Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis

Abstract

Background Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 were measured by ELISA. Glomeruli were stained for CD80. Results After abatacept, urinary CD80 became undetectable with concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in one patient with primary FSGS and in two recurrent FSGS subjects despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. One patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before abatacept. After Abatacept, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since urinary CD80 is only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.

Podocyte directed therapy of nephrotic syndrome—can we bring the inside out?

“…Sera from MCD patients in relapse, but not in remission, were found to stimulate CD80 expression in cultured podocytes [93]. In addition, urinary concentrations of soluble CD80 in patients with relapsed MCD were significantly higher than those in patients with MCD in remission and with other glomerular diseases including FSGS and in healthy controls [94]. Serum and urinary CTLA-4 levels tend to be low in MCD patients in relapse, and the urinary CTLA-4 level returns to higher levels during remission [95].…”

Recurrent focal segmental glomerulosclerosis after kidney transplantation

“…There have been isolated case reports documenting resolution of recurrent FSGS in patients who received abatacept in doses that have been utilized for the treatment of systemic lupus erythematosus [81]. However, this observation has not been replicated by other investigators who failed to achieve permanent remission in patients with recurrent FSGS [82]. Differences in response to abatacept may be related to variable expression of B7-1 in the glomerulus.…”

A Brief Overview Of Childhood Nephrotic Syndrome: Review

“…Ancak, Alachkar ve ark.ları ile Garin ve ark.ları, transplant sonrası FSGS olmuş ve CD80 boyası ile böbrek biyopsisi pozitif boyanan hastalarda abatasept ve belatasepti (CD80'e daha kuvvetli bağlanan bir başka CD80 blokeri) başarısız bulmuşlardır. 89,90 Garin ve ark., aynı çalışmada MDH olan bir çocuğa abatasept vermiş ve proteinüride belirgin azalma elde etmişler-dir. 89 Ancak bu azalma kısa süreli olmuş, ilk abatasept infüzyonundan üç gün sonra proteinü-ride azalma elde edilmiş ve 11 gün sürmüş, ikinci infüzyondan 15 gün sonra proteinüride azalma elde edilmiş ve iki gün sürmüştür.…”