1.Anemia aggravates clinical and pathological changes in patients with IgA nephropathy
Ting HE ; Haiping MAO ; Zhibin LI ; Na GUO ; Ricong XU ; Xiao YANG ; Xueqing YU ; Zhijian LI
Chinese Journal of Nephrology 2012;28(6):460-463
Objective To analyze the changes of clinical and pathological features in the patients of IgA nephropathy with anemia.Methods Four hundred and nine patients of IgA nephropathy diagnosed by renal biopsy were classified into two groups:IgA nephropathy with nonanemia (group 1) and IgA nephropathy with anemia (group 2).Changes were studied retrospectively between the groups.Results Serum hemoglobin level was correlated with the clinical parameters of IgA nephropathy.Companed to group 1,changes in group 2 were as followed:serum creatinine increased,eGFR decreased,proteinuria increased; the global sclerosis,segmental sclerosis,crescents and tubulointerstitial lesions worsened.The glomerular and tubulointerstitial lesions were negatively correlated with serum hemoglobin and eGFR,but positively correlated with serum uric acid and proteinuria (P<0.05).Multivariate Logistic regression analysis revealed that anemia was an independent risk factor for the tubulointerstitial lesion.Conclusion Clinical feature and pathological damages in the patients of IgA nephropathy with anemia are more serious than those with non-anemia.
2.Crescents proportion no lower than 14% were significantly associated with renal function and outcomes of IgA nephropathy patients
Xian LIAO ; Haofei HU ; Yongcheng HE ; Ricong XU
Chinese Journal of Nephrology 2018;34(7):500-507
Objective To explore the clinicopathological features and outcomes of IgA nephropathy patients with different proportions of crescents.Methods A total of 270 patients who were diagnosed as IgA nephropathy by renal biopsies from January 2010 to December 2015 in the First Affiliated Hospital of Shenzhen University were enrolled.All patients were divided into 3 groups according to the optimal cutoff level of crescents proportion in the Receiver Operating Characteristic Curve (ROC) as follows:0%,< 14%;≥ 14%.The endpoint was defined as the doubling of baseline serum creatinine (Scr) and/or end-stage renal disease (ESRD).Kaplan-Meier curve and Cox regression model were used to analyze the renal survival among three groups.Results One hundred and four patients (38.5%) without any crescents;84 patients (31.1%) with crescents proportion < 14% and 82 patients (31.4%) with crescents proportion ≥14%.Patients with crescents proportion ≥14% group were older and had higher level of systolic blood pressure and diastolic blood pressure,24-hour urine protein and serum uric acid level;more patients treated with RAS blocker,glucocorticoid and immunotherapy,but lower eGFR,hemoglobin and serum albumin level than those with crescents proportion < 14%.Compared with those without crescents and crescent proportion < 14%,patients with crescent proportion ≥ 14% also had higher proportion of global glomerulosclerosis,more endocapillary hypercellularity and severe tubulointerstitial lesions,higher degree of IgA and C3 depositions in renal.24-hour proteinuria,serum uric acid level,low hemoglobin level,endocapillary hypercellularity and renal C3 depositions were risk factors for crescents formation.Patients were followed-up for a median of (31.7±21.0) months,and Kaplan-Meier analysis revealed that renal survival rate was significantly lower in patients with crescents proportion ≥ 14% compared with other groups (P=0.001).But there was no significant difference between no crescent group and crescents proportion < 14% group.However,multivariate Cox analysis showed no significant difference between crescents proportion and renal survival.Conclusion Crescents proportion is associated with higher risk of renal function and renal progression.
3.Association between serum C3 and progression of renal function in IgA nephropathy
Tao CAO ; Ricong XU ; Yi XU ; Qijun WAN
Chinese Journal of Nephrology 2021;37(12):974-979
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.
4.Analysis of association between segmental glomerulosclerosis and renal function decline in IgA nephropathy
Ricong XU ; Tao CAO ; Yi XU ; Ying LIAO ; Zhijian LI ; Qijun WAN
Chinese Journal of Nephrology 2020;36(11):851-857
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.
5.Association between hemoglobin levels and renal progression in patients with IgA nephropathy
Xiaojie CHEN ; Ricong XU ; Haofei HU ; Haiying SONG ; Qijun WAN
Chinese Journal of Nephrology 2021;37(9):730-738
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.
6.Correlation analysis of anemia and renal function decline in patients with IgA nephropathy by using generalized additive mixed model
Xiaojie CHEN ; Haofei HU ; Ricong XU ; Haiying SONG ; Qijun WAN
Chinese Journal of Nephrology 2022;38(6):504-510
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.
7.Establishment of a diagnostic model for glomerular micro thrombosis in patients with lupus nephritis based on machine learning
Haofei HU ; Ricong XU ; Yang LIU ; Jianyu CHEN ; Zheyi CHANG ; Qijun WAN
Chinese Journal of Rheumatology 2022;26(11):721-729,C11-1
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.