Clinical significance of Mtype phospholipase A2 receptor and thrombospondin Type 1 domaincontaining 7A in primary membranous nephropathy / 中南大学学报(医学版)

OBJECTIVES@#To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis.@*METHODS@#Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.@*RESULTS@#The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group.@*CONCLUSIONS@#PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.

Clinicopathological analysis for IgA nephropathy with isolated hematuria and/or mild proteinuria / 中南大学学报(医学版)

To investigate the correlation of different types of urinary abnormalities or different proteinuria and hematuria with the pathological injury of kidney in IgA nephropathy with isolated hematuria and/or mild proteinuria.
 Methods: Patients with primary IgA nephropathy, isolated hematuria and/or mild proteinuria were enrolled in the Department of Nephrology, the Second Xiangya Hospital, Central South University from January 2013 to January 2018. According to the difference of red blood cell count in urinary sediment and quantitative of 24-hour urinary protein (24 h-UP) during renal biopsy, the patients were grouped in 3 ways: a simple hematuria group, a hematuria and proteinuria group, and a simple proteinuria group; a proteinuria I group, a proteinuria II group, and a proteinuria III group; a hematuria I group, a hematuria II group, and a hematuria III group. The clinical parameters such as age, mean arterial pressure, blood urea nitrogen, serum creatinine, blood uric acid, 24 h-UP, and renal pathological damage were compared.
 Results: A total of 157 patients met the inclusion criteria, including 71 males and 86 females. The most common pathological type was focal and/or segmental glomerulosclerosis. The Lee's classification were dominated by grade III and IV, and the renal pathological injury was heavy. Immunoglobulin deposition was dominated by simple IgA deposition. The most common fluorescence intensity of IgA deposition was +++. 97 (61.78%) patients were accompanied by complement deposition and were mainly composed of simple complement C3 deposition. There were 18 patients (11.47%) in the simple hematuria group, 111 patients (70.70%) in the hematuria and proteinuria group, and 28 patients (17.83%) in the simple proteinuria group. Compared with the simple hematuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injuries was increased (χ2=7.053, P=0.008). Compared with the hematuria and proteinuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injury was increased (χ2=4.294, P=0.038). Compared with the proteinuria I group, the proportion of patients with mild injury was lower in the proteinuria III group, and the proportion of patients with moderate-to-severe injury was increased (χ2=5.433, P=0.020). There was no significant difference in the proportion of patients with renal pathological injury among different hematuria groups (P>0.05).
 Conclusion: The clinical manifestations of patients with IgA nephropathy with hematuria and/or mild proteinuria are inconsistent with renal pathological damage. Some patients with mild clinical manifestations have severe renal pathological damage and the renal pathological damage is more serious in simple proteinuria. The more proteinuria, the heavier the renal pathological damage.

Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase A2 receptor antibody in membranous nephropathy / 中南大学学报(医学版)

Objective:To examine the expression ofphospholipase A2 receptor (PLA2R) in renal tissues and the level of anti-PLA2R antibody in serum in patients with idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (SMN),and to evaluate their diagnostic value in IMN.Methods:A total of 73 patients,who were diagnosed between May,2014 and February,2015 in the Department of Nephrology of the Second Xiangya Hospital,Central South University,were divided into three groups:an IMN group (n=48),an SMN group (n=17) and a minimal change disease group (n=8) according to the renal biopsy.PLA2R expression in renal tissues and the level of antiPLA2R antibody in serum were detected by indirect immunofluorescence technique.Results:The positive rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group were higher than those in the SMN group (91.7％ in the IMN group vs 29.4％ in the SMN group,P＜0.05),while the positive rate and serum level for anti-PLA2R antibody in the IMN group were higher than those in the SMN group (85.4％ in the IMN group vs 29.4％ in the SMN group,P＜0.05);the expression of PLA2R in renal tissues and the serum level for anti-PLA2R antibody were not detected in the minimal change disease group,The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (r=0.432,P＜0.01) and negatively correlated with serum albumin (r=-0.307,P＜0.05).Conclusion:The expression of PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be potential markers for diagnosis oflMN.

Effect of high glucose peritoneal dialysis solution on PGC-1α expression and mitochondria related oxidative injury in human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of mitochondrial oxidative injury induced by high glucose peritoneal dialysis solution (PDS) and the protective effect of peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α) in the mitochondria of human peritoneal mesothelial cells (HPMC) in the high glucose ambience.@*METHODS@#HPMC was cultured in a PDS containing 1.5%, 2.5% and 4.25% glucose for 24 hours. Western blot analysis was used to detect PGC-1α expression. MitoSOX? Red staining, respiratory chain complexes and antioxidant enzyme activities were determined.@*RESULTS@#The activities of respiratory chain complex III and antioxidant enzymes decreased significantly in a concentration- and time-dependent manner, along with the increased production of mitochondrial reactive oxygen species (ROS) and cellular apoptosis. In addition, protein expression of PGC-1α was also decreased in the high glucose PDS ambience.@*CONCLUSION@#High glucose PDS might inhibit PGC-1α expression, resulting in the inhibition of mitochondrial function and increase of mitochondrial ROS and cellular apoptosis.