Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants
Looking for antibodies bound to the kidney's filtration slit on biopsy identified children and adults with steroid-resistant nephrotic syndrome who responded to second-line immunosuppression — over 90% responded when the antibodies were present, versus 20% when they were not.
Background
Podocytopathies presenting as minimal change or FSGS lesion patterns respond heterogeneously to steroids. Antinephrin antibodies had been reported in some patients, but serology alone may miss autoantibodies directed at other slit-diaphragm proteins.
Study design
High-resolution confocal microscopy was applied to kidney biopsies from 128 pediatric patients and a second cohort of 48 adults with minimal change or FSGS, with serum antinephrin ELISA and stimulated emission depletion microscopy used to test whether the bound IgG co-localised with nephrin specifically.
Key findings
IgG lined the slit diaphragm in 30% of pediatric minimal change and 25% of FSGS biopsies, and in no other lesion pattern. IgG-nephrin co-localisation was seen in only 77.8% of pediatric and 44.4% of adult positive cases, implying autoantibodies against additional slit proteins. Anti-slit antibodies were present in 27% of primary steroid-resistance but 87.5% of secondary steroid-resistance, irrespective of histopathology.
Clinical implications
Anti-slit antibody status separated treatment-responsive from treatment-refractory steroid-resistant disease far better than the biopsy lesion pattern did: 92.3% versus 20% response to second-line immunosuppressants, and no progression to kidney failure among antibody-positive patients versus 51.7% among antibody-negative patients. This argues for adding slit-diaphragm IgG staining to the diagnostic work-up of steroid-resistant nephrotic syndrome.
Category
Research
Source
Kidney International
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