Investigation of NOD-Like Receptor Thermal Protein Domain Associated Protein 3 Inflammasome/Pyroptosis Stimulation through the CD36 Activation in Adults with Minimal Change Disease

Background: Minimal change disease (MCD) basically occurs in childhood. Although MCD well reacts to the steroid therapy, adult onset MCD have frequent recurrency and need prolonged immunosuppressive therapy, compared to childhood MCD. Accordingly, the investigation for the pathogenesis of adult MCD has been required. MCD is usually accompanied with severe dyslipidemia. Oxidized low-density lipoprotein (ox-LDL) is known to work as a damage-associated molecular patterns through CD36, and trigger NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. The relationship between the pathogenesis of MCD and NLRP3 inflammasome/ pyroptosis has not been understood fully. In this study, we assessed the factors which are regarding to NLRP3 inflammasome/ pyroptosis cascade in the patients diagnosed as MCD in our university hospital. Methods: We performed histological and clinical assessment using kidney sections and urine samples taken from the MCD patinets (N=56), compared to the kidney doners (N=15) and health volunteers (N=15). Secondary MCD, the patients with any clinical data defect, and the patients without urine sample at the timing of renal biopsy (RBx) were excluded. Results: Total 26 MCD patients were finally enrolled in this study. The number of the podocytes was lower in MCD than that of the control. Urinary ox-LDL levels were higher in MCD, compared to the control. Analysis of immunofluorescent staining revealed that NLRP3 and CD36 were activated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in the MCD patients. Steroid therapy applied before RBx contributed to maintaining the number of podocytes in glomeruli and reduce urinary ox-LDL and IL-18 levels. Conclusion: In this study, NLRP3 inflammasome cascade seemed to be activated via upregulation of CD36 in podocytes and the elevation of urinary ox-LDL. The elevation of urinary IL-18 levels could suggest that pyroptosis might occur in MCD, further studies are required to detect certain pyroptosis in podocytes.