Genetic Determinants of IgA Nephropathy: Western Perspective

Neugut, Y. Dana; Kiryluk, Krzysztof

doi:10.1016/j.semnephrol.2018.05.014

Cited by 26 publications

(18 citation statements)

References 93 publications

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“…The degree of tubular atrophy or interstitial fibrosis is the strongest predictive factor for the progression of renal disease. While the majority of IgAN cases are sporadic, an estimated 15% have a heritable component [ 9 ]. Genome wide association studies (GWAS) identified certain ACE gene polymorphisms as independent risk factors for disease progression [ 10 ] and implicated multiple genes in the pathogenesis of FIgAN, including mutations occurring in the genes that also cause Alport Syndrome [ 5 – 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…While the majority of IgAN cases are sporadic, an estimated 15% have a heritable component [ 9 ]. Genome wide association studies (GWAS) identified certain ACE gene polymorphisms as independent risk factors for disease progression [ 10 ] and implicated multiple genes in the pathogenesis of FIgAN, including mutations occurring in the genes that also cause Alport Syndrome [ 5 – 9 ]. A disease susceptibility locus for FIgAN has been identified at locus 2q36 [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Genomic testing can also be used to locate SNPs on genes which appear to reduce the risk of developing IgAN [ 12 ], though further studies would be required to assess prognosticating value for patients with Alport Syndrome. Finally, we suggest the adoption of widespread genetic screening, allowing for more retrospective and prospective GWAS [ 9 ]. Such studies have the potential to increase our understanding of Alport Syndrome and FIgAN as well as other potential causes of hematuria.…”

Section: Discussionmentioning

confidence: 99%

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Tale of two nephropathies; co-occurring Alport syndrome and IgA nephropathy, a case report

et al. 2021

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Background Alport Syndrome and IgA Nephropathy (IgAN) are both disorders that can cause hematuria. Alport syndrome is most commonly an X-linked disease, caused by COL4A5 mutation. Mutations of COL4A3 and COL4A4 on chromosome two are also common causes of Alport syndrome. IgAN is the most common glomerulonephritis worldwide. Though IgAN is usually sporadic, an estimated 15% of cases have an inheritable component. These cases of Familal IgA Nephropathy (FIgAN) can have mutations on genes which are known to cause Alport Syndrome. Case presentation We report a case of a 27-year-old man with strong family history of renal disease, who presented with hematuria and new non-nephrotic range proteinuria. Physical exam showed no abnormalities. His creatinine remained persistently elevated, and renal ultrasound exhibited bilaterally increased echogenicity consistent with Chronic Kidney Disease. Twenty-four-hour urinary collection revealed non-nephrotic range proteinuria of 1.4 g, with otherwise negative workup. On biopsy, he had IgA positive immunofluorescent staining as well as moderate interstitial fibrosis and tubular atrophy. Electron microscopy showed a basket-weave pattern of thickening and splitting of the lamina densa-consistent with Alport Syndrome, as well as mesangial expansion with electron-dense deposits -consistent with IgAN. Conclusions Mutations of COL4A5 on the X chromosome, as well as mutations of COL4A3 and COL4A4 on chromosome 2, can cause both Alport Syndrome and FIgAN. Genome wide association studies identified certain Angiotensin Converting Enzyme gene polymorphisms as independent risk factors for progression of IgAN. Our Presentation with this co-occurring pathology suggests a new paradigm where Alport Syndrome and FIgAN may represent manifestations of a single disease spectrum rather than two disparate pathologies. Appreciating hematuria through this framework has implications for treatments and genetic counseling. Further genome wide association studies will likely increase our understanding of Alport Syndrome, FIgAN, and other causes of hematuria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Tale of two nephropathies; co-occurring Alport syndrome and IgA nephropathy, a case report

et al. 2021

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“…Of note, evidence exists for the presence of other susceptibility alleles for kidney disease in addition to ApoL1, particularly for diabetic nephropathy (41) and for IgA nephropathy (42). Before consideration of incorporation of these susceptibility alleles into clinical practice, additional research to define the magnitude (and hopefully mechanisms) of the risks will be required, as is ongoing for ApoL1 alleles.…”

Section: Cystic Kidney Diseasementioning

confidence: 99%

Clinical Applications of Genetic Discoveries in Kidney Transplantation: a Review

Marin

Cohen

2020

Kidney360

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Growth in knowledge of the genetics of kidney disease has revealed that significant percentages of patients with diverse types of nephropathy have causative mutations. Genetic testing is poised to play an increasing role in the care of patients with kidney disease. The role of genetic testing in kidney transplantation is not well established. This review will explore the ways in which genetic testing may be applied to improve the care of kidney transplant recipients and donors.

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“…Genetic factors that are unique to an Asian population may influence response to the surgical intervention. 6 Mutational analysis of genes related to the alternate pathway of complement that are linked to IgA nephropathy might shed light on which patients are more likely to benefit from tonsillectomy. The authors attribute the benefit of tonsillectomy to a decreased mucosal production of abnormally galactosylated IgA 1 molecules.…”

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confidence: 99%