Role of Mast Cells and Their Mediators in Chronic Kidney Diseases

Chronic kidney disease (CKD) affects as many as 10% of the population, which translates to about 850 million globally. Even though genetics, diabetes, and hypertension contribute to CKD, the underlying pathologic processes remain poorly understood. Mast cells (MCs) are unique tissue immune cells capable of secreting numerous biologically active molecules. MCs have been associated with kidney diseases and poor CKD outcomes, but they have received limited attention in CKD research. MCs are typically located perivascularly and are identified through kidney biopsies, which limits their diagnostic utility. MC-specific biomarkers such as histamine and the proteases chymase and tryptase show potential, but signature biomarker profiles are needed. While MC biomarkers have been studied in non-renal diseases, their clinical relevance in kidney disease remains underexplored. This review aims to clarify the role of MCs in kidney diseases, such as diabetic nephropathy, IgA nephropathy, hypertensive nephropathy, pruritus, parathyroidism, renal amyloidosis, and lupus nephritis, as well as in conditions such as kidney fibrosis, inflammation, and kidney transplant rejection. Evidence indicates an increased number of MCs, as judged by increased urine levels of histamine, chymase, IL-33, metalloproteinase-9 (MMP-9), and tryptase. In conclusion, MCs are involved in the pathogenesis of CKD and may represent new targets for early diagnosis, prevention, and treatment.