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Focal segmental glomerulosclerosis(FSGS) is a histologic lesion primarily affecting podocytes. Age of onset, proteinuria at onset, plasma creatinine at biopsy, duration of treatment with corticosteroids, genetics and histopathologic subtype are important prognostic factors in determining the outcome of primary FSGS. Genetic causes of FSGS are often under-diagnosed in India. Genetic analysis in FSGS have implications on prognostication, therapy, transplantation and pre-implantation genetic diagnosis.
This was a hospital based, observational, longitudinal study where 50 patients with biopsy proven primary FSGS were included from January 2021 till December 2022. Secondary causes were ruled out. Genetic testing was performed by next generation sequencing and the variants were classified as per ACMG classification. All patients were treated as per KDIGO 2021 guidelines. Outcome was assessed at the end of one year. Primary outcomes were: attainment of remission(complete remission CR/partial remission PR), relapses, doubling of baseline serum creatinine or onset of ESRD(end stage renal disease). Institutional ethical clearance was taken and necessary statistical analysis was performed.
The mean age was 7.80±6.57 years. Renal syndromes- SRNS(60%); infantile nephrotic syndrome(20%), SDNS(12%) and congenital nephrotic syndrome(8%). 66% patients with perihilar variant presented as SRNS, whereas majority with tip variant presented as congenital NS(16%) or infantile NS(26%). 58% had age of onset of proteinuria 1-18 years, 30% had onset 3 months-1 year. Nephrotic syndrome was present in 78%. All patients of perihilar variant presented with nephrotic syndrome. Patient with collapsing variant of FSGS had significantly elevated systolic blood pressure. Hypertension was more common in cellular variant(40%) followed by tip variant(25%). The mean eGFR was 105.60±15.78 ml/min/1.73 m2. The mean serum creatinine was 0.90±0.67 mg/dl. The comparison between different histological variants and the biochemistry is given in Table 1. 60% of patients with severe hypo albuminemia had cellular variant. On histology, NOS(52%), tip(24%), perihilar(12%), cellular(10%). 68% had segmental glomerular sclerosis. Involved glomeruli <30% was most commonly seen in tip variant(75%). 25-50% IFTA was most commonly seen in cellular variant (40%). 46% attained PR and 26% patients attained CR. 8% underwent frequent relapses and 12% underwent infrequent relapses. 6% had doubling of serum creatinine and 1 patient progressed to ESRD. NOS variant(53.4%) achieved CR more commonly. Genetic mutations were detected in 62%. 16.7% had pathogenic mutations; more commonly in NOS(20%) and tip(16%). VUS mutations were common in tip and perihilar variants. 24 hours urine protein 3.5-6 g/day, creatinine levels 0.5-1 mg/dl, use of steroids as the only immunosuppression and presence of VUS predicted frequently relapsing NS in this population.
Prolonged treatment with corticosteroids increases the chances of remission and preserves renal function in FSGS nephrotic patients. Addition of cyclophosphamide and prolonged use of low‐dose tacrolimus are also effective. None of the histological features were independently significant as predictors of ESRD. The severity of interstitial fibrosis is the only predictor of response to the therapy.