Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status.
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ABSTRACT:
SUBMITTER: Gong S
PROVIDER: S-EPMC8733336 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status.
Gong Shaomin S Jin Shi S Li Yang Y Jiang Wuhua W Zhang Zhen Z Shen Ziyan Z Wang Jialin J Zhou Huili H Liu Xiao X Xu Xialian X Ding Xiaoqiang X Shi Yiqin Y Liu Hong H
Frontiers in immunology 20211223
Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured <i>via</i> enzyme-linked immunosorben ...[more]
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Project description:IntroductionThe TESTING trial demonstrated that corticosteroids reduce the risk of kidney failure in patients with IgA nephropathy (IgAN) but increase the risk of serious adverse events. Reliable noninvasive biomarkers are needed to identify patients who would benefit most from corticosteroid therapy. Previous studies suggest glomerular macrophage infiltration is associated with response to immunosuppressive therapy in IgAN and urinary soluble CD163 ([u-sCD163], a marker of alternatively activated macrophages [M2]c macrophage) is correlated with clinical remission in vasculitis. This study aims to investigate the association between u-sCD163 and response of steroids therapy in IgAN.MethodsWe measured u-sCD163 in patients from a large IgAN cohort and Chinese participants of the TESTING trial. The correlation of baseline or serial u-sCD163 and their response of corticosteroids therapy or kidney outcomes were investigated.ResultsIn cross-sectional analysis, u-sCD163 levels correlated with kidney macrophage infiltration, especially in crescentic areas, and with active lesions. Subgroup analysis of the TESTING cohort showed higher levels u-sCD163 were associated with greater benefits from corticosteroids therapy in proteinuria remission (odds ratio, 35.56 [95% confidence interval, CI: 7.62-292.34] vs. 3.94 [95% CI: 1.39-12.93], P for interaction: 0.036). Corticosteroids therapy significantly reduced u-sCD163 levels at 6 months compared to placebo group (79% [interquartile range: 58%-91%] vs. 37% [-11% to 58%], P <0.001). There was no difference in the suppressive effects on u-sCD163 by either dosage of corticosteroids (full and reduced-dose). The suppression of u-sCD163 was significantly associated with a reduced risk of kidney progression events (adjusted hazard ratio: 0.52, 95% CI: 0.30-0.93, P = 0.027).Conclusionu-sCD163 is a reliable noninvasive biomarker associated with active pathological lesions in IgAN and can guide glucocorticoid therapy.
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Project description:BackgroundThis study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN).MethodsWe included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria.ResultsPatients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05-4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02-15.88).ConclusionsUrinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN.ImpactHigh levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.
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Project description:BackgroundNovel criteria for the remission of Immunoglobulin A nephropathy (IgAN) based on an opinion survey of Japanese nephrologists and literature review were proposed in 2013. This single-center, longitudinal retrospective cohort study was conducted to validate this criteria.MethodsPresent study included the IgAN patients diagnosed between 2001 and 2005 in the Juntendo University Hospital. Remission of hematuria was defined as three consecutive dipstick test results of ( -) to ( ±) or a red blood cell count < 5 in urinary sediment per high-power field during at least 6 months. Remission of proteinuria was defined as three consecutive dipstick results of ( -) to ( ±) during at least 6 months. We categorized four groups according to the remission status which was assessed 2 years after the renal biopsy. The primary outcome was a 50% increase in the serum creatinine over the baseline. We evaluated the slope of eGFR decline (mL/min/1.73 m2/year) and a decrease in the eGFR of 30% from baseline eGFR as the secondary outcome, respectively.ResultsA total of 74 patients (male: 47.3%, median age: 30 years) were included and were followed for a median of 86.5 months. During the period, forty-one patients achieved neither remission of proteinuria nor hematuria (NR). Twelve patients met the primary study outcome. A survival analysis revealed that the NR had the worst prognosis and the steepest slope of eGFR decline.ConclusionAlthough further validation in a large cohort is necessary, these novel remission criteria for IgAN patients appear to predict the renal prognosis.
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