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Hannsjorg W Seyberth - One of the best experts on this subject based on the ideXlab platform.

  • Pathophysiology and Clinical Presentations of Salt-Losing Tubulopathies
    Pediatric nephrology (Berlin Germany), 2015
    Co-Authors: Hannsjorg W Seyberth
    Abstract:

    At least three renal tubular segments are involved in the pathophysiology of salt-losing tubulopathies (SLTs). Whether the pathogenesis starts either in the thick ascending limb of the loop of Henle (TAL) or in the distal convoluted tubule (DCT), it is the function of the downstream-localized aldosterone sensitive distal tubule (ASDT) to contribute to the adaptation process. In isolated TAL defects (loop disorders) ASDT adaptation is supported by upregulation of DCT, whereas in DCT disorders the ASDT is complemented by upregulation of TAL function. This upregulation has a major impact on the clinical presentation of SLT patients. Taking into account both the symptoms and signs of primary tubular defect and of the secondary reactions of adaptation, a clinical diagnosis can be made that eventually leads to an appropriate therapy. In addition to salt wasting, as occurs in all SLTs, characteristic features of loop disorders are hypo- or isosthenuric polyuria and hypercalciuria, whereas characteristics of DCT disorders are hypokalemia and (symptomatic) hypomagnesemia. In both SLT categories, replacement of urinary losses is the primary goal of treatment. In loop disorders COX inhibitors are also recommended to mitigate polyuria, and in DCT disorders magnesium supplementation is essential for effective treatment. Of note, the combination of a salt- and potassium-rich diet together with an adequate fluid intake is always the basis of long-term treatment in all SLTs.

  • clcn5 mutation r347x associated with hypokalaemic metabolic alkalosis in a turkish child an unusual presentation of dent s disease
    Nephrology Dialysis Transplantation, 2005
    Co-Authors: Nesrin Besbas, Hannsjorg W Seyberth, Nikola Jeck, Fatih Ozaltin, Michael Ludwig
    Abstract:

    Dent’s disease, an X-linked recessive tubular disorder, is characterized by low molecular weight proteinuria (LMWP) and nephrolithiasis associated with nephrocalcinosis and hypercalciuria. It is due to mutations that inactivate the renal voltage-gated chloride channel ClC-5 [1,2], which is encoded by a gene (CLCN5) located on chromosome Xp11.22. It is possible, however, that causative mutations were not identified in some patients with Dent’s disease [3–6]. Renal acidification abnormalities have not been a consistent feature of the phenotype, probably being secondary to long-standing hypercalciuria and nephrocalcinosis. Hypokalaemic metabolic alkalosis, however, has not been reported previously in Dent’s disease. Inherited disorders that manifest hypokalaemic metabolic alkalosis, such as the Bartter–Gitelman syndrome or the hyperprostaglandin E syndrome (also referred to as antenatal Bartter’s syndrome), are caused by the malfunction of renal tubular electrolyte transporters or ion channels. The hyperprostaglandin E syndrome is linked to the dysfunction of the sodium– potassium–chloride co-transporter (NKCC2) [7] or the renal outer medullary potassium channel (ROMK) [8]. The cardinal features of the syndrome are its antenatal onset—with polyhydramnios due to fetal polyuria, isothenuria and medullary nephrocalcinosis. When associated with sensorineural deafness or autosomal dominant hypocalcaemia, the hyperprostaglandin E syndrome is due to mutations in barttin, a b subunit of voltage-gated chloride channels [9], and the calcium-sensing receptor CaSR [10]. Bartter–Gitelman syndrome is linked to mutations in the basolateral chloride channel (ClC-Kb) [11] or in the sodium– chloride co-transporter (NCCT) [12]. The course of this disease is usually milder, mimicking chronic use of thiazides. ROMK, NKCC2 and NCCT mutations usually have uniform clinical presentations, whereas mutations in CLCNKB, encoding ClC-Kb, occasionally lead to phenotypic overlaps with the ROMK/ NKCC2 cohort. This study describes the first case of Dent’s disease due to a loss-of-function mutation in the CLCN5 gene, R347X, associated with a Bartter-like syndrome that is characterized by hypokalaemic metabolic alkalosis and secondary hyper-reninaemic hyperaldosteronism.

  • clinical presentation of genetically defined patients with hypokalemic salt losing tubulopathies
    The American Journal of Medicine, 2002
    Co-Authors: Melanie Peters, Stephan C Reinalter, Nikola Jeck, Andreas Leonhardt, B Tonshoff, Unter G Klaus, Martin Konrad, Hannsjorg W Seyberth
    Abstract:

    Abstract Purpose Hypokalemic salt-losing tubulopathies (Bartter-like syndromes) comprise a set of clinically and genetically distinct inherited renal disorders. Mutations in four renal membrane proteins involved in electrolyte reabsorption have been identified in these disorders: the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, the potassium channel ROMK, the chloride channel ClC-Kb, and the thiazide-sensitive sodium-chloride cotransporter NCCT. The aim of this study was to characterize the clinical features associated with each mutation in a large cohort of genetically defined patients. Patients and methods The phenotypic characteristics of 65 patients with molecular defects in NKCC2, ROMK, ClC-Kb, or NCCT were collected retrospectively. Results ROMK and NKCC2 patients presented with polyhydramnios, nephrocalcinosis, and hypo- or Isosthenuria. Hypokalemia was less severe in the ROMK patients compared with the NKCC2 patients. In contrast, NCCT patients had hypocalciuria, hypomagnesemia, and marked hypokalemia. While this dissociation of renal calcium and magnesium handling was also observed in some ClC-Kb patients, a few ClC-Kb patients presented with hypercalciuria and hypo- or Isosthenuria. Conclusions ROMK, NKCC2, and NCCT mutations usually have uniform clinical presentations, whereas mutations in ClC-Kb occasionally lead to phenotypic overlaps with the NCCT or, less commonly, with the ROMK/NKCC2 cohort. Based on these results, we propose an algorithm for the molecular diagnosis of hypokalemic salt-losing tubulopathies.

  • impaired response to furosemide in hyperprostaglandin e syndrome evidence for a tubular defect in the loop of henle
    The Journal of Pediatrics, 1996
    Co-Authors: Arnold Kockerling, Stephan C Reinalter, Hannsjorg W Seyberth
    Abstract:

    Abstract In hyperprostaglandin E syndrome (HPS) renal wasting of electrolytes and water is consistently associated with enhanced synthesis of prostaglandin E 2 . In contrast to Bartter or Gitelman syndrome (BS/GS), HPS is characterized by its severe prenatal manifestation, leading to fetal polyuria, development of polyhydramnios, and premature birth. This disorder mimics furosemide treatment with hypokalemic alkalosis, hypochloremia, Isosthenuria, and impaired renal conservation of both calcium and magnesium. Therefore the thick ascending limb of the loop of Henle seems to be involved in HPS. To characterize the tubular defect we investigated the response to furosemide (2 mg/kg) in HPS (n = 8) and BS/GS (n = 3) 1 week after discontinuation of long-term indomethacin treatment. Sensitivity to furosemide was completely maintained in patients with BS/GS. The diuretic, saluretic, and hormonal responses were similar to those of a control group of healthy children (n = 13), indicating an intact function of the thick ascending limb of the loop of Henle in BS/GS. In contrast, patients with HPS had a marked resistance to this loop diuretic. Furosemide treatment increased urine output by 7.5 ± 0.7 ml/kg per hour in healthy control subjects but only by 4.4 ± 1.2 ml/kg per hour ( p urine 0.14 ± 0.04 mmol/kg per hour vs 0.85 ± 0.09 mmol/kg per hour, p urine 0.23 ± 0.06 mmol/kg per hour vs 0.77 ± 0.09 mmol/kg per hour, p 2 excretion in patients with HPS (54 ± 17 to 107 ± 28 ng/hr per 1.73 m 2 , p 2 ). We conclude that a defect of electrolyte reabsorption in the thick ascending limb of the loop of Henle plays a major role in HPS. (J P EDIATR 1996;129:519-28)

  • RESISTANCE TO FUROSEMIDE IN HYPERPROSTAGLANDIN E SYNDROME: EVIDENCE FOR A PROSTAGLANDIN-INDEPENDENT DEFECT IN THE LOOP OF HENLE. † 2162
    Pediatric Research, 1996
    Co-Authors: Arnold Kockerling, Stephan C Reinalter, Hannsjorg W Seyberth
    Abstract:

    Hyperprostaglandin E syndrome (HPS), a prenatal variant of Bartter's syndrome, is characterized by impaired renal salt conservation and fetal polyuria leading to poly-hydramnios and premature birth. Moreover HPS mimics chronic furosemide treatment with Isosthenuria, hypochloremia, hypercalciuria, hypokalemic alkalosis, and hyperaldosteronism. To date inadequate formation of PGE2 is considered to be a primary event in HPS. In a group of 9 children with HPS (median age 10.3, range 7.7 to 11.7 years) long-term indomethacin treatment sufficiently suppressed urinary excretion of PGE2 (54±18 to 5±2 ng/h/1.73m2) and corrected hyperreninemia, hyperaldosteronism and hyperkaliuria. However, renal loss of sodium chloride persisted (2.8±0.4 to 3.3±0.3 and 3.2±0.2 to 3.0±0.4 mmol/kg/d, resp.) and the children still remained isosthenuric (227±18 to 270±18 mosmol/kg). In addition polyuria, hypercalciuria and hypermagnesiuria were improved only partially. These observations indicate a tubular defect independent of renal PGE2 release. To study the capacity of electrolyte reabsorption in the thick ascending limb of Henle's loop (TALH), furosemide was administered to the patients 7 days after interruption of indomethacin treatment. Compared to a group of 13 healthy children (median age 10.2, range 6.4 to 15.1 years) patients with HPS presented a marked resistance to the loop diuretic. Data were obtained from 3-hour urine collections subsequent to a single oral dose of 2 mg/kg furosemide (means ± SEM; *p

Claudio Ronco - One of the best experts on this subject based on the ideXlab platform.

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia, 2017
    Co-Authors: Gianluca Villa, Aashish Sharma, Stefano Romagnoli, Claudio Ronco
    Abstract:

    Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, Isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry’s disease: an example of cardiorenal syndrome type 5
    Heart Failure Reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Heart failure reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

Stephan C Reinalter - One of the best experts on this subject based on the ideXlab platform.

  • clinical presentation of genetically defined patients with hypokalemic salt losing tubulopathies
    The American Journal of Medicine, 2002
    Co-Authors: Melanie Peters, Stephan C Reinalter, Nikola Jeck, Andreas Leonhardt, B Tonshoff, Unter G Klaus, Martin Konrad, Hannsjorg W Seyberth
    Abstract:

    Abstract Purpose Hypokalemic salt-losing tubulopathies (Bartter-like syndromes) comprise a set of clinically and genetically distinct inherited renal disorders. Mutations in four renal membrane proteins involved in electrolyte reabsorption have been identified in these disorders: the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, the potassium channel ROMK, the chloride channel ClC-Kb, and the thiazide-sensitive sodium-chloride cotransporter NCCT. The aim of this study was to characterize the clinical features associated with each mutation in a large cohort of genetically defined patients. Patients and methods The phenotypic characteristics of 65 patients with molecular defects in NKCC2, ROMK, ClC-Kb, or NCCT were collected retrospectively. Results ROMK and NKCC2 patients presented with polyhydramnios, nephrocalcinosis, and hypo- or Isosthenuria. Hypokalemia was less severe in the ROMK patients compared with the NKCC2 patients. In contrast, NCCT patients had hypocalciuria, hypomagnesemia, and marked hypokalemia. While this dissociation of renal calcium and magnesium handling was also observed in some ClC-Kb patients, a few ClC-Kb patients presented with hypercalciuria and hypo- or Isosthenuria. Conclusions ROMK, NKCC2, and NCCT mutations usually have uniform clinical presentations, whereas mutations in ClC-Kb occasionally lead to phenotypic overlaps with the NCCT or, less commonly, with the ROMK/NKCC2 cohort. Based on these results, we propose an algorithm for the molecular diagnosis of hypokalemic salt-losing tubulopathies.

  • impaired response to furosemide in hyperprostaglandin e syndrome evidence for a tubular defect in the loop of henle
    The Journal of Pediatrics, 1996
    Co-Authors: Arnold Kockerling, Stephan C Reinalter, Hannsjorg W Seyberth
    Abstract:

    Abstract In hyperprostaglandin E syndrome (HPS) renal wasting of electrolytes and water is consistently associated with enhanced synthesis of prostaglandin E 2 . In contrast to Bartter or Gitelman syndrome (BS/GS), HPS is characterized by its severe prenatal manifestation, leading to fetal polyuria, development of polyhydramnios, and premature birth. This disorder mimics furosemide treatment with hypokalemic alkalosis, hypochloremia, Isosthenuria, and impaired renal conservation of both calcium and magnesium. Therefore the thick ascending limb of the loop of Henle seems to be involved in HPS. To characterize the tubular defect we investigated the response to furosemide (2 mg/kg) in HPS (n = 8) and BS/GS (n = 3) 1 week after discontinuation of long-term indomethacin treatment. Sensitivity to furosemide was completely maintained in patients with BS/GS. The diuretic, saluretic, and hormonal responses were similar to those of a control group of healthy children (n = 13), indicating an intact function of the thick ascending limb of the loop of Henle in BS/GS. In contrast, patients with HPS had a marked resistance to this loop diuretic. Furosemide treatment increased urine output by 7.5 ± 0.7 ml/kg per hour in healthy control subjects but only by 4.4 ± 1.2 ml/kg per hour ( p urine 0.14 ± 0.04 mmol/kg per hour vs 0.85 ± 0.09 mmol/kg per hour, p urine 0.23 ± 0.06 mmol/kg per hour vs 0.77 ± 0.09 mmol/kg per hour, p 2 excretion in patients with HPS (54 ± 17 to 107 ± 28 ng/hr per 1.73 m 2 , p 2 ). We conclude that a defect of electrolyte reabsorption in the thick ascending limb of the loop of Henle plays a major role in HPS. (J P EDIATR 1996;129:519-28)

  • RESISTANCE TO FUROSEMIDE IN HYPERPROSTAGLANDIN E SYNDROME: EVIDENCE FOR A PROSTAGLANDIN-INDEPENDENT DEFECT IN THE LOOP OF HENLE. † 2162
    Pediatric Research, 1996
    Co-Authors: Arnold Kockerling, Stephan C Reinalter, Hannsjorg W Seyberth
    Abstract:

    Hyperprostaglandin E syndrome (HPS), a prenatal variant of Bartter's syndrome, is characterized by impaired renal salt conservation and fetal polyuria leading to poly-hydramnios and premature birth. Moreover HPS mimics chronic furosemide treatment with Isosthenuria, hypochloremia, hypercalciuria, hypokalemic alkalosis, and hyperaldosteronism. To date inadequate formation of PGE2 is considered to be a primary event in HPS. In a group of 9 children with HPS (median age 10.3, range 7.7 to 11.7 years) long-term indomethacin treatment sufficiently suppressed urinary excretion of PGE2 (54±18 to 5±2 ng/h/1.73m2) and corrected hyperreninemia, hyperaldosteronism and hyperkaliuria. However, renal loss of sodium chloride persisted (2.8±0.4 to 3.3±0.3 and 3.2±0.2 to 3.0±0.4 mmol/kg/d, resp.) and the children still remained isosthenuric (227±18 to 270±18 mosmol/kg). In addition polyuria, hypercalciuria and hypermagnesiuria were improved only partially. These observations indicate a tubular defect independent of renal PGE2 release. To study the capacity of electrolyte reabsorption in the thick ascending limb of Henle's loop (TALH), furosemide was administered to the patients 7 days after interruption of indomethacin treatment. Compared to a group of 13 healthy children (median age 10.2, range 6.4 to 15.1 years) patients with HPS presented a marked resistance to the loop diuretic. Data were obtained from 3-hour urine collections subsequent to a single oral dose of 2 mg/kg furosemide (means ± SEM; *p

Aashish Sharma - One of the best experts on this subject based on the ideXlab platform.

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia, 2017
    Co-Authors: Gianluca Villa, Aashish Sharma, Stefano Romagnoli, Claudio Ronco
    Abstract:

    Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, Isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry’s disease: an example of cardiorenal syndrome type 5
    Heart Failure Reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Heart failure reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

Gianluca Villa - One of the best experts on this subject based on the ideXlab platform.

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia, 2017
    Co-Authors: Gianluca Villa, Aashish Sharma, Stefano Romagnoli, Claudio Ronco
    Abstract:

    Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, Isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry’s disease: an example of cardiorenal syndrome type 5
    Heart Failure Reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

  • Fabry's disease: an example of cardiorenal syndrome type 5
    Heart failure reviews, 2015
    Co-Authors: Aashish Sharma, Marco Sartori, Jose J. Zaragoza, Gianluca Villa, Elena Faggiana, Alessandra Brocca, Luca Lullo, Sandro Feriozzi, Claudio Ronco
    Abstract:

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry’s disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, Isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors—and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).