Inflammasome Mechanisms in Kidney Disease

Inflammasomes are intracellular multiprotein complexes that detect danger signals and orchestrate innate immune responses by activating caspase-1 and driving the maturation of interleukin-1β and interleukin-18. In the kidney, aberrant inflammasome activation contributes to both acute and chronic injury through induction of a lytic form of cell death known as pyroptosis and by perpetuating inflammatory crosstalk between tubular epithelial cells, podocytes and infiltrating immune cells. The nucleotide-binding oligomerization domain and leucine-rich repeat–containing receptor pyrin domain-containing 3 (NLRP3) inflammasome is the most extensively characterised sensor in renal pathologies, responding to metabolic stress, crystal deposition, hypoxia and toxins. Persistent NLRP3 activation underpins the progression of diabetic nephropathy, ischaemia–reperfusion injury and fibrosis, and links to systemic complications such as cardiovascular disease. Emerging evidence also highlights inflammasome-independent roles of NLRP3 in mitochondrial regulation within tubular cells. Together, these insights underscore the global significance of targeting inflammasome pathways to prevent end-stage disease and preserve renal function.

Research from Nature Portfolio

Recent investigations have clarified the role of NLRP3 in contrast-induced acute kidney injury. In both proximal tubule cell models and unilateral nephrectomy mice, exposure to iodinated contrast media markedly increased expression of NLRP3 and its adaptor ASC, driving caspase-1 activation, secretion of pro-inflammatory cytokines and tubular apoptosis. Genetic deletion of NLRP3 or ASC preserved renal architecture and function by dampening apoptotic signalling and inflammatory mediator release. These findings position selective modulation of the NLRP3 inflammasome as a viable therapeutic approach to mitigate contrast-associated kidney damage.

Inflammasome Mechanisms in Kidney Disease publication trend

The graph below shows the total number of articles in inflammasome mechanisms in kidney disease across all publications each year (not limited to Nature Index journals).

Technical terms

Inflammasome: A cytoplasmic complex that senses danger signals and activates caspase-1 to process pro-inflammatory cytokines.

NLRP3: The most studied inflammasome sensor in renal disease, responsive to diverse stressors and crystals.

Pyroptosis: An inflammatory form of programmed cell death characterised by gasdermin-mediated pore formation.

Caspase-1: A protease activated within inflammasomes that cleaves IL-1β and IL-18 into their active forms.

Gasdermin E: A pore-forming effector cleaved by caspase-3 or caspase-1 to execute pyroptosis.

References

1. NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis. Scientific Reports (2016).
2. Tonabersat suppresses priming/activation of the NOD-like receptor protein-3 (NLRP3) inflammasome and decreases renal tubular epithelial-to-macrophage crosstalk in a model of diabetic kidney disease. Cell Communication and Signaling (2024).
3. Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy. Journal of Translational Medicine (2023).
4. GSDME-dependent pyroptosis signaling pathway in diabetic nephropathy. Cell Death Discovery (2023).
5. Inflammasome-Independent Role of NLRP3 Mediates Mitochondrial Regulation in Renal Injury. Frontiers in Immunology (2018).