Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression, and proteinuria remission.

BACKGROUND The associations of focal segmental glomerulosclerosis (FSGS) histologic variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. METHODS Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression, and proteinuria remission (PR, proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression, and PR with outcomes were examined for each variant. RESULTS The distribution of variants was 48% (n = 145) FSGS not otherwise specified (NOS), 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular, and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants (hazard ratio adjusted for histologic variant and potential confounders [adjusted HR]: 0.19 [95% confidence interval (CI), 0.10-0.34]). NS was marginally associated with better outcome compared with non-NS (adjusted HR: 0.50 [95% CI, 0.25-1.01]. CONCLUSIONS FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.