients and review of the literature. Ren Fail. 2010; 32(2): 277-80. https://doi.org/10.3109/08860221003592804
• 19.Yildiz B, Durmuş Aydoğdu S, Kural N, et al. A patient with cystinosis presenting transient features of Bartter syndrome. Turk J Pediatr. 2006; 48(3): 260-2.
• 20.Özkan B, Çayır A, Koşan C, et al. Cystinosis presenting with findings of Bartter syndrome. J Clin Res Pediatr Endocrinol. 2011; 3(2): 101-4. https://doi.org/10.4274/jcrpe.v3i2.21
• 21.Levtchenko E, Servais A, Hulton SA, et al. Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients. Clin Kidney J. 2022; 15(9): 1675-84. https://doi.org/10.1093/ckj/sfac099