RIPK3-deficient mice were not protected from nephrotoxic nephritis

Necrotizing glomerular lesions are a feature of severe glomerulonephritis. Unlike apoptosis, cellular necrosis has the potential to release damage-associated proteins into the microenvironment, thereby potentiating inflammation. Until recently necrosis was thought to be an unregulated cellular response to injury. However, recent evidence suggests that under certain circumstances receptor mediated necrosis occurs in response to death ligand signalling, one form of which is termed necroptosis. RIPK3, a receptor interacting protein, is a limiting step in the intracellular signalling pathway of necroptosis. A non-redundant role for RIPK3 has been implicated in mouse models of renal ischaemia reperfusion injury and toxic renal injury. The aim of this study was to investigate the role of RIPK3 in nephrotoxic nephritis (NTN), a model of immune complex glomerulonephritis in mice.

We induced NTN in RIPK3−/− and WT mice, comparing histology and renal function in both groups.

There was no improvement in urinary albumin creatinine ratio, serum urea, glomerular thrombosis or glomerular macrophage infiltration in the RIPK3−/− mice compared to WT. There was also no difference in number of apoptotic cells in glomeruli as measured by TUNEL staining between the RIPK3−/− and WT mice.

The data suggests that RIPK3 is not on a critical pathway in the pathogenesis of nephrotoxic nephritis.