Open AccessUpregulation of CD 80 on glomerular podocytes plays an important role in development of proteinuria following pig‐to‐baboon xeno‐renal transplantation – an experimental study
Author(s) -
Rivard Christopher J.,
Tanabe Tatsu,
Lanaspa Miguel A.,
Watanabe Hironosuke,
Nomura Shunichiro,
AndresHernando Ana,
Garth Krystle,
Sekijima Mitsuhiro,
Ishimoto Takuji,
Ariyoshi Yuichi,
Garcia Gabriela E.,
Shah Jigesh,
Lennan Boyd,
Tasaki Masayuki,
Pomposelli Thomas,
Shimizu Akira,
Sachs David H.,
Johnson Richard J.,
Yamada Kazuhiko
Publication year - 2018
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.13273
Subject(s) - baboon , medicine , proteinuria , downregulation and upregulation , transplantation , podocyte , urology , pathology , kidney , biology , biochemistry , gene
Summary We have previously reported that co‐transplantation of the kidney with vascularized donor thymus from α‐1,3‐galactosyltransferase gene knockout pigs with an anti‐ CD 154 with rituximab‐based regimen led to improved xenograft survival in baboons with donor‐specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease ( MCD ) in humans. Since MCD is associated with CD 80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD 80 in xenograft nephropathy. Study 1 confirmed high urinary CD 80 excretion in nephrotic animals with renal xenografts showing CD 80 expression in glomeruli. In Study 2, baboons receiving xenografts received CTLA 4‐Ig once a week from the second postoperative week or no CTLA 4‐Ig. The non‐ CTLA 4‐Ig group developed severe proteinuria with modest mesangial expansion with high urinary excretion of CD 80 and documented CD 80 expression in glomerular podocytes. All of the recipients in non‐ CTLA 4‐Ig groups had to be euthanized before POD 60. In contrast, CTLA 4‐Ig group showed a marked reduction in proteinuria and survived significantly longer, up to 193 days. These results demonstrate that anti‐ CD 80 targeted therapy represents a promising strategy for reduction of proteinuria following renal xeno‐transplantation with improved survival.