RESUMEN
Background: In contrast to childhood minimal change disease (MCD), adult-onset MCD frequently recurs and requires prolonged immunosuppressive therapy. Accordingly, an investigation of the pathogenesis of adult MCD is required. MCD is usually accompanied by severe dyslipidaemia. Oxidized low-density lipoprotein (ox-LDL) is known to function in a damage-associated molecular pattern (DAMP) through CD36, triggering the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. However, the relationship between MCD pathogenesis and NLRP3 inflammasome/pyroptosis activation via CD36 is not fully understood. Methods: We conducted comprehensive histological and clinical evaluations by analysing renal biopsy (RBx) specimens and urine samples obtained from 26 patients with MCD. These samples were compared with control kidneys from 15 transplant donors and urine samples from 15 healthy volunteers. Results: The number of podocytes was lower in the MCD group than in the control group. Urinary ox-LDL levels were higher in the MCD group than in the control group. Immunofluorescence staining revealed that NLRP3 and CD36 were upregulated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in patients with MCD. Steroid therapy performed before RBx appeared to maintain the podocyte number and reduce urinary ox-LDL and IL-18 levels. Conclusion: In MCD, the NLRP3 inflammasome and pyroptosis cascade seem to be activated via upregulation of CD36 in podocytes, associated with increased urinary ox-LDL. Elevated urinary IL-18 levels suggest that pyroptosis may occur in MCD. Further research is required to confirm the significance of the podocyte NLRP3 inflammasome/pyroptosis in MCD.
RESUMEN
BACKGROUND: Clinical data supporting the target haemoglobin range in patients undergoing peritoneal dialysis (PD) are scarce. This study investigated the association between haemoglobin levels and all-cause mortality in Japanese patients undergoing PD using data from a nationwide dialysis registry. METHODS: A total of 4875 patients aged ≥18 years who were undergoing PD at the end of 2012 were analysed. Patients receiving combination therapy with haemodialysis or missing haemoglobin data were excluded. Haemoglobin values were categorised into six groups (<9.0, 9.0-9.9, 10.0-10.9, 11.0-11.9, 12.0-12.9 and ≥13.0 g/dL) and their association with mortality evaluated. RESULTS: Patients' mean age was 63 years, and 62% were men. The mean haemoglobin level was 10.7 g/dL, and 14% were anuric. Erythropoiesis-stimulating agents were used in 89%. During a median follow-up of 3.5 years, 1586 patients died. Haemoglobin levels <9.0 and ≥13.0 g/dL were significantly associated with mortality, as compared with levels of 10.0-10.9 g/dL (adjusted hazard ratios [95% confidence intervals]: 1.25 [1.06-1.48] and 1.45 [1.13-1.88], respectively). Restricted cubic spline analysis revealed a U-shaped association between haemoglobin levels and mortality. A haemoglobin level ≥12 g/dL was associated with mortality in patients with a history of cardiovascular disease (p interaction = 0.023). CONCLUSION: We provide important insights into the target haemoglobin in patients undergoing PD. Our findings suggest that setting a lower upper limit for haemoglobin levels may be beneficial for patients with a history of cardiovascular disease.
