Adult ; Female ; Gene Expression ; Glomerulonephritis, Membranous ; etiology ; genetics ; pathology ; Hepatitis B ; complications ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Mutation ; Receptors, Phospholipase A2 ; genetics ; metabolism ; Trans-Activators ; genetics ; metabolism ; Viral Regulatory and Accessory Proteins ; genetics ; metabolism

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. METHODS: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model. RESULTS: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P < 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of I, II, III, IV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 ± 5.95 vs. 6.06 ± 3.63, 5.92 ± 2.97, 5.41 ± 1.73, and 8.41 ± 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 ± 162.21 vs. 80.42 ± 24.75, 103.79 ± 72.72, 96.41 ± 33.79, and 163.04 ± 47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 ± 7.56, 67.16 ± 6.94, 63.22 ± 8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB) (2.34 ± 1.23, 2.58 ± 1.40, 1.91 ± 0.97, and 1.81 ± 1.44 vs. 0.74 ± 0.57 μmol/L, respectively), and IgA (310.35 ± 103.78, 318.48 ± 107.54, 292.58 ± 81.85, and 323.29 ± 181.67 vs. 227.17 ± 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05). CONCLUSIONS The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.
Adult ; Biomarkers ; blood ; Blood Urea Nitrogen ; Cholesterol ; blood ; Creatinine ; blood ; Female ; Fibrinogen ; metabolism ; Glomerulonephritis, IGA ; blood ; diagnosis ; pathology ; Humans ; Immunoglobulin A ; blood ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve

Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Male ; Renal Insufficiency, Chronic ; metabolism ; pathology

BACKGROUNDAccording to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.

METHODSA total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.

RESULTSOf the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month.

CONCLUSIONSThere were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Adult ; Autoantibodies ; metabolism ; Female ; Glomerulonephritis, Membranous ; drug therapy ; metabolism ; pathology ; urine ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Phospholipase A2 ; metabolism ; Retrospective Studies

OBJECTIVETo investigate the prevalence of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy (IMN) and explore the relationship between PLA2R1 and IMN.

METHODSA total of 108 adult patients with biopsy-proved glomerular diseases were enrolled in this study, including 41 with IMN, 2 with hepatitis B-associated membranous nephropathy, 8 with V lupus nephritis, 27 with IgA nephropathy, 19 with minimal change nephropathy, 5 with mild mesangial proliferative glomerulonephritis, and 6 with focal segmental glomeruloselerosis (FSGS). Indirect immunofluorescence assay was used to detect PLA2R1 in the biopsy specimens and the clinical variables of the IMN patients were analyzed.

RESULTSIn 35 of the 41 (85.37%) patients with IMN, PLA2R1 was detected with a fine granular pattern in the subepithelial deposits along the glomerular capillary loops. PLA2R1 antigen was not detected in patients with other glomerulopathies. No significant differences were found in age, serum creatinine, serum albumin, or 24-h urinary protein level between PLA2R1-positive and negative patients with IMN (P>0.05).

CONCLUSIONAccording to our results, 85.37% of adult patients with biopsy-proven IMN are positive for PLA2R1 antigen, which, however, does not contribute to variations of the patients' clinical manifestations.

Adult ; Biopsy ; Glomerulonephritis, Membranous ; metabolism ; Humans ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; pathology ; Nephrosis, Lipoid ; metabolism ; Receptors, Phospholipase A2 ; metabolism

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.
Acute-Phase Proteins/*urine ; Adult ; Biomarkers/blood/urine ; Biopsy ; Chi-Square Distribution ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology/*urine ; Humans ; Kaplan-Meier Estimate ; Kidney/*metabolism/pathology/physiopathology ; Lipocalins/*blood/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood/*urine ; Retrospective Studies ; Risk Factors ; Young Adult

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Biopsy ; Chi-Square Distribution ; Creatinine/blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology ; Humans ; Kidney/*metabolism/pathology/physiopathology ; Linear Models ; Lipocalins/*blood ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood ; Renal Insufficiency, Chronic/blood/etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Young Adult

OBJECTIVETo investigate the clinical significance of transforming growth factor-beta 1 (TGF-β1) in children with primary IgA nephropathy (IgAN).

METHODSThirty children who were diagnosed with primary IgAN by renal biopsy between May 2008 and October 2012 were included in the study. Thirty healthy children were used as the control group. Urinary and blood TGF-β1 levels were measured using enzyme-linked immunosorbent assay, and the protein expression of TGF-β1 in the renal tissue was measured by immunohistochemistry. The correlation between TGF-β1 levels in blood, urine, and renal tissue and their relationship with clinical indices were analyzed.

RESULTSChildren with primary IgAN had significantly higher urinary and blood TGF-β1 levels than the control group (P<0.01). Urinary TGF-β1 level was positively correlated with the pathological grade of renal tissue (r=0.557, P=0.001), and a significant positive correlation was also found between the TGF-β1 expression in the renal tissue and the pathological grade of renal tissue (r=0.682, P<0.01). There was no correlation between TGF-β1 levels in blood and renal tissue (r=0.038, P=0.844).

CONCLUSIONSUrinary TGF-β1 level is significantly positively correlated with the pathological severity of disease in children with primary IgAN. Clinical measurement of urinary TGF-β1 may be of great practical value in predicting the progression and prognosis of chronic nephropathy.

Adolescent ; Child ; Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Kidney ; chemistry ; pathology ; Male ; Transforming Growth Factor beta1 ; analysis ; physiology ; urine

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.
Adult ; Cyclophosphamide/therapeutic use ; Female ; Glomerulonephritis/drug therapy/*metabolism/pathology ; Humans ; Immunosuppressive Agents/therapeutic use ; Interleukin 1 Receptor Antagonist Protein/*analysis/blood/urine ; Lymphocyte Activation ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Receptors, Tumor Necrosis Factor, Type I/*analysis/blood/urine ; Receptors, Tumor Necrosis Factor, Type II/*analysis/blood/urine ; Steroids/therapeutic use ; T-Lymphocytes/immunology/metabolism

Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important role in glomerulonephritis (GN). The study assed the influence of immunosuppressive treatment on serum and urine sFas in patients with proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential of sFas measurements in predicting outcomes. Eighty-four patients with GN (45 males and 39 females) were included. Serum concentration (ng/mL) and urinary excretion (ng/mg of urinary creatinine) of sFas were measured before and after the treatment. After 12 months of therapy with steroids and cyclophosphamide, patients were divided into two subgroups according to the treatment results: Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008 and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas serum concentration remained unchanged. In PGN, pre-treatment urinary sFas concentration was significantly lower in the Responders than in Non-Responders (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment reduced sFas urinary excretion in proliferative and non-proliferative GN and results suggest that the lower urinary sFas may be linked with favorable therapy outcomes in patients with PGN.
Adult ; Antigens, CD95/blood/*urine ; Cyclophosphamide/therapeutic use ; Female ; Glomerulonephritis/*drug therapy/metabolism/pathology ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Middle Aged ; Steroids/therapeutic use ; Treatment Outcome