21 - Histopathology analysis suggests secondary FSGS is a common cause of non-nephrotic range proteinuria in the NEPTUNE cohort

Poster Number: 21
Publication Number: 21.1835

Background: While there are clinical practice recommendations for nephrotic syndrome (NS), the approach to diagnosis and management of non-nephrotic range proteinuria (NNP) is not well defined.

Objective: The goal of this study is to better understand the histopathology findings in NNP and what factors are associated with remission and eGFR decline.

Design/Methods: This is a secondary analysis of the Nephrotic Syndrome Study Network (NEPTUNE) cohort. We included adult and pediatric NEPTUNE participants who did not receive treatment for NS prior to screening, and who presented with urine protein creatinine ratio (UPCR) ≧ 0.5 g/g up to < 2 g/g in children and < 3 g/g in adults at the time of screening. A NS comparison group was identified using clinical diagnoses of NS and/or UPC ≧ 2 g/g in children and untreated adults with UPC ≧ 3 g/g at screening.

Results: Total 70 NNP and 123 NS in adults and 34 NNP and 326 NS in children were eligible for study inclusion. Subjects presenting with NNP were more likely to have FSGS than those presenting with NS [In adults, 37.1% in NNP vs 29.3 % in NS (p=0.002). In children, 41.2% in NNP vs 18.1% in NS (p < 0.0001).] (Table.1) In those with FSGS in NNP, detailed histopathology analyses suggested majority of patients with NNP had a secondary/maladaptive FSGS in both adults and children (Table 2.) In those with NNP, histopathology diagnosis of IgAN (vs FSGS) and/or overweight/obesity at baseline predicted faster eGFR decline [-8.63 ml/min/year (p=0.038), -7.04 ml/min/year (p=0.021) respectively]. Children with NNP had slower eGFR decline compared to NS [ - 0.2 ml/min/year (-3.4, 3.3), - 4.5 ml/min/year ( -12.6, 3.0) (p=0.04) respectively.] In those with NNP, histopathology diagnosis of FSGS (vs diagnosis of other) [OR=3.27, p=0.03] and/or high blood pressure at baseline [OR=0.51, p=0.02] predicted decrease rate of remission. While this study had a limited sample size, RAAS therapy was not statistically significantly associated with either remission or eGFR decline in this cohort.

Conclusion(s): This study highlights that a majority of NNP patients with FSGS exhibit secondary/maladaptive FSGS. This study supports the need for kidney biopsy in subjects with NNP. Further study is needed to identify the effective therapies for subjects with NNP.