ESPN 54th Annual Meeting

ESPN 2022


 
DO SPHINGOMYELIN PHOSPHODIESTERASE ACID-LIKE 3B (SMPDL-3B) LEVELS IN KIDNEY BIOPSY SPECIMENS PREDICT RESPONSE TO IMMUNOSUPPRESSIVE THERAPY IN CHILDREN WITH NEPHROTIC SYNDROME?
MUHAMMET KAYA 1 İLKNUR GİRİŞGEN 1 NAGIHAN YALÇIN 3 TÜLAY BECERİR 1 HANDE ŞENOL 4 GÜLSÜN GÜLTEN 3 SELÇUK YÜKSEL 2

1- DEPARTMENT OF PEDIATRIC NEPHROLOGY, FACULTY OF MEDICINE, PAMUKKALE UNIVERSITY
2- DEPARTMENT OF PEDIATRIC NEPHROLOGY AND RHEUMATOLOGY, FACULTY OF MEDICINE, PAMUKKALE UNIVERSITY
3- DEPARTMENT OF PATHOLOGY, PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE
4- DEPARTMENT OF BIOSTATISTICS, PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE
 
Introduction:

Idiopathic nephrotic syndrome (INS) is a common glomerular disease in children. Some patients who develop steroid-resistant nephrotic syndrome (SRNS) are also resistant to steroids and other immunosuppressants and can progress to chronic kidney disease (CKD). The treatment of SRNS remains a challenge for pediatric nephrologists. Sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b) contributes to the regulation of the podocyte cytoskeleton by enabling ceramide synthesis in the cell membrane. Recent studies suggest that rituximab prevents proteinuria independent of B-cell depletion by inhibiting the downregulation of SMPDL-3b expression or binding to SMPDL-3b. However, the question remains whether the low amount of SMPDL-3b for rituximab to bind in treatment-resistant NS patients with advanced podocyte injury could be the cause of treatment resistance. The present study was conducted to evaluate whether SMPDL-3b level in pre-treatment kidney biopsy is predictive of the clinical effectiveness of immunosuppressive drugs, especially rituximab, in patients with SRNS and FSGS.

Material and methods:

Kidney biopsy specimens from 48 patients diagnosed with INS were analyzed by immunohistochemical staining with anti-SMPDL3B and real-time polymerase chain reaction (PCR) for SMPDL-3b mRNA expression. The results were compared according to treatment response. Real time PCR evaluation was done with 2-∆∆CT method. Fold change (FC)>1.5 was considered stastically significant.

 

Results:

SMPDL-3b expression levels were higher in patients responding to all immunosuppressive treatments, including rituximab and steroids, but it was not considered significant because the fold change (FC) was less than 1.5.  SMPDL-3b expression was 1.788 times greater in patients who achieved remission with treatment compared to patients with CKD. When SMPDL-3b expression was compared between patients with SRNS who achieved remission and those who developed CKD, expression was 2.18 times higher and significant in remitted patients (FC>1.5). 

Conclusions:

In our study, we sought to determine whether low SMPDL-3b levels in pre-treatment kidney biopsies were associated with resistance to immunosuppressive therapies, especially rituximab. We showed that SMPDL-3b mRNA expression and anti-SMPDL3B staining did not differ significantly between patient groups with different responses to immunosuppressive therapies. Our results indicate that SMPDL-3b expression is higher in patients with complete remission, both among all patients and within the SRNS subgroup, when compared with patients who progressed to CKD. These results suggest that SMPDL-3b may actually be an indicator of disease progression rather than a marker predicting response to a particular immunosuppressive agent. Our study is the first in the literature to examine SMPDL-3b levels in human kidney biopsy specimens using both immunohistochemical and molecular PCR methods.