Table 4.


Open Questions
What determines the dynamics of transient versus persistent and local versus systemic necroinflammation?
Does expression of NLRP3 and ASC in renal cells also imply the possibility for pyroptosis?
Are there endogenous inhibitors of regulated necrosis in addition to MLKL phosphatase?
Is regulated necrosis controlled by miRNAs, epigenetics, metabolic status…?
Do gene variants in regulated necrosis-related genes determine clinical phenotypes?
Are there more forms of regulated necrosis? Which signaling molecules are involved?
Are there kidney- or renal cell–specific pathways of regulated necrosis?
What is the relative contribution of regulated necrosis pathways to organ damage in AKI?
Is the role of apoptosis restricted to physiologically occurring events in the kidney? Are there any pathophysiologies mediated by apoptosis?
What is the role of necroinflammation in CKD?
What is the role of apoptosis versus regulated necrosis inside the kidney?
Is it sufficient to block either necrosis or inflammation to suppress necroinflammation or do respective inhibitors have synergistic additive effects when given in combination?
Can we prevent delayed graft function or other forms of expected AKI by preemptive cell death inhibitor prophylaxis in high-risk patients?
How broad is the therapeutic window to prevent full-blown AKI?
What are the risks of short-term or long-term cell death inhibitor exposure?
Will inhibition of primary necrosis in transplants lead to less priming of memory B cells in the first moment at reperfusion and reduce the rate of long-term antibody-mediated rejection?
Which Food and Drug Administration–approved drugs in every day clinical use, other than cyclosporin and ponatinib, interfere with regulated necrosis?
  • ASC, adapter protein apoptosis associated speck-like protein containing a CARD; miRNAs, microRNAs.