Učestalost i vrsta oštećenja bubrežne funkcije u djece i mlađih odraslih s hemofilijom A i B

doctoral thesis

• Title (english): Frequency and type of renal damage in children and young adults with haemophilia A and B
• Author: Zrinko Šalek
• Mentor: Ernest Bilić (mentor)
• Mentor: Danko Milošević (komentor)
• Committee member: Ivica Horvatić (predsjednik povjerenstva)
• Committee member: Jurica Vuković (član povjerenstva)
• Committee member: Irena Jukić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2025-01-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Uvod: Stupanj bubrežnog oštećenja u djece i mladih odraslih ispitanika s hemofilijom nepoznat je i nedovoljno istražen. Svrha ovog rada je istražiti učestalost bubrežnog oštećenja u ispitanika s hemofilijom A/B laboratorijskim, ultrazvučnim i metodama nuklearno medicinske dijagnostike. Svi su ispitanici bili bez simptoma bubrežnog oštećenja s normalnim vrijednostima kreatinina i ureje.
Metode: U istraživanje je uključeno 73 muška ispitanika s hemofilijom A ili B. Od toga 34 mlađih do 18 godina i 39 odraslih muškaraca do 32 godine liječenih u KBC Zagreb. Metode procjene bubrežnog oštećenja bile su ultrazvuk bubrega, dinamička scintigrafija bubrega, mjerenje korigiranog klirensa kreatinina, cistatina C, eritropoetina i procjena tubularne funkcije bubrega pomoću parametara iz 24-satnog urina (kreatinin, klirens kreatinina, proteinurija, kalciurija, natriurija, kaliurija, magnezurija).
Rezultati: Najveća učestalost poremećene bubrežne funkcije utvrđena je mjerenjem radioizotopnog klirensa s 99m Tc-DTPA i to u 45,3% ispitanika. Mjerenjem poremećaja tubularne funkcije nađeno je odstupanje od normale u 36,9 % ispitanika, a povišeni cistatin C utvrđen je u 17,4 % ispitanika. UZV analizom urotrakta morfološko oštećenje bilo je prisutno u 7,5% ispitanika. U svega 6,3% ispitanika bio je snižen klirens kreatinina. Statistički je značajna povezanost morfološkog oštećenja bubrega s prisutnim inhibitorima na FVIII/FIX. Oštećenje je prisutno u 4,9 % bolesnika bez i 33,3 % bolesnika s inhibitorima. Osim toga, statistički je značajna povezanost morfološkog oštećenja s tipom terapije i prisutno je u 40% bolesnika na „ostaloj terapiji“.
Zaključak: Kao najbolja metoda za procjenu pa i najmanjeg otklona bubrežne funkcije od normale u djece i mladih odraslih s hemofilijom utvrđena je metoda dinamičke scintigrafije bubrega. Mjerenje DTPA iGF i u našem istraživanju potvrdilo je ranije dokazanu visoku osjetljivost i specifičnost.. Analizom ROC krivulje vidi se kako različite metode procjene bubrežnog oštećenja ne posjeduju dobra diskriminatorna svojstva za prepoznati ispitanike s poremećenim DTPA iGF.

Abstract (english)

Introduction: The extent of kidney damage in children and young adults with haemophilia is not well studied and a lot is still unknown. The aim of this study is to evaluate the incidence of kidney damage in subjects with haemophilia A/B using laboratory, ultrasound, and nuclear medicine diagnostic methods. None of the subjects had renal damage symptoms and all of them had normal creatinine and urea values.
Methods: We included 73 male subjects with haemophilia A or B. Among them, 34 were minors, while 39 were young adults, all treated in UHC Zagreb. To estimate renal damage ultrasound, dynamic renal scintigraphy, corrected creatinine clearance, cystatin C, erythropoietin, and 24 urine excretion to evaluate tubular renal function were performed. All subjects were examined, and blood samples and 24-hour urine were collected (creatinine, creatinine clearance, proteinuria, calcuria, natriuria, kaliuria, magnesuria).
Results: The highest prevalence of impaired renal function was determined by measuring the radioisotope clearance with 99m Tc-DTPA in 45,3% of the subjects. Tubular function measurement discovered a deviation in 36,9% of subjects, and elevated cystatin C was found in 17,4% of subjects. Urinary tract imaging damage showed morphological abnormalities in 7,5% of subjects. Only 6,3% of the subjects had decreased creatinine clearance. There was a statistically significant association between morphological kidney damage and the presence of FVIII/FIX inhibitors. Damage was present in 4,9% of patients without and 33,3% of patients with inhibitors. Additionally, there was a statistically significant association between morphological damage with the type of therapy and was present in 40% of patients treated with "other" therapy. Conclusion: Dynamic renal scintigraphy was established as the best method for assessing even the smallest renal function deviation in children and young adults with haemophilia. DTPA iGF measurement was also in our research shown to be highly sensitive and specific. The ROC curve analyses showed that the different methods of kidney damage assessment do not have good discriminatory characteristics for recognizing subjects with impaired DTPA iGF.

• Keywords: Tehnecij-99m; Hemofilija A; Cistatin C; Kreatinin; Urea; ROC krivulja; Bubreg; Radionuklidno snimanje; Bolesti bubrega; Radioizotopi; Eritropoetin; Proteinurija
• Keywords (english): Technetium-99m; Hemophilia A; Cystatin C; Creatinine; Urea; ROC Curve; Kidney; Radionuclide Imaging; Kidney Diseases; Radioisotopes; Erythropoietin; Proteinuria
• Language: croatian
• URN:NBN: urn:nbn:hr:105:179591
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 92 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-24 09:01:55