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Serum complement C4 is an important prognostic factor for IgA nephropathy: a retrospective study.

ABSTRACT: BACKGROUND:IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and is an important cause of end-stage renal disease (ESRD). Exploring novel biomarkers is necessary for predicting the disease activity and progression of IgAN patients. The present study sought to investigate the value of serum C4 for predicting the prognosis of IgAN patients. METHODS:The primary endpoint of this retrospective study was a composite event of either a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. The associations between serum C4 and clinicopathological parameters and prognosis of this cohort of IgAN patients were evaluated. RESULTS:The present study included 1356 IgAN patients. Serum C4 levels correlated significantly with clinical prognostic factors. Serum C4 levels correlated positively with urinary protein excretion (r = 0.307, P < 0.001), and negatively correlated with estimated glomerular filtration rate (r = - 0.281, P < 0.001). Furthermore, serum C4 levels increased with aggravation of tubulointerstitial injury, crescents and ratios of global sclerosis (all P < 0.05). Prognostic analyses with the Cox proportional hazards regression model and Kaplan-Meier survival curves further identified serum C4 as an independent risk factor for the prognosis of IgAN. CONCLUSIONS:The present study identified serum C4 as a useful predictor for the prognosis of IgAN patients. The mechanism of the trend of serum C4 in IgAN needs to be illustrated in further research.

SUBMITTER: Bi TD

PROVIDER: S-EPMC6610919 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.MethodsOne hundred IgAN patients with various proportions of crescents-24 with 1%-24%, 27 with 25%-49%, 21 with 50%-74% 12 with more than 75%, and 16 without crescents-were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.ResultsIgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652-62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0-1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127-66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859-2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058-1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916-11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.ConclusionExcess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.

Project description:ObjectivesThis study was aimed to assess the relationship between serum uric acid (SUA) level and the clinical, pathological phenotype of IgA nephropathy (IgAN), and to determine the role of SUA level in the progression and prognosis of IgAN.MethodsA total of 208 patients with IgAN were included in this study, and were classified into the normo-uricemia group and hyperuricemia group according to the SUA level. The clinical data at baseline, IgAN Oxford classification scores (MEST-C scoring system), and other pathological features were collected and further analyzed. All patients were followed up and the prognosis was assessed using Kaplan-Meier survival curves. GraphPad Prism 7.0 and SPSS 23.0 were used for statistical analyses.ResultsIn clinical indicators, patients with hyperuricemia had the significantly higher proportion of males to females, mean arterial pressure, the levels of total cholesterol, triglyceride, Scr, BUN, 24 hour-urine protein, C3, and C4, the lower levels of high-density lipoprotein cholesterol and eGFR than those without (p < 0.05). In terms of pathological characteristics, the tubular atrophy/interstitial fibrosis scores, vascular injury scores, and glomerular sclerosis percentage were significantly higher in patients with hyperuricemia compared with those without (p < 0.01). There was no significant difference in the scores of mesangial hypercellularity, endocapillary hypercellularity, focal segmental glomerulosclerosis, as well as crescents between the two groups (p > 0.05). As for the depositions of immune complexes deposition in IgAN, the hyperuricemia group had less deposition of immunoglobulin G and FRA than the normo-uricemia group (p < 0.05), while the deposition of immunoglobulin A, immunoglobulin M, and complement C3 in the two groups showed no statistical difference. The survival curve suggested that patients in the hyperuricemia group have significantly poorer renal outcome than those in the normo-uricemia group (p = 0.0147). Results also revealed that the SUA level is a valuable predictor of renal outcome in patients with IgAN. The optimal cutoff value was 361.1 µmol/L (AUC = 0.76 ± 0.08167) and 614 µmol/L (AUC = 0.5728 ± 0.2029) for female and male, respectively.ConclusionsThe level of SUA is associated with renal function level and pathological severity of IgAN, and maybe a prognostic indicator of IgAN.

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Serum complement C4 is an important prognostic factor for IgA nephropathy: a retrospective study.

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