P0313POLYCLONAL FREE LIGHT CHAINS IN IGA-NEPHROPATHY: CORRELATION WITH CLINICAL AND MORPHOLOGICAL PARAMETERS AND PROGNOSTIC SIGNIFICANCE.

Abstract Background and Aims Mechanisms of kidney injury by monoclonal free light chains in myeloma kidney are well established. The role polyclonal free light chains (pFLC) in pathogenesis of renal interstitial inflammation and fibrosis in primary glomerulonephritis is still poorly investigated. We hypothesize that increased level of pFLC could have the similar role in activation of interstitial inflammation and fibrosis formation and impact chronic kidney disease (CKD) progression in the most prevalent form of chronic glomerulonephritis - IgA-nephropathy (IgAN). 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 cohort. Method In this study we enrolled 23 patients with biopsy-confirmed diagnosis of IgAN. pFLC-κ and pFLC-λ levels were assessed in all cases at the time of kidney biopsy (KBx) by Freelite method. Normal range for pFLC-κ and pFLC-λ was 3,3-19,4 mg/l and 5,7-26,3 mg/l, respectively. The following clinical parameters were evaluated at the time of KBx: estimated glomerular filtration rate (eGFR) by CKD-EPI, daily proteinuria, serum albumin and microhematuria. Morphological findings were investigated by light and immunofluorescence (IgA, IgM, IgG, C3, C1, lambda, kappa, fibrinogen) microscopy. Oxford MEST-C score was evaluated as well as % of sclerotic glomeruli. Additionally we semiquantitatively measured (0- absent, 1- mild, 2 – moderate, 3 - severe) mesangial proliferation, endocapillary proliferation, glomerular basement membrane (GBM) thickening, interstitial inflammation, interstitial edema, tubular atrophy (TA), peritubular capillaritis (PTC), interstitial fibrosis (IF) according to currently accepted criteria. The demographic, clinical and morphological parameters at the time of KBx are presented in Table 1. Patients were treated with nephroprotective agents (n=23) and steroids/cyclophosphamide (n=21). Correlation between parameters were assessed by Spearman’s coefficient. Progression of CKD was determined as decline of eGFR >25% from the initial level at the end of follow-up period. Prognostic analysis was performed with Cox proportional hazards regression. Median follow-up was 28 (7; 37) months. Results Correlations between clinical and morphological parameters and pFLC levels are presented in Table 2. Univariate Cox regression analysis has shown that pFLC-κ (Exp(β)=1,051; 95% CI: 1,001-1,104, p=0,045) and FLC- λ (Exp(β)=1,040; 95% CI: 1,001-1,081, p=0,044) as well as other well-known clinical (daily proteinuria (Exp(β)=1,177; 95% CI: 1,003-1,382, p=0,045), eGFR at the KBx time (Exp(β)=2,981; 95% CI:1,112-20,124, p=0,042)) and morphological parameters (% of sclerotic glomeruli (Exp(β)=1,031; 95% CI: 1,001-1,062, p=0,046), T-score (Expβ=10,784; 95% СI: 1,364-85,246, p=0,024) are associated with CKD progression. Conclusion In IgAN higher levels of pFLC, both kappa and lambda, are associated with renal interstitial inflammation and fibrosis, tubular atrophy and chronic glomerular injury and could be used as predictors of CKD progression. Mechanisms of pFLC effects on the formation of renal tubular and interstitial inflammation and fibrosis require further studies.

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

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2021-25-2-52-59 ◽

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.

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MO307POLYCLONAL FREE LIGHT CHAINS AS A PREDICTOR OF CKD PROGRESSION IN NONPROLIFERATIVE GLOMERULOPATHIES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0065 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Anna Churko ◽

Maria Khrabrova ◽

Alexei Smirnov ◽

Vassili Sipovski ◽

Iraida Panina

Keyword(s):

Cox Regression ◽

Interstitial Fibrosis ◽

Light Chains ◽

Morphological Parameters ◽

Free Light Chains ◽

Ckd Progression ◽

Glomerular Lesion ◽

Mesenchymal Transition ◽

Normal Ranges

Abstract Background and Aims The mechanism of the epithelial-mesenchymal transition of kidney tubular cells leading to kidney fibrosis formation and CKD progression is well described for monoclonal free light chains (FLC) in patients with monoclonal gammopathies. As far as the interaction of FLC with megalin/cubulin receptors on proximal tubular epithelial cells is considered to be universal we hypothesize that polyclonal free light chains (pFLC) could have the same effect on tubulointerstitial compartment in patients with primary glomerulopathies. This retrospective study was performed to reveal the association of serum pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed by Freelite® with clinical and morphological parameters and CKD progression in patients with nonproliferative glomerulopathies. Method 36 patients with morphologically proven diagnosis of nonproliferative glomerulopathies (minimal changed disease (n=11), membranous nephropathy (n=11) and focal segmental glomerulosclerosis (n=14)) were included. Serum levels of pFLC-κ and pFLC-λ were assessed by Freelite® (normal ranges: κ=3.3-19.4 mg/l; λ=5.7-26.3 mg/l; κ/λ ratio=0.26-1.65) at the time of kidney biopsy (KBx) in all cases. Patients with abnormal κ/λ-ratio due to monoclonal gammapathies were excluded. Apart demographical parameters, serum creatinine, estimated GFR (eGFR) by CKD-EPI, serum albumin and 24-hour proteinuria were measured. Morphological findings defined by light microscopy were measured semiquantitatively according to currently accepted criteria (0 - <10%, 1 - 10-25%, 2 – 26-50%, 3 - >50% of tissue involved). Data are presented as median and interquartile range (M (25%; 75%)) and mean and the standard error of mean (m±SEM) for semiquantitative parameters or %. Correlation between parameters was assessed by Spearman’s coefficient. Progression of CKD was determined as decline of eGFR >15% from the initial level at the end of follow-up. Cox proportional hazards regression was used to estimate the association of pFLC and other parameters with CKD progression. Differences were considered statistically significant at p <0.05. Median follow-up was 11 (1; 53) months. Results Demographic and clinical parameters at the time of KBx are shown in the Figure 1. Clinical and morphological parameters as well as correlation analysis data are presented in the Figure 2. Univariant Cox regression shows that pFLC-λ >N (Exp(β)=5.120; 95% CI: 1.011-25.924, p<0.05), both pFLC-κ and pFLC-λ >N (Exp(β)=6.646; 95% CI: 1.327-33.287, p=0.02), κ/λ ratio (Exp(β)=4.656; 95% CI: 1.411-15.362, p=0.01), as well as percent of sclerotic glomeruli (Exp(β)=1.039; 95% CI: 1.006-1.073, p=0.01), glomerular basement membrane segmental thickening (Exp(β)=3.129; 95% CI: 1.213-8.071, p<0.01), mesangial proliferation (Exp(β)=5.177; 95% CI: 1.146- 23.396, p=0.03), interstitial cell infiltration (Exp(β)=3.777; 95% CI: 1.258-11.340, p=0.02) and peritubular capillaritis (Exp(β)=5.177; 95% CI: 1.146- 23.396, p=0.03) were associated with CKD progression. Conclusion In nonproliferative glomerulopathies increased level of pFLC, either kappa or lambda, is associated with glomerular lesion, interstitial inflammation, tubular atrophy and interstitial fibrosis. Moreover, elevated levels of pFLC could be proposed as a predictor of CKD progression in studied patient cohort. The mechanisms of kidney injury by pFLC requires further investigation.

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Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia

Advances in Hematology ◽

10.1155/2013/359071 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Katerina Sarris ◽

Dimitrios Maltezas ◽

Efstathios Koulieris ◽

Vassiliki Bartzis ◽

Tatiana Tzenou ◽

...

Keyword(s):

Prognostic Significance ◽

Lymphocytic Leukemia ◽

Light Chains ◽

Free Light Chains ◽

Prognostic Implication ◽

Time To Treatment ◽

Serum Free ◽

Binet Stage ◽

Serum Free Light Chains

Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients.Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series.Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228).Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005andP=0.000003, resp.) and overall survival (P=0.05andP=0.003, resp.). They also correlated withβ2-microglobulin (P=0.009andP=0.03, resp.), serum albumin (P=0.009for summated sFLC), hemoglobin (P<0.001), abnormal LDH (P=0.037andP=0.001, resp.), Binet stage (P<0.05) and with the presence of beta symptoms (P=0.004for summated sFLC).Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.

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Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia (cll) Prognosis

Blood ◽

10.1182/blood.v120.21.4568.4568 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4568-4568 ◽

Cited By ~ 1

Author(s):

Katerina Sarris ◽

Vassiliki Bartzis ◽

Dimitris Maltezas ◽

Efstathios Koulieris ◽

Tatiana Tzenou ◽

...

Keyword(s):

Prognostic Factors ◽

Light Chain ◽

Free Light Chain ◽

Light Chains ◽

Free Light Chains ◽

Cox Regression Analysis ◽

Serum Free ◽

Serum Free Light Chain ◽

Serum Free Light Chains

Abstract Abstract 4568 Background and Aim: Symptomatic CLL patients need treatment immediately. For these patients, molecular-genetic factors (mutated-unmutated, ZAP 70, ATM, p53) are important prognostic factors of response and survival. Nevertheless, 2/3 of newly diagnosed patients are asymptomatic and require only of follow up that can last for months or years. For these patients overall survival (OS) depends on the time to first treatment (TFT). The most frequent paraprotein produced in CLL is serum free light chain in 50% of the patients. It has recently been shown that serum free light chains (sFLC) and their sum above 60 (κ+λ above 60) are useful prognostic factors for TFT. We therefore studied the eventual prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods: 143 CLL patients were studied of which 18 needed immediate treatment while 37 more needed treatment during their follow up. 64% and 72%, 28% and 18%, 7.5% and 10%, were in stage 0 and A, 1 and β, 2 and C according to Rai and Binet respectively. Median patients' follow up was 32 months (range 4–228). Light chain restriction was established by flow cytometry or bone marrow biopsy immunohistochemistry. Serum free light chain values were retrospectively determined by nephelometry (Freelite™, the Binding Site Birmingham, UK) in frozen sera drawn at diagnosis. Elevated sFLC values were defined using as cut-off values the 95th percentile range of healthy individuals. Statistical analysis was performed using SPSS v15.0. Hazard ratios and prognostic significance of abnormal sFLC, HLC and ratios were determined by univariate Cox regression analysis. Kaplan Meier method was used for pictorial representation of survival and time to treatment. Results: Increased sFLC were found in 45% of the patients while the summated FLC-kappa plus FLC-lambda was higher than 60 mg/dl in 14%. Increased sFLC values as well as values of FLC κ+λ>60 were related to shorter TFT (p=0,0005 and p=0,000003 respectively). In addition, high levels of sFLC and FLC κ+λ >60 correlated with β2-microglobulin (r=0.2, p=0.009 και r=0.2, p=0.03 respectively), serum albumin (r=0.2, p=0.009 only for FLC κ+λ > 60), negatively with hemoglobin (r=-0.3, p=0.000003 και r=-0.2, p=0.0002 respectively), increased LDH (p=0.037 και 0.001 respectively), Rai stage (p=0.03 και 0.003 respectively) and Binet stage (p=0.02 only for FLC κ+λ > 60) and with the presence of beta-symptoms (p=0.004 only for FLC κ+λ > 60). Finally, increased sFLC and FLC κ+λ>60 values correlated with shorter OS (p=0.05 and p=0.003 respectively). Conclusion: The results of our study confirmed the significance of sFLC in CLL with regard to TFT and their relationship with adverse prognostic clinical and laboratory parameters but also demonstrated for the first time their impact on OS. Disclosures: No relevant conflicts of interest to declare.

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A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

Scientific Reports ◽

10.1038/s41598-021-84715-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Li Tan ◽

Yi Tang ◽

Gaiqin Pei ◽

Zhengxia Zhong ◽

Jiaxing Tan ◽

...

Keyword(s):

Risk Factors ◽

Iga Nephropathy ◽

Cox Regression ◽

Renal Outcome ◽

Matched Cohort ◽

Negative Group ◽

Renal Survival ◽

Cox Regression Analysis ◽

Renal Outcomes

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

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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

European Journal of Inflammation ◽

10.1177/2058739218802680 ◽

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.

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IgA nephropathy: analysis of progression in pediatric patients

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2021-25-3-61-67 ◽

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.

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

Journal of Clinical Medicine ◽

10.3390/jcm9113549 ◽

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.

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Prognostic Significance of Fragmented QRS in Patients with Hypertrophic Cardiomyopathy

Cardiology ◽

10.1159/000471845 ◽

2017 ◽

Vol 138 (1) ◽

pp. 26-33 ◽

Cited By ~ 3

Author(s):

Xili Lu ◽

Wei Wang ◽

Ling Zhu ◽

Yilu Wang ◽

Kai Sun ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Outcomes ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Fragmented Qrs ◽

All Cause Mortality ◽

The Relationship ◽

Cvd Mortality

Objectives: The relationship between a fragmented QRS (fQRS) and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) remains unclear. This study aimed to investigate the prognostic significance of fQRS in patients with HCM. Methods: Between 2000 and 2012, 326 unrelated patients with HCM (72% male with a mean age of 52 years) were included and were divided into 2 groups: those with fQRS and those without fQRS. Results: A total of 105/326(32.2%) patients with HCM presented with fQRS at enrollment. During a follow-up of 5.3 ± 2.4 years, 33 patients died, 30 of cardiovascular disease (CVD). Cox regression analysis revealed that fQRS predicted a higher risk of all-cause mortality (adjusted hazard ratio [HR] 2.24; 95% confidence interval [CI] 1.08-4.64; p = 0.030) and CVD mortality (adjusted HR 2.68; 95% CI 1.22-5.91; p = 0.014). Our study also showed that fQRS increased the risk of heart failure-related death (adjusted HR 3.75; 95% CI 1.24-11.30; p = 0.019). Conclusions: Our results indicate that fQRS is associated with adverse clinical outcomes in patients with HCM.

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Interstitial Inflammatory and Chronic Tubulointerstitial Lesions in Lupus Nephritis: Comparison with those in IgA Nephropathy

Lupus ◽

10.1177/096120339300200114 ◽

1993 ◽

Vol 2 (1_suppl) ◽

pp. 261-268 ◽

Cited By ~ 9

Author(s):

Tatsuo Yamamoto ◽

Mitsumasa Nagase ◽

Akira Hishida ◽

Nishio Honda

Keyword(s):

Lupus Nephritis ◽

Iga Nephropathy ◽

Immune Complexes ◽

Prognostic Significance ◽

Underlying Disease ◽

Inflammatory Lesions ◽

Tubulointerstitial Lesions ◽

Glomerular Lesions ◽

Renal Prognosis

The significance of interstitial inflammatory and chronic tubulointerstitial lesions was studied in relation to the severity of glomerular lesions in 62 patients with lupus nephritis and 88 with IgA nephropathy. Severe interstitial inflammatory and chronic tubulointerstitial lesions were found in patients with severe glomerular lesions in both lupus nephritis and IgA nephropathy. In such cases, the serum creatinine levels at biopsy were high and the renal prognosis was poor regardless of the underlying disease (lupus nephritis or IgA nephropathy). No IgA nephropathy patients with nil or mild glomerular lesions had moderate or severe interstitial inflammatory and/or chronic tubulointerstitial lesions. In contrast, predominantly severe interstitial inflammatory lesions were found in 36% of lupus nephritis patients with nil or mild glomerular lesions. The prevalence of interstitial immune complexes deposition was markedly high in those with predominant interstitial inflammatory lesions. However, the severity of chronic tubulointerstitial lesions was mild and renal function did not deteriorate in the mean follow-up periods of 68.6 months. It is suggested that, besides the tubulointerstitial lesions attributable to the severe concomitant glomerular damage, the interstitial deposition of immune complexes per se plays a pathogenic role in the interstitial inflammatory lesions in lupus nephritis. Its prognostic significance, however, was considered to be minor.

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