Abstract:

Objective: Obesity-related glomerulopathy has become an increasing renal disease in China. Inflammatory responses play an important role in the progression of ORG. Mast cells contribute to diet-induced obesity by producing cytokines and protease. To investigate if mast cells are also involved in ORG, we examined mast cell infiltration and its correlation with the progression of renal injury.  Methodology: Thirty-nine patients with biopsy-proven ORG and 10 non-obese donors as control were included in this study. Tryptase and CD68 were used for detecting mast cells and macrophages, respectively, by immunohistochemistry in both groups.  Results: Mast cells were detected in fibrotic interstitial and periglomerular areas mostly, but not within glomeruli. Tubulitis were observed. The density of mast cells was significantly increased in ORG compared with the control group, and it was well correlated with body mass index (BMI) (r=0.364, P=0.023), systolic blood pressure (r=0.459, P=0.003), diastolic blood pressure (r=0.347, P=0.003), N-acetyl-β-D-glucosaminidase (r=0.324, P=0.044), serum creatinine (r=0.637, P<0.001), tubular atrophy (r=0.47, P=0.003) and interstitial fibrosis (r=0.669, P<0.001). In contrast, it was negatively correlated with eGFR (r=－0.559, P<0.001). Macrophages were accumulated focally in the tubular interstitium with other infiltrated cells, and their density was positively correlated with the number of interstitial infiltrated cells (r=0.476, P=0.002). Multivariate regression showed that the number of mast cells was the critical factor for eGFR level (R2=0.44，P=0.036).  Conclusions: Our data show that patients with ORG have an increase in the number of interstitial mast cells, which was correlated positively with BMI, blood pressure, serum creatinine, and tubular injury, but negatively with eGFR, suggesting a role for mast cells in tubular atrophy and interstitial fibrosis. Further functional studies are required to determine the role of mast cells in tubular injury of ORG.