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.

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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Churko ◽  
Maria Khrabrova ◽  
Vasiliy Sipovskii ◽  
Alexei Smirnov
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Significance ◽  
Light Chains ◽  
Morphological Parameters ◽  
Free Light Chains ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Cox Regression Analysis ◽  
Interstitial Inflammation

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 &gt;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.

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

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 - &lt;10%, 1 - 10-25%, 2 – 26-50%, 3 - &gt;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 &gt;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 &lt;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 &gt;N (Exp(β)=5.120; 95% CI: 1.011-25.924, p&lt;0.05), both pFLC-κ and pFLC-λ &gt;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&lt;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.

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.

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.

MO278IMMUNOSUPPRESSIVE THERAPY VERSUS SUPPORTIVE CARE IN IGA NEPHROPATHY PATIENTS WITH STAGE 3 AND 4 CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gabriel Stefan ◽  
Simona Stancu ◽  
Adrian Dorin Zugravu ◽  
Nicoleta Petre ◽  
Gabriel Mircescu
Keyword(s):  
Chronic Kidney Disease ◽  
Retrospective Study ◽  
Kidney Disease ◽  
Supportive Care ◽  
Survival Time ◽  
Immunosuppressive Therapy ◽  
Iga Nephropathy ◽  
Composite Endpoint ◽  
Renal Survival ◽  
Cox Regression Analysis

Abstract Background and Aims The use of immunosuppressive therapy for IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial. Method We performed a monocentric retrospective study on 83 consecutive IgAN patients (age 41 [33-56] years, 72% male, eGFR 36.1 [25.4-47.5] mL/min) with stage 3 or 4 CKD and proteinuria ≥ 0.75g/day who received uncontrolled supportive care (Supp) (n=36), corticosteroids (CS) (n=14) or CS combined with monthly pulses of cyclophosphamide (CS+CFM) (n=33) between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018). Results Patients were followed for a median of 29 (95%CI 25.2, 32.7) months, and 12 (15%) patients experienced the composite endpoint. There were no differences between the three studied groups regarding age (Supp 46 [33.5-61.0] vs CS 40 [33-47] vs CS+CFM 41 [34-48] years), eGFR (Supp 37.7 [27.5-49.2] vs CS 40.3 [32.5-54.6] vs CS+CFM 31.5 [22.7-44.3] mL/min), proteinuria (Supp 1.9 [1.4-3.5] vs CS 1.3 [1.0-1.7] vs CS+CFM 1.7 [1.1-2.9] g/g creatinine), MESTC score (Supp 2.5 [1.5-4.0] vs CS 2 [0-2] vs CS+CFM 3 [2-3]), hypertension (Supp 94% vs CS 86% vs CS+CFM 94%) and therapy with renal angiotensin system inhibitors (Supp 83% vs CS 64% vs CS+CFM 67%). Mean renal survival time for the entire cohort was 81.0 (95%CI 73.1, 89.0) months; we found similar renal survival time between the three groups (Supp 79.0 (95%CI 66.5, 91.6) vs CS 69.3 (95%CI 47.7, 91.0) vs CS+CFM 73.7 (95%CI 66.0, 81.4) months, p=0.4). In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better renal survival when compared to supportive therapy (Table 1). Conclusion Within the limitation of a retrospective study, we found no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared to supportive care.

ANCA-associated vasculitis with dominant renal involvement: clinical and morphological presentation and outcomes

2019 ◽  
Vol 23 (6) ◽  
pp. 29-44
Author(s):  
V. A. Dobronravov ◽  
A. V. Karunnaya ◽  
A. V. Kazimirchik ◽  
A. V. Smirnov
Keyword(s):  
Kidney Disease ◽  
Serum Creatinine ◽  
Clinical Remission ◽  
Kidney Biopsy ◽  
Morphological Parameters ◽  
Baseline Serum ◽  
Interstitial Inflammation ◽  
Baseline Serum Creatinine

THE AIM: The analysis of clinical and morphological presentations and outcomes of primary systemic vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA-V) with dominant kidney involvement; the determination of clinical and morphological parameters associated with prognosis.PATIENTS AND METHODS. Eighty nine patients with morphologically confirmed ANCA-associated kidney vasculitis on standard immunosuppressive therapy (IST) were included in this retrospective study. Clinical, immunological, and histological indices were analyzed at the time of the kidney biopsy, and early in the short-term (3-6 months) and in the long-term follow-up. The following outcomes were evaluated: the achievement of clinical and immunological remission of the disease; eGFR at the end of follow-up, the progression of renal disease (by the composite point: initiation of renal replacement therapy (RRT) or the estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 or decrease in eGFR >50 %); all-cause mortality. The prognostic significance of clinical and morphological parameters was evaluated in multivariable regression models.RESULTS. Most of cases (78 %) were represented by rapidly progressive or acute nephritic syndrome. Mean eGFR was 23 ml/min/1.73 m2. Fifteen percent of patients required acute dialysis. Dominant morphological phenotypes of glomerular lesions were sclerotic (34 %) and mixed (36 %) according to the International Pathology Classification (IPC). Median follow-up was 24 (8; 55) months. Cumulative 5-year and 10-year patient’s survivals and were 92 % and 86 %, respectively. Cumulative 5-year and 10-year renal survivals were 86 % and 68 %, respectively. The cumulative 5-year and 10-year proportions of cases without progression of kidney disease were 80 % and 55 %, respectively. Within 3-6 months of the induction IST 81 % of patients achieved clinical remission (complete (59 %) or partial (22 %)) (CR3-6), while 84 % of patients had immunological remission. Serum creatinine (Pcr) at the time of kidney biopsy was only the factor associated with the risk of renal progression (Expβ=1.73 (95 %CI 1.40-2.14) per 0.1 mmol/l increase). IPC classes and ANCA Renal Risk Score (ARRS) groups as well as other morphological indices of kidney injury had no independent associations with the renal outcomes in Cox models adjusted for Pcr. The independent factors associated with eGFR at the end of follow-up were: CR3-6 (β=0.36±0.08, p<0.001); age (β=-0.34±0.09, p<0.001), Pcr (β=-0.35±0.09, p<0.001) and the global glomerulosclerosis (β=0.28±0.08, p<0.001). CR3-6 (β=0.57±0.10, p<0.001), and the proportion of cellular crescents (β=0.26±0.12, p=0.023) and interstitial inflammation (β=0.27±0.11, p=0.026) were also independently associated with the change of eGFR by the end of follow-up.CONCLUSION. An unfavorable renal prognosis for ANCA-V determined by severe renal dysfunction due to inflammatory and fibrotic alterations of the organ can be significantly improved by adequate therapy with the achievement of higher patient’s and kidney’s survival. The baseline serum creatinine is only the factor associated with the long-term risks of dialysis and kidney disease progression. In addition to baseline serum creatinine and the development of early clinical remission, the separate assessment of global glomerular sclerosis, cellular crescents, and interstitial inflammation may be more useful for the individual prediction of long-term eGFR changes than IPC classes or ARRS.

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

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4568-4568 ◽  
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.

Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes in patients with advanced chronic kidney disease

2017 ◽  
Vol 66 (3) ◽  
pp. 669-675 ◽  
Author(s):  
Qi-feng Liu ◽  
Jian-ming Ye ◽  
Li-xia Yu ◽  
Ao-lin He ◽  
Qiang Sun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Replacement Therapy ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Replacement Therapy ◽  
Kidney Function ◽  
Control Group ◽  
Ckd Progression ◽  
Cox Regression Analysis ◽  
Renal Outcomes

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3–5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.

scholarly journals RETROSPECTIVE STUDY OF HISTOLOGICAL ANALYSIS AND ITS CORRELATION WITH CLINICAL PRESENTATION AND OUTCOME OF IGA NEPHROPATHY FROM A TERTIARY CENTRE OF GUWAHATI ASSAM.

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Manjuri Sharma ◽  
Manzoor Ahmad Parry ◽  
Hamad Jeelani ◽  
Pranab Jyoti Mahanta
Keyword(s):  
Retrospective Study ◽  
Iga Nephropathy ◽  
Clinical Presentation ◽  
Interstitial Fibrosis ◽  
Clinical Manifestations ◽  
Tubular Atrophy ◽  
Glomerular Diseases ◽  
Mesangial Hypercellularity ◽  
Endocapillary Hypercellularity

Background: IgA nephropathy (IgAN) is one of the most common glomerular diseases with varied presentations. We aimed to study clinical presentation and outcome of IgAN and correlate with histopathology at the time of presentation. Methods: This is a retrospective study in which we analyzed kidney biopsy data, clinical manifestations and outcome of 137 patients with a diagnosis of primary IgAN from 2012 to 2016. Kidney biopsies were reviewed as per Oxford classification assessing mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis/adhesion, tubular atrophy/interstitial fibrosis. Correlation analysis was done for biopsy findings and clinical presentation/outcome. P score less than 0.05 was taken as significant. Results: Mean age for presentation was 27.35 years with 83 males and 54 females. Asymptomatic urinary abnormality was the most common clinical presentation (28.5%). Mean serum creatinine was 2.23 ± 2.06mg/dl with mean proteinuria of 1.49 ± 1.43g/day. Mesangial hypercellularity (M) and Endocapillary hypercellularity (E) lesions were significantly associated with proteinuria at the time of biopsy (p=0.02& 0.04 respectively). Segmental glomerulosclerosis (S) and tubular atrophy (T) were significantly associated with eGFR and mean arterial pressure at the time of biopsy. Mean time of follow up was 1.6 years. M1, E0, S1, T0 were the most common lesions. M, S and T lesions in biopsy were significantly associated with decrease in GFR at the end of follow up. Conclusion: In our study, most common presentation of IgAN was AUA with rarity of macroscopic hematuria. M, S and T lesions were associated with decreased GFR on follow up. Key words: IgA Nephropathy, Nephrotic Syndrome, Oxford MEST classification

scholarly journals The Relationship between Cigarette Smoking and IgA Nephropathy

2021 ◽  
Author(s):  
Siqing Wang ◽  
Aiya Qin ◽  
Gaiqin Pei ◽  
Zheng Jiang ◽  
Lingqiu Dong ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Renal Outcome ◽  
Study Endpoint ◽  
Tubular Atrophy ◽  
Cox Regression Analysis

Abstract Background and aim: Regarding that whether cigarette smoking is associated with the progression of IgA nephropathy (IgAN) remains uncertain, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN.Methods: 1239 IgAN patients who meet inclusion criteria from West China Hospital of Sichuan University were divided into smoker and non-smoker group. The endpoint was end stage renal disease (ESRD: eGFR <15 mL/min/1.73 m2 or having renal replacement treatment) and/or eGFR decreased>50%. Kaplan-Meier and Cox proportional hazards analyses were performed. Association of cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis.Results: During the mean follow-up period of 61 months, 40 out of 209 (19%) patients in smoker group and 110 out of 1030 (11%) in non-smoker group reached study endpoint(p<0.001). Multivariate Cox regression analysis revealed that cigarette smoking (HR=1.58,p=0.043), female gender (HR=2.00,p=0.002), Hypertension (HR=1.50,p=0.029), Serum creatinine (HR=1.01,p<0.001), segmental glomerulosclerosis (HR=1.59,p=0.026), and tubular atrophy/interstitial fibrosis (HR=3.13,p<0.001) were independent risk factors for prediction of poor renal outcome of IgAN. After matching with propensity scores, the significant correlation between cigarette smoking and the renal outcomes of IgAN patients can be seen.Conclusion: Smoking is an independent risk factor for the progression of IgAN, especially for female subjects.

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