Objective:To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min -1·(1.73 m 2) -1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min -1·(1.73 m 2) -1]. Kaplan-Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results:This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min -1·(1.73 m 2) -1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group ( Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log-rank χ2=0.26, P=0.612) and renal composite endpoint event survival rates (log-rank χ2=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log-rank χ2=0.77, P=0.381) and renal composite endpoint event survival rates (log-rank χ2=1.41, P=0.236) between eGFR ≥ 60 ml·min -1·(1.73 m 2) -1 and < 60 ml·min -1·(1.73 m 2) -1 groups. Multivariate Cox regression analysis showed that hypertension history ( HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history ( HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min -1·(1.73 m 2) -1 ( HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml ( HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis ( HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride ( HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g ( HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event ( HR=7.31, 95% CI 1.23-43.62). Conclusions:The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min -1·(1.73 m 2) -1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.

Objective:To investigate the relationship between anemia and renal function prognosis in IgA nephropathy (IgAN) patients.Methods:Patients diagnosed with IgAN by renal biopsy in Shenzhen Second People′s Hospital (The First Affiliated Hospital of Shenzhen University) from January 1, 2010 to December 31, 2018 were retrospectively analyzed. Patients who lacked baseline estimated glomerular filtration rate (eGFR), or patients with the baseline eGFR<15 ml·min -1·(1.73 m 2) -1, or patients who lacked baseline hemoglobin data were excluded. Clinical data, laboratory data, pathological data and follow-up data of renal function were collected. Patients were divided into anemic group (hemoglobin level<120 g/L in males and<110 g/L in females) and non-anemic group. A generalized additive mixed model (GAMM) was used to analyze the relationship between anemia at baseline and decreased renal function (eGFR) in follow-up. Results:A total of 821 IgAN patients were enrolled in this study, including 666 non-anemia patients and 155 anemia patients. There were 397 males (48.36%), aged (34.91±9.46) years. The median baseline eGFR was 72.00(15.00, 167.46) ml·min -1·(1.73 m 2) -1, and the median baseline urinary protein quantification was 1.00(0.01, 15.82) g/24 h. The median follow-up time was 176(0, 3 770) days. A total of 2 352 repeated measurements were performed of which 1 268 (53.91%) repeated measurements were from males. Compared with those in non-anemia group, patients in anemia group had lower levels of baseline eGFR, body mass index (BMI) and serum albumin, higher proportion of females, and higher pathologic manifestations of glomerular segmental sclerosis (S1), tubulointerstitial atrophy/fibrosis (T1 and T2), and crescent (C1 and C2) (all P<0.05). Using the single-factor GAMM, the eGFR decreased by 4.778 ml·min -1·(1.73 m 2) -1 (95% CI 2.727-6.830, P<0.001) more per year in the anemia group than that in the non-anemia group. After adjusting for age, gender, BMI, blood uric acid, mean arterial pressure, serum albumin, blood cholesterol, 24 h urinary protein, glomerular mesangial cell proliferation (M), capillary cell proliferation (E), glomerular segmental sclerosis (S), tubulointerstitial atrophy/fibrosis (T), and crescent formation (C), each additional year of time, eGFR decreased by 6.817 ml·min -1·(1.73 m 2) -1 (95% CI 4.245-9.388, P<0.001) more in the anemia group than that in the non-anemia group. Conclusions:Anemia is correlated with renal function decline in IgAN patiens. IgAN patients with anemia have accelerated deterioration of progress. Early intervention of anemia might delay renal function progression.

Objective:To establish a diagnostic model for glomerular micro thrombosis (GMT) in lupus nephritis through clinical indicators.Methods:A continuous collection of patients diagnosed with lupus nephritis (LN) by renal biopsy in the Department of Nephrology, Shenzhen Second People's Hospital, from January 2010 to March 2021. All patients were admitted and discharged through the inclusion and exclusion criteria. Demographic data, clinical characteristics, biochemical indicators, and immune indicators were collected. A GMT diagnosis model was established from the most important variables among the abovementioned variables through machine learning and Logistic stepwise regression analysis. The model was presented through a nomogram. The receiver operating characteristic curve (ROC), the clinical decision curve and the calibration curve were used to evaluate the model discrimination, clinical use and accuracy, respectively. The internal verification of the model was carried out by repeated sampling 500 times by the Bootstrap method.Results:There were a total of 129 patients with lupus nephritis including the study, including 117 females (90.7%); the average age was (34±11) years. There were 39 patients with GMT (30.2%). Using machine learning to screen out the top 10 important variables from 47 candidate variables, then through logistic stepwise regression analysis, five variables were further screened to establish the diagnostic model of GMT, namely hemoglobin [ OR(95% CI)=0.966(0.943, 0.990), P=0.005], serum C3 [ OR(95% CI)=0.133(0.022, 0.819), P=0.030], systolic blood pressure [ OR(95% CI)=1.027(1.005, 1.049), P=0.017], lymphocyte count [ OR(95% CI)=0.462(0.213, 0.999), P=0.049], and TT [ OR(95% CI)=1.260(0.993, 1.597), P=0.057]. Draw up the equation of the GMT diagnosis model of lupus nephritis and establish a nomogram to present the model. The area under curve (AUC) of the diagnostic model was 0.823, 95% CI(0.753, 0.893), indicating that the model had a reasonable degree of discrimin-ation. The Hosmer-Lemeshow test showed a perfect fit between the predicted GMT risk and the observed GMT risk ( χ2= 14.62, P=0.067). The clinical decision curve and clinical impact curve reflect that the model had a good clinical application value, especially when the threshold probability is between 0.4 and 0.6, the application value is more significant. In addition, after 500 repeated samplings by the Bootstrap method, the average AUC was 0.825, 95% CI(0.753, 0.893), which is basically the same as the AUC obtained by the original model. Conclusion:We established a diagnostic model of GMT inLN based on clinical indicators through machine learning and logistic stepwise regression analysis. It is used for early diagnosis of the risk of GMT before the renal biopsy.

Objective:To investigate the relationship between hemoglobin levels and renal prognosis in patients with IgA nephropathy (IgAN).Methods:The clinical data and pathological examination results of IgAN patients diagnosed by renal biopsy at the Second People's Hospital of Shenzhen from February 25, 2010 to September 9, 2020 were retrospectively collected and analyzed. The patients were divided into anemic group and non-anemic group according to the anemia diagnostic criteria (The hemoglobin levels were<120 g/L and<110 g/L in males and females respectively at sea level area). Endpoint event was defined as a decrease in estimated glomerular filtration rate (eGFR) of>50% from baseline and/or progression to stage 5 chronic kidney disease [eGFR<15 ml·min -1·(1.73 m 2) -1]. Cox regression analysis was used to analyze the factors affecting the poor renal prognosis. The relationship between hemoglobin and renal function prognosis was analyzed by smoothing curve fitting and threshold effect. Kaplan-Meier survival curve was used to compare and analyze the difference of renal survival rate between the anemic and non-anemic IgAN patients. Results:A total of 1 263 IgAN patients were included in this study, 255(20.19%) patients were in the anemia group and 1 008 (79.81%) patients were in the non-anemia group. The anemia group had lower body mass index, baseline eGFR, serum albumin, and triglyceride than those in the non-anemia group (all P<0.05). The proportion of females, 24 h urinary protein content, and the proportion of renal tubule atrophy/interstitial fibrosis, segmental sclerosis and crescents in the anemia group were higher than those in the non-anemia group (all P<0.05). Multivariate Cox regression analysis showed that low hemoglobin was an independent influencing factor for renal endpoint event ( HR=0.25, 95% CI 0.07-0.90, P=0.022). Smoothing curve fitting analysis and threshold effect analysis showed that a curving relationship was detected between hemoglobin and relative risk of renal endpoint event. As hemoglobin increased, there was a protective effect on renal function when hemoglobin level was lower than 147 g/L ( β=0.96, 95% CI 0.94-0.99, P=0.008). Kaplan-Meier survival curve analysis suggested that patients with anemia had a lower cumulative renal survival rate than that of patients without anemia (Log-rank test χ2=10.106, P=0.002). Conclusions:Low hemoglobin is an independent influencing factor for poor prognosis of renal function in IgAN patients. Cumulative renal survival rate is lower in IgAN patients with anemia than that of patients without anemia.

Objective:To explore the correlation between hemoglobin (Hb) and progression of renal function in patients with proliferative lupus nephritis (PLN).Methods:Data of biopsy-proven PLN patients from January 2010 to February 2019 in Department of Nephrology, the First Affiliated Hospital of Shenzhen University were retrospectively analyzed. The patients were divided into stable renal function group and renal function progression group according to changes of renal function including serum creatinine doubling/end-stage renal disease (ESRD) and the demographic, clinical, and pathological characteristics were compared between the two groups. Cox regression and smooth curve fitting of generalized additive model analysis were used to explore the correlation between Hb and progression of renal function.Results:A total of 87 patients were included in this study. The age was (34.97±11.95) years old and 79 cases (90.80%) were females. During follow-up of 19.0(6.5, 43.5) months, renal function of 15 patients (17.24%) progressed. Compared with stable renal function group, Hb level of patients in renal function progression group were lower ( t=3.887, P<0.001), and serum creatinine ( Z=-2.466, P=0.003) and uric acid ( t=-2.154, P=0.034) were higher. As to the pathological characteristics, the proportion of class lupus nephritis-IV, renal tubular atrophy and interstitial fibrosis in renal function progression group were higher than those in stable renal function group, but there was no statistical difference between the two groups (all P>0.05). Multivariate Cox regression analysis indicated that high Hb was an independent protective factor of renal function progression in PLN patients ( HR=0.893, 95% CI 0.836-0.954, P=0.001). The risk of progression to serum creatinine doubling/ESRD would decrease by 10.7% when Hb increased by 1 unit (g/L). Smooth curve fitting of generalized additive model analysis showed that Hb was linearly correlated with the risk of renal function progression ( P=0.100). Receiver operating characteristic curve indicated that the risk of doubling serum creatinine/ESRD in PLN patients would be relatively low when Hb level was above 77 g/L (area under the curve 0.788, best threshold 77 g/L, sensitivity 0.600, specificity 0.903). Conclusions:Hb is closely related to progression of renal function in patients with PLN. More attention and management of Hb levels in patients with PLN can play an important role in improving renal prognosis.

Objective:To investigate the relationship between serum C3 and progression of renal function in IgA nephropathy.Methods:A single-center retrospective cohort study was conducted in patients with IgA nephropathy confirmed by renal biopsy who were admitted to the Second People's Hospital of Shenzhen from January 2011 to June 2020 and the patients were followed up until January 2021. Patients with secondary IgA nephropathy, baseline estimated glomerular filtration rate (eGFR)<30 ml·min -1·(1.73 m 2) -1, lack of baseline serum C3 or creatinine, and follow-up time<6 months were excluded. The clinical data, laboratory examination and renal pathology were collected. The threshold effect analysis was used to obtain the cut-off point, and inflection point and 95% confidence interval were obtained using bootstrapping resampling technique. According to the cut-off point, the patients were divided into serum C3<0.97 g/L group and C3≥0.97 g/L group. The baseline data between the two groups were compared. Cox regression model was used to analyze the correlation between serum C3 level and renal function progression. Results:A total of 414 patients were enrolled in this study, with 145 males (35.0%), and age of (35.15±9.18) years old. The baseline eGFR was 77.80(46.67, 106.10) ml·min -1·(1.73 m 2) -1, and the serum C3 was (1.04 ± 0.19) g/L. There were 153 patients with serum C3<0.97 g/L and 261 patients with serum C3≥0.97 g/L. Compared to patients with serum C3≥0.97 g/L, those patients with serum C3<0.97 g/L were younger and had higher proportion of females, higher levels of hemoglobin and eGFR, and lower levels of mean arterial pressure, total cholesterol, triglyceride, serum uric acid, serum creatinine, 24 h urinary protein, IgA and C4 (all P<0.05). The relationship between serum C3 and progression of renal function was found to be U-shaped by smooth curve fitting. After adjustment for confounding factors such as age, sex, mean arterial pressure, serum uric acid, 24 h urinary protein, and renal pathology (MESTC), the results of the threshold effect and multivariate Cox regression showed, for patients with C3<0.97 g/L, the risk of renal function progression decreased by 40% for every 0.1 g/L increase of C3 ( HR=0.60, 95% CI 0.39-0.94, P=0.024), but for patients with C3≥0.97 g/L, every 0.1 g/L increase in serum C3 increased the risk of renal function progression by 27%( HR=1.27, 95% CI 1.03-1.57, P=0.027). The inflection point was 0.97(95% CI 0.92-1.01) g/L. Conclusions:Serum C3 is nonlinear correlated with the progression of renal function in patients with IgA nephropathy. Serum C3 level maintaining at 0.92-1.01 g/L is associated with better renal prognosis.

Objective:To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN).Methods:Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve.Results:A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older ( t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006), higher urine protein quantitation ( Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 ( Z=3.469, P<0.001; t=1.744, P<0.001), higher systemic lupus erythematosus disease activity index ( t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher ( Z=-1.866, P=0.002; t=-5.005, P<0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P<0.001; χ2=15.695, P<0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients ( OR=0.966, 95% CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine/end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions:Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.

Objective:To explore the relationship between segmental glomerulosclerosis and the change of renal function in IgA nephropathy (IgAN).Methods:It was a single-center retrospective cohort study. The patients with biopsy-proven primary IgAN who were hospitalized in Shenzhen Second People's Hospital from January 1, 2011 to December 31, 2018 were included. Participants with a secondary cause of IgAN, without baseline serum creatinine or renal pathology data for Oxford classification, baseline estimated glomerulofiltration rate (eGFR)<30 ml·min -1·(1.73 m 2) -1, follow-up time<6 months, or less than three times measurements of followed-up serum creatinine were excluded. The clinical data, laboratory tests and renal pathology data and so on were collected. Patients were divided into absence of segmental glomerulosclerosis (S0) group and segmental glomerulosclerosis (S1) group according to the Oxford classification. The generalized additive mixed model was used to analyze the associations of segmental glomerulosclerosis and longitudinal renal function decline (Renal function was evaluated by using the eGFR). Results:There were 280 patients included in this study, with 199 patients in S0 group, and 81 patients in S1 group. Compared with S0 group, patients in S1 group exhibited higher levels of triglyceride, serum uric acid as well as 24-hour urinary protein, and a lower level of eGFR, and had higher proportions of tubular atrophy and interstitial fibrosis (T) (all P<0.05). After adjusting for age, gender, mean arterial pressure, 24-hour urinary protein, mesangial hypercellularity (M), endocapillary hypercellularity (E), T and crescent (C) in the generalized additive mixed model, the effect value of S1 (the difference of baseline eGFR between S1 group and S0 group) was -14.09 ml·min -1·(1.73 m 2) -1. For every additional year, the eGFR of S0 group decreased 1.29 ml·min -1·(1.73 m 2) -1 (95% CI 0.47-2.12, P=0.002) in average, and eGFR decline in S1 group had 2.85 ml·min -1·(1.73 m 2) -1 more than that in S0 group [95% CI 1.05-4.64, P=0.002]. Conclusion:Segmental glomerulosclerosis is independently associated with the longitudinal decrease in renal function in patients with IgAN, which suggests therapies targeted for improving the early damages of segmental glomerulosclerosis may be essential to delay the renal function decline progression.

Objective: To clarify the relationship between the hemoglobin level and renal tubular atrophy/interstitial fibrosis (T) in the Oxford stage of renal pathology in IgA nephropathy (IgAN) patients. Methods: Patients diagnosed with IgAN by renal biopsy from January 1^st 2010 to December 31^st 2015 in Shenzhen Second People's Hospital with complete laboratory and imaging data were retrospectively analyzed. Patients were divided into anemic group and non-anemic group. The relationship between hemoglobin level and renal tubular atrophy/interstitial fibrosis was determined by logistic regression analysis. The possible curve relationship between hemoglobin and renal tubular atrophy/interstitial fibrosis was analyzed by smooth curve fitting analysis. The diagnostic value of hemoglobin for renal tubular atrophy/interstitial fibrosis was analyzed by the receiver operating curve (ROC). Results: A total of 630 patients with IgAN were included in this study, 130 patients in the anemia group (20.63%) and 500 patients in the non-anemia group (79.37%). There was no statistically significant difference in age between the two groups, but the difference of the gender was statistically significant (male 35.38% vs 53.80%, χ²=10.740, P<0.001). Compared with the non-anemia group, the anemia group had a higher proportion of tubular atrophy/interstitial fibrosis (χ²=62.586, P<0.001), higher 24 h urinary protein quantification (Z=-6.082, P<0.001), and lower eGFR (t=7.126, P<0.001). Multivariate logistic regression analysis showed that increasing hemoglobin level was an independent protective factor for reducing the risk of renal tubular atrophy/interstitial fibrosis (OR=0.973, 95%CI 0.958-0.987, P<0.001). Smooth curve fitting analysis showed that there was a linear negative correlation between hemoglobin and tubular atrophy/interstitial fibrosis. The ROC curve suggested that the best threshold of hemoglobin was 120.5 g/L when renal tubular atrophy/interstitial fibrosis occurred. That was, when hemoglobin was above 120.5 g/L, the severity level of renal tubular atrophy interstitial fibrosis might be reduced. Conclusion The incidence of renal tubular atrophy/interstitial fibrosis is higher in IgAN patients with anemia, and hemoglobin>120.5 g/L may reduce the risk of tubular atrophy/interstitial fibrosis.

Objective To compare the influence degree of laparoscopic operation and open operation on peripheral blood T lymphocyte subsets and Th1Th2 in patients with severe acute pancreatitis.Methods 54 patients who underwent surgical treatment in our hospital from February 2013 to December 2014 were selected as the subjects, 27 patients with severe acute pancreatitis who were treated with open operation as group A , 27 cases who were treated with laparoscopic operation at the same time were selected as group B , and then the peripheral blood T lymphocyte subsets and serum Th1Th2 indexes of two groups before the operation and at first,third and seventh day after the operation were respectively detected, then the detection results of two groups were compared.Results The peripheral blood T lymphocyte subsets and serum Th1Th2 indexes of group B at first, third and seventh day after the operation were all significantly better than those of group A , the difference was statistically significant ( P<0.05 ) , and the detection results of group A and group B at third day after the operation were worse than those at other time , the difference was statistically significant (P<0.05).Conclusion The influence of laparoscopic operation and open operation on T lymphocyte subsets and Th1Th2 in peripheral blood of patients with severe acute pancreatitis, the adverse effects of laparoscopic operation on the above indicators were relatively small.