Published in:
01-07-2021 | Nephrectomy | Original article
Involvement of necroptosis in contrast-induced nephropathy in a rat CKD model
Authors:
Satoru Shibata, Norihito Moniwa, Atsushi Kuno, Ayumu Kimura, Wataru Ohwada, Hirohito Sugawara, Yufu Gocho, Marenao Tanaka, Toshiyuki Yano, Masato Furuhashi, Masaya Tanno, Takayuki Miki, Tetsuji Miura
Published in:
Clinical and Experimental Nephrology
|
Issue 7/2021
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Abstract
Background
The risk of contrast-induced nephropathy (CIN) is high in patients with chronic kidney disease (CKD). However, the mechanism of CIN in CKD is not fully understood. Here, we prepared a clinically relevant model of CIN and examined the role of necroptosis, which potentially cross-talks with autophagy, in CIN.
Methods
In Sprague–Dawley rats, CKD was induced by subtotal nephrectomy (SNx, 5/6 nephrectomy) 4 weeks before induction of CIN. CIN was induced by administration of a contrast medium (CM), iohexol, following administration of indomethacin and N-omega-Nitro-l-arginine methyl ester. Renal function and tissue injuries were assessed 48 h after CM injection.
Results
Serum creatinine (s-Cre) and BUN were increased from 0.28 ± 0.01 to 0.52 ± 0.02 mg/dl and from 15.1 ± 0.7 to 29.2 ± 1.2 mg/dl, respectively, after SNx alone. CM further increased s-Cre and BUN to 0.69 ± 0.03 and 37.2 ± 2.1, respectively. In the renal tissue after CM injection, protein levels of receptor-interacting serine/threonine-protein kinase (RIP) 1, RIP3, cleaved caspase 3, and caspase 8 were increased by 64 ~ 212%, while there was reduction in LC3-II and accumulation of p62. Necrostatin-1, an RIP1 inhibitor, administered before and 24 h after CM injection significantly suppressed elevation of s-Cre, BUN and urinary albumin levels, kidney injury molecule-1 expression and infiltration of CD68-positive macrophages in renal tissues after CM injection.
Conclusion
The results suggest that necroptosis of proximal tubular cells contributes to CIN in CKD and that suppression of protective autophagy by pro-necroptotic signaling may also be involved.