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Kidney Week

Abstract: TH-PO629

Anti-slit Antibodies on Kidney Biopsy Identify Patients with Steroid-Resistant Nephrotic Syndrome Responsive to Second-Line Immunosuppressant and Hence Have a Good Prognosis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Raglianti, Valentina, Azienda Ospedaliero Universitaria Meyer, Firenze, Italy
  • Angelotti, Maria Lucia, Universita degli Studi di Firenze, Firenze, Italy
  • Cirillo, Luigi, Azienda Ospedaliero Universitaria Meyer, Firenze, Toscana, Italy
  • Landini, Samuela, Azienda Ospedaliero Universitaria Meyer, Firenze, Toscana, Italy
  • Palazzo, Viviana, Azienda Ospedaliero Universitaria Meyer, Firenze, Toscana, Italy
  • Melica, Maria Elena, Universita degli Studi di Firenze, Firenze, Italy
  • Antonelli, Giulia, Universita degli Studi di Firenze, Firenze, Italy
  • Conte, Carolina, Azienda Ospedaliero Universitaria Meyer, Firenze, Toscana, Italy
  • Mazzinghi, Benedetta, Azienda Ospedaliero Universitaria Meyer, Firenze, Toscana, Italy
  • Becherucci, Francesca, Universita degli Studi di Firenze, Firenze, Italy
  • Romagnani, Paola, Azienda Ospedaliero Universitaria Meyer, Firenze, Italy
Background

Anti-nephrin antibodies have been recently reported in patients with Minimal Change and steroid-sensitive Nephrotic Syndrome (NS), as well as in post-transplant recurrence of Focal Segmental Glomerulosclerosis, supporting an autoimmune etiology in a subset of podocytopathies. We hypothesized that the presence of autoantibodies against slit diaphragm antigens would identify also a subset of patients with steroid resistant NS (SRNS) and explain response to second-line immunosuppressant and hence prognosis

Methods

We evaluated 45 patients with SRNS out of 128 patients with available kidney biopsy samples followed up at Meyer University Hospital IRCCS. By using high-resolution confocal microscopy, we assessed the colocalization between IgG and nephrin staining. To further determine the specificity of the IgG deposition STED microscopy and two different ELISA for anti-nephrin antibodies have been performed

Results

STED microscopy and anti-nephrin ELISA assays suggest that a subset of patients with podocytopathies showed antibodies against either nephrin or non-nephrin slit antigens, i.e. slit antibodies. We observed anti-slit antibodies in 48.5% of non-genetic patients and only in 8.3% of genetic one with SRSN, irrespective of histology lesion patterns. Almost all anti-slit positive patients (92.3%) showed response to second-line immunosuppressive therapy. The only multidrug-resistant anti-slit positive patient reached kidney failure was a diagnosed case of Nail-Patella syndorme. He experienced recurrence after kidney transplantation and anti-slit antibodies have been detected on graft biopsy. Kaplan Meier analysis confirm anti-slit positive patients had a favourable outcome. On the contrary, genetic patient, independently of anti-slit status, and non-genetic anti-slit negative patients, showed poor prognosis at 10 years, both achieving chronic kidney disease and kidney failure

Conclusion

Detection of anti-slit antibodies represents a novel tool for personalized management, by allowing identification of patients more likely to responds to second-line immunosuppressive therapy and have better long term kidney prognosis, i.e. autoimmune podocytopathies