Effect of roxadustat on red blood cell lifespan in patients with long-term haemodialysis: a single-centre, prospective, single-arm study.

Background: Reduced survival of red blood cells (RBCs) in patients with chronic kidney disease (CKD) is thought to contribute to renal anaemia. Although renal anaemia improved greatly because of the wide use of erythropoiesis-stimulating agents (ESAs) and the advancement of dialysis techniques, RBC longevity seems not to be obviously ameliorated. Methods: In this single-centre, single-arm trial, patients who had been undergoing haemodialysis and ESA therapy with epoetin alfa for at least 12 weeks changed their anti-anaemia drugs from epoetin alfa to oral roxadustat three times per week for 24 weeks. The primary endpoint was the change in RBC lifespan from baseline at week 24. The change in the circulating percentage of eryptotic RBCs, RBC deformability and RBC oxygen transport ability were also assessed. Results: A total of 27 patients were enrolled, with 26 completing the full course of intervention. At baseline, the average RBC lifespan was 60.1 days [standard deviation (SD) 14.4; n = 27]. At the end of the study period, 26 patients had an RBC lifespan measurement (83.9 days on average; SD 21.9). The RBC lifespan increased by 22.8 days on average [95% confidence interval (CI) 15.5-30.0, P < .001]. This equated to an average RBC lifespan increase of 39.2% (95% CI 27.8-50.6). The percentage of circulating eryptotic RBCs, erythrocyte filtration index and the pressure at which haemoglobin is 50% saturated decreased significantly from baseline to week 24 (1.39 ± 0.44% versus 0.89 ± 0.25%, P < .0001; 0.29 ± 0.12 versus 0.16 ± 0.08, P < .0001 and 32.54 ± 4.83 versus 28.40 ± 2.29, P < .001, respectively). Conclusion: Roxadustat prolonged RBC lifespan in patients with long-term haemodialysis.

Association of circulating proprotein convertase subtilisin/kexin type 9 concentration with coagulation abnormalities in patients with primary membranous nephropathy.

OBJECTIVES: The aims of the study were to explore the potential associations between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and coagulation indexes in patients with primary membranous nephropathy (PMN). METHODS: A total of 87 patients diagnosed with PMN were enrolled in our study. 30 healthy participants were recruited to match PMN participants. Plasma PCSK9 concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Correlations between PCSK9 and coagulation abnormalities in patients with PMN were analyzed using univariate and multiple linear regression analysis. RESULTS: Plasma PCSK9 levels in patients with PMN were significantly higher than that in healthy controls [232.0 (143.5, 359.5) ng/mL vs. 166.8 (129.7, 199.7) ng/mL; p = 0.001]. Plasma levels of PCSK9 were positively correlated with factor VIII, factor IX, factor XI, log-transformed tissue factor, protein C and protein S (r = 0.267, p = 0.013; r = 0.496, p < 0.001; r = 0.217, p = 0.045; r = 0.584, p < 0.001; r = 0.372, p = 0.001; r = 0.282, p = 0.011). In multiple linear regression analysis, PCSK9 concentration was independently and positively correlated with factor VIII, factor IX, and tissue factor (ß = 0.186, p = 0.047; ß = 0.325, p = 0.001; ß = 0.531, p < 0.001; respectively). PCSK9 concentration was independently and negatively correlated with PT (ß= -0.343, p = 0.011). CONCLUSION: Plasma PCSK9 levels had good positive correlations with procoagulant clotting factors and negative correlations with PT in PMN, which might provide novel information with regard to PCSK9 and hypercoagulability in PMN.

Associations of left renal vein entrapment with IgA nephropathy and Henoch-Schönlein purpura nephritis.

OBJECTIVES: The aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition. METHODS: A total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens. RESULTS: LRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01). CONCLUSIONS: LRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

Anti-PLA2R antibody measured by ELISA predicts the risk of vein thrombosis in patients with primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) is associated with the highest risk for developing venous thrombosis compared with other nephrotic diseases. The aim of the study was to assess the predictive value of the pathognomonic anti-phospholipase A2 receptor (PLA2R) antibody with regard to incidence of venous thrombosis in PMN. METHODS: A total of 365 in-hospital patients diagnosed with PMN were enrolled in the study. Anti-PLA2R antibody was detected by commercial enzyme-linked immunosorbent assay. Multivariate logistic regression was used to detect the independent risk factors for venous thrombosis. RESULTS: Thirty-seven patients (10.14%) had venous thrombosis. Patients with venous thrombosis had higher levels of cholesterol (CHOL), low-density lipoprotein (LDL), and D-dimer than those without venous thrombosis (p < .05). Patients with venous thrombosis had significantly lower levels of albumin (23.95 ± 5.53 vs. 26.18 ± 6.59 g/L, p = .049). No significant differences were found in proteinuria, serum creatinine, estimated glomerular filtration rate, platelets, and fibrinogen between patients with and without thrombosis. Anti-PLA2R antibody levels in patients with venous thrombosis were significantly higher than in patients without it (p = .002). In the univariate logistic regression, Ln anti-PLA2R antibody (OR: 1.340; p = .004), albumin (OR: 0.945; p = .050), CHOL (OR: 1.191; p = .006), and LDL (OR: 1.271, p = .006) were associated with venous thrombosis. Ln anti-PLA2R antibody (OR = 1.269; 95%CI: 1.032-1.561), and LDL (OR = 1.213; 95%CI: 1.017-1.448) were the independent risk factors for venous thrombosis (p < .05) in multivariate analysis. CONCLUSIONS: Anti-PLA2R antibody was the independent risk factor for venous thrombosis in PMN. Larger prospective studies were warranted to verify the results in future.