Delayed kidney graft function: from mechanism to translation Bernd Schröppel, Christophe Legendre  Kidney International  Volume 86, Issue 2, Pages 251-258 (August 2014) DOI: 10.1038/ki.2014.18 Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 1 Schematic depiction of the autophagy pathway. Stressors, pro-inflammatory signals, and mechanistic target of rapamycin (mTOR) inhibition induce autophagy leading to the nucleation of the phagosome membrane, which surrounds cytoplasmic proteins and even whole organelles. Two conjugation systems, LC3 and Atg5-12, serve to elongate the nucleation complex to form the limiting membrane. The forming limiting membrane sequesters cytosolic cargo and seals it to form an autophagosome that subsequently fuses with lysosomes in which cargo gets degraded followed by the release of nutrients to the cytosol. Autophagy can either mediate cell death (e.g., by exhaustion of substrates) or it can act as a pro-survival mechanism depending upon cellular contexts and stimuli. Kidney International 2014 86, 251-258DOI: (10.1038/ki.2014.18) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 2 Toll-like receptor 4 (TLR4) signaling pathways. TLR4 is tightly bound to myeloid differentiation-2 (MD-2) on the cell surface. TLR4 signaling consists of a MyD88 (myeloid differentiation primary response gene (88))-dependent and -independent cascade. MyD88 and TIRAP (Toll/interleukin 1 receptor (TIR) domain–containing adaptor protein) are adaptors for the MyD88-dependent pathways, which mainly activate pro-inflammatory cytokine production. TRIF (TIR domain–containing adaptor inducing interferon) and TRAM (TRIF-related adaptor molecule) are adapters for IRF3 (interferon regulatory factor 3) activation, resulting in production of type I interferon (IFN). HMGB1, high-mobility group box protein-1; HSP, heat-shock protein. Kidney International 2014 86, 251-258DOI: (10.1038/ki.2014.18) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 3 The three complement activation pathways. Eculizumab binds with high affinity to C5, thereby inhibiting its cleavage, and blocks terminal complement C5a and C5b-C9 activity. Kidney International 2014 86, 251-258DOI: (10.1038/ki.2014.18) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 4 Schematic representation of renal function recovery after kidney transplantation. Recovery may be immediate, slow (serum creatinine >2.5mg/dl within 5 days), or delayed (most often defined by at least one dialysis session within 7 days), or never occurring (primary nonfunction). Screat, serum creatinine. Kidney International 2014 86, 251-258DOI: (10.1038/ki.2014.18) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 5 Modifiable and non-modifiable risk factors and tools to assess early kidney graft dysfunction. Effects of peri-transplant acute kidney injury on long-term transplant function of ideal and marginal kidneys. DCD, donation after cardiac death; ECD, expanded criteria donor; SCD, standard criteria donor. Kidney International 2014 86, 251-258DOI: (10.1038/ki.2014.18) Copyright © 2014 International Society of Nephrology Terms and Conditions