Prognosis Of Idiopathic Membranous Nephropathy Research Articles

Idiopathic membranous nephropathy with focal segmental sclerosis

To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=0.039) were associated with the CKD progression. In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

Clinical characteristics and prognosis of patients with idiopathic membranous nephropathy with kidney tubulointerstitial damage

Background To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID). Methods Based on the presence or absence of kidney TID by kidney biopsy, 300 patients diagnosed with IMN were categorized into non-TID (TID−) and tubulointerstitial injury (TID+) groups. The clinical and pathological data were analyzed retrospectively. All patients were followed up for 6–24 months after treatment with glucocorticoids (GCs) combined with cyclophosphamide or GCs combined with calcineurin inhibitors (CNIs) to observe treatment effects on patient prognosis. Results The patients in the TID + group were older and more likely to be male. The 24-h urine protein, blood urea nitrogen, serum creatinine, cystatin C, β2-microglobulin, and antiphospholipase A2 receptor antibody levels were higher than those in the TID − group and the pathological manifestations were more severe. After 1 year of follow-up, the overall response rate (complete response + partial response) in the TID + group was lower (66.67% vs. 80.89%, p = .022) than in the other. After combined GC and CNI therapy, the complete remission rate in the TID + group was significantly lower than that in the TID − group (13.79% vs. 35.46%, p = .022). The 24-h urine protein level was an independent risk factor for worsening kidney condition (p = .038). Conclusion Patients with IMN with TID have more severe clinical manifestations and pathological damage and lower remission rates. IMN with TID is a risk factor for worsening kidney condition; however, it is not an independent risk factor.

Clinicopathological features and prognosis of idiopathic membranous nephropathy with thyroid dysfunction.

Thyroid dysfunction is common in patients with kidney disease. However, the relationship between thyroid dysfunction and idiopathic membranous nephropathy (IMN) remains unclear. This retrospective study aimed to investigate the clinicopathological characteristics and prognosis of patients with IMN and thyroid dysfunction compared to patients with IMN and without thyroid dysfunction. A total of 1052 patients with IMN diagnosed by renal biopsy were enrolled in this study, including 736 (70%) with normal thyroid function and 316 (30%) with abnormal thyroid function. We analyzed the clinicopathological features and prognostic data between the two groups, using propensity score matching (PSM) to reduce the bias. Logistic regression analysis was performed to investigate the risk factors for IMN combined with thyroid dysfunction. Kaplan-Meier curves and Cox regression analysis were used to evaluate the association between thyroid dysfunction and IMN. Patients with IMN and thyroid dysfunction exhibited more severe clinical features. Female sex, lower albumin level, higher D-dimer level, severe proteinuria, and decreased estimated glomerular filtration rate were predictors of thyroid dysfunction in patients with IMN. After PSM, 282 pairs were successfully matched. Results from the Kaplan-Meier curves indicated that the thyroid dysfunction group had a lower complete remission rate (P = 0.044), higher relapse rate (P < 0.001), and lower renal survival rate (P = 0.004). The multivariate Cox regression analysis revealed that thyroid dysfunction was an independent risk factor for complete remission [hazard ratio (HR) = 0.810, P = 0.045], relapse (HR = 1.721, P = 0.001), and composite endpoint event (HR = 2.113, P = 0.014) in IMN. Thyroid dysfunction is relatively common in patients with IMN, and the clinical indicators are more severe in these patients. Thyroid dysfunction is an independent risk factor for poor prognosis in patients with IMN. More attention should be paid to thyroid function in patients with IMN.

GDF-15 and sST-2 act as biomarkers of disease severity but not independent predictors in idiopathic membranous nephropathy

BackgroundWe aimed to explore biomarkers of disease severity in idiopathic membranous nephropathy (IMN) and independent predictors of prognosis in IMN. MethodsClinical data were collected from 79 IMN patients. Serum levels of growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity (sST-2) were tested by enzyme-linked immunosorbent assay (ELISA) in IMN patients and subgroups, and correlation analysis was performed. Univariate and multiple logistic regression analyses were performed to identify independent predictors of IMN, and a combined-factors model was constructed. Moreover, the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prognostic efficacy. ResultsThe levels of GDF-15 were significantly higher in the IMN group and subgroups with low estimated glomerular filtration rate (eGFR) and high 24 hour-urine protein (24 h-UP), whiles sST-2 level was only significantly higher in the IMN group. GDF-15 levels were positively correlated with creatinine (Crea), cystatin C (Cys-C) and 24 h-UP and negatively correlated with GFR and albumin (Alb), while sST-2 levels were positively correlated with Urea and Cys-C and negatively correlated with eGFR. After one year of follow-up, 54 patients had incomplete remission. Serum phospholipase A2 receptor antibody (PLA2R-Ab), Urea, high-density lipoprotein cholesterol (HDL-C) and 24 h-UP but not GDF-15 and sST2 were independent predictors of prognosis in IMN patients, but combined factors showed the best prognostic efficacy. ConclusionSerum levels of GDF-15 and sST-2 may be potential biomarkers for the severity of IMN, while the combined-factors model is effective for predicting the risk factors of incomplete remission in IMN.

Correlation of Body Mass Index with Clinicopathologic Parameters in Patients with Idiopathic Membranous Nephropathy.

ObjectiveTo investigate the association between body mass index (BMI) and clinicopathologic parameters in patients with idiopathic membranous nephropathy (IMN).MethodsThis study was retrospective and included patients with biopsy-proven IMN from 2018 to 2021 in Hebei General Hospital. Patients were categorized into two groups based on BMI. Clinical and histopathologic data were analyzed at the time of renal biopsy. Pathological data included immunofluorescence staining, glomerulosclerosis (GS, 0–2), mesangial cell proliferation (MCP, 0–1), tubular atrophy (TA, 0–1), interstitial fibrosis (IF, 0–1), vascular wall thickness (VWT, 0–1) and a combination score (GMTIV) graded from 0 to 5.ResultsOur study revealed that the obese group had a higher prevalence of hypertension and diabetes than the overweight/normal weight group (P=0.001, P=0.002). Systolic blood pressure (P=0.005), diastolic blood pressure (P<0.001), haemoglobin (P=0.006), triglycerides (P<0.001), serum uric acid (P=0.05), 24 h urine proteinuria concentration (UP) (P=0.012), MCP (P=0.042), IF (P=0.033), and GMITV (P=0.033) score were higher in obese group compared to the other group, while the high-density lipoprotein-cholesterol (P=0.034) and immunoglobulin A deposition score (P=0.005) were lower. Factors significantly associated with UP were the ratio of lymphocyte count to white blood cell count, serum pre-albumin, immunoglobulin G, microscopic hematuria, anti-phospholipase A2 receptor (anti-PLA2R), C3 deposit on multivariable analysis (adjusted R2=0.343). Binary logistic regression analysis illustrated that MCP was correlated to BMI (OR=2.528, P=0.036). Ordinal logistic regression analysis demonstrated that GMTIV was associated with BMI (OR=1.114, P=0.010) and C3 deposit (OR=1.655, P=0.001).ConclusionHigh BMI was associated with MCP and GMTIV score in IMN patients. Obesity may play an essential role in mesangial lesions of IMN. This study emphasized the relation between BMI and histological parameters under the universal usage of anti-PLA2R antibodies for diagnosis and prognosis in IMN.

Analysis of glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels

Objective To verify glomerular PLA2R antigen and serum PLA2R antibody expression in membranous nephropathy as well as to explore glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy (IMN) in the background of different serum anti-PLA2R levels. Methods We retrospectively analyzed 155 patients who were diagnosed with IMN by kidney biopsy. Patients were divided into six groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum anti-PLA2R titer. Both clinical features and pathological characteristics were recorded, and the remission time was compared among groups. Correlation between clinical figures and the anti-PLA2R titer or semi-quantity of glomerular PLA2R antigen was detected. Results A positive correlation between time to partial remission and serum anti-PLA2R titer was found. Among patients with serum anti-PLA2R titer <150 RU/ml, there were shorter remission time in negative glomerular PLA2R antigen group compared with positive glomerular PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of glomerular PLA2R antigen was found. Conclusion Both glomerular PLA2R antigen and serum anti-PLA2R play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum anti-PLA2R titer is less than 150RU/ml, while serum anti-PLA2R has predominant role in IMN prognosis when serum anti-PLA2R titer is above 150RU/ml.

Clinicopathologic characteristic and prognosis in idiopathic membranous nephropathy patients with focal segmental sclerosis lesion: A retrospective observational study.

To explore the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis lesions (FSL).A total of 70 IMN patients with FSL (FSL+group) were enrolled in this study, and 140 patients were randomly selected by age and sex matching as disease controls (FSL-group). The clinical and renal histopathological data on renal biopsy and clinical data of patients regularly followed were collected. Serum anti-phospholipase A2 receptor (PLA2R) autoantibody, thrombospondin type-1 domain-containing 7A (7A) autoantibody, glomerular PLA2R and 7A expression, and IgG4 deposition were detected. First, the clinical and pathological significance of IMN combined with the FSL group was analyzed. Whether FSL is a risk factor for renal outcomes was further analyzed. 1.Compared with the FSL- group, patients in the FSL+ group had a significantly higher incidence of hypertension and a longer duration of hypertension as well as higher levels of systolic blood pressure, serum creatinine, serum triglycerides, serum cholesterol, 24-hour urinary protein excretion, and lower eGFR and urine osmotic pressure. Patients in the FSL+ group had an increased frequency of Churg stage III and more severe glomerulosclerosis and interstitial fibrosis. The remission rate was significantly lower in the FSL+ group than in the FSL- group (50.0% vs 75.9%, P = .027).2.Multivariate Cox regression analysis showed that FSL (HR = 3.01, 95%CI = 1.07–8.52, P = .038) was an independent risk factor for progression of renal function deterioration, and FSL (HR = 3.25, 95%CI = 1.43–7.38, P = .005) and high levels of serum anti-PLA2R antibody (HR = 1.89, 95%CI = 1.27–2.82, P = .002) were independent risk factors for nonremission of IMN.IMN patients who developed FSL had more severe clinical and pathological characteristics than those without FSL. FSL was an independent risk factor for poorer prognosis. When the appearance of FSL in IMN patients with a high level of serum anti-PLA2R antibody, the treatment needs to be more aggressive to promote remission and to delay the progression of renal function.

SPLA2-IB Level Correlates with Hyperlipidemia and the Prognosis of Idiopathic Membranous Nephropathy.

Recent studies suggested that serum secretory phospholipase A2 group IB (sPLA2-IB) was increased in idiopathic membranous nephropathy (IMN). However, the interference of high lipemia on the sPLA2-IB levels was not taken into account in these studies. The present study aimed to investigate the correlation between sPLA2-IB and lipemia, and the clinical merit of sPLA2-IB in the prediction of prognosis of IMN patients. A total of 64 IMN patients, 39 immunoglobulin A nephropathy (IgAN) patients and 64 healthy controls were included in the study. The levels of serum sPLA2-IB, lipemia and proteinuria were measured. Fifty IMN patients were followed up for 6 months. Pathologic stages were made for all IgAN and IMN patients. The results showed that the levels of serum sPLA2-IB, cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly higher, and the levels of albumin and high-density lipoprotein cholesterol (HDL-C) were significantly lower in IMN patients than in healthy controls and IgAN patients. Serum sPLA2-IB levels were also found to be higher in IgAN patients than in heathy controls, but the association of serum sPLA2-IB levels with proteinuria, cholesterol and albumin was only shown in IMN patients. Antibody against M-type receptor for secretory phospholipase A2 (PLA2R1) was positive in 81.3% IMN patients. Glomerular sPLA2-IB deposition, podocyte fused processes, and density deposition on thickened basement membrane were seen in IMN patients, but not in IgAN patients. IMN patients with lower sPLA2-IB and proteinuria levels were found to have better outcome after the 6-month follow-up. In IMN patients, sPLA2-IB levels were significantly increased in both serum and renal tissue. In conclusion, serum sPLA2-IB was closely correlated with proteinuria, albumin and cholesterol, and IMN patients with lower sPLA2-IB levels were more likely to achieve a better outcome.

Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody.

BackgroundTo discuss the clinicopathological features and prognosis of patients with idiopathic membranous nephropathy (IMN) who are serum-negative for the anti-PLA2R antibody.MethodOverall, 229 IMN patients were retrospectively collected in this study and classified into anti-PLA2R antibody-negative (PLA2R−, 59 cases) and antibody-positive (PLA2R+, 170 cases) groups. The clinical and pathological features of the PLA2R− group were analyzed; 162 patients in both groups were followed up, and the PLA2R antigen was detected in renal biopsies from the PLA2R− group. Kaplan-Meier and survival analyses were used to compare differences in prognosis.ResultsSerum albumin levels were higher and 24-hour urine protein, creatinine, and beta 2-microglobulin (BMG) levels were lower in the PLA2R− group than in the PLA2R+ group; the proportion of acute and chronic tubular lesions was also significantly lower in the PLA2R− group than in in the PLA2R+ group. After treatment, the remission rate was significantly higher in the negative group than in the positive group (93.02% vs 74.78%,), especially the rate of complete remission (51.16% vs 23.47%). Furthermore, the PLA2R antigen-positive staining rate of 43 patients in the PLA2R− group was 62.79%. Although not significant, the survival rate was higher in the PLA2R− group than in the PLA2R+ group. BMG, 24-hour urine protein and acute and chronic tubular lesions were risk factors for kidney death, and 24-hour urine protein was an independent risk factor for kidney death.ConclusionsCompared with the PLA2R+ group, the PLA2R− group had mild clinical manifestations and pathological damage and a higher clinical treatment remission rate. Renal tissue PLA2R antigen testing can be considered for patients with seronegative IMN to increase the diagnostic rate.

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m²), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis

ObjectiveTo investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN).MethodsA literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis.ResultsEighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (− 12.09, − 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate.ConclusionAs compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis

BackgroundThe goal of this study was to investigate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental lesions.MethodsIn our hospital, 305 patients with nephrotic syndrome confirmed as IMN by renal biopsy were divided into a non-focal segmental lesion group (FSGS- group) and a focal segmental glomerulosclerosis (FSGS) group (FSGS+ group) and retrospectively analyzed. In all, 180 patients were followed for periods ranging from 6 months to 2 years. The general clinicopathological data of both groups were compared, and the effects of different treatment schemes on the prognosis of both groups were observed.ResultsThe FSGS+ group had a longer disease course, higher blood pressure levels, and higher serum creatinine and β2-microglobulin levels than did the FSGS- group (all P < 0.05). Pathologically, the FSGS+ group had increased glomerular sclerosis, glomerular mesangial hyperplasia, and acute and chronic tubular lesion rates (all P < 0.05). The remission rate was lower in the FSGS+ group than in the FSGS- group (64.7% vs 82.2%) and, among patients in the FSGS+ group, was lower in patients treated with calmodulin inhibitors than in those treated with cyclophosphamide (P < 0.01). Survival analysis showed that the FSGS+ group had a poor prognosis (χ2 = 4.377, P = 0.036), and risk factor analysis suggested that age at renal biopsy (P = 0.006), 24-h urinary protein quantity (P = 0.01), chronic tubulointerstitial lesions (P = 0.055), and FSGS lesions (P = 0.062) were risk factors for worsening renal condition; furthermore, 24-h urinary protein quantity was an independent risk factor for worsening renal condition.ConclusionsMembranous nephropathy with FSGS is a risk factor, but not an independent risk factor, for IMN. Patients with membranous nephropathy with FSGS often present hypertension and tubule injury. The nonselective drug cyclophosphamide is preferred, and calcineurin inhibitors should be used with caution.

Relationship between the status of phospholipase A2 receptor and prognosis of idiopathic membranous nephropathy.

Serum levels of phospholipase A2 receptor antibody (PLA2R; SAb) and glomerular deposits of PLA2R antigen (GAg) have been detected in patients with idiopathic membranous nephropathy (IMN). However, the correlation between these immunologic factors and their associations with the status and prognosis of IMN remain uncertain. Fifty-one patients with biopsy-proven IMN diagnosed between March of 2015 and December of 2016 were enrolled in this study. All the patients were followed until March of 2017.We used enzyme-linked immunosorbent assay and immunofluorescence to measure the SAb and GAg, respectively. The positive rate of GAg was significantly higher than SAb in patients with IMN (88.24 vs 66.77%, P = 0.017). Compared with SAb- patients, SAb+ patients had a higher baseline proteinuria (6.21 vs 3.40 g/24 h), lower serum albumin (22.49 ± 6.59 vs 29.09 ± 7.40 g/L) and poorer renal function (88.96 ± 21.17 vs 107.25 ± 20.04 mL/min per 1.73 m2 ), as well as a higher renal IgG4 level (P < 0.05). A comparison of SAb+/GAg+ and SAb-/GAg+ tissues yielded similar results (P < 0.01). Regarding prognosis, SAb- patients had a higher rate of complete remission after immunosuppressive treatment than SAb+ patients (P = 0.042). The disease status and prognosis correlated more closely with the SAb than with the GAg in our cohort of patients with IMN. Furthermore, SAb+ patients had more severe clinical symptoms and a worse prognosis, which was probably associated with increased IgG4 deposition.

SUN-022 SERUM GDF15 AS A PROGNOSTIC MARKER OF MEMBRANOUS GLOMERULONEPHRITIS

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzymelinked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16–72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p = 0 007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p = 0 012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p = 0 032). The GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.

Calcineurin B1 subunit in human peripheral blood mononuclear cells and its role in idiopathic membranous nephropathy.

The immune responses involved in the pathogenesis of idiopathic membranous nephropathy (IMN) have not been fully understood. Calcineurin, a key signaling enzyme in T-cell activation, may be implicated in IMN. The present study aimed to investigate the role of calcineurin B1 subunit (CnB1) in IMN and the potential mechanism.A total of 59 biopsy-proven IMN patients and 28 healthy controls were recruited. The CnB1 expression in human peripheral blood mononuclear cells (PBMCs) was assessed by Western blotting. Knockdown and overexpression of CnB1 in Jurkat T cell line were achieved by small interference RNA (siRNA) transfection and lentiviral transduction, respectively.It was found that PBMCs CnB1 expression was significantly increased in IMN patients (P = .002), but unrelated to the severity and prognosis of IMN. Knockdown of CnB1 in Jurkat cells inhibited the nuclear factor of activated T cells (NFAT)-regulated gene expression required for T-cell activation.Our study suggested the potential role of CnB1 in the occurrence of IMN. The mechanism maybe involved the effect of CnB1 on the T-cell activation mediated by calcineurin-NFAT signaling.

Clinical characteristics and prognosis of idiopathic membranous nephropathy in adolescent

Objective Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults, but it is relatively rare in adolescent. The aim of this study was to elucidate the clinical features and prognosis of IMN in adolescent. Methods All patients were admitted to our hospital from January 2005 to December 2014 with biopsy proven IMN, and at least 12 months follow-up in this retrospective study. Adult patients with IMN were served as the controls, and their clinical manifestations, laboratory tests and prognosis were collected. Results ①The renal function of IMN in adolescent were normal at onset, they had lower serum albumin (P=0.0235) and serum IgG levels (P<0.0001) compared with adult IMN, but the peripheral blood CD4 and CD20 count were significantly increased (P=0.0256, P<0.0001), also there were no difference of 24 h urinary protein, renal tubular injury index and hematuria. ②The positive rate of PLA2R antibody in adolescent was 58.82% (40/68), which was similar to adults (P=0.857). ③Adolescent IMN were followed up 12~130 months (median 40 months), the total efficiency (complete and partial remission rate) was 88.89%(80/90), and the renal survival rate was 98.8% , 97.0% and 87.3% at 2, 3 and 6 years after renal biopsy. ④Multivariate Cox regression analysis showed that hypertension, urinary RBP, and renal creatinine were the independent risk factors for double creatinine. Conclusions The positive rate of PLA2R antibody in adolescent IMN is similar to that of adult IMN, and its treatment response and prognosis are similar to adult IMN. Key words: Glomerulonephritis, Membranous; Adolescent; Prognosis

Application of miR-193a/WT1/PODXL axis to estimate risk and prognosis of idiopathic membranous nephropathy

Background: This investigation was managed to explore whether miR-193a in combination with two podocytes, namely, Wilms tumor type 1 (WT1) and podocalyxin (PODXL), were feasible in estimating onset and prognosis of idiopathic membranous nephropathy (IMN).Methods: We recruited a total of 189 healthy controls and 364 IMN patients, whose urine samples were prepared to measure the expression of miR-193a and PODXL. Meanwhile, renal tissues collected from above-mentioned IMN patients (n = 364) and renal cell carcinoma patients (n = 189) were arranged to determine the expression of WT1. Ultimately, receiver operating characteristic curves were constructed to appraise the performance of miR-193a, WT1, and PODXL in predicting renal survival of IMN patients.Results: The IMN patients were measured with up-regulated miR-193a expression and down-regulated WT1/PODXL expression, when compared with healthy controls (p < 0.05). Moreover, highly expressed miR-193a, lowly expressed WT1/PODXL, elevated amounts of proteinuria (>3.79 g/24 h)/serum creatinine (>174.63 μmol/L), and declined GFR (≤68.13 mL/min/1.73 m2) were implicated as prominent biomarkers for the poor renal survival of IMN patients (all p < 0.05). Notably, miR-193a combined with PODXL and WT1 generated optimal effects in differentiating IMN patients from healthy controls (AUC = 0.994) and also in anticipating the renal survival state of IMN patients (AUC = 0.824), when compared with strategies that merely employed ≤2 of the biomarkers.Conclusion: The combination of miR-193a, WT1, and PODXL might serve as a favorable strategy for expecting IMN prognosis.

Baseline proteinuria level is associated with prognosis in idiopathic membranous nephropathy

Objectives: This study aimed to investigate the unique prognostic, clinical, and renal histopathological characteristics of patients with idiopathic membranous nephropathy (IMN) with different levels of proteinuria.Methods: This retrospective observational study included 190 IMN patients with low levels of proteinuria (low group), 193 IMN patients with medium levels of proteinuria (medium group), and 123 IMN patients with high levels of proteinuria (high group) treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared among the three groups. Poor prognostic events included the occurrence of a persistent 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or all-cause mortality.Results: The severity of clinical symptoms and laboratory indices, such as blood pressure; extent of edema and hematuria; levels of fibrinogen, immunoglobulin (Ig)-G, complement (C)-4, total protein, albumin (ALB), and serum creatinine (SCr); and eGFR increased with increasing proteinuria (all p< .001). Based on renal histopathology, the extent of segmental sclerosis and balloon adhesion and renal interstitial lesion stage also increased in severity with increasing proteinuria (all p< .001). The Kaplan–Meier analysis showed that compared with patients with low and medium levels of proteinuria, patients with high levels of proteinuria had significantly lower cumulative poor event-free renal survival rates (p= .0039).Conclusions: Baseline proteinuria level is indicative of prognosis in IMN patients; the greater the extent of proteinuria is, the worse the prognosis.

Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (<3.5 g/day), however, has not been well described.Methods: This multicenter, retrospective cohort study included 171 patients with IMN from 10 nephrology centers in Japan. The relationship between urinary protein over time and a decrease of 30% in estimated glomerular filtration rate (eGFR) was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors.Results: During the observation period (median, 37 months; interquartile range, 16–71 months), 37 (21.6%) patients developed a 30% decline in eGFR, and 2 (1.2%) progressed to end-stage renal disease. Time-dependent multivariate Cox regression models revealed that lower proteinuria over time were significantly associated with a lower risk for a decrease of 30% in eGFR (primary outcome), adjusted for clinically relevant factors. Complete remission (adjusted hazard ratio [HR], 0.005 [95%CI, 0.0–0.09], p < .001), incomplete remission with <1.0 g/day of urine protein (ICR I) (adjusted HR, 0.01 [95%CI, 0.001–0.20], p = .002), and 1.0 to 3.5 g/day (ICR II) (adjusted HR, 0.12 [95%CI, 0.02–0.64], p = .013) were significantly associated with avoiding a 30% decrease in eGFR, compared to that at no remission.Conclusions: Attaining lower proteinuria predicts good renal survival in Japanese patients with IMN. This study quantifies the impact of proteinuria reduction in IMN and the clinical relevance of achieving subnephrotic proteinuria in IMN as a valuable prognostic indicator for both the clinician and patient.

Clinical and Histological Features of Phospholipase A2 Receptor-Associated and Thrombospondin Type-I Domain-containing 7A-Associated Idiopathic Membranous Nephropathy: A Single Center Retrospective Study from China

BackgroundM-type phospholipase A2 receptor (PLA2R) was identified as the major target antigen in idiopathic membranous nephropathy (IMN). Another target antigen, namely thrombospondin type-1 domain-containing 7A (THSD7A), was recently detected in approximately 10% of non-PLA2R-associated IMN. In this single center retrospective study, clinical and histological features of PLA2R-associated and THSD7A-associated IMN patients were evaluated.Material/MethodsA total of 192 IMN patients, who were receiving no glucocorticoids or immunosuppressant before renal biopsy, were enrolled in this study and followed for a median duration of 25.5 months. IMN with enhanced glomerular PLA2R and THSD7A staining by immunohistochemistry (IHC) were designated as PLA2R-associated IMN and THSD7A-associated IMN respectively. Serum anti-PLA2R and anti-THSD7A antibodies levels were assessed by enzyme linked immunosorbent assay and indirect immunofluorescence testing in PLA2R-associated and THSD7A-associated IMN.ResultsOf 192 IMN patients, 164 patients (85.4%) had PLA2R-associated IMN and 3 patients (1.6%) had THSD7A-associated IMN. Compared with non-PLA2R-associated IMN patients, the 24-hour urinary protein levels were significantly higher (P=0.008), whereas, the proteinuria remission rates were significantly lower (P=0.03) in PLA2R-associated IMN patients. No pathological differences were found between PLA2R-associated IMN and non-PLA2R-associated IMN. Among 3 THSD7A-associated IMN patients, 1 patient had elevated serum anti-THSD7A antibody levels, which was below detectable levels after achieving partial proteinuria remission with combined glucocorticoid and cyclosporine treatment.ConclusionsCompared with non-PLA2R-associated IMN patients in our cohort, PLA2R-associated IMN patients presented with more severe proteinuria and lower remission rates after treatment, with no distinct histological differences. Glomerular expression of PLA2R could be a useful marker to indicate the severity, treatment response, and prognosis of IMN.