Genetic focal segmental glomerulosclerosis with steroid-resistant nephrotic syndrome in adults. Case reports

Two cases of genetic FSGS associated with mutations in the NPHS2 (podocin) and COL4A3 (collagen type IV alpha3 chain) genes are presented. A patient with a mutation in the NPHS2 gene had an early onset of kidney disease at the age of 3 years with a mild proteinuria of 0.33 g/l and a manifestation of nephrotic syndrome (NS) at the age of 13 years. A patient with a COL4A3 gene mutation developed NS at.age of 23 years. In both cases, there was no family history, the steroid-resistant NS was noted, and a patient with an NPHS2 gene mutation achieved partial remission with calcineurin inhibitor. The discussion provides literature data on the prevalence and currently known gene mutations that underlie genetic FSGS in adults. It has been shown that in cases of monogenic FSGS in adults, mutations of the COL4A3 (collagen type 4) and NPHS2 (podocin) genes are the most frequent, mutations of various podocyte protein genes, including the NPHS1 (nephrin), NPHS2 (podocin) genes, are in second place in frequency. LMX1B (LIM homeobox transcription factor 1 beta), COQ8B (coenzyme Q8), IFN2 (inverted formin 2), and others. Some features of the course of genetic FSGS, the time of manifestation of kidney disease, the end-stage.renal disease, possible extrarenal manifestations, as well as cases of partial remission in the treatment with calcineurin inhibitors are provided. The clinical cases presented demonstrate the main trends established in different studies of genetic FSGS in adults. The main directions of treatment of patients with a genetic form of the disease are discussed, for example, the priority of nephroprotective therapy. Thus, FSGS patients with steroid-resistant NS should be tested for mutations, since the identification of the genetic FSGS will allow avoiding long-term immunosuppressive therapy and choosing the optimal treatment strategy.

нефротический синдром, фокальный сегментарный гломерулосклероз, мутации, NPHS2, COL4A, взрослые, nephrotic syndrome, focal segmental glomerulosclerosis, mutations, NPHS2, COL4A, adults

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