Clonal haematopoiesis, ageing and kidney disease

Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - more than 10% of individuals over 65 years of age are affected - and is associated with an increased risk of disease across several organ systems and premature death. Emerging evidence suggests that CHIP has a role in kidney health, including associations with predisposition to acute kidney injury, impaired recovery from acute kidney injury and kidney function decline, both in the general population and among those with chronic kidney disease. Beyond its direct effect on the kidney, CHIP elevates the susceptibility of individuals to various conditions that can detrimentally affect the kidneys, including cardiovascular disease, obesity and insulin resistance, liver disease, gout, osteoporosis and certain autoimmune diseases. Aberrant pro-inflammatory signalling, telomere attrition and epigenetic ageing are potential causal pathophysiological pathways and mediators that underlie CHIP-related disease risk. Experimental animal models have shown that inhibition of inflammatory cytokine signalling can ameliorate many of the pathological effects of CHIP, and assessment of the efficacy and safety of this class of medications for human CHIP-associated pathology is ongoing. Clonal haematopoiesis of indeterminate potential (CHIP) is associated with increased risk of disease, including cardiovascular and kidney disease. Here, the authors discuss the consequences of CHIP across various organ systems, including direct and indirect effects on kidney health. Clonal haematopoiesis of indeterminate potential (CHIP) is a common, acquired condition wherein mutated white blood cells form an expanded clonal population in the blood and cause chronic organ damage through dysregulated inflammation.CHIP has been associated with a greater risk of acute kidney injury (AKI) and impaired recovery from AKI in human population cohorts and in mouse models, as well as loss of kidney function in the general population and in those with chronic kidney disease.In addition to its direct effects on the kidney, CHIP predisposes individuals to several conditions that impact kidney health, including cardiovascular disease, gout, osteoporosis and insulin resistance.CHIP affects 10-20% of individuals aged 65 and older; other than age, risk factors include smoking, male sex, chronic inflammation, cytotoxic therapies and certain inherited genetic variants.In preclinical models, cytokine blockade strategies mitigate many of the pathological effects of CHIP; these strategies are being evaluated in humans.