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

BACKGROUNDIn vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.

METHODSBovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.

RESULTSCompared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).

CONCLUSIONSOur study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

Animals ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA ; drug therapy ; genetics ; metabolism ; Interleukin-1beta ; genetics ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Inbred Lew ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; genetics ; Thiazolidinediones ; therapeutic use ; Toll-Like Receptor 4 ; genetics ; metabolism

Azathioprine is commonly used as immunosuppressive therapy for various inflammatory diseases including chronic glomerulonephritis. Myelosuppression is a common side effect of azathioprine, resulting in the need for dose reduction. However, severe pancytopenia or alopecia is not often encountered. Here, we report a case of severe myelosuppression, and alopecia totalis that occurred after azathioprine treatment in a patient with IgA nephropathy. A 10-year-old boy with IgA nephropathy was treated with oral deflazacort and later with azathioprine. After 4 weeks, the patient complained of hair loss, and despite a dose reduction in azathioprine, he developed bone marrow suppression and alopecia totalis in two weeks. The blood indices and alopecia of the patient had returned to normal after azathioprine withdrawal and 3 consecutive doses of granulocyte colony-stimulating factor. We suggest that physicians remain vigilant to the side effects of azathioprine. Unusual hair loss after azathioprine treatment might suggest a defect in the metabolism of the drug, warranting the discontinuation of azathioprine to prevent more severe side effects.
Alopecia* ; Azathioprine* ; Bone Marrow ; Child ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Granulocyte Colony-Stimulating Factor ; Hair ; Humans ; Immunoglobulin A* ; Male ; Metabolism ; Pancytopenia

No abstract available.
Acute-Phase Proteins/*urine ; Female ; Glomerulonephritis, IGA/*blood/*urine ; Humans ; Kidney/*metabolism ; Lipocalins/*blood/*urine ; Male ; Proto-Oncogene Proteins/*blood/*urine

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

Azacitidine ; pharmacology ; Base Sequence ; Chromosomes, Human, X ; genetics ; DNA Methylation ; drug effects ; DNA Mutational Analysis ; Galactosyltransferases ; metabolism ; Gene Expression Regulation ; drug effects ; Glomerulonephritis, IGA ; etiology ; genetics ; metabolism ; Glycosylation ; Humans ; Immunoglobulin A ; metabolism ; Lipopolysaccharides ; pharmacology ; Lymphocytes ; metabolism ; Molecular Chaperones ; genetics ; metabolism ; Mutation ; Polymorphism, Single Nucleotide

PURPOSE: Behcet's disease (BD) theoretically affects all sizes and types of blood vessels and results in multi-organ involvement. However, renal BD has not been fully characterized, though the kidneys are histologically rich in blood vessels. MATERIALS AND METHODS: A total of 2007 patients who fulfilled the diagnostic criteria for BD were enrolled in this study. We reviewed the medical records and test results of the BD patients and used univariate and multivariate logistic regression analyses to determine the clinical significance of renal involvement in BD. RESULTS: Among the 2007 BD patients, we noted hematuria in 412 (20.5%) and proteinuria in 29 (1.4%). Univariate analysis showed that the BD patients with hematuria were predominantly female and older, had higher erythrocyte sedimentation rates (ESRs), and more frequently presented with genital ulcerations. BD patients with proteinuria had higher ESR levels compared to BD patients without proteinuria. In the multivariate analysis, age, sex, and ESR were found to be significantly associated with hematuria in BD patients, whereas only ESR was associated with proteinuria in BD patients. We also found that IgA nephropathy was the most common pathologic diagnosis in 12 renal BD patients who underwent renal biopsies. CONCLUSION: We suggest that routine urinalysis and serum renal function tests be performed for the early detection of renal BD, especially in older female BD patients with recurrent hematuria, high ESR levels, and frequent genital ulcers, as well as in BD patients with proteinuria and high ESR levels.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Behcet Syndrome/*complications/epidemiology/*metabolism ; Biopsy ; Female ; Glomerulonephritis, IGA/complications/diagnosis ; Hematuria/complications/diagnosis ; Humans ; Kidney/*pathology ; Kidney Diseases/*diagnosis ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Proteinuria/complications/diagnosis ; Republic of Korea ; Young Adult