Bojan Vujkovac - Academia.edu (original) (raw)
Papers by Bojan Vujkovac
Molecular genetics and metabolism, Feb 1, 2024
DOAJ (DOAJ: Directory of Open Access Journals), 2002
Background. Fulminant meningococcemia is a rare but severest manifestation of infection with Neis... more Background. Fulminant meningococcemia is a rare but severest manifestation of infection with Neisseria meningitidis. Despite the most advanced treatment the death rate remains between 30–70%. Usually, it occurs in children, while immune system deficiencies are frequently discovered in elderly patients. The incidence of meningococcal infections in Slovenia is about 0.43/100,000 inhabitants and 4.1% of these are in the form of fulminant meningococcal sepsis. Patients and methods. The paper describes the case of a 17year-old patient with fulminant meningococcal sepsis, which he had already recovered from once before as a child. According to the prognostic factors, the expected mortality was above 75%. Continuous dialysis was implemented in addition to conventional treatment. The patient died due to central nervous system involvement after 10 days. Conclusions. We propose that the described treatment succeeded in slowing the expected fulminant course of the disease. A disturbance in the patient’s immune system was demonstrated and Neisseria meningitidis W-135 was isolated.
Frontiers in Medicine, Mar 23, 2023
Introduction: Early initiation is essential for successful treatment of Fabry disease, but sensit... more Introduction: Early initiation is essential for successful treatment of Fabry disease, but sensitive and noninvasive biomarkers of Fabry nephropathy are lacking. Urinary extracellular vesicles (uEVs) represent a promising source of biomarkers of kidney involvement. Among them, microRNAs (miRNAs) are important posttranscriptional regulators of gene expression that contribute to the development and progression of various kidney diseases. We aimed to identify uEV-derived miRNAs involved in the development and/or progression of Fabry nephropathy. Methods: Patients with genetically confirmed Fabry disease and matched control subjects were included. EVs were isolated from the second morning urine by size exclusion chromatography, from which miRNAs were extracted. miRNA urine exosome PCR panels were used to characterize the miRNA signature in a discovery cohort. Individual qPCRs were performed on a validation cohort that included chronological samples. We identified the target genes of dysregulated miRNAs and searched for potential hub genes. Enrichment analyses were performed to identify their potential function. Results: The expression of miR-21-5p and miR-222-3p was significantly higher in patients with stable renal function and those with progressive nephropathy compared with the corresponding controls. In addition, the expression of miR-30a-5p, miR-10b-5p, and miR-204-5p was significantly lower in patients with progressive nephropathy, however, in the chronological samples, this was only confirmed for miR-204-5p. Some of the identified hub genes controlled by the dysregulated miRNAs have been associated with kidney impairment in other kidney diseases. Conclusion: The miRNA cargo in uEVs changes with the development and progression of Fabry nephropathy and, therefore, represents a potential biomarker that may provide a new option to prevent or attenuate the progression of nephropathy. Furthermore, dysregulated miRNAs were shown to be potentially associated with pathophysiological pathways in the kidney.
Blood Coagulation & Fibrinolysis, Oct 1, 2006
We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patien... more We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patient with autosomal dominant polycystic kidney disease (ADPKD) with tranexamic acid (TXA), a potent antifibrinolytic agent. The bleeding could not be controlled by intensive conservative treatment, it became life-threatening and urgent bilateral nephrectomy was intended. Since local and systemic hyperfibrinolysis play a role in bleeding in ADPKD patients, we tried TXA treatment. In fact, the massive bleeding promptly stopped, and haematuria gradually ceased. Removal of both kidneys was prevented. After 5 days both ureters became obstructed by blood clots, but placing J-catheters in each pyelon successfully solved this complication. Our case shows that it is reasonable to try antifibrinolytic treatment with TXA in such devastating uncontrolled bleeding. Blood Coagul Fibrinolysis 17:589-591 ß 2006 Lippincott Williams & Wilkins.
Kidney International Reports, 2021
Journal of Medical Genetics
BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALAN... more BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than −2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year.MethodsPatients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms.ResultsSeventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18–60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2and median (range) eGFR slope was −7.3 (−30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was −0.36 mL/min/1.73 m2/...
Clinical Therapeutics, Apr 1, 2012
Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decr... more Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decreased or absent activity of lysosomal ␣-galactosidase A. As a result of this enzyme deficiency, globotriaosylceramide (GL-3) and other glycosphingolipids accumulate within various tissues and eventually impair vital organ function, putting patients with FD at risk for developing renal failure, cardiovascular dysfunction, and stroke. The initial signs and symptoms of FD, including neuropathic pain in the extremities, hypohidrosis, angiokeratomas, and gastrointestinal discomfort, generally appear during childhood. More serious complications of FD can also occur during childhood, including proteinuria, valvular dysfunction, conduction abnormalities, left ventricular hypertrophy and arrhythmia. Aim & Methods: In view of the growing recognition that significant manifestations of FD can occur during childhood, an international group of physicians who have pediatric patients enrolled in the Fabry Registry developed a set of specific guidelines for assessing FD in children based on evidence from the Fabry Registry and published literature. Results: The general types of assessments recommended for children with FD include: medical/family history (gastrointestinal, pain, sweating; heat/cold intolerance); physical examination (vital signs, height, weight, blood pressure); patient-reported outcomes (quality of life, fatigue, pain); laboratory testing (measured glomerular filtration rate, albuminuria/proteinuria); diagnostic testing (enzyme activity, genotype); specialized laboratory testing (antibodies, plasma GL-3); ophthalmology (slit-lamp examination); other studies (audiologic evaluation, cranial magnetic resonance imaging [T 1 , T 2 , FLAIR], echocardiography and ECG); and treatment/medication history (enzyme-replacement therapy status, concurrent medications). Conclusions: This new Pediatric Minimum Recommended Schedule of Assessments will increase the medical community's awareness of the burden of FD in children, assist with monitoring, and improve the outcome for these young patients.
Molecular Genetics and Metabolism, Sep 1, 2022
Nephrology Dialysis Transplantation, Oct 21, 2009
Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female ... more Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.
Molecular Genetics and Metabolism, Feb 1, 2016
Background Nephropathy is an important feature of classical Fabry disease, which results in alpha... more Background Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. Methods and design The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment. Results 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (−3.6 (−4.8 to −1.1) versus −7.0 (−9.0 to −5.6) mL/min/ 1.73 m 2 /year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <−2 mL/min/1.73 m 2 /year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events. Conclusions This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy. Trial registration number NCT00446862.
Journal of Clinical Medicine
Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, wi... more Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged >16 years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high (>0.5 g/24 h) baseline proteinuria and by ‘classic’ or ‘non-classic’ phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year; p < 0.0001). Patients with classic Fabry disease had similar ra...
Néphrologie & Thérapeutique, 2019
Slovenian Medical Journal, 2006
Background: Fabry disease is a rare X-chromosome linked disease. Due to gene mutation, activity o... more Background: Fabry disease is a rare X-chromosome linked disease. Due to gene mutation, activity of enzyme α galactosidase A is lowered or absent and sphingolipids are deposited in different organ cells. All males with gene mutation are affected but females too, due to X chromosome inactivation, can frequently be affected as well, although usually to a lesser extend. Disease is slowly progressive and there is an early dysfunction of several organs, specially endothelium, kidney, heart and central nervous system, which all leads to early death of the patient. Conclusions: Recently, a specific enzyme replacement therapy, based on recombinant technology, was discovered. Specific therapy is effective and safe. Due to a new therapy there was a need to set objective criteria when to start with enzyme replacement therapy, but also a need to more complex, multidisciplinary approach to those patients. This article is an initial proposal for systematic management of Fabry disease in our country.
Podrucje nasljednih metabolickih bolesti zadnjih se godina razvija vrlo brzo. Otkrivaju se nove b... more Podrucje nasljednih metabolickih bolesti zadnjih se godina razvija vrlo brzo. Otkrivaju se nove bolesti, nove dijagnosticke metode i nove mogucnosti lijecenja. Glavna tema ove knjige su nasljedne metabolicke bolesti koje zahvacaju krvne žile.
Genetics in Medicine Open, 2023
![Research paper thumbnail of Referee report. For: First two years of reimbursed enzyme replacement therapy in the treatment of Fabry disease in Poland [version 1; peer review: 2 approved with reservations]](https://attachments.academia-assets.com/102806748/thumbnails/1.jpg)
](Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene v... more Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene variants resulting in insufficient expression of α-galactosidase A. This enzyme deficiency leads to accumulation of globotriaosylceramide and globotriaosylsphingosine in plasma and in different cells throughout the body, causing major cardiovascular, renal, and nervous system complications. Until 2018, reimbursed enzyme replacement therapy (ERT) for FD was available in all European Union countries except Poland. We present the preliminary results of the first two years of reimbursed ERT in Poland. We obtained data from the seven largest academic centers in Katowice, Cracow, Wrocław, Poznań, Gdańsk, Warsaw, and Łódź. The questionnaire included the following data: number of patients treated, number of patients qualified for ERT, and patient characteristics. All centers returned completed questionnaires that included data for a total of 71 patients (28 men and 43 women) as of June 2021. Thirty-five patients with the diagnosis of FD confirmed by genetic testing (22 men and 13 women) had already qualified for reimbursed ERT. Mean (SD) age at the commencement of the ERT program was 39.6 (15.5) years (range 18-79 years). Mean time from the first clinical symptoms reported by the patients to the FD diagnosis was 21.1 (8.9) Open Peer Review Reviewer Status
Nephrology Dialysis Transplantation, 2021
Background and Aims Females with Fabry disease (FD) often develop symptoms and disease complicati... more Background and Aims Females with Fabry disease (FD) often develop symptoms and disease complications later in life than males. However, they can experience significant health declines, including renal function impairment. Pegunigalsidase alfa is a novel PEGylated alpha-galactosidase A enzyme in development for the treatment of patients with FD with potential pharmacokinetic benefits. We previously reported that males with FD showed improvements in several parameters including median (minimum, maximum) estimated glomerular filtration rate (eGFR) slope from -4.6 (-20.5, 4.8) to -1.1 (-18.6, 14.2) mL/min/1.73m2/year after treatment with pegunigalsidase alfa.(Tondel et al. ASN 2020. PO0562. www.asn.scientificposters.com) Here we report a subgroup analysis of the safety and efficacy of pegunigalsidase alfa treatment in females with FD. Method BRIDGE (PB-102-F30; NCT03018730) is a phase 3, open-label, switch-over study designed to assess the safety and efficacy of pegunigalsidase alfa in ...
Clinical Nephrology, 2017
Fabry disease (FD; OMIM 301500) is a rare X-linked systemic disease caused by a mutation of the G... more Fabry disease (FD; OMIM 301500) is a rare X-linked systemic disease caused by a mutation of the GLA gene. Consequently, there is very low, or even absent, activity of the lysosomal enzyme α-galactosidase A (α-Gal A), resulting in the progressive accumulation of glycosphingolipids (predominantly, globotriaosylceramide (GL-3)) in various cells of different organs. Chronic progressive proteinuric kidney disease is one of the hallmarks of this disease, and it constitutes an important component of this condition's clinical picture. Many patients with FD develop advanced chronic kidney disease, and half of them progress to end-stage renal disease. Most male patients die before the age of 60 years. Specific treatment with enzyme replacement therapy (ERT) has been shown to be effective when treatment is started early enough, before irreversible changes can occur. Therefore, the early diagnosis of FD has become very important. However, in nephrology practice, too many patients are still being diagnosed in late and very advanced stages of the disease. Also, the number of diagnosed patients varies among different countries and regions. The reasons for this are numerous and diverse, and they mostly depend on the knowledge, awareness, and availability of diagnostic procedures. .
Clinical Kidney Journal, 2021
Background Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results... more Background Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results in chronic proteinuric nephropathy. Podocytes are one of the most affected renal cells and play an important role in the development and progression of kidney disease. Detached podocytes found in urine (podocyturia) are considered as a non-invasive early marker of kidney injury; however, the dynamics of podocyte loss remains unknown. Methods In this 10-year follow-up study, podocyturia and other renal clinical data were evaluated in 39 patients with FD. From 2009 to 2019, podocyturia was assessed in 566 fresh urine samples from 13 male and 26 female FD patients using immunocytochemical detection of podocalyxin. Results Podocyturia (number of podocytes per 100 mL of urine) was found in 311/566 (54.9%) of the samples, more frequently (68.9 ± 21.9% versus 50.6 ± 25.9%; P = 0.035) and with higher values (364 ± 286 versus 182 ± 180 number of podocytes per gram of creatinine (Cr) in urine; P ...
Molecular genetics and metabolism, Feb 1, 2024
DOAJ (DOAJ: Directory of Open Access Journals), 2002
Background. Fulminant meningococcemia is a rare but severest manifestation of infection with Neis... more Background. Fulminant meningococcemia is a rare but severest manifestation of infection with Neisseria meningitidis. Despite the most advanced treatment the death rate remains between 30–70%. Usually, it occurs in children, while immune system deficiencies are frequently discovered in elderly patients. The incidence of meningococcal infections in Slovenia is about 0.43/100,000 inhabitants and 4.1% of these are in the form of fulminant meningococcal sepsis. Patients and methods. The paper describes the case of a 17year-old patient with fulminant meningococcal sepsis, which he had already recovered from once before as a child. According to the prognostic factors, the expected mortality was above 75%. Continuous dialysis was implemented in addition to conventional treatment. The patient died due to central nervous system involvement after 10 days. Conclusions. We propose that the described treatment succeeded in slowing the expected fulminant course of the disease. A disturbance in the patient’s immune system was demonstrated and Neisseria meningitidis W-135 was isolated.
Frontiers in Medicine, Mar 23, 2023
Introduction: Early initiation is essential for successful treatment of Fabry disease, but sensit... more Introduction: Early initiation is essential for successful treatment of Fabry disease, but sensitive and noninvasive biomarkers of Fabry nephropathy are lacking. Urinary extracellular vesicles (uEVs) represent a promising source of biomarkers of kidney involvement. Among them, microRNAs (miRNAs) are important posttranscriptional regulators of gene expression that contribute to the development and progression of various kidney diseases. We aimed to identify uEV-derived miRNAs involved in the development and/or progression of Fabry nephropathy. Methods: Patients with genetically confirmed Fabry disease and matched control subjects were included. EVs were isolated from the second morning urine by size exclusion chromatography, from which miRNAs were extracted. miRNA urine exosome PCR panels were used to characterize the miRNA signature in a discovery cohort. Individual qPCRs were performed on a validation cohort that included chronological samples. We identified the target genes of dysregulated miRNAs and searched for potential hub genes. Enrichment analyses were performed to identify their potential function. Results: The expression of miR-21-5p and miR-222-3p was significantly higher in patients with stable renal function and those with progressive nephropathy compared with the corresponding controls. In addition, the expression of miR-30a-5p, miR-10b-5p, and miR-204-5p was significantly lower in patients with progressive nephropathy, however, in the chronological samples, this was only confirmed for miR-204-5p. Some of the identified hub genes controlled by the dysregulated miRNAs have been associated with kidney impairment in other kidney diseases. Conclusion: The miRNA cargo in uEVs changes with the development and progression of Fabry nephropathy and, therefore, represents a potential biomarker that may provide a new option to prevent or attenuate the progression of nephropathy. Furthermore, dysregulated miRNAs were shown to be potentially associated with pathophysiological pathways in the kidney.
Blood Coagulation & Fibrinolysis, Oct 1, 2006
We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patien... more We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patient with autosomal dominant polycystic kidney disease (ADPKD) with tranexamic acid (TXA), a potent antifibrinolytic agent. The bleeding could not be controlled by intensive conservative treatment, it became life-threatening and urgent bilateral nephrectomy was intended. Since local and systemic hyperfibrinolysis play a role in bleeding in ADPKD patients, we tried TXA treatment. In fact, the massive bleeding promptly stopped, and haematuria gradually ceased. Removal of both kidneys was prevented. After 5 days both ureters became obstructed by blood clots, but placing J-catheters in each pyelon successfully solved this complication. Our case shows that it is reasonable to try antifibrinolytic treatment with TXA in such devastating uncontrolled bleeding. Blood Coagul Fibrinolysis 17:589-591 ß 2006 Lippincott Williams & Wilkins.
Kidney International Reports, 2021
Journal of Medical Genetics
BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALAN... more BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than −2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year.MethodsPatients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms.ResultsSeventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18–60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2and median (range) eGFR slope was −7.3 (−30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was −0.36 mL/min/1.73 m2/...
Clinical Therapeutics, Apr 1, 2012
Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decr... more Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decreased or absent activity of lysosomal ␣-galactosidase A. As a result of this enzyme deficiency, globotriaosylceramide (GL-3) and other glycosphingolipids accumulate within various tissues and eventually impair vital organ function, putting patients with FD at risk for developing renal failure, cardiovascular dysfunction, and stroke. The initial signs and symptoms of FD, including neuropathic pain in the extremities, hypohidrosis, angiokeratomas, and gastrointestinal discomfort, generally appear during childhood. More serious complications of FD can also occur during childhood, including proteinuria, valvular dysfunction, conduction abnormalities, left ventricular hypertrophy and arrhythmia. Aim & Methods: In view of the growing recognition that significant manifestations of FD can occur during childhood, an international group of physicians who have pediatric patients enrolled in the Fabry Registry developed a set of specific guidelines for assessing FD in children based on evidence from the Fabry Registry and published literature. Results: The general types of assessments recommended for children with FD include: medical/family history (gastrointestinal, pain, sweating; heat/cold intolerance); physical examination (vital signs, height, weight, blood pressure); patient-reported outcomes (quality of life, fatigue, pain); laboratory testing (measured glomerular filtration rate, albuminuria/proteinuria); diagnostic testing (enzyme activity, genotype); specialized laboratory testing (antibodies, plasma GL-3); ophthalmology (slit-lamp examination); other studies (audiologic evaluation, cranial magnetic resonance imaging [T 1 , T 2 , FLAIR], echocardiography and ECG); and treatment/medication history (enzyme-replacement therapy status, concurrent medications). Conclusions: This new Pediatric Minimum Recommended Schedule of Assessments will increase the medical community's awareness of the burden of FD in children, assist with monitoring, and improve the outcome for these young patients.
Molecular Genetics and Metabolism, Sep 1, 2022
Nephrology Dialysis Transplantation, Oct 21, 2009
Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female ... more Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.
Molecular Genetics and Metabolism, Feb 1, 2016
Background Nephropathy is an important feature of classical Fabry disease, which results in alpha... more Background Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. Methods and design The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment. Results 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (−3.6 (−4.8 to −1.1) versus −7.0 (−9.0 to −5.6) mL/min/ 1.73 m 2 /year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <−2 mL/min/1.73 m 2 /year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events. Conclusions This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy. Trial registration number NCT00446862.
Journal of Clinical Medicine
Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, wi... more Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged >16 years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high (>0.5 g/24 h) baseline proteinuria and by ‘classic’ or ‘non-classic’ phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year; p < 0.0001). Patients with classic Fabry disease had similar ra...
Néphrologie & Thérapeutique, 2019
Slovenian Medical Journal, 2006
Background: Fabry disease is a rare X-chromosome linked disease. Due to gene mutation, activity o... more Background: Fabry disease is a rare X-chromosome linked disease. Due to gene mutation, activity of enzyme α galactosidase A is lowered or absent and sphingolipids are deposited in different organ cells. All males with gene mutation are affected but females too, due to X chromosome inactivation, can frequently be affected as well, although usually to a lesser extend. Disease is slowly progressive and there is an early dysfunction of several organs, specially endothelium, kidney, heart and central nervous system, which all leads to early death of the patient. Conclusions: Recently, a specific enzyme replacement therapy, based on recombinant technology, was discovered. Specific therapy is effective and safe. Due to a new therapy there was a need to set objective criteria when to start with enzyme replacement therapy, but also a need to more complex, multidisciplinary approach to those patients. This article is an initial proposal for systematic management of Fabry disease in our country.
Podrucje nasljednih metabolickih bolesti zadnjih se godina razvija vrlo brzo. Otkrivaju se nove b... more Podrucje nasljednih metabolickih bolesti zadnjih se godina razvija vrlo brzo. Otkrivaju se nove bolesti, nove dijagnosticke metode i nove mogucnosti lijecenja. Glavna tema ove knjige su nasljedne metabolicke bolesti koje zahvacaju krvne žile.
Genetics in Medicine Open, 2023
Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene v... more Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene variants resulting in insufficient expression of α-galactosidase A. This enzyme deficiency leads to accumulation of globotriaosylceramide and globotriaosylsphingosine in plasma and in different cells throughout the body, causing major cardiovascular, renal, and nervous system complications. Until 2018, reimbursed enzyme replacement therapy (ERT) for FD was available in all European Union countries except Poland. We present the preliminary results of the first two years of reimbursed ERT in Poland. We obtained data from the seven largest academic centers in Katowice, Cracow, Wrocław, Poznań, Gdańsk, Warsaw, and Łódź. The questionnaire included the following data: number of patients treated, number of patients qualified for ERT, and patient characteristics. All centers returned completed questionnaires that included data for a total of 71 patients (28 men and 43 women) as of June 2021. Thirty-five patients with the diagnosis of FD confirmed by genetic testing (22 men and 13 women) had already qualified for reimbursed ERT. Mean (SD) age at the commencement of the ERT program was 39.6 (15.5) years (range 18-79 years). Mean time from the first clinical symptoms reported by the patients to the FD diagnosis was 21.1 (8.9) Open Peer Review Reviewer Status
Nephrology Dialysis Transplantation, 2021
Background and Aims Females with Fabry disease (FD) often develop symptoms and disease complicati... more Background and Aims Females with Fabry disease (FD) often develop symptoms and disease complications later in life than males. However, they can experience significant health declines, including renal function impairment. Pegunigalsidase alfa is a novel PEGylated alpha-galactosidase A enzyme in development for the treatment of patients with FD with potential pharmacokinetic benefits. We previously reported that males with FD showed improvements in several parameters including median (minimum, maximum) estimated glomerular filtration rate (eGFR) slope from -4.6 (-20.5, 4.8) to -1.1 (-18.6, 14.2) mL/min/1.73m2/year after treatment with pegunigalsidase alfa.(Tondel et al. ASN 2020. PO0562. www.asn.scientificposters.com) Here we report a subgroup analysis of the safety and efficacy of pegunigalsidase alfa treatment in females with FD. Method BRIDGE (PB-102-F30; NCT03018730) is a phase 3, open-label, switch-over study designed to assess the safety and efficacy of pegunigalsidase alfa in ...
Clinical Nephrology, 2017
Fabry disease (FD; OMIM 301500) is a rare X-linked systemic disease caused by a mutation of the G... more Fabry disease (FD; OMIM 301500) is a rare X-linked systemic disease caused by a mutation of the GLA gene. Consequently, there is very low, or even absent, activity of the lysosomal enzyme α-galactosidase A (α-Gal A), resulting in the progressive accumulation of glycosphingolipids (predominantly, globotriaosylceramide (GL-3)) in various cells of different organs. Chronic progressive proteinuric kidney disease is one of the hallmarks of this disease, and it constitutes an important component of this condition's clinical picture. Many patients with FD develop advanced chronic kidney disease, and half of them progress to end-stage renal disease. Most male patients die before the age of 60 years. Specific treatment with enzyme replacement therapy (ERT) has been shown to be effective when treatment is started early enough, before irreversible changes can occur. Therefore, the early diagnosis of FD has become very important. However, in nephrology practice, too many patients are still being diagnosed in late and very advanced stages of the disease. Also, the number of diagnosed patients varies among different countries and regions. The reasons for this are numerous and diverse, and they mostly depend on the knowledge, awareness, and availability of diagnostic procedures. .
Clinical Kidney Journal, 2021
Background Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results... more Background Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results in chronic proteinuric nephropathy. Podocytes are one of the most affected renal cells and play an important role in the development and progression of kidney disease. Detached podocytes found in urine (podocyturia) are considered as a non-invasive early marker of kidney injury; however, the dynamics of podocyte loss remains unknown. Methods In this 10-year follow-up study, podocyturia and other renal clinical data were evaluated in 39 patients with FD. From 2009 to 2019, podocyturia was assessed in 566 fresh urine samples from 13 male and 26 female FD patients using immunocytochemical detection of podocalyxin. Results Podocyturia (number of podocytes per 100 mL of urine) was found in 311/566 (54.9%) of the samples, more frequently (68.9 ± 21.9% versus 50.6 ± 25.9%; P = 0.035) and with higher values (364 ± 286 versus 182 ± 180 number of podocytes per gram of creatinine (Cr) in urine; P ...