Primary FSGS is not associated with worse kidney outcome compared with other FSGS subtypes

Studies that compare kidney outcomes across patients with different forms of focal segmental glomerulosclerosis (FSGS) are lacking.

This retrospective study compared annual estimated glomerular filtration rate (eGFR) slope and kidney failure rate (eGFR <15 mL/min/1.73 m² or initiation of kidney replacement therapy) across patients with biopsy-proven primary, maladaptive, genetic and undetermined FSGS. Patients were included from two Belgian tertiary referral hospitals, from 2010 until 2022. Associations between covariates and kidney failure were estimated using Cox and Fine and Gray models. eGFR slopes were estimated using linear mixed-effects models.

Eighty-two patients were subdivided into primary (28.1%), maladaptive (40.2%), genetic (14.6%) and undetermined FSGS (17.1%) groups. Kidney failure occurred in 22 patients (26.8%). Primary FSGS patients exhibited higher baseline eGFR and less chronic changes on biopsy. The annual eGFR slope was -2.5 mL/min in primary, -2.5 mL/min in maladaptive, -4.6 mL/min in genetic and -4.4 mL/min in undetermined FSGS. Female sex was associated with a lower kidney failure rate and higher eGFR slope. Higher proteinuria at biopsy was associated with a higher kidney failure rate, lower eGFR slope and a higher mortality rate. Global sclerosis on kidney biopsy was associated with lower baseline eGFR, while a higher percentage of segmental sclerosis rather associated with more rapid eGFR decline [-1.5 mL/min/year per 10% increase, 95% confidence interval (-2.2, -0.7)].

Patients with primary FSGS were biopsied earlier in their disease course and exhibited surprisingly good kidney outcome. Overall, sex, baseline eGFR, proteinuria and the degree of focal and global glomerulosclerosis play a more important role in estimating the prognosis of patients with FSGS than merely the FSGS etiology.