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Diagnosis: Recurrence of Podocytopathy (Focal Segmental Glomerulosclerosis)

Although in this patient the NS was considered congenital (because the age of onset of the disease in the first year of life) with genetic etiology, the recurrent disease rapidly after transplantation suggests another etiology. In the first days or weeks of a SN by FSGS it is likely to fail to highlight the sclerosing lesions, but the podocyte damage is evidenced by the presence of severe proteinuria and other signs and symptoms of NS. In this case also the ultrastructure evidenced the podocyte damage, with severe and diffuse dettachment of podocytes that left an almost completely denuded GBM.

Primary idiopathic FSGS can occur in isolation and frequently progresses to end-stage renal disease, requiring dialysis or kidney transplantation. In 30-50% of these patients, proteinuria and FSGS recur in the renal allograft, suggesting the presence of a podocyte-toxic factor/s in the recipient's serum. Currently, there is no reliable way to quantify the serum activity or predict the subset of FSGS patients at risk for recurrence after transplantation (Kachurina N, et al. Am J Physiol Renal Physiol. 2015 Dec [Epub ahead of print] [PubMed link]).

The 45 genes currently associated with human NS explain not more than 20-30% of hereditary and only 10-20% of sporadic cases. It is becoming increasingly clear both from genetic analysis and phenotypic data - including occasional response to immunosuppressive agents and post-transplant disease recurrence in Mendelian disease - that monogenic inheritance of abnormalities in podocyte-specific genes disrupting filter function is only part of the story. Recent advances in genetic screening technology combined with increasingly robust bioinformatics are set to allow identification and characterization of novel disease causing variants and more importantly, disease modifying genes. Emerging data also support a significant but incompletely characterized immunoregulatory component (Bierzynska A, et al. Genes and podocytes - new insights into mechanisms of podocytopathy. Front Endocrinol (Lausanne). 2015 Jan 23;5:226. [PubMed link]).

Visit the chapter: Focal and Segmental Glomerulosclerosis of our Tutorial.

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References

• Canaud G, Delville M, Legendre C. Recurrence of Focal and Segmental Glomerulosclerosis After Transplantation. Transplantation. 2016 Feb;100(2):284-7. [PubMed link]
• Kachurina N, Chung CF, Benderoff E, Babayeva S, Bitzan M, Goodyer PR, Kitzler T, Matar D, Cybulsky AV, Alachkar N, Torban E. NOVEL UNBIASED ASSAY FOR CIRCULATING PODOCYTE-TOXIC FACTORS ASSOCIATED WITH RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS. Am J Physiol Renal Physiol. 2015 Dec [Epub ahead of print] [PubMed link]
• Bierzynska A, Soderquest K, Koziell A. Genes and podocytes - new insights into mechanisms of podocytopathy. Front Endocrinol (Lausanne). 2015;23;5:226. [PubMed link]
• Vlachopanos G, Georgalis A, Gakiopoulou H. Plasma Exchange for the Recurrence of Primary Focal Segmental Glomerulosclerosis in Adult Renal Transplant Recipients: A Meta-Analysis. J Transplant. 2015;2015:639628. [PubMed link]
• Canaud G, Loupy A. Focal Segmental Glomerulosclerosis Recurrence: Soluble Urokinase Receptor Left Out? Transplantation. 2015;99(12):2449-50. [PubMed link]
• Sun ZJ, Ng KH, Liao P, Zhang Y, Ng JL, Liu ID, Tan PH, Chong SS, Chan YH, Liu J, Davila S, Heng CK, Jordan SC, Soong TW, Yap HK. Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis. Am J Transplant. 2015;15(12):3229-38. [PubMed link]

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