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Alport syndrome

For patient information on this page, click here Template:DiseaseDisorder infobox

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Leena Josephin Jetty, M.B.B.S[3]

Synonyms and keywords: Hereditary nephritis; hemorrhagic familial nephritis; X-linked nephropathy and deafness; hematuria-nephropathy-deafness; hereditary deafness and nephropathy

Overview

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Alport’s syndrome (hereditary nephritis) is a familial nephropathy characterized by renal impairment, auditory manifestations, and may also have ocular defects. It has an X-linked form characterized by the mutation of COL4A5 gene on the long arm of X-chromosome, and another much less common autosomal recessive form characterized by the homogeneous mutation of COL4A3 or COL4A4 on chromosome 2. The mutation leads to abnormal alpha chain of type IV collagen, which is normally responsible for the structure and function of basement membranes in the body. Alport’s syndrome most commonly presents in childhood with persistent hematuria; a presentation that should always consider a range of more common differential diagnoses before the diagnosis of Alport’s syndrome is made. Prognosis of Alport’s syndrome is generally poor with inevitable progression to end-stage renal disease (ESRD) at varying rates. Management is by multidisciplinary approach, involving established and promising pharmacologic therapy along with renal replacement methods.

References

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Historical Perspective

Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Historical Perspective

The first report of Alport’s syndrome (hereditary nephritis) was published by the English physician Arthur Cecil Alport in the British Medical Journal in 1927. In the original description of one family with 3 generations, Alport reports that sensorineural deafness was associated with a form of progressive familial nephropathy that led to severe uremia in males but not in females. Alport first believed the syndrome was caused by a streptococcal infection responsible for the glomerular involvement.[1]

Originally, ocular symptoms were not mentioned by Alport himself; it was not until 1954 when Sohar and colleagues showed that 50% of patients with Alport’s syndrome have spherophakia, a congenital bilateral ocular anomaly involving the lens of the eye.[2]

References

  1. ↑ Alport AC (1927). “HEREDITARY FAMILIAL CONGENITAL HAEMORRHAGIC NEPHRITIS”. Br Med J. 1 (3454): 504–6. PMC 2454341. PMID 20773074.
  2. ↑ SOHAR E (1954). “A heredo-familial syndrome characterized by renal disease, inner ear deafness, and ocular changes”. Harefuah. 47 (8): 161–2. PMID 13210749.

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Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2]Associate Editor(s)-in-Chief: Krzysztof Wierzbicki M.D. [3]

Overview

Pathogenesis

Alport Syndrome occurs due to a mutation in the α-3, α-4, α-5 chains. These chains are essential in forming the basement membrane. The mutations of these chains are caused by a gene mutation in COL4A5 that encodes the alpha-5 chain on the X-chromosome . A gene mutation of COL4A3 that encodes the alpha-3 chain and COL4A4 that affects the alpha-4 chain. [1]

A mutation in any of these genes results in misfolded polypeptides and improperly assembled proteins. This is due to mRNA being misread by the ribosomes. The improper reading of mRNA leads to α-3,α-4,α-5 chains to be shutdown. The shutdown of these chains results in immature development of the glomerular basement membrane, as α-3,α-4,α-5 chains are essential in producing a mature and well functioning glomerular basement membrane. When these chains are shutdown, embryonic developmental chains (α-1.,α-1., α-2.) are still being produced in the glomerular basement membrane. The production of only these chains in the glomerular basement membrane results in the glomerular basement membrane to be prone to endoproteolysis and oxidative stressors. As time progresses, the renal under constant oxidative stressors and endoproteolysis conforms the glomerular basement membrane to become unevenly thick, split, and unfortunately damaged in a way that it is no longer able to function properly.[2]

Genetics

Alport syndrome is a rare inherited disease, that is passed down by the mother’s or father’s X chromosome or a mutation involving chromosome 2. There are three forms of inheritance. It can either be x-linked, autosomal dominant, or autosomal recessive.[3]

[4] [4] [4] [4]

Microscopic Pathology

Alport’s syndrome is characterized by the defect of alpha chains of type IV collagen that constitute a triad of manifestations: renal, auditory, and ocular. Involvement of the glomerular basement membrane is the hallmark of Alport’s syndrome.[5][6] It is still controversial as to whether the basement membrane becomes thicker or thinner to induce splitting.

Molecular and Histopathological Changes in Alport’s Syndrome
Manifestations Renal Auditory Ocular
Molecular Findings Absence of collagen network of the glomerular basement membrane (GBM) that is normally formed by podocytes and endothelial cells[7][8][9] Cellular loss, including hair cells of Corti, and edema associated with atrophy of tissue[10][11][12][13] Cellular loss and mitochondrial edema. Honeycombing of broken abnormal filaments that are surrounded by vacuolated spheres and membranes[14][11]
Histopathological Changes Lamellated GBM and splitting with appearance of false layers of the basement membrane leading to focal sclerosis of glomeruli[10][11][12][5] Basement changes of the stria vascularis of the cochlea Pathological changes involving the lens capsule, the largest basement membrane in the eye[14][11]


Alpha chains of type IV collagen are located at specific regions in the body. However, the involvement of one type of alpha chain does not necessarily have to involve all corresponding beds that are known to be composed of that same collagen type. To date, there has been no valid hypothesis of why renal, auditory, and ocular manifestations are observed in Alport’s syndrome, but other basement membrane beds involving alpha-5 type IV collagen are no involved, such as the epidermal basement membrane of the skin.[11][15]

References

  1. ↑ Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003). “Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen”. N Engl J Med. 348 (25): 2543–56. doi:10.1056/NEJMra022296. PMID 12815141.
  2. ↑ Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003). “Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen”. N Engl J Med. 348 (25): 2543–56. doi:10.1056/NEJMra022296. PMID 12815141.
  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.
  4. ↑ 4.0 4.1 4.2 4.3 Alport Syndrome Foundation. www.alportsyndrome.org/alport-syndrome/alport-syndrome-genetics/ Accessed on November 2, 2016
  5. ↑ 5.0 5.1 Bodziak KA, Hammond WS, Molitoris BA (1994). “Inherited diseases of the glomerular basement membrane”. Am J Kidney Dis. 23 (4): 605–18. PMID 8154501.
  6. ↑ Kashtan CE, Michael AF (1993). “Alport syndrome: from bedside to genome to bedside”. Am J Kidney Dis. 22 (5): 627–40. PMID 8238007.
  7. ↑ Abrahamson DR, Hudson BG, Stroganova L, Borza DB, St John PL (2009). “Cellular origins of type IV collagen networks in developing glomeruli”. J Am Soc Nephrol. 20 (7): 1471–9. doi:10 .1681/ASN.2008101086 Check |doi= value (help). PMC 2709682. PMID 19423686.
  8. ↑ Miner JH (1998). “Developmental biology of glomerular basement membrane components”. Curr Opin Nephrol Hypertens. 7 (1): 13–9. PMID 9442357.
  9. ↑ St John PL, Abrahamson DR (2001). “Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains”. Kidney Int. 60 (3): 1037–46. doi:10.1046/j.1523-1755.2001.0600031037.x. PMID 11532098.
  10. ↑ 10.0 10.1 Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
  12. ↑ 12.0 12.1 Andreoli SP, Deaton M (1992). “Alport’s syndrome”. Ear Nose Throat J. 71 (10): 508–11. PMID 1425373.
  13. ↑ Grondalski SJ, Bennett GR (1989). “Alport’s syndrome: review and case report”. Optom Vis Sci. 66 (6): 396–8. PMID 2771325.
  14. ↑ 14.0 14.1 Streeten BW, Robinson MR, Wallace R, Jones DB (1987). “Lens capsule abnormalities in Alport’s syndrome”. Arch Ophthalmol. 105 (12): 1693–7. PMID 3689194.
  15. ↑ Barker DF, Hostikka SL, Zhou J, Chow LT, Oliphant AR, Gerken SC; et al. (1990). “Identification of mutations in the COL4A5 collagen gene in Alport syndrome”. Science. 248 (4960): 1224–7. PMID 2349482.

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Causes

Causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Leena Josephin Jetty, M.B.B.S[2]

Overview

Causes

Genetics

Alport’s syndrome (AC) or hereditary nephritis is a familial nephropathy caused by a genetic defect in the alpha-5 chains of type IV collagen, which comprises approximately 50% of the basement membrane and is responsible for its plasticity and strength.[1]

In 1990, Barker and colleagues discovered that Alport’s syndrome is caused by a defect of the COL4A5 gene on the long arm of the X chromosome located at Xq22-23 region. It normally codes for alpha-5 chains that have been found to be defective in Alport’s syndrome.[2][3][4] It is notable to realize that most cases of Alport’s syndrome are caused by an X-linked dominant pattern of inheritance[1][5] vs. only 15% of cases are due to autosomal inheritance.[1][5][6] Autosomal recessive inheritance most likely is not caused by a defect of alpha-5 chains, but rather a defect of alpha-3 and alpha-4 chains of type IV collagen on chromosome 2.[7] On the other hand, autosomal dominant pattern of inheritance is presumable in cases of reduced severity; it is due to heterozygous COL4A3 or COL4A4 mutations.[8][9][10] To sum up, more than 85% of patients with Alport’s syndrome have a mutation of COL4A5 gene, leading to an X-linked Alport’s syndrome. Less common mutations that cause Alport’s syndrome are due to COL4A3 and COL4A4 genes mutations that cause the autosomal recessive type of Alport’s syndrome.[11][12]

Alpha-5 chains are responsible for giving solidity in the final step of collagen synthesis. Thus, a defect of the alpha-5 chains is likely to cause a defect of all 3 intertwined collagen chains and affecting the entire collagen product.[6][13][14][15]

The exact type of defect is difficult to characterize; there are at least 40 mutations that have been already described in Alport’s syndrome; some of which involve insertion, point or multiple deletions, or genetic rearrangement.[3][4] Common mutations that are involved in Alport’s syndrome are cysteine to serine point mutations[8], glycine substitutions[6], and mutations of NC1 domains that affect intermolecular interactions[6]. There does not seem to be a clear correlation between the severity of symptoms in Alport’s syndrome and the amount or quality of genetic mutations. To date, the literature is still uncertain about obvious genetic and clinical associations[8][15][6], but the association of male gender with severity has been well verified since the very first description of the disease by AC Alport himself.[16]

  • Further studies showed that the phenotypic variations are associated with difference in the modes of variation and the location and types of variant within the genes encoding type IV collagen.
  • In Cases of CKD due to aport syndrome without its classical features studies shows that under-appreciated variants in genes encoding type IV collagen are responsible for it.
  • X-linked disease is caused by pathogenic variants in COL4A5 .
  • Autosomal recessive or autosomal dominant inheritance of pathogenic variants in COL4A3 or COL4A4 are identified.
  • Highest risk of renal failure is associated with X-linked and Autosomal Recessive inheritance.
  • Disease resulting from pathogenic variants in two different genes encoding type IV collagen (digenic inheritance) may have worse clinical outcomes than disease due to a single-gene heterozygous variant.
  • Truncated variants have worse outcome when compared to missense variants.

Missense variants affect glycine residues there by altering the assembly of collagen heterotrimer structure.

Classification

Phenotypic expressions of Alport’s syndrome differ from one patient to another. They have become the basis for classification of Alport’s syndrome, according to Atkin and colleagues in 1993.[9][10]

According to Atkin and colleagues, the main classification differentiates adult vs. juvenile Alport’s syndrome. The classification is based on time to reach end-stage renal disease (ESRD), mode of inheritance, and presence of ocular and auditory anomalies.[9][10]

  • Adult: XD inheritance and time to reach ESRD is generally after 31 years of age. Its extra-renal manifestations are typically less commonly seen compared to its juvenile counterpart. In adult subtype, only 50% of patients have auditory anomalies, whereas visual defects are almost never seen.[9][10]
  • Juvenile: XD or autosomal mode of inheritance. Patients rapidly reach ESRD before 31 years of age. Almost all patients have auditory deficient and ocular manifestations are generally present.[9][10]


However, Atkin and colleagues[9][10],further classified Alport’s syndrome into 6 types from I-VI with 6 characteristics to differentiate various subtypes: The characteristics are not exclusive to different subtypes; some of which may be present or absent within the same subtype.

  • Inheritance: XD for I, II, III, IV vs. AD for I, V, VI
  • Adult vs. juvenile: Adult: III, IV, V vs. juvenile I, II, V, VI
  • Presence of auditory deficit: I, II, V, VI
  • Presence of ocular anomalies: I, II, VI
  • Presence of subtypes: III and VI
  • Presence of AS variant, such as Epstein syndrome: V

According to this classification, types I and VI only differ by the inability of the former to produce offspring, compared to the normal ability to reproduce in the latter.[9][10] Otherwise, all 6 characteristics are generally similar in both subtypes.

References

  1. ↑ 1.0 1.1 1.2 Bodziak KA, Hammond WS, Molitoris BA (1994). “Inherited diseases of the glomerular basement membrane”. Am J Kidney Dis. 23 (4): 605–18. PMID 8154501.
  2. ↑ Gehrs KM, Pollock SC, Zilkha G (1995). “Clinical features and pathogenesis of Alport retinopathy”. Retina. 15 (4): 305–11. PMID 8545576.
  3. ↑ 3.0 3.1 Yoshioka K, Hino S, Takemura T, Maki S, Wieslander J, Takekoshi Y; et al. (1994). “Type IV collagen alpha 5 chain. Normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody”. Am J Pathol. 144 (5): 986–96. PMC 1887361. PMID 8178947.
  4. ↑ 4.0 4.1 Hostikka SL, Eddy RL, Byers MG, Höyhtyä M, Shows TB, Tryggvason K (1990). “Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome”. Proc Natl Acad Sci U S A. 87 (4): 1606–10. PMC 53524. PMID 1689491.
  5. ↑ 5.0 5.1 Knebelmann B, Antignac C, Gubler MC, Grünfeld JP (1993). “Molecular genetics of Alport syndrome: the clinical consequences”. Nephrol Dial Transplant. 8 (8): 677–9. PMID 8414149.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Hudson BG, Reeders ST, Tryggvason K (1993). “Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis”. J Biol Chem. 268 (35): 26033–6. PMID 8253711.
  7. ↑ Turco AE, Rossetti S, Bresin E, Corrá S (1995). “Erroneous genetic risk assessment of Alport syndrome”. Lancet. 346 (8984): 1237. PMID 7475699.
  8. ↑ 8.0 8.1 8.2 Flinter F (1993). “Molecular genetics of Alport’s syndrome”. Q J Med. 86 (5): 289–92. PMID 8327646.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
  11. ↑ Barker DF, Hostikka SL, Zhou J, Chow LT, Oliphant AR, Gerken SC; et al. (1990). “Identification of mutations in the COL4A5 collagen gene in Alport syndrome”. Science. 248 (4960): 1224–7. PMID 2349482.
  12. ↑ Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y; et al. (1994). “Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome”. Nat Genet. 8 (1): 77–81. doi:10.1038/ng0994-77. PMID 7987396.
  13. ↑ Kashtan CE, Michael AF (1993). “Alport syndrome: from bedside to genome to bedside”. Am J Kidney Dis. 22 (5): 627–40. PMID 8238007.
  14. ↑ Rumpelt HJ (1987). “Alport’s syndrome: specificity and pathogenesis of glomerular basement membrane alterations”. Pediatr Nephrol. 1 (3): 422–7. PMID 3153312.
  15. ↑ 15.0 15.1 Cheong HI, Kashtan CE, Kim Y, Kleppel MM, Michael AF (1994). “Immunohistologic studies of type IV collagen in anterior lens capsules of patients with Alport syndrome”. Lab Invest. 70 (4): 553–7. PMID 8176894.
  16. ↑ Alport AC (1927). “HEREDITARY FAMILIAL CONGENITAL HAEMORRHAGIC NEPHRITIS”. Br Med J. 1 (3454): 504–6. PMC 2454341. PMID 20773074.

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Differentiating Alport syndrome from other Diseases

Differentiating Alport syndrome from other Diseases

The differential diagnosis of Alport’s syndrome includes other conditions that involve persistent familial hematuria, renal failure, hearing loss, retinal fleck, and lamellated GBM.[1]Some of the common diseases are listed in the table below.[2][3][4][5][6]

Common Differential Diagnoses of Alport’s Syndrome
Differential Diagnosis Distinguishing Features Comments
Polycystic Kidney Disease Generally, absence of auditory or ocular manifestations Ocular manifestations such as retinal dystrophy might be present
Medullary Cystic Disease Absence of auditory or ocular manifestations Ocular manifestations such as congenital cataracts may be present
Epstein Syndrome Renal, auditory, and hematological manifestations Type V AS variant
Fechtner Syndrome Renal, auditory, and hematological manifestations Type III AS variant
Leiomyomatosis Cataract, auditory manifestations, and glomerulonephritis with multiple benign lesions made of smooth muscle cells May be present with Alport’s syndrome due to involvement of adjacent gene, COL4A6


According to expert opinion[1], the differential diagnosis of Alport’s syndrome is very wide and includes the following:

Familial Hematuria

  • TBMN
  • Familial IgA nephropathy
  • MYH9-related disorder, such as Fechtner and Epstein syndromes
  • Membranoproliferative GN type 2
  • Familail hemolytic uremic syndrome
  • C3 nephropathy
  • ADPKD
  • Sickle cell disease or trait
  • Familial hypercalciuria or familial urolithiasis

Renal Impairment and Hearing Loss

  • MYH-9 related disorders such as Fechtner syndrome
  • Nephronophthisis
  • Bartter syndrome
  • Distal renal tubular acidosis
  • MELAS syndrome
  • Fabry disease
  • Branchio-oto-renal syndrome
  • Townes-Brock syndrome
  • CHARGE syndrome
  • Kallmann syndrome
  • Alstrom disease
  • Muckle-Wells syndrome

Hearing Loss

  • Middle-ear infections
  • Age
  • Industrial noise exposure
  • Ototoxic drugs
  • Renal failure and dialysis

Retinal Flecks

  • Membranoproliferative GN type 2
  • IgA nephropathy
  • Systemic lupus erythematosus
  • Other forms of GN
  • Severe hypertension
  • C3 nephropathy

Lamellated Glomerular Basement Membrane

  • Focal damage
  • MYH9-related disorders, such as Fechtner and Epstein syndromes
  • Pierson syndrome
  • Nail-patella syndrome
  • Mutations in the tetraspanin (CD151) gene
  • Frasier syndrome
  • Galloway-Mowat syndrome


Alport syndrome should be differentiated from other glomerular diseases based on associations, presence of pitting edema, hematuria, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features. The following table differentiates between various types of glumerular diseases:

Glomerular diseases Disease History and Symtoms Laboratory Findings Pathology
History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
Acute Nephritic Syndromes Poststreptococcal Glomerulonephritis[7][8][9] +/- + +/- +/- +/- +/- +/- +/-
  • Immune complex GN
  • Granular deposit
Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt (Atrioventricular)[10][11] +/- + +/- +/- +/- +/- +/- +/-
  • Crescentic GN is the most common pathological features
  • Mesangial deposits,
  • Subendothelial deposits
  • Subepithelial “humps,” in minority of cases
  • Pauci-immune GN
Lupus Nephritis[12]
  • History of SLE features
 +/- + +/- +/- +/- +/- +/- +/-
  • Differs based on the disease classification
  • Differs based on the disease classification
  • Differs based on the disease classification, mostly immune complex GN
  • Granular deposit
Antiglomerular Basement Membrane Disease (Goodpasture’s syndrome)[13][14]
  • Young adults
 + + + + + + – – Diffuse thickening of the glomerular basement membrane with absence of sub-epithelial and sub-endothelial deposits 
  • Immune complex GN
  • Linear deposit
IgA Nephropathy[15][16] + +/- + +/- + – + –
  • Immune complex deposition
  • Crescent formation
  • Immune complex GN, granular deposite
Disease History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
ANCA Small-Vessel Vasculitis[17][18] Granulomatosis with Polyangiitis (Wegener’s)[19][20][21]
  • Middle age male
 + + + +/- + – + –
  •  Pauci-immune GN
Microscopic Polyangiitis[22] +/- + + + + + + –
  •  Pauci-immune GN
Churg-Strauss Syndrome[23] +/- + + + + + + –
  •  Pauci-immune GN
Membranoproliferative Glomerulonephritis[24][25] + + + +/- + + – – –
  • Immune complex GN
  • Granular deposite
Henoch-Schönlein purpura [26] + + + +/- + + – – –
  • Diffuse mesangial IgA deposits often associated with mesangial hypercellularity
  • Diffuse mesangial IgA deposits often associated with mesangial hypercellularity
  • Immune complex GN, granular deposite
Disease History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
Cryoglobulinemia[27] Patients having cryoglobulinemia may have positive history of: Pulmonary symptoms:
  • Cough

Cutaneous symptoms:

Gastrointestinal symptoms:

  • Abdominal pain

General symptoms:

+/- + +/- + +/- +/- +/- +/- +/-
  • Prominent IgM and C3
Nephrotic Syndrome Minimal Change Disease[28][29] – + – + +/- + – +
  • Normal
 –
Focal Segmental Glomerulosclerosis[30][31][32] – + – + +/- + – + –
Membranous Glomerulonephritis[33][34] – + – + +/- + – + Immune complex deposition Immune complex GN, granular deposite
Diabetic Nephropathy[35][36][37][38][39][40][41][42][43][44] For more information on diabetes click here. – + – + +/- + – +
  • Diffuse mesangial matrix expansion (nodular glomerulosclerosis)
  • Increased mesangial hypercellularity
  • Prominent glomerular basement membranes
  • Thick basement membrane without any deposit
  • Nodular glomerulosclerosis
 –
Disease History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
 Glomerular Deposition Diseases  Light Chain Deposition Disease[45]
  • Occurs in the setting of high tumor burden
 – – + – + +/- + – + –
  • Light-chain deposits
  • Granular deposits on electron microscopy
  • Detection of light chain deposits using anti–light chain antibody
Renal Amyloidosis[46][47][48][49] – + – + +/- + – + –
  • Diffuse glomerular deposition of amorphous hyaline material (nodular pattern), in mesangium (weakly staining with periodic acid-Schiff (PAS)
  • Nodular deposit
  • AA amyloidosis type: negative for immunoglobulins and complement
  • AL amyloidosis type: Positive for lambda or kappa light chains
Fibrillary-Immunotactoid Glomerulopathy[50] – +/- + +/- +/- +/- + +/- +/- –
  • Diffuse sclerosing glomerulonephritis
  • Diffuse proliferative glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Mesangioproliferative/sclerosing disease
  • Membranous glomerulonephritis
  • Large fibrillar deposits in the mesangium randomly
  • Glomerular capillary walls different from amloidosis
  • No staining with Congo red or thioflavine-T or with antibodies to a specific type
  • Positive for immunoglobulin G (IgG), C3
  • Kappa and lambda (ie, polyclonal) light chains
Fabry’s Disease[51][52][53] – + – + +/- + – + –
  • Vacuolization of visceral glomerular epithelial cells (podocytes) and distal tubular epithelial cells
  • Glycolipid accumulation
  • Myeloid or zebra bodies: Gb3 deposition within enlarged secondary lysosomes as lamellated membrane structures
  • Inclusions, composed of concentric layers (onion skin appearance)
 –
Basement Membrane Syndrome Alport’s Syndrome[54][55][56][6][3][57]
  • Positive family history
 Auditary:

Occular problems:

  • Refractory Error
 – + – + +/- + – + –
  • Early stage: unremarkable
Disease History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
Thin Basement Membrane Disease[58][59] – – + -/+ – -/+ – -/+ – – – Diffuse thinning of the glomerular basement membranes (GBM) –
Nail-Patella Syndrome[60][61]
  • Positive family history
  • Poorly developed fingernails, toe nails, and patellae (kneecaps).
  • Elbow deformities
  • Abnormally shaped pelvis bone (hip bone)
  • Knee may be small, deformed or absent
 + + – – – – – – –
  • Mostly unremarkable changes
  • Secondary FSGS
  • Late stages:
    • Global glomerulosclerosis,
    • Tubulointerstitial fibrosis
  • Glomerular basement membranes (GBMs): Focal or diffuse irregular thickening with electron-lucent areas (moth-eaten appearance) containing type III collagen bundles.
  • Similar collagen fibrils can be seen in mesangial matrix.
  • Podocytes: Segmental effacement of foot processes.
  • Nonspecific IgM and C3 deposition may be seen in sclerotic glomeruli.
 Glomerular-Vascular Syndromes  Hypertensive Nephrosclerosis[62] Chronic hypertension +/- +/- + +/- +/- +/- – +/- –
  • Interstitial fibrosis and atrophy
  • Medial thickening and intimal fibrosis of medium-sized and larger vessels
  • Arteriolar thickening, and hyalinosis
  • Chronic stages:
Cholesterol Emboli[63]
  • Depends on the organ involved
 +/- +/- + +/- +/- +/- – +/- –
  • Atheroemboli are seen in interlobular and arcuate arteries, as lance-shaped clefts, due to dissolution of cholesterol crystals
  • Acute lesions:
    • Atheroemboli are surrounded by red blood cells, fibrin, and leukocytes, with multinucleated giant cell reactions
  • Chronic lesions:
    • Cholesterol clefts are surrounded by intimal fibrosis
    • Vessel recanalization of chronic lesions can occur.
  • Global and segmental sclerosis of glomeruli may be present.
  • Extensive foot process effacement can be seen
  • Not specific changes
Disease History Systemic symptoms Hemeturia Proteinuria Hypertension Pitting edema Oliguria Nephrotic features Nephritic features Hyperlipidemia and hypercholesterolemia Auto-antibodies,

Complements

Light microscope Electron microscope Immunoflourescence pattern
Sickle Cell Disease[64]
  • Positive family history
 +/- +/- +/- – – – – – –
  • Glomerular hypertrophy
  • Hemosiderin deposits
  • Focal areas of hemorrhage or necrosis
  • Chronic stage: interstitial inflammation, edema, fibrosis, tubular atrophy, and papillary infarcts
  • Glomerular enlargement and focal segmental glomerulosclerosis (FSGS)
Thrombotic Microangiopathies[65] Click for more information on Thrombotic Microangiopathies. + +/- + +/- +/- +/- – – –
  • Acute stage:
    • Inravasculr fibrin thrombi
  • Chronic stage:
    • Endocapillary hypercellularity.
    • Intimal proliferation of arterioles
  • Swollen glomerular endothelial cells with loss of fenestrations
  • Chronic stage: interposed cells with new GBM matrix material deposition.
Antiphospholipid Antibody Syndrome [66][67][68] + +/- + +/- +/- +/- – – –
  • Swollen glomerular endothelial cells with loss of fenestrations
  • Chronic stage: interposed cells with new GBM matrix material deposition.


Some infectious diseases such as HIV, HBV, HCV, syphilis, leprosy, malaria, and schistosomiasis may cause glomerular diseases.

References

  1. ↑ 1.0 1.1 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.
  2. ↑ Hudson BG, Reeders ST, Tryggvason K (1993). “Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis”. J Biol Chem. 268 (35): 26033–6. PMID 8253711.
  3. ↑ 3.0 3.1 Amari F, Segawa K, Ando F (1994). “Lens coloboma and Alport-like glomerulonephritis”. Eur J Ophthalmol. 4 (3): 181–3. PMID 7819734.
  4. ↑ Lonsdale RN, Roberts PF, Vaughan R, Thiru S (1992). “Familial oesophageal leiomyomatosis and nephropathy”. Histopathology. 20 (2): 127–33. PMID 1559666.
  5. ↑ García-Torres R, Orozco L (1993). “Alport-leiomyomatosis syndrome: an update”. Am J Kidney Dis. 22 (5): 641–8. PMID 8238008.
  6. ↑ 6.0 6.1 McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
  7. ↑ GERMUTH FG (1953). “A comparative histologic and immunologic study in rabbits of induced hypersensitivity of the serum sickness type”. J Exp Med. 97 (2): 257–82. PMC 2136196. PMID 13022878.
  8. ↑ Germuth FG, Senterfit LB, Dreesman GR (1972). “Immune complex disease. V. The nature of the circulating complexes associated with glomerular alterations in the chronic BSA-rabbit system”. Johns Hopkins Med J. 130 (6): 344–57. PMID 5031005.
  9. ↑ Radhakrishnan J, Cattran DC (2012). “The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines–application to the individual patient”. Kidney Int. 82 (8): 840–56. doi:10.1038/ki.2012.280. PMID 22895519.
  10. ↑ Neugarten J, Baldwin DS (August 1984). “Glomerulonephritis in bacterial endocarditis”. Am. J. Med. 77 (2): 297–304. PMID 6380288.
  11. ↑ Arze RS, Rashid H, Morley R, Ward MK, Kerr DN (January 1983). “Shunt nephritis: report of two cases and review of the literature”. Clin. Nephrol. 19 (1): 48–53. PMID 6831779.
  12. ↑ Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M (February 2004). “The classification of glomerulonephritis in systemic lupus erythematosus revisited”. Kidney Int. 65 (2): 521–30. doi:10.1111/j.1523-1755.2004.00443.x. PMID 14717922.
  13. ↑ Bolton WK (November 1996). “Goodpasture’s syndrome”. Kidney Int. 50 (5): 1753–66. PMID 8914046.
  14. ↑ Mathew TH, Hobbs JB, Kalowski S, Sutherland PW, Kincaid-Smith P (February 1975). “Goodpasture’s syndrome: normal renal diagnostic findings”. Ann. Intern. Med. 82 (2): 215–8. PMID 1090223.
  15. ↑ Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA (October 2011). “The pathophysiology of IgA nephropathy”. J. Am. Soc. Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMC 3892742. PMID 21949093.
  16. ↑ Wyatt RJ, Julian BA (June 2013). “IgA nephropathy”. N. Engl. J. Med. 368 (25): 2402–14. doi:10.1056/NEJMra1206793. PMID 23782179.
  17. ↑ Higgins RM, Goldsmith DJ, Connolly J, Scoble JE, Hendry BM, Ackrill P, Venning MC (January 1996). “Vasculitis and rapidly progressive glomerulonephritis in the elderly”. Postgrad Med J. 72 (843): 41–4. PMC 2398323. PMID 8746284.
  18. ↑ Jennette JC (March 2003). “Rapidly progressive crescentic glomerulonephritis”. Kidney Int. 63 (3): 1164–77. doi:10.1046/j.1523-1755.2003.00843.x. PMID 12631105.
  19. ↑ Renaudineau Y, Le Meur Y (October 2008). “Renal involvement in Wegener’s granulomatosis”. Clin Rev Allergy Immunol. 35 (1–2): 22–9. doi:10.1007/s12016-007-8066-6. PMID 18172777.
  20. ↑ Weiss MA, Crissman JD (October 1984). “Renal biopsy findings in Wegener’s granulomatosis: segmental necrotizing glomerulonephritis with glomerular thrombosis”. Hum. Pathol. 15 (10): 943–56. PMID 6384024.
  21. ↑ Pagnoux C (March 2008). “[Wegener’s granulomatosis and microscopic polyangiitis]”. Rev Prat (in French). 58 (5): 522–32. PMID 18524109.
  22. ↑ Chung SA, Seo P (August 2010). “Microscopic polyangiitis”. Rheum. Dis. Clin. North Am. 36 (3): 545–58. doi:10.1016/j.rdc.2010.04.003. PMC 2917831. PMID 20688249.
  23. ↑ Sinico RA, Di Toma L, Maggiore U, Tosoni C, Bottero P, Sabadini E, Giammarresi G, Tumiati B, Gregorini G, Pesci A, Monti S, Balestrieri G, Garini G, Vecchio F, Buzio C (May 2006). “Renal involvement in Churg-Strauss syndrome”. Am. J. Kidney Dis. 47 (5): 770–9. doi:10.1053/j.ajkd.2006.01.026. PMID 16632015.
  24. ↑ Alchi B, Jayne D (August 2010). “Membranoproliferative glomerulonephritis”. Pediatr. Nephrol. 25 (8): 1409–18. doi:10.1007/s00467-009-1322-7. PMC 2887509. PMID 19908070.
  25. ↑ Davis AE, Schneeberger EE, Grupe WE, McCluskey RT (May 1978). “Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease (DDD) in children”. Clin. Nephrol. 9 (5): 184–93. PMID 657595.
  26. ↑ Jennette JC, Falk RJ (July 1994). “The pathology of vasculitis involving the kidney”. Am. J. Kidney Dis. 24 (1): 130–41. PMID 8023818.
  27. ↑ Fogo AB, Lusco MA, Najafian B, Alpers CE (February 2016). “AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis”. Am. J. Kidney Dis. 67 (2): e5–7. doi:10.1053/j.ajkd.2015.12.007. PMID 26802335.
  28. ↑ Saha TC, Singh H (November 2006). “Minimal change disease: a review”. South. Med. J. 99 (11): 1264–70. doi:10.1097/01.smj.0000243183.87381.c2. PMID 17195422.
  29. ↑ Saleem MA, Kobayashi Y (2016). “Cell biology and genetics of minimal change disease”. F1000Res. 5. doi:10.12688/f1000research.7300.1. PMC 4821284. PMID 27092244.
  30. ↑ Rosenberg AZ, Kopp JB (March 2017). “Focal Segmental Glomerulosclerosis”. Clin J Am Soc Nephrol. 12 (3): 502–517. doi:10.2215/CJN.05960616. PMC 5338705. PMID 28242845.
  31. ↑ Jefferson JA, Shankland SJ (September 2014). “The pathogenesis of focal segmental glomerulosclerosis”. Adv Chronic Kidney Dis. 21 (5): 408–16. doi:10.1053/j.ackd.2014.05.009. PMC 4149756. PMID 25168829.
  32. ↑ Gephardt GN, Tubbs RR, Popowniak KL, McMahon JT (October 1986). “Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens”. Arch. Pathol. Lab. Med. 110 (10): 902–5. PMID 2429634.
  33. ↑ Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, Wu KD, Tsai TJ (February 2015). “Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment”. J. Formos. Med. Assoc. 114 (2): 102–11. doi:10.1016/j.jfma.2014.11.002. PMID 25558821.
  34. ↑ Wasserstein AG (April 1997). “Membranous glomerulonephritis”. J. Am. Soc. Nephrol. 8 (4): 664–74. PMID 10495797.
  35. ↑ Drummond K, Mauer M, International Diabetic Nephropathy Study Group (2002). “The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes”. Diabetes. 51 (5): 1580–7. PMID 11978659.
  36. ↑ Hørlyck A, Gundersen HJ, Osterby R (1986). “The cortical distribution pattern of diabetic glomerulopathy”. Diabetologia. 29 (3): 146–50. PMID 3699305.
  37. ↑ Alpers CE, Hudkins KL (2011). “Mouse models of diabetic nephropathy”. Curr Opin Nephrol Hypertens. 20 (3): 278–84. doi:10.1097/MNH.0b013e3283451901. PMC 3658822. PMID 21422926.
  38. ↑ Kimmelstiel P, Wilson C (1936). “Intercapillary Lesions in the Glomeruli of the Kidney”. Am J Pathol. 12 (1): 83–98.7. PMC 1911022. PMID 19970254.
  39. ↑ Alpers CE, Biava CG (1989). “Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity”. Clin Nephrol. 32 (2): 68–74. PMID 2766585.
  40. ↑ Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M (2007). “Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy”. Diabetes. 56 (8): 2155–60. doi:10.2337/db07-0019. PMID 17536064.
  41. ↑ Najafian B, Crosson JT, Kim Y, Mauer M (2006). “Glomerulotubular junction abnormalities are associated with proteinuria in type 1 diabetes”. J Am Soc Nephrol. 17 (4 Suppl 2): S53–60. doi:10.1681/ASN.2005121342. PMID 16565248.
  42. ↑ Najafian B, Kim Y, Crosson JT, Mauer M (2003). “Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy”. J Am Soc Nephrol. 14 (4): 908–17. PMID 12660325.
  43. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.
  44. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.
  45. ↑ Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, Dispenzieri A, Winters JL, Kumar S, Rajkumar SV, Kyle RA, Leung N (June 2011). “Early reduction of serum-free light chains associates with renal recovery in myeloma kidney”. J. Am. Soc. Nephrol. 22 (6): 1129–36. doi:10.1681/ASN.2010080857. PMC 3103732. PMID 21511832.
  46. ↑ Baker KR, Rice L (2012). “The amyloidoses: clinical features, diagnosis and treatment”. Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
  47. ↑ Gillmore JD, Hawkins PN (October 2013). “Pathophysiology and treatment of systemic amyloidosis”. Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
  48. ↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). “Primary systemic amyloidosis as a real diagnostic challenge – case study”. Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
  49. ↑ Pepys MB (2006). “Amyloidosis”. Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
  50. ↑ Korbet SM, Schwartz MM, Lewis EJ (March 1991). “Immunotactoid glomerulopathy”. Am. J. Kidney Dis. 17 (3): 247–57. PMID 1996564.
  51. ↑ Alroy J, Sabnis S, Kopp JB (June 2002). “Renal pathology in Fabry disease”. J. Am. Soc. Nephrol. 13 Suppl 2: S134–8. PMID 12068025.
  52. ↑ Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). “Prevalence of lysosomal storage disorders”. JAMA : the Journal of the American Medical Association. 281 (3): 249–54. PMID 9918480. Unknown parameter |month= ignored (help)
  53. ↑ Branton MH, Schiffmann R, Sabnis SG; et al. (2002). “Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course”. Medicine. 81 (2): 122–38. PMID 11889412. Unknown parameter |month= ignored (help)
  54. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
  55. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.
  56. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.
  57. ↑ Govan JA (1983). “Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes?”. Br J Ophthalmol. 67 (8): 493–503. PMC 1040106. PMID 6871140.
  58. ↑ Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY (2003). “Thin basement membrane nephropathy”. Kidney Int. 64 (4): 1169–78. doi:10.1046/j.1523-1755.2003.00234.x. PMID 12969134. Unknown parameter |month= ignored (help)
  59. ↑ Hou P, Chen Y, Ding J, Li G, Zhang H (2007). “A novel mutation of COL4A3 presents a different contribution to Alport syndrome and thin basement membrane nephropathy”. Am. J. Nephrol. 27 (5): 538–44. doi:10.1159/000107666. PMID 17726307.
  60. ↑ Najafian B, Smith K, Lusco MA, Alpers CE, Fogo AB (October 2017). “AJKD Atlas of Renal Pathology: Nail-Patella Syndrome-Associated Nephropathy”. Am. J. Kidney Dis. 70 (4): e19–e20. doi:10.1053/j.ajkd.2017.08.001. PMID 28941488.
  61. ↑ Guidera KJ, Satterwhite Y, Ogden JA, Pugh L, Ganey T (1991). “Nail patella syndrome: a review of 44 orthopaedic patients”. J Pediatr Orthop. 11 (6): 737–42. PMID 1960197.
  62. ↑ Hughson MD, Puelles VG, Hoy WE, Douglas-Denton RN, Mott SA, Bertram JF (July 2014). “Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race”. Nephrol. Dial. Transplant. 29 (7): 1399–409. doi:10.1093/ndt/gft480. PMC 4071048. PMID 24327566.
  63. ↑ Lusco MA, Najafian B, Alpers CE, Fogo AB (April 2016). “AJKD Atlas of Renal Pathology: Cholesterol Emboli”. Am. J. Kidney Dis. 67 (4): e23–4. doi:10.1053/j.ajkd.2016.02.034. PMID 27012950.
  64. ↑ Wesson DE (June 2002). “The initiation and progression of sickle cell nephropathy”. Kidney Int. 61 (6): 2277–86. doi:10.1046/j.1523-1755.2002.00363.x. PMID 12028473.
  65. ↑ Lusco MA, Fogo AB, Najafian B, Alpers CE (December 2016). “AJKD Atlas of Renal Pathology: Thrombotic Microangiopathy”. Am. J. Kidney Dis. 68 (6): e33–e34. doi:10.1053/j.ajkd.2016.10.006. PMID 27884283.
  66. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
  67. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
  68. ↑ Popa A, Voinea L, Pop M, Stana D, Dascalu AM, Alexandrescu C; et al. (2008). “[Primary antiphospholipid syndrome]”. Oftalmologia. 52 (1): 13–7. PMID 18714484.

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Epidemiology and Demographics

Epidemiology and Demographics

Epidemiology and Demographics

Alport’s syndrome or hereditary nephritis is considered one of the most common familial nephropathies. Its incidence is 1 in 50,000 – 1/100,000 live births in the United States.[1] Since the original description, male gender has been noted to be associated with worse severity, suggesting maternal transmittance. Onset of symptoms often starts during infancy in X-linked Alport’s syndrome; patients reach ESRD during adolescence.[1] Patients with autosomal recessive Alport’s syndrome sometimes progress less rapidly; although they may still progress to ESRD early, they may reach ESRD during adult life.[1]


Worldwide, Alport’s syndrome is not predominant in a specific race, ethnicity, or within a geographic distribution.[2][3][4] In the USA, however, Western states have a significantly higher rate of Alport’s syndrome and is up to two-fold more common than other regions within the USA.

Although a hereditary disorder, spontaneous mutations comprise approximately 15-20% of new cases of Alport’s syndrome.[5]

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ Gehrs KM, Pollock SC, Zilkha G (1995). “Clinical features and pathogenesis of Alport retinopathy”. Retina. 15 (4): 305–11. PMID 8545576.
  3. ↑ Yoshioka K, Hino S, Takemura T, Maki S, Wieslander J, Takekoshi Y; et al. (1994). “Type IV collagen alpha 5 chain. Normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody”. Am J Pathol. 144 (5): 986–96. PMC 1887361. PMID 8178947.
  4. ↑ Myers JC, Jones TA, Pohjolainen ER, Kadri AS, Goddard AD, Sheer D; et al. (1990). “Molecular cloning of alpha 5(IV) collagen and assignment of the gene to the region of the X chromosome containing the Alport syndrome locus”. Am J Hum Genet. 46 (6): 1024–33. PMC 1683837. PMID 2339699.
  5. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.

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Natural History, Complications and Prognosis

Natural History, Complications and Prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Natural History

Recognition of Alport’s syndrome based on the clinical presentation and distinguishing it from other causes of hematuria or extra renal manifestations is important because Alport’s syndrome usually carries a poor prognosis with inevitable progression to end-stage renal disease (ESRD).[1]

Complications

Prognosis

Onset of symptoms often starts during infancy in X-linked Alport’s syndrome; patients reach end-stage renal disease (ESRD) during adolescence.[1] All patients with Alport’s syndrome eventually progress to ESRD.

Patients with autosomal recessive Alport’s syndrome sometimes progress less rapidly. Although they may still progress to ESRD early, they may reach ESRD during adult life.[1]

References

  1. ↑ 1.0 1.1 1.2 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.

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Diagnosis

Diagnosis

Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | Echocardiography or Ultrasound | Other Diagnostic Studies

Treatment

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case Studies

Case #1

This article incorporates public domain text from The U.S. National Library of Medicine


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