Pathogenic role of mast cells in the development of diabetic nephropathy: a study of patients at different stages of the disease.

ABSTRACT

AIMS/HYPOTHESIS: Increased renal mast cells have been detected in diabetic nephropathy. However, only a few patients have been examined. Evidence of the involvement of mast cells in diabetic nephropathy is still scarce, and no observation of mast cells during the development of diabetic nephropathy has yet been reported in humans. Here, we examined changes in renal mast cells in patients at different stages of diabetic nephropathy and related these to the development of the disease. METHODS: Eighty patients at different clinical stages of diabetic nephropathy and 16 normal kidney donors were recruited. Immunohistochemical staining for tryptase, chymase, TGF-ß1, renin and TNF-α was done on renal sections from patients and control participants. Changes in mast cell number, degranulation, subtype and phenotype were examined. Correlation between mast cells and patients' clinical and pathological indices was analysed. RESULTS: With progression of diabetic nephropathy, the number and degranulation level of mast cells increased. Increase in mast cell number and degranulation level correlated significantly with tubular interstitial injury. Almost all renal mast cells in patients with diabetic nephropathy were found to produce chymase, renin, TGF-ß1 and TNF-α. The level of TNF-α in mast cells increased with progression of diabetic nephropathy. CONCLUSIONS/INTERPRETATION: This study suggests that mast cells are involved in development of diabetic nephropathy. Through release of bioactive substances, such as tryptase, chymase, TGF-ß1, renin and TNF-α, into the tubular interstitium by degranulation, mast cells could promote renal inflammation and fibrosis, and thus contribute to diabetic nephropathy.