Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.
Chronic kidney disease is driven by a pro-inflammatory state that accelerates both renal decline and major cardiovascular events. This review outlines key inflammatory pathways and highlights potential therapeutic targets, ranging from investigational agents (ASK1, JAK, and IL-1β/IL-6 inhibitors) to established cardiorenal medications with proven anti-inflammatory effects, including SGLT2 inhibitors, GLP-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists. Integrating anti-inflammatory strategies into CKD management offers a promising avenue to mitigate cardiovascular risk and preserve kidney function.
Summary
Chronic kidney disease (CKD) is a leading cause of premature death due to the loss of kidney function and development of kidney failure, and because of attendant major adverse cardiovascular events. High-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, is associated with increased risks of cardiovascular events and CKD progression. CKD is characterized by a pro-inflammatory state with upregulation of inflammatory pathways and disruption of anti-inflammatory mechanisms. The resulting systemic inflammation, along with local tissue-based inflammatory mechanisms, are key contributors to kidney damage, atherosclerosis and cardiac dysfunction. As a result, a series of inflammatory pathways and mediators have emerged as potential therapeutic targets for CKD and its major cardiovascular complications. Investigational treatments that have targeted inflammation include inhibition of apoptosis signal-regulating kinase-1 (ASK1) by selonsertib, Janus kinase (JAK) 1/2 inhibition with baricitinib, protein kinase C-β (PKCβ) inhibition with ruboxistaurin, nuclear factor erythroid 2-related factor 2 (Nrf2) activation with bardoxolone, phosphodiesterase inhibition with pentoxifylline and monoclonal antibodies against IL-1β and IL-6. Furthermore, proven therapies for CKD, including renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid antagonists, possess anti-inflammatory properties that might contribute to their previously established clinical benefits.
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