Inflammation and Cell Death in Kidney Disease

Inflammation and regulated cell death lie at the heart of both acute and chronic kidney injury. The renal tubular epithelium and glomerular cells are highly susceptible to inflammatory stimuli, leading to activation of resident and infiltrating immune cells, release of cytokines and chemokines, and engagement of multiple programmed‐cell‐death pathways. Early on, necrosis and apoptosis predominate, whereas inflammasome‐driven pyroptosis and receptor‐interacting‐kinase‐mediated necroptosis contribute to propagation of injury and fibrotic remodelling. Parallel activation of the cGAS–STING axis by cytosolic DNA fragments amplifies interferon signalling, while oxidative and metabolic stress provoke mitochondrial dysfunction and ferroptosis. These interconnected processes promote tubular atrophy, interstitial inflammation and, ultimately, a decline in glomerular filtration. Beyond acute events, a maladaptive repair response characterised by prolonged inflammatory signalling, epithelial‐to‐mesenchymal transition and impaired autophagy drives progression to end‐stage renal disease. Understanding the molecular crosstalk between inflammatory pathways and distinct modes of cell death is critical for the development of targeted therapies to preserve renal structure and function.

Research from Nature Portfolio

A novel star-shaped polyglutamate–curcuminoid conjugate has been shown to accumulate selectively in injured kidneys and inhibit key cell‐death pathways. In cultured tubular cells, this conjugate blocked apoptosis, necroptosis and markers of ferroptosis and attenuated activation of NF-κB and downstream inflammatory genes. In a folic acid–induced acute kidney injury model, treated animals displayed preserved renal architecture, reduced expression of injury markers and maintenance of the protective factor Klotho. These results establish a proof of concept for polymer-based delivery of bioactive polyphenols to dampen inflammation and limit regulated necrosis in kidney disease.

Inflammation and Cell Death in Kidney Disease publication trend

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

Technical terms

Apoptosis: Programmed cell death characterised by caspase activation, chromatin condensation and membrane blebbing without provoking inflammation.

Pyroptosis: Inflammatory form of cell death triggered by inflammasome assembly, caspase-1 activation and gasdermin‐mediated membrane pore formation.

Necroptosis: Regulated necrotic cell death dependent on receptor-interacting kinases RIPK1 and RIPK3, leading to membrane rupture and inflammation.

Inflammasome: Multiprotein cytosolic complex that senses danger signals and activates inflammatory caspases to process cytokines such as IL-1β.

Autophagy: Lysosome-dependent degradation pathway that removes damaged organelles and proteins, contributing to cellular homeostasis and survival.

cGAS–STING pathway: Cytosolic DNA sensing mechanism that activates type I interferon responses and promotes pro-inflammatory gene expression.

NF-κB: Family of inducible transcription factors central to the regulation of inflammatory, immune and cell-survival genes.

References

1. Effective Nephroprotection Against Acute Kidney Injury with a Star-Shaped Polyglutamate-Curcuminoid Conjugate. Scientific Reports (2020).
2. Ibudilast Attenuates Folic Acid–Induced Acute Kidney Injury by Blocking Pyroptosis Through TLR4-Mediated NF-κB and MAPK Signaling Pathways. Frontiers in Pharmacology (2021).
3. Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis. Pharmaceutics (2020).
4. NF-κB in inflammation and renal diseases. Cell & Bioscience (2015).