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==Overview== | ==Overview== | ||
As there is no known cure for the condition, treatments are regimented for the symptoms of the condition. | As there is no known cure for the condition, treatments are regimented for the symptoms of the condition. | ||
== | ==Management== | ||
===Work-Up=== | |||
When suspecting a patient has Alport’s syndrome, the following tests are recommended according to expert opinion published in February 2013 by Savige and colleagues in the Journal of American Society of Nephrology (JASN)<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref>: | |||
*Microalbuminuria/proteinuria | |||
*Audiometry | |||
*Ophthalmologic exam | |||
*Renal biopsy ''(optional)'' | |||
*Genetic testing ''(optional)'' | |||
Although no cure is available for Alport’s syndrome, patients may benefit from optimizing blood pressure, reducing proteinuria, and delaying renal progression into ESRD and subsequent dialysis and/or transplantation. In addition, multidisciplinary professional approach, including ophthalmologic, genetic, psychosocial, and educational aid is required to improve patients’ quality of life. | |||
===Goals of Treatment=== | |||
Goals of management in Alport's syndrome are summarized as follows<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref>: | |||
*Optimize hypertension | |||
*Optimize dyslipidemia | |||
*Reduce degree of proteinuria | |||
*Reduce hearing loss by preventing environmental exposure | |||
===Pharmacologic Therapy=== | |||
Generally, anti-hypertensive medications and anti-lipidemic medications are used to control blood pressure and dyslipidemia. | |||
====Angiotensin-Converting Enzyme Inhibitors==== | |||
To start ACE-I even before the presence of proteinuria<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref> | |||
====Cyclosporine==== | |||
The use of cyclosporine has been debatable and insufficiently valid. One study with only ___ subjects showed improved outcome.<ref name="pmid12595505">{{cite journal| author=Chen D, Jefferson B, Harvey SJ, Zheng K, Gartley CJ, Jacobs RM et al.| title=Cyclosporine a slows the progressive renal disease of alport syndrome (X-linked hereditary nephritis): results from a canine model. | journal=J Am Soc Nephrol | year= 2003 | volume= 14 | issue= 3 | pages= 690-8 | pmid=12595505 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12595505 }} </ref> | |||
====Matrix metalloproteinase inhibitors==== | |||
**MMP inhibitors in mouse models and in early phase seem promising since MMP is upregulated in Alport’s syndrome and contributes to the disease progression and degradation of the GBM.<ref name="pmid12675849">{{cite journal| author=Rao VH, Lees GE, Kashtan CE, Nemori R, Singh RK, Meehan DT et al.| title=Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS). | journal=Kidney Int | year= 2003 | volume= 63 | issue= 5 | pages= 1736-48 | pmid=12675849 | doi=10.1046/j.1523-1755.2003.00939.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12675849 }} </ref> | |||
===Protein Restriction=== | |||
One study in dogs showed that protein restriction delays progression of GBM splitting seen in patients with Alport’s syndrome, suggesting a possible lifestyle intervention for improved survival.<ref name="pmid2072666">{{cite journal| author=Valli VE, Baumal R, Thorner P, Jacobs R, Marrano P, Davies C et al.| title=Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis. | journal=Lab Invest | year= 1991 | volume= 65 | issue= 1 | pages= 67-73 | pmid=2072666 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2072666 }} </ref> | |||
===Renal Replacement Therapy=== | |||
====Dialysis==== | |||
====Renal transplantation==== | |||
Choice of donor must be made carefully only between non-carrier and non-affected family members. Patients with TBMN can be donors only if have normal BP, level of proteinuria, and kidney function and have confirmed genetic and pathological work-up to rule out X-linked Alport’s syndrome.<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref Despite transplantation, there is up to 5% risk of developing anti-GBM disease among males. The risk is higher with subsequent transplantations. If anti-GBM is suspected following transplant with symptoms of renal impairment, allograft biopsy is required.<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref> Females usually have better outcome with transplantation. 15% still develop ESRD by 60 years of age. Regular follow-up is recommended.<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref> | |||
===Future Therapies=== | |||
Gene therapy and stem cell therapy are currently contemplated to be promising therapeutic options for patients with Alport’s syndrome; but their true value has not yet been in effect because they require further evaluation.<ref name="pmid4026716">{{cite journal| author=Robinson WF, Huxtable CR, Gooding JP| title=Familial nephropathy in cocker spaniels. | journal=Aust Vet J | year= 1985 | volume= 62 | issue= 4 | pages= 109-12 | pmid=4026716 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4026716 }} </ref><ref name="pmid12958072">{{cite journal| author=Bailey AS, Jiang S, Afentoulis M, Baumann CI, Schroeder DA, Olson SB et al.| title=Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. | journal=Blood | year= 2004 | volume= 103 | issue= 1 | pages= 13-9 | pmid=12958072 | doi=10.1182/blood-2003-05-1684 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12958072 }} </ref><ref name="pmid11348593">{{cite journal| author=Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R et al.| title=Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. | journal=Cell | year= 2001 | volume= 105 | issue= 3 | pages= 369-77 | pmid=11348593 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11348593 }} </ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 20:53, 31 October 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
As there is no known cure for the condition, treatments are regimented for the symptoms of the condition.
Management
Work-Up
When suspecting a patient has Alport’s syndrome, the following tests are recommended according to expert opinion published in February 2013 by Savige and colleagues in the Journal of American Society of Nephrology (JASN)[1]:
- Microalbuminuria/proteinuria
- Audiometry
- Ophthalmologic exam
- Renal biopsy (optional)
- Genetic testing (optional)
Although no cure is available for Alport’s syndrome, patients may benefit from optimizing blood pressure, reducing proteinuria, and delaying renal progression into ESRD and subsequent dialysis and/or transplantation. In addition, multidisciplinary professional approach, including ophthalmologic, genetic, psychosocial, and educational aid is required to improve patients’ quality of life.
Goals of Treatment
Goals of management in Alport's syndrome are summarized as follows[1]:
- Optimize hypertension
- Optimize dyslipidemia
- Reduce degree of proteinuria
- Reduce hearing loss by preventing environmental exposure
Pharmacologic Therapy
Generally, anti-hypertensive medications and anti-lipidemic medications are used to control blood pressure and dyslipidemia.
Angiotensin-Converting Enzyme Inhibitors
To start ACE-I even before the presence of proteinuria[1]
Cyclosporine
The use of cyclosporine has been debatable and insufficiently valid. One study with only ___ subjects showed improved outcome.[2]
Matrix metalloproteinase inhibitors
- MMP inhibitors in mouse models and in early phase seem promising since MMP is upregulated in Alport’s syndrome and contributes to the disease progression and degradation of the GBM.[3]
Protein Restriction
One study in dogs showed that protein restriction delays progression of GBM splitting seen in patients with Alport’s syndrome, suggesting a possible lifestyle intervention for improved survival.[4]
Renal Replacement Therapy
Dialysis
Renal transplantation
Choice of donor must be made carefully only between non-carrier and non-affected family members. Patients with TBMN can be donors only if have normal BP, level of proteinuria, and kidney function and have confirmed genetic and pathological work-up to rule out X-linked Alport’s syndrome. Females usually have better outcome with transplantation. 15% still develop ESRD by 60 years of age. Regular follow-up is recommended.[1]
Future Therapies
Gene therapy and stem cell therapy are currently contemplated to be promising therapeutic options for patients with Alport’s syndrome; but their true value has not yet been in effect because they require further evaluation.[5][6][7]
References
- ↑ 1.0 1.1 1.2 1.3 Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F (2013). "Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy". J Am Soc Nephrol. 24 (3): 364–75. doi:10.1681/ASN.2012020148. PMID 23349312.
- ↑ Chen D, Jefferson B, Harvey SJ, Zheng K, Gartley CJ, Jacobs RM; et al. (2003). "Cyclosporine a slows the progressive renal disease of alport syndrome (X-linked hereditary nephritis): results from a canine model". J Am Soc Nephrol. 14 (3): 690–8. PMID 12595505.
- ↑ Rao VH, Lees GE, Kashtan CE, Nemori R, Singh RK, Meehan DT; et al. (2003). "Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS)". Kidney Int. 63 (5): 1736–48. doi:10.1046/j.1523-1755.2003.00939.x. PMID 12675849.
- ↑ Valli VE, Baumal R, Thorner P, Jacobs R, Marrano P, Davies C; et al. (1991). "Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis". Lab Invest. 65 (1): 67–73. PMID 2072666.
- ↑ Robinson WF, Huxtable CR, Gooding JP (1985). "Familial nephropathy in cocker spaniels". Aust Vet J. 62 (4): 109–12. PMID 4026716.
- ↑ Bailey AS, Jiang S, Afentoulis M, Baumann CI, Schroeder DA, Olson SB; et al. (2004). "Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells". Blood. 103 (1): 13–9. doi:10.1182/blood-2003-05-1684. PMID 12958072.
- ↑ Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R; et al. (2001). "Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell". Cell. 105 (3): 369–77. PMID 11348593.