engleski

CLINICAL COURSE AND RESPONSE TO TREATMENT OF FAMILIAL FORM OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS CAUSED BY MUTATION IN THE INF2 GENE - A CASE REPORT

INTRODUCTION AND AIMS: Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid resistant nephrotic syndrome where injury of podocytes plays a central role in pathogenesis. In recent years, many inheritable forms of FSGS caused by mutations in proteins important for podocyte function have been reported. We are presenting two patients (mother and son) with familial FSGS caused by INF2 mutation as the first case detected in Croatia. METHODS: Clinical case: RESULTS: A 19-year-old patient was admitted to our Department for evaluation of 24h-proteinuria 2.2 g/dU and slightly decreased eGFR (75 ml/min). At admission he had normal serum creatinine (sCr) (108 µmol/l), urine sediment was unremarkable and blood pressure was normal. A renal biopsy revealed FSGS. He was treated with ACE inhibitor. After one year of follow-up sCr increased to 144 µmol/l and 24h-proteinuria to 3.9 g/dU. Moreover, he had remarkable family history. At age of 20 yrs. patient' s mother was also diagnosed with FSGS and had similar clinical course - from non- nephrotic to nephrotic proteinuria, gradually progressing over 10 years to ESRD. She was transplanted and until now no relapse in transplanted kidney was observed. Interestingly, she was also resistant to immunosuppressive treatment (steroids, cyclosporine).Clinical course and positive family history were indicative for inherited FSGS (particularly the INF2 gene mutation). Analysis of the INF2 gene was performed in the Molecular Biology Laboratory of Fundacio Puigvert in Barcelona, Spain. Genetic analysis revealed that the proband carried the sequence variant c.658G>A>C (p.E220K) in heterozygosity in exon 4 of the INF2 gene. The identified mutation was found in his affected mother but not in his father, who had normal renal function without proteinuria. Two years after kidney biopsy progression of kidney disease was observed (sCr 166 µmol/l, eGFR 61 ml/min, 24- h proteinuria 4.93 g/dU). Although data from the literature are scarce and sometimes contradictory, we introduced a trial of cyclosporine 5 mg/kg and after 6 months observed moderate decline in proteinuria to 3.0 g/dU however accompanied with further deterioration of kidney function (SC 181 µmol/l , eGFR 54.9 ml/min). CONCLUSIONS: This case report emphasized again the importance of family history in renal disorders especially in young patients. Genetic screening is justified in particular group of patients where it might have crucial role in making treatment decision and avoiding of prolonged unhelpful exposure to corticosteroids or cyclophosphamide. Finally, this case report adds evidence for potential antiproteinuric effect of cyclosporine treatment.

INF2 gene; focal segmental glomerulosclerosis

nije evidentirano