scholarly journals Clinical Relevance of Serum Galactose Deficient IgA1 in Patients with IgA Nephropathy

2020 ◽  
Vol 9 (11) ◽  
pp. 3549
Author(s):  
Jin Sug Kim ◽  
Hyeon Seok Hwang ◽  
Sang Ho Lee ◽  
Yang Gyun Kim ◽  
Ju-Young Moon ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Clinical Relevance ◽  
Interstitial Fibrosis ◽  
Healthy Controls ◽  
Ckd Progression ◽  
Serum Samples ◽  
Tubular Atrophy ◽  
Appropriate Treatment ◽  
Cox Proportional Hazard Models ◽  
New Biomarkers

New biomarkers of IgA nephropathy (IgAN) are needed for non-invasive diagnosis and appropriate treatment. There is emerging evidence that galactose deficient IgA1 (Gd-IgA1) is a pivotal molecule in the pathogenesis of IgAN. However, few studies have investigated the role of Gd-IgA1 as a biomarker in IgAN. In this study, we investigated the clinical relevance of serum Gd-IgA1 levels in patients with IgAN. Two hundred and thirty biopsy-proven IgAN patients, 74 disease controls (patients with non-IgAN nephropathy), and 15 healthy controls were enrolled in this study. Levels of serum Gd-IgA1 were measured using an ELISA kit in serum samples obtained the day of renal biopsy. We compared levels of serum Gd-IgA1 according to the type of glomerular disease and analyzed the association between Gd-IgA1 levels and clinical and pathological parameters in patients with IgAN. We then divided IgAN patients into two groups according to Gd-IgA1 level and investigated the predictive value of Gd-IgA1 for progression of chronic kidney disease (CKD). Serum Gd-IgA1 levels were significantly higher in IgAN patients than disease controls and healthy controls. In patients with IgAN, serum Gd-IA1 levels were significantly correlated with estimated glomerular filtration rate, serum IgA level, and tubular atrophy/interstitial fibrosis. CKD progression was more frequent in IgAN patients with higher serum Gd-IgA1 levels than in those with lower serum Gd-IgA1 levels. Cox proportional hazard models showed that high GdIgA1 level was an independent risk factor for CKD progression after adjusting for several confounders. Our results suggest that serum Gd-IgA1 level is a useful diagnostic and prognostic marker in IgAN patients. Further studies with a larger sample size and longer follow-up duration are needed.

scholarly journals miR-148b Differentiates Tubular Atrophy/Interstitial Fibrosis Histopathological Stages in IgA Nephropathy

2020 ◽  
Author(s):  
Santosh Kumar ◽  
Priscilla C ◽  
Sreejith Parameswaran ◽  
Deepak Shewade ◽  
Pragasam Viswanathan ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Histopathological Examination ◽  
Complement C3 ◽  
Receiver Operating Curve ◽  
Transcriptional Level ◽  
Healthy Controls ◽  
Tubular Atrophy ◽  
Receiver Operating

IgA nephropathy (IgAN) is one of the most common forms of glomerular disease. It is diagnosed by the dominant or co-dominant IgA deposition in the mesangial region by histopathological examination of kidney biopsy. Kidney biopsy has its own complication and not performed frequently. microRNA (miRNA) is a small RNA, which plays an important role at the post transcriptional level by downregulating mRNAs. We have tried to establish a miRNA based biomarker for IgAN. We quantified miR-148b and let-7b from plasma in IgAN patients and healthy controls. Logistic regression models and receiver operating curve analysis used to analyze the miRNAs quantity and Oxford MEST-C scoring parameters (M- Mesangial hypercellularity, E- Endocapillary hypercellularity, S- Segmental glomerulosclerosis, T- Tubular atrophy/Interstitial fibrosis, C- Crescents). miR-148b and let-7b levels in IgAN were found to be higher by 2.9 and 5.48 times than the healthy controls, respectively. let-7b was positively correlated with complement C3 levels. Similarly, miR-148b was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with S, T, and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of miR-148b concentration was found to be 8479 to differentiate the severe condition of IgAN. Furthermore, the decrease in miR-148b concentration at a threshold point indicated the progression of the severity of the IgAN. It can also be used to predict the IgAN at an earlier stage.

scholarly journals Is mycophenolate mofetil combined with low-dose prednisone a treatment option for advanced IgA nephropathy? A 10-year follow-up case and brief literature review

2018 ◽  
Vol 16 ◽  
pp. 205873921880268
Author(s):  
Qijun Wan ◽  
Yongcheng He ◽  
Hongtao Chen ◽  
Hongping Liu ◽  
Saodong Luan ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Iga Nephropathy ◽  
Treatment Option ◽  
Low Dose ◽  
Interstitial Fibrosis ◽  
Immunosuppressive Treatment ◽  
Channel Blockers ◽  
Tubular Atrophy ◽  
Dose Prednisone

IgA nephropathy (IgAN) is now widely recognized as the most common primary glomerulonephritis worldwide, especially in China. The immunosuppressive treatment option for IgAN is still controversial. Previously, we proved that mycophenolate mofetil (MMF; Shanghai Roche, China) combined with low-dose prednisone was an effective and safe option for biopsy-proven mild to moderate IgAN patients in a short term of follow-up. This article we first reported the safety and efficacy of this regimen in a 42-year-old male biopsy-proven advanced 10-year follow-up IgAN case (Lee’s Class V; the patient was biopsied 10 years ago, so the Oxford Mesangial hypercellularity Endocapillary hypercellularity Segmental glomerulosclerosis Tubular atrophy/interstitial fibrosis (MEST) classification was not used). The mycophenolate and prednisone were only given for a limited time. The other main medications included calcium channel blockers and antiplatelet agents. Clinical and laboratory indexes were aperiodic assessed during the 10-year follow-up. The serum creatinine decreased from 356 to around 210 μmol/L and urine excretion protein reduced from 3.4 g/d to about 0.5 g/d after 6 months of the initiation of this regimen, respectively. These perfect treatment effects could maintain well during the whole follow-up period. No obvious complications were observed.

Polyclonal free light chains in IgA-nephropathy: correlation with clinical and morphological parameters and prognostic significance

2021 ◽  
Vol 25 (2) ◽  
pp. 52-59
Author(s):  
A. A. Churko ◽  
M. S. Khrabrova ◽  
A. V. Smirnov
Keyword(s):  
Retrospective Study ◽  
Serum Creatinine ◽  
Iga Nephropathy ◽  
Light Chains ◽  
Morphological Parameters ◽  
Free Light Chains ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Cox Regression Analysis ◽  
Interstitial Inflammation

BACKGROUND. Mechanisms of the initiation of renal interstitial inflammation and fibrosis caused by immunoglobulin monoclonal free light chains (mFLC) in monoclonal gammopathy are well established. As far as these damage pathways are considered to be universal we hypothesize that polyclonal free light chains (pFLC) could have a similar effect on tubular and interstitial tissue and lead to chronic kidney disease (CKD) progression in primary glomerulopathies. THE AIM of this retrospective study was to analyze the association of pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed in serum by Freelite® with clinical and morphological parameters and CKD progression in IgA-nephropathy (IgAN) cohort.PATIENTS AND METHODS. In this retrospective study, we enrolled 24 patients with IgAN proven by kidney biopsy (KBx). pFLC-κ and pFLC-λ levels were assessed in all cases at the time of KBx by Freelite® method (N pFLC-κ=3.3-19.4 mg/l, N pFLC-λ=5.7-26.3 mg/l). The normal κ/λ ratio was the inclusion criterion. In all cases, we determined serum creatinine, estimated glomerular filtration rate by CKD-EPI method (eGFRCKD-EPI), and daily proteinuria. Morphological findings were defined semiquantitatively by light and immunofluorescence microscopy. Oxford MEST-C score was evaluated as well as % of glomerulosclerosis. Correlation between parameters was assessed by Spearman’s coefficient. Cox proportional hazards regression was used to analyze the association of parameters with the progression of CKD estimated as an elevation of serum creatinine ≥25 % from the initial level or the initiation of renal replacement therapy at the end of the follow-up period (median was 28 (7; 37) months).RESULTS. Median of pFLC-κ 30.2 (6.1; 67.5) mg/l, median of pFLC-λ 27.6 (11.1; 92.1) mg/l. Levels of pFLC-κ and pFLC-λ were increased in 66.7 % and 50 % of patients, respectively. eGFR CKD-EPI median was 41 (26; 65) ml/min/1.73m2. Serum creatinine correlates with pFLC-κ (R=0.62, p<0.01) and pFLC-λ (R=0.45, p=0.03). Among morphological parameters pFLC-κ correlates with interstitial inflammation (R=0.47, p=0.02), tubular atrophy (R=0.54, p<0.01), interstitial fibrosis (R=0.44, p=0.03), peritubular capillaritis (R=0.42, p=0.04), T-score (R=0.66, p<0.01) and combined MEST-C score (R=0.45, p=0.03). For pFLC-λ the correlations with tubular atrophy (R=0.45, р=0.03) and Т-score (R=0.56, p<0.01) were shown. In Univariate Cox regression analysis pFLC-κ and pFLC-λ were associated with CKD progression (Exp(ß)=1.053; 95,0 %CI 1.003-1.105; p=0.038 and Exp(ß)= 1.041; 95,0 %CI 1.002-1.082; p=0.038, respectively) CONCLUSION. Polyclonal FLC, mostly pFLC-κ, were associated with tubulointerstitial inflammation and fibrosis in patients with IgAN. Increased levels of either pFLC-κ or λ could be proposed as a predictor of CKD progression in patients with IgAN.

IgA nephropathy: analysis of progression in pediatric patients

2021 ◽  
Vol 25 (3) ◽  
pp. 61-67
Author(s):  
I. A. Kazyra ◽  
А. V. Sukalo
Keyword(s):  
Iga Nephropathy ◽  
B Lymphocyte ◽  
Interstitial Fibrosis ◽  
Prognostic Significance ◽  
Pediatric Nephrology ◽  
Lymphocyte Activation ◽  
Healthy Children ◽  
Tubular Atrophy ◽  
Factors Affecting ◽  
Highly Active

The aim of the study was to analyze the rate of progression of IgA nephropathy (IgAN) in childhood and factors affecting prognosis. The study included 54 children with a morphologically verified diagnosis of IgAN (36 boys, 18 girls) aged 2 to 17 years, who were under observation in the nephrology department of the "2nd Children's City Clinical Hospital" of the National Center for Pediatric Nephrology and Renal Replacement therapy in Minsk in the period from 2013 to 2020. The participation of deGal-IgA1, markers of T- and B-lymphocyte activation, pro-inflammatory and pro-fibrotic molecules in the development of the disease has been shown. AG was registered in 18 of 54 (33,3 %) children, nocturnal AG in 11/43 (23,4 %), signs of cardiac remodeling in 10/49 (20,4 %). A decrease in the level of adiponectin, vitamin D, an increase in obestatin in comparison with healthy children makes it possible to attribute patients with IgAN to the risk group for the development of cardiovascular disorders, which implies the need for timely monitoring and correction. In most cases in childhood IgAN is characterized by a benign course without signs of progression. The prognostic significance of highly active nephritis, impaired renal function at the onset of the disease, T1 (tubular atrophy / interstitial fibrosis in 25–50 %) by MEST, proteinuria over 0,8 g/24 hours as risk factors for progression was shown.

scholarly journals P0470IS GLYCOSURIA A MARKER OF TUBULO-INTERSTITITAL FIBROSIS AND PROGNOSIS IN PRIMARY GLOMERULOPATHIES?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carolina Ormonde ◽  
Ivo Laranjinha ◽  
Augusta Gaspar ◽  
Margarida Gonçalves ◽  
Célia Gil ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Similar Proportion ◽  
Tubular Damage ◽  
Tubular Dysfunction ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Glomerular Diseases ◽  
Glomerular Lesion ◽  
Ckd Stage

Abstract Background and Aims Multiple studies have shown that tubular damage is common in glomerular diseases and that it correlates better with chronic kidney disease (CKD) progression than glomerular lesion itself. The link between glomerular and tubular damage is not entirely established. Glycosuria can be found in (proximal) tubular dysfunction and may be used as a marker of tubular lesion and CKD progression. The aim of this study was to evaluate the association between glycosuria (at the diagnosis) and known histological prognostic markers (glomerular sclerosis (%GS) and interstitial fibrosis/tubular atrophy (IFTA)) and CKD progression, in patients with primary glomerulopathies (GP). Method We conducted a 36-month retrospective cohort study with 110 patients with primary GP confirmed by renal biopsy in the last 10 years in our centre – 39 (35.5%) IgA Nephropathy, 27 (24.5%) Membranous Nephropathy, 26 (23.6%) Focal Segmental Glomerulosclerosis and 18 (16.4%) Minimal Change Disease. Patients were divided in two groups according to their glycosuric status at the time of the diagnosis. Data was collected from patients’ charts. Exclusion criteria: patients with diabetes or glucose intolerance, use of SGLT2 inhibitors, secondary GP and transplant kidney patients. Results The global prevalence of glycosuria was 9.1% (n=10). Glycosuric patients had, at baseline, higher serum creatinine (3.9±5.1 vs 1.7±1.3mg/dL, p=0.001), higher baseline albuminuria (7.1±6.3 vs 3.2±3.4 g/g, p=0.002) and lower serum albumin (2.3±0.7 vs 3.2±1.1 g/dL, p=0.022). Both groups had similar proportion of patients that underwent immunosuppressive therapy. At the end of the follow-up, in glycosuric patients, only albuminuria was higher (3.3±0.6 vs 0.7±0.8 g/g, p&lt;0.0001); the eGFR decline rate (ml/min/year), 3-year eGFR and 3-year CKD stage 5D incidence were not statistically different. Glomerular sclerosis (%GS) and interstitial fibrosis and tubular atrophy (IFTA) were not different between groups. These results were confirmed by multivariate analysis. Conclusion Patients with primary GP with glycosuria at diagnosis had higher baseline creatinine and albuminuria. Even though a worse clinical presentation, glycosuria was not associated with well-known prognostic factors (%GS and IFTA) or CKD progression. We can hypothesize that patients with primary GP with glycosuria have severe diseases at diagnosis, but the lesions may have greater reversibility. Prospective and longer studies are needed to confirm these results.

scholarly journals Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy

2016 ◽  
Vol 44 (6) ◽  
pp. 481-492 ◽  
Author(s):  
Jin Ho Hwang ◽  
Jung Pyo Lee ◽  
Clara Tammy Kim ◽  
Seung Hee Yang ◽  
Jin Hyuk Kim ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Glomerular Sclerosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matricellular Protein ◽  
Tubular Atrophy ◽  
Renal Outcomes ◽  
Group 3

Background: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). Methods: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). Results: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. Conclusion: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.

Metabolomic approach to Alzheimer’s disease diagnosis based on mass spectrometry

2012 ◽  
Vol 66 (9) ◽  
Author(s):  
Raúl González-Domínguez ◽  
Tamara García-Barrera ◽  
José-Luis Gómez-Ariza
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Diagnosis ◽  
Healthy Controls ◽  
Serum Samples ◽  
Statistical Tools ◽  
Multivariate Statistical ◽  
New Biomarkers ◽  
Metabolomic Approach

AbstractAlzheimer’s disease is the most common neurodegenerative disease, but there is still no cure and early diagnosis remains very difficult. For this reason, the discovery of new biomarkers is of great importance. The application of metabolomics is emerging in this field, based on the use of mass spectrometry as a technique of analysis. In this work, blood serum samples (from Alzheimer’s disease patients and healthy controls) were analysed by mass spectrometry in order to search for potential metabolomic biomarkers. The application of multivariate statistical tools (PLS-DA) enabled us to discriminate between groups. In addition, some phosphatidylcholine compounds were identified as markers of the disease.

P0136COMPARISON OF SECONDARY IGA NEPHROPATHY OF ANKYLOSING SPONDYLITIS AND PRIMARY IGA NEPHROPATHY IN CLINICAL AND PATHOLOGICAL FEATURES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Qin Xue ◽  
Guang Li Zhang ◽  
Zebo Tian
Keyword(s):  
Retrospective Study ◽  
Ankylosing Spondylitis ◽  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Renal Involvement ◽  
Control Group ◽  
Pathological Features ◽  
Tubular Atrophy ◽  
The Difference ◽  
Clinical And Pathological Features

Abstract Background and Aims Renal involvement is one of the most common extra-articular complications caused by ankylosing spondylitis (AS). The main pathological manifestation is secondary IgA nephropathy(SIgAN) in Chinese AS patients. The difference between SIgAN and primary IgAN (PIgAN) remains unclear due to the lack of cases. Therefore, the aim of this retrospective study was to compare the clinical and pathological features of SIgAN of AS (SIgAN-AS) and PIgAN, to detect the pathogenesis of SIgAN Method Clinical characteristics and pathological data were collected in patients who were diagnosed with IgAN by renal biopsy in our hospital from Jan 2008 to Oct 2018. Patients with SIgAN-AS were recruited by the ratio 1:5 of patients with primary IgAN as the control group in the study. Fifteen patients with SIgAN-AS and Seventy-five patients with PIgAN were enrolled in this retrospective study. Results There were 15 cases in AS group, including 13 male and 2 female. The cohort of 75 patients with PIgAN included 34 male and 41 female. There were more males in AS group 13/15 (86.7%) vs 37/75(49.3%) ,P &lt; 0.05. Compared with PIgAN patients, SIgAN-AS patients had higher incidences of hematuria( 13/15(86.7%)vs 44/75 (58.7%) , P &lt; 0.05), lower levels of 24-hour urinary protein(0.85±0.68 vs 1.57±1.54g, P &lt; 0.05), but higher levels of eGFR (CKD-MDRD formula) (117.60±37.33 vs 85.35±31.36, P &lt; 0.05),eGFR (CKD-EPI formula) (128.01±41.58 vs 92.75±36.09, P &lt; 0.05), Albumin (44.67±3.48 vs 41.09±7.07 g/L, P &lt; 0.05) ESR (43.20 ±33.94 vs 18.79±16.26mm/h, P &lt; 0.001) , and CRP (21.19±30.61 vs 2.11±4.58mg/L, P &lt; 0.001) . From the perspective of renal pathology of PIgAN, SIgA-AS patients had fewer incidences of renal tubular atrophy / interstitial fibrosis of nephropathy (P &lt;0.05). The immunohistostaining analysis showed higher incidences of dominant deposits of single IgA in mesangial cell area (P &lt; 0.05). Conclusion Patients with SIgAN-AS is more common in male and display a milder progression than those with primary IgAN. Majority of the SIgAN-AS can be improved with early intervention.

scholarly journals Oxford MEST classification in Iranian patients with IgA nephropathy, with regards to extracapillary proliferation; a single center experience

2020 ◽  
Vol 5 (1) ◽  
pp. e14-e14
Author(s):  
Mohsen Akhavansepahi ◽  
Maryam Rafieyan ◽  
Hamid Nasri
Keyword(s):  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Laboratory Data ◽  
Clinical Findings ◽  
Reference Laboratory ◽  
Tubular Atrophy ◽  
Single Center Experience ◽  
Medical Centers ◽  
Two Samples ◽  
The Mean

Introduction: IgA nephropathy is the most common glomerulonephritis in the world. Objectives: In this study we aimed to find the relationship between morphological lesions of Oxford classification for IgA nephropathy with clinical findings and some laboratory data. Patients and Methods: All kidney biopsy conducted from 2009 to 2019 conducted in medical centers and were sent to a reference laboratory in Isfahan. All kidney biopsies included two samples for immunofluorescence and light microscopy. After definitive diagnosis of IgAN (IgA nephropathy), the slides were examined to classify the disease based on the Oxford-MEST (M; mesangial hypercellularity, E; endocapillary hypercellularity, S; segmental glomerulosclerosis, and T; tubular atrophy/interstitial fibrosis and also C; crescent) classification. Results: Our study on 238 biopsy proven IgA nephropathy patients showed that 78 patients (32.8%) were male. Mean ± SD of age individuals was 38.00 ±13.68 years. The mean± SD of serum creatinine level was 1.42 ± 0.79 mg/dL and the mean ± SD of proteinuria was 1780.94 ± 1168.75 mg/d. Our study showed no significant association between M, E and S variables with patients’ age. However, a statistically significant relationship between T variable and patients’ age (P=0.028) was detected. Furthermore, morphologic variables of M, E and S were not significantly associated with proteinuria while T variable was positively associated with the quantity of proteinuria (P=0.021). Conclusion: The association of tubular atrophy/interstitial fibrosis (T variable) with quantity of proteinuria showed significance of interstitial lesion on the prognosis IgA nephropathy.

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