Association between urinary VEGFA and renal pathology of IgA nephropathy patients.
Ontology highlight
ABSTRACT: Background
Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes.Methods
Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated.Results
Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders.Conclusions
Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.
SUBMITTER: Feng S
PROVIDER: S-EPMC8551689 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. This study aimed to determine the effect of serum hemoglobin on the progression of IgA nephropathy. We retrospectively analyzed 4326 patients with biopsy-proven IgA nephropathy. We evaluated the effect of serum hemoglobin on IgA nephropathy progression using Kaplan-Meier survival analyses, the log-rank test, and the Cox proportional hazards model. The primary end-point was progression of IgA nephropathy, defined as dialysis initiation or kidney transplantation. Serum hemoglobin showed a nonlinear relationship with the progression of IgA nephropathy. The Cox proportional hazards model showed that the risk of progression of IgA nephropathy decreased 0.87 times for every 1.0 g/dL increase in serum hemoglobin. In subgroup analyses, reduced serum hemoglobin was an independent risk factor for IgA nephropathy progression only in women. There was no statistically significant interaction of serum hemoglobin between men and women (Pinteraction = 0.177). Results of Sensitivity analysis were robust and consistent. Serum hemoglobin at diagnosis was an independent predictor for IgA nephropathy progression.
| S-EPMC7835832 | biostudies-literature
Project description:IntroductionIgA nephropathy (IgAN) is the commonest global cause of glomerulonephritis. Extent of fibrosis, tubular atrophy and glomerulosclerosis predict renal function decline. Extent of renal fibrosis is assessed with renal biopsy which is invasive and prone to sampling error. We assessed the utility of non-contrast native T1 mapping of the kidney in patients with IgAN for assessment of renal fibrosis.MethodsRenal native T1 mapping was undertaken in 20 patients with IgAN and 10 healthy subjects. Ten IgAN patients had a second scan to assess test-retest reproducibility of the technique. Native T1 times were compared to markers of disease severity including degree of fibrosis, eGFR, rate of eGFR decline and proteinuria.ResultsAll patients tolerated the MRI scan and analysable quality T1 maps were acquired in at least one kidney in all subjects. Cortical T1 times were significantly longer in patients with IgAN than healthy subjects (1540 ms ± 110 ms versus 1446 ± 88 ms, p = 0.038). There was excellent test-retest reproducibility of the technique, with Coefficient-of-variability of axial and coronal T1 mapping analysis being 2.9 and 3.7% respectively. T1 correlated with eGFR and proteinuria (r = - 0.444, p = 0.016; r = 0.533, p = 0.003 respectively). Patients with an eGFR decline > 2 ml/min/year had increased T1 times compared to those with a decline < 2 ml/min/year (1615 ± 135 ms versus 1516 ± 87 ms, p = 0.068), and T1 time was also higher in patients with a histological 'T'-score of > 0, compared to those with a 'T'-score of 0 (1575 ± 106 ms versus 1496 ± 105 ms, p = 0.131), though not to significance.ConclusionsCortical native T1 time is significantly increased in patients with IgAN compared to healthy subjects and correlates with markers of renal disease. Reproducibility of renal T1 mapping is excellent. This study highlights the potential utility of native T1 mapping in IgAN and other progressive nephropathies, and larger prospective studies are warranted.
| S-EPMC6621982 | biostudies-literature
Project description:BackgroundThe objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN).MethodsA total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed.ResultsCompared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P < 0.001) was lower in IgAN group. The pathological results revealed that patients with IgAN have a greater degree of chronic kidney injury compared to patients with IgAVN. In addition, the levels of plasma D-Dimers (1415.92 ± 1774.69 vs. 496.78 ± 711.91 ng/mL, P < 0.001) and fibrinogen degradation products (FDP) (3.92 ± 4.73 vs. 1.63 ± 2.46 µg/mL, P = 0.001) were significantly higher in IgAVN patients than in IgAN patients. The deposition of fibrinogen in the renal tissues was more severe and the cumulative partial remission rate was higher in patients with IgAVN as compared to those with IgAN (P = 0.001).ConclusionsIn comparison, IgAN patients had poorer renal function, whereas IgAVN patients had more severe coagulation abnormalities. These findings provide a basis for the differentiation of the two diseases at an early stage.
| S-EPMC10811929 | biostudies-literature
Project description:BackgroundStudies have shown that the occurrence and development of IgA nephropathy (IgAN) are genetically susceptible, but the relationship between vitamin D receptor (VDR) gene polymorphisms and renal function in IgAN patients is unclear.MethodsWe investigated the relationship between VDR FokI (rs2228570) single nucleotide polymorphism (SNP) and renal function and related clinicopathologic parameters in IgAN patients. Clinical and pathological data of 282 IgAN patients treated at the First Affiliated Hospital of Guangxi Medical University were collected, and FokI genotypes were determined by PCR and direct sequencing. Patients were divided into the renal dysfunction group and normal renal function (control) group by estimated glomerular filtration rate (eGFR) and serum creatinine level.ResultsFrequencies of TT genotype and T allele in the renal dysfunction group were higher than those of the control group. Blood urea nitrogen, serum phosphorus (P), proportions of mesangial cell proliferation, interstitial fibrosis/tubular atrophy and crescents in T allele carriers were higher than those in non-T allele carriers, while eGFR and 25-Hydroxyvitamin D3 were lower in T allele carriers than non-T allele carriers. Multiple linear regression analysis showed that eGFR was affected by FokI genotypes in IgAN patients. Logistics regression analysis showed that middle and elderly age, elevated P, intact parathyroid hormone and TT genotype were independent risk factors for renal dysfunction in IgAN patients; the odds ratio of carrying the TT genotype was as high as 84.77 (P < 0.05 for all).ConclusionsIgA nephropathy patients carrying the VDR FokI TT genotype have an increased risk of renal dysfunction. VDR FokI SNP is closely related to renal function, calcium-phosphate metabolism, and related pathological damage in IgAN patients.
| S-EPMC6563792 | biostudies-literature
Project description:Backgroundα-1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients.MethodsSerum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed.ResultsRelative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p < .05). Among IgAN patients, there was a positive correlation of serum FUT8 activity with renal FUT8 protein expression (p < .05). Multivariable logistic regression analyses showed that serum FUT8 activity was significantly associated with serum creatinine and eGFR (p < .05). Based on a cut-off value determined from ROC curve analysis, we divided IgAN patients into a low serum FUT8 activity group (≤12.2 pmol/h/mL, n = 40) and a high serum FUT8 activity group (>12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p < .05).ConclusionSerum FUT8 activity was positive association with renal tubulointerstitial injury in IgAN patients.
| S-EPMC9425009 | biostudies-literature
Project description:We demonstrated previously that the blood pressure of patients with IgA nephropathy becomes salt sensitive as renal damage progresses. We also showed that increased urinary angiotensinogen levels in such patients closely correlate with augmented renal tissue angiotensinogen gene expression and angiotensin II levels. Here, we investigated the relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy. Forty-one patients with IgA nephropathy consumed an ordinary salt diet (12 g/d of NaCl) for 1 week and a low-salt diet (5 g/d of NaCl) for 1 week in random order. The salt-sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linking 2 data points obtained during consumption of each diet. The urinary angiotensinogen:creatinine ratio was significantly higher in patients who consumed the ordinary salt diet compared with the low-salt diet (17.5 ?g/g [range: 7.3 to 35.6 ?g/g] versus 7.9 ?g/g [range: 3.1 to 14.2 ?g/g] of creatinine, respectively; P<0.001). The sodium sensitivity index in our patients positively correlated with the glomerulosclerosis score (r=0.43; P=0.008) and changes in logarithmic urinary angiotensinogen:creatinine ratio (r=0.37; P=0.017) but not with changes in urinary protein excretion (r=0.18; P=0.49). In contrast, changes in sodium intake did not alter the urinary angiotensinogen:creatinine ratio in patients with Ménière disease and normal renal function (n=9). These data suggest that the inappropriate augmentation of intrarenal angiotensinogen induced by salt and associated renal damage contribute to the development of salt-sensitive hypertension in patients with IgA nephropathy.
| S-EPMC3161117 | biostudies-literature
Project description:Both IgA nephropathy (IgAN) and lupus nephritis (LN) are immunity-related diseases with a complex, polygenic, and pleiotropic genetic architecture. However, the mechanism by which the genetic variants impart immunity or renal dysfunction remains to be clarified. In this study, using gene expression datasets as a quantitative readout of peripheral blood mononuclear cell (PBMC)- and kidney-based molecular phenotypes, we analyzed the similarities and differences in the patterns of gene expression perturbations associated with the systematic and kidney immunity in IgAN and LN. Original gene expression datasets for PBMC, glomerulus, and tubule from IgAN and systemic lupus erythematosus (SLE) patients as well as corresponding controls were obtained from the Gene Expression Omnibus (GEO) database. The similarities and differences in the expression patterns were detected according to gene differential expression. Weighted gene co-expression network analysis (WGCNA) was used to cluster and screen the co-expressed gene modules. The disease correlations were then identified by cell-specific and functional enrichment analyses. By combining these results with the genotype data, we identified the differentially expressed genes causatively associated with the disease. There was a significant positive correlation with the kidney expression profile, but no significant correlation with PBMC. Three co-expression gene modules were screened by WGCNA and enrichment analysis. Among them, blue module was enriched for glomerulus and podocyte (P < 0.05) and positively correlated with both diseases (P < 0.05), mainly via immune regulatory pathways. Pink module and purple module were enriched for tubular epithelium and correlated with both diseases (P < 0.05) through predominant cell death and extracellular vesicle pathways, respectively. In genome-wide association study (GWAS) enrichment analysis, blue module was identified as the high-risk gene module that distinguishes LN from SLE and contains PSMB8 and PSMB9, the susceptibility genes for IgAN. In conclusion, IgAN and LN showed different systematic immunity but similarly abnormal immunity in kidney. Immunological pathways may be involved in the glomerulopathy and cell death together with the extracellular vesicle pathway, which may be involved in the tubular injury in both diseases. Blue module may cover the causal susceptibility gene for IgAN and LN.
| S-EPMC8039522 | biostudies-literature
Project description:Background and objectivesPodocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN).Design, setting, participants, & measurementsUrine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA.ResultsHistologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P<0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22) (0.49 [interquartile range (IQR), 0.20-0.88] g/g creatinine versus 0.20 [IQR, 0.10-0.33] g/g creatinine; P<0.01). The number of urinary podocytes in patients with segmental sclerosis was higher than in patients without (1.05 [IQR, 0.41-1.67] per mg creatinine versus 0.28 [IQR, 0.10-0.66] per mg creatinine; P<0.01).ConclusionsLevels of u-PCX and the number of urinary podocytes are associated with histologic abnormalities in adults with IgAN.
| S-EPMC3430952 | biostudies-literature
Project description:BackgroundFor IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis.MethodsThe study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells.ResultsmiRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis.ConclusionUrinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.
| S-EPMC10902439 | biostudies-literature
Project description:Background and objectivesMegalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN).Design, setting, participants, & measurementsUrine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years) and 5 patients with membranous nephropathy (MN). Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA.ResultsHistological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR = 1.76, 95% CI: 1.04-3.27, P<0.05). There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (β = 0.33, P = 0.008). The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05). The levels of urinary C-megalin were significantly higher in MN patients compared to the control group.ConclusionsThe levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is an independent predictor of disease progression of IgAN. In addition, our results suggest that urinary C-megalin is a marker of glomerular abnormalities in various glomerular diseases as well as IgAN.
| S-EPMC4264761 | biostudies-literature