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Chapter 4 - Haematuric Glomerular Diseases (Collagenopathies)

from Section 2 - Glomerular Diseases

Published online by Cambridge University Press:  10 August 2023

By
Catherine Horsfield  and
Helen Liapis
Edited by
Helen Liapis
Helen Liapis
Affiliation:
Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
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Summary

This chapter will present clinical and histopathologic findings, pathophysiology and molecular genetics of glomerular basement membrane (GBM) diseases presenting primarily with hematuria. The GBM is a complex structure mainly composed of collagen IV in its mature form, but also other components such as nidogen, agrin and perlecan. Diseases of collagen IV disorders include Alport syndrome and thin basement membrane disease, Pierson syndrome, caused by mutations in the LAMB2 gene, nail–patella syndrome caused by LMX1B mutations with collagen type III accumulation that requires unmasking, and type III collagenopathy characterised by increased type III collagen in the GBM and the glomerular mesangium. Current and future therapies will also be discussed

Keywords

Alport syndromethin membrane diseasePierson syndromenail–patella syndrometype III collagenopathycollagen IV a3–5LMX1B
Type
Chapter
Information
Pediatric Nephropathology & Childhood Kidney Tumors , pp. 56 - 86
Publisher: Cambridge University Press
Print publication year: 2023

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References

Funk, S. D., Lin, M.-H., Miner, J. H.. Alport syndrome and Pierson syndrome: diseases of the glomerular basement membrane. Matrix Biol 2018; 71–72: 250–61.CrossRefGoogle ScholarPubMed
Harvey, S. J., Jarad, G., Cunningham, J. et al. Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular perm selectivity. Am J Pathol 2007; 171: 139–52.CrossRefGoogle ScholarPubMed
Muller-Diele, J., Dannenberg, J., Schroder, P. et al. Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases. Kidney Int 2017; 92: 836–49.CrossRefGoogle Scholar
Zimmermann, S. E., Hiremath, C., Tsunezumi, J. et al. Nephronectin regulates mesangial cell adhesion and behaviour in glomeruli. J Am Soc Nephrol 2018; 29: 1128–40.Google Scholar
Brown, K. L., Cummings, C. F., Vanacore, R. M., Hudson, B. G.. Building collagen IV smart scaffolds on the outside of cells. Protein Sci 2017; 26: 2151–61.Google Scholar
Abrahamson, D. R., Hudson, B. G., Sroganova, L., Borza, D.-B., St John, P. L.. Cellular origins of type IV collagen networks in developing glomeruli. J Am Soc Nephrol 2009; 20: 1471–79.CrossRefGoogle ScholarPubMed
Matthaiou, A., Poulli, T., Deltas, C.. Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or Col4A4 mutations: a systematic review. Clin Kidney J 2020; 13: 1025–36.Google Scholar
Kashtan, C. E., Ding, J., Garosi, G. et al. Alport syndrome: a unified classification of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int 2018; 93: 1045–51.CrossRefGoogle ScholarPubMed
Jais, J. P., Knebelmann, B., Giatris, I. et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: A ‘European Community Alport Syndrome Concerted Action’ study. J Am Soc Nephrol 2003; 14: 2603–10.CrossRefGoogle ScholarPubMed
Malone, A. F., Phelan, P. J., Hall, G. et al. Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int 2014; 86: 1253–59.Google Scholar
Savige, J., Storey, H., Watson, E. et al. Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria. Eur J Hum Genet 2021; 29: 1186–97.Google Scholar
Jais, J. P., Knebelmann, B., Giatris, I. et al. X-linked Alport syndrome: natural history in 195 families and genotype-phenotype correlations in males. J Am Soc Nephrol 2000; 11: 649–57.Google Scholar
Yamamura, T., Horinouchi, T., Nagano, C. et al. Genotype-phenotype correlations influence the response to angiotensin-targeting drugs in Japanese patients with male X-linked Alport syndrome. Kidney Int 2020; 98: 1605–14.Google Scholar
Nozu, K., Nakanishi, K., Abe, Y. et al. A review of clinical characteristics and genetic backgrounds in Alport syndrome. Clin Exp Nephrol 2019; 23: 158–68.Google Scholar
Gross, O., Netzer, K. O., Lambrecht, R., Seibold, S., Weber, M.. Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant 2002; 17: 1218–27.Google Scholar
Savige, J., Sheth, S., Leys, A. et al. Ocular features in Alport syndrome: pathogenesis and clinical significance. Clin J Am Soc Nephrol 2015; 10: 703–9.Google Scholar
Lee, J. M., Nozu, K., Choi, D. E. et al. Features of autosomal recessive Alport syndrome: a systematic review. J Clin Med 2019; 8: 178.CrossRefGoogle ScholarPubMed
Furlano, M., Martinez, V., Pybus, M. et al. Clinical and genetic features of autosomal dominant Alport syndrome: a cohort series. Am J Kidney Dis 2021; 78: 560–70.Google Scholar
Randels, M., Collinson, S., Starborg, T. et al. Three-dimensional electron microscopy reveals the evolution of glomerular barrier injury. Sci Rep 2016; 6: 35068.CrossRefGoogle Scholar
Wickman, L., Hodgin, J. B., Wang, S. Q. et al. Podocyte depletion in thin GBM and Alport syndrome. PLoS ONE 2018; 11: e0155255.Google Scholar
Savige, J., Ariani, F., Mari, F. et al. Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Ped Nephrol 2019; 34: 1175–89.CrossRefGoogle ScholarPubMed
Torra, R., Furlano, M., Ars, E.. How genomics reclassifies diseases: the case of Alport syndrome. Clin Kidney J 2020; 13: 933–35.CrossRefGoogle ScholarPubMed
Gross, O., Beirowski, B., Koepke, M. L. et al. Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int 2003; 63: 438–46.CrossRefGoogle ScholarPubMed
Gross, O., Licht, C., Anders, H. J. et al. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 2012; 81: 494–501.Google Scholar
Gross, O., Tonshoff, B., Weber, L. T. et al. GPN study group and EARLY PRO-TECT Alport Investigators: a multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome. Kidney Int 2020; 97: 1275–86.Google Scholar
Kashtan, C. E., Gross, O.. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Published correction appears in Pediatr Nephrol 2021; 36: 731.CrossRefGoogle Scholar
Torra, R., Furlano, M.. New therapeutic options for Alport syndrome. Nephrol Dial Transplant 2019; 34: 1272–9.CrossRefGoogle ScholarPubMed
Quinlan, C., Rheault, M. N.. Genetic basis of type IV collagen disorders of the kidney. CJASN 2021; CJN.19171220.Google Scholar
Savige, J., Rana, K., Tonna, S. et al. Thin basement membrane nephropathy. Kidney Int 2003; 64: 1169–78.Google Scholar
Wang, Y. Y., Rana, K., Tonna, S., Lin, T., Sin, L., Savige, J.. COL4A3 mutations and their clinical consequences in thin basement membrane nephropathy (TBMN). Kidney Int 2004; 65: 786–90.Google Scholar
Savige, J.. A further genetic cause of thin basement membrane nephropathy. Nephrol Dial Transplant 2016; 31: 1758–60.Google Scholar
Tryggvasan, K., Patrakka, J.. Thin basement membrane nephropathy. J Am Soc Nephrol 2006; 17: 813–22.Google Scholar
Haas, M.. Alport syndrome and thin glomerular basement membrane nephropathy. A practical approach to diagnosis. Arch Pathol Lab Med 2009; 133: 2224–32.CrossRefGoogle ScholarPubMed
Lemmink, H. H., Nillesen, W. N., Mochizuki, T. et al. Benign familial haematuria due to mutation of the type IV collagen α4 gene. J Clin Invest 1996; 9: 1114–18.Google Scholar
Frasca, G. M., Onetti-Muda, A., Mari, F. et al. Thin glomerular basement membrane disease: clinical significance of a morphological diagnosis-a collaborative study of the Italian Renal Immunopathology Group. Nephrol Dial Transplant 2005; 20: 545–51.Google Scholar
Thomas, D. M., Coles, G. A., Griffiths, D. F., Williams, J. D.. Perm selectivity in thin basement membrane nephropathy. J Clin Invest 1994; 93: 1881–4.CrossRefGoogle Scholar
Berthoux, F. C., Laurent, B., Alamartine, E., Diab, N.. New subgroup of primary IgA nephritis with thin glomerular basement membrane (GBM): syndrome or association. Nephrol Dial Transplant 1996; 11: 558–9.CrossRefGoogle ScholarPubMed
Taguchi, T., von Bassewitz, D. B., Grundmann, E., Takebayashi, S.. Ultrastructural changes of glomerular basement membrane in IgA nephritis: relationship to hematuria. Ultrastruct Pathol 1988; 12: 17–26.Google Scholar
Das, A. K., Pickett, T. M., Tungekar, M. F.. Glomerular basement membrane thickness-a comparison of two methods of measurement in patients with unexplained hematuria. Nephrol Dial Transplant 1996; 11: 1256–60.Google Scholar
Dische, F. E.. Measurement of glomerular basement membrane thickness and its application to the diagnosis of thin-membrane nephropathy. Arch Pathol Lab Med 1992; 116: 43–9.Google Scholar
Tiebosch, A. T. M. G., Frederik, P. M., van Breda Vriesman, P. J. C. et al. Thin-basement-membrane nephropathy in adults with persistent hematuria. N Eng J Med 1989; 320: 14–18.Google Scholar
Foster, K., Markowitz, G. S., D’Agati, V. D.. Pathology of thin basement membrane nephropathy. Semin Nephrol 2005; 25: 149–58.Google Scholar
Vogler, C., McAdam, A. J., Homan, S. M.. Glomerular basement membrane and lamina densa in infants and children: an ultrastructural evaluation. Pediatr Pathol 1987; 7: 527–34.Google Scholar
Collar, J. E., Ladva, S., Cairns, T. D. H., Cattell, V.. Red cell traverse through thin glomerular basement membranes. Kidney Int 2001; 59: 2069–72.CrossRefGoogle ScholarPubMed
Deltas, C., Pierides, A., Voskarides, K.. The role of molecular genetics in diagnosing familial hematuria(s). Pediatr Nephrol 2012; 27: 1221–31.Google Scholar
Pierides, A., Voskarides, K., Kkolou, M., Hadjigavriel, M., Deltas, C.. X-linked, COL4A5 hypomorphic Alport mutations such as G624D and P628L may only exhibit thin basement membrane nephropathy with microhematuria and late onset kidney failure. Hippokatia 2013; 17: 207–13.Google Scholar
Koskarides, K., Demosthenous, P., Papazachariou, L. et al. Epistatic role of the MYH9/APOL1 region on familial hematuria genes. PLoS ONE 2013; 8(3): e57925.Google Scholar
Gale, D., Deren Oygar, D., Lin F, F. et al. A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen. Nephrol Dial Transplant 2016; 31: 1908–14.Google Scholar
Ghoumid, J., Petit, F., Holder-Espinasse, M. et al. Nail-patella syndrome: clinical and molecular data in 55 families missing the hypothesis of a genetic heterogeneity. Eur J Hum Genet 2016; 24: 44–50.Google Scholar
Boyer, O., Woerner, S., Yang, F. et al. LMX1B mutations cause hereditary FSGS without extrarenal involvement. J Am Soc Nephrol 2013; 24: 1216–22.Google Scholar
Harita, Y., Kitanaka, S., Isojima, T., Ashida, A., Hattori, M.. Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy. Pediatr Nephrol 2017; 32: 1845–50.Google Scholar
Morello, R., Zhou, G., Dreyer, S. D. et al. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001; 27: 205–8.Google Scholar
Heidet, L., Bongers, E. M. H. F., Sich, M. et al. In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. Am J Pathol 2003; 163: 145–55.Google Scholar
Miner, J. H., Morello, R., Andrews, K. L. et al. Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J Clin Invest 2002; 109: 1065–72.Google Scholar
Rohr, C., Prestel, J., Heidet, L. et al. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest 2002; 109: 1073–82.Google Scholar
Bongers, E. M. H. F., Gubler, M. C., Knoers, N. V. A. M.. Nail-patella syndrome. Overview on clinical and molecular findings. Pediatr Nephrol 2002; 17: 703–12.Google Scholar
Lemley, K. V.. Kidney disease in nail-patella syndrome. Pediatr Nephrol 2009; 24: 2345–54.CrossRefGoogle ScholarPubMed
Sweeney, E., Fryer, A., Mountford, R., Green, A., McIntoch, I.. Nail patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet 2003; 40: 153–62.CrossRefGoogle ScholarPubMed
Harita, Y., Urae, S., Akashio, R. et al. Clinical and genetic characterization of nephropathy in patients with nail-patella syndrome. Eur J Hum Genet 2020; 28: 1414–21.Google Scholar
Aboobacker, I. N., Krishnakumar, A., Narayanan, S. et al. Nail-patella syndrome: a rare cause of nephrotic syndrome in pregnancy. Indian J Nephrol 2018; 28: 76–8.Google Scholar
Konomoto, T., Imamura, H., Orita, M. et al. Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation. Nephrology 2016; 21: 765–73.Google Scholar
Pinto e Vairo, F., Pichurin, P. N., Fervenza, F. C. et al. Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report. BMC Nephrology 2020; 21: 341.Google Scholar
Zenker, M., Aigner, T., Wendler, O. et al. Human laminin β2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 2004; 13: 2625–32.Google Scholar
Chew, C., Lennon, R.. Basement membrane defects in genetic kidney diseases. Front Pediatr 2018; 6: 11.Google Scholar
Pierson, M., Cordier, J., Hervouuet, F., Rauber, G.. An unusual congenital and familial congenital malformative combination involving the eye and kidney. J Genet Hum 1963; 12: 184–213.Google ScholarPubMed
Nishiyama, K., Kurokawa, M., Torio, M. et al. Gastrointestinal symptoms as an extended clinical feature of Pierson syndrome: a case report and review of the literature. BMC Medical Genetics 2020; 21: 80.Google Scholar
Kulali, F., Calkavur, S., Basaran, C. et al. A new mutation associated with Pierson syndrome. Arch Argent Pediatr 2020; 118: e288–91.Google ScholarPubMed
Hasselbacher, K., Wiggins, R. C., Matejas, V. et al. Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int 2006; 70: 1008–12.CrossRefGoogle ScholarPubMed
Sakuraya, K., Nozu, K., Murakami, H. et al. An extremely mild clinical course in a case with LAMB2-associated nephritis diagnosed with next-generation sequencing. CEN Case Rep 2021; 10: 359–63.Google Scholar
Kikkawa, Y., Hashimoto, T., Takizawa, K. et al. Laminin β2 variants associated with isolated nephropathy that impact matrix regulation. JCI Insight 2021; 22: e145908.Google Scholar
Zenker, M., Pierson, M., Jonveaux, P., Reis, A.. Demonstration of two novel LAMB2 mutations in the original Pierson syndrome family reported 42 years ago. Am J Med Genet A 2005; 138: 73–4.Google Scholar
Arakawa, M., Fueki, H., Hirano, H. et al. Idiopathic mesangio-degenerative glomerulopathy. Jpn J Nephrol 1979; 21: 914–15.Google Scholar
Imbasciati, E., Gherardi, G., Morozumi, K. et al. Collagen type III glomerulopathy: a new idiopathic glomerular disease. Am J Nephrol 1991; 11: 422–9.Google Scholar
Bao, H., Chen, H., Zhu, X. et al. Clinical and morphological features of collagen type III glomerulopathy: a report of nine cases from a single institution. Histopathology 2015; 67: 568–76.Google Scholar
Miyake, M., Katayama, K., Ehara, T. et al. Collagenofibrotic glomerulopathy. Intern Med 2021; 60: 911–15.Google Scholar
Rortveit, R., Lingaas, F., Bonsdorff, T. et al. A canine autosomal recessive model of collagen type III glomerulopathy. Lab Invest 2012; 92: 1483–91.Google Scholar
Duggal, R., Nada, R., Singh Rayat, C. et al. Collagenofibrotic glomerulopathy-a review. Clin Kidney J 2012; 5: 7–12.Google Scholar
Yasuda, T., Imai, H., Nakamoto, Y. et al. Collagenofibrotic glomerulopathy: a systemic disease. Am J Kidney Dis 1999; 33: 123–7.CrossRefGoogle ScholarPubMed
Manocha, A., Gupta, P.. Collagenofibrotic glomerulopathy: a rare diagnosis and seldom thought of differential for nodular glomerular mesangial expansion. J Clin Diagn Res 2020; 14: ED01–ED02.Google Scholar
Mizuiri, S., Hasegawa, A., Kikuchi, A. et al. A case of collagenofibrotic glomerulopathy associated with hepatic perisinusoidal fibrosis. Nephron 1993; 63: 183–7.CrossRefGoogle ScholarPubMed
Gubler, M. C., Dommergues, J. P., Foulard, M. et al. Collagen type III glomerulopathy: a new type of hereditary nephropathy. Pediatr Nephrol 1993; 7: 354–60.CrossRefGoogle ScholarPubMed
Salcedo, J. R.. An autosomal recessive disorder with glomerular basement membrane abnormalities similar to those seen in nail patella syndrome: report of a kindred. Am J Med Genet 1984; 19: 579–84.Google Scholar
Aoki, T., Hayashi, K., Morinaga, T. et al. Two brothers with collagenofibrotic glomerulopathy. CEN Case Rep 2015; 4: 85–9.Google Scholar
Alsaad, K. O., Edrees, B., Rahim, K. A. et al. Collagenofibrotic (collagen type III) glomerulopathy in association with diabetic nephropathy. Saudi J Kidney Dis Transpl 2017; 28: 898–905.Google Scholar
Vogt, B. A., Wyatt, R. J., Burke, B. A. et al. Inherited factor H deficiency and collagen type III glomerulopathy. Pediatr Nephrol 1995; 9: 11–15.Google Scholar
Suzuki, T., Okubo, S., Ikezumii, Y. et al. Favourable course of collagenofibrotic glomerulopathy after kidney transplantation and questionnaire survey about the prognosis of collagenofibrotic glomerulopathy. Nihon Jinzo Gakkai Shi 2004; 46: 360–4.Google Scholar
Ferreira, R. D. R., Custodio, F. B., Guimaraes, C. S. O., Correa, R. R. M., Reis, M. A.. Collagenofibrotic glomerulopathy: three case reports in Brazil. Diagn Pathol 2009; 4: 33.Google Scholar
Fukami, K., Yamagishi, S., Minezaki, T. et al. First reported case of collagenofibrotic glomerulopathy with a full house pattern of immune deposits. Clin Nephrol 2014; 81: 290–5.Google Scholar
Guo, Q., Liu, L., Nie, P., Luo, P.. Telmisartan alleviated collagen type III glomerulopathy: a case report with literature review. Exp Ther Med 2020; 20: 140.Google Scholar

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