Necroinflammation in Kidney Disease.
The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury-related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; and.
Shrikant R
SR
Mulay
Clinic for Nephrology and Hypertension, Christian-Albrechts-University Kiel, Kiel, Germany.
Andreas
A
Linkermann
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; and hjanders@med.uni-muenchen.de.
Hans-Joachim
HJ
Anders
D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology; D009336:Necrosis / Q000209:etiology / Q000517:prevention & control; D009393:Nephritis / Q000473:pathology* / Q000517:prevention & control; D015398:Signal Transduction
Immunology and pathology; acute renal failure; kidney failure