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A validation study of crescents in predicting ESRD in patients with IgA nephropathy.

ABSTRACT: BACKGROUND:A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in kidney tissue predicted a worse renal outcome. However, this finding must be validated in independent cohorts before it can be widely applied to clinical practice. METHODS:Biopsy-proven IgAN patients were continuously recruited from two large renal centers in China from 1989 to 2014. All patients were followed for more than 1 year unless end stage renal disease (ESRD) occurred within 12 months. Crescents were defined as focal cellular or fibrocellular crescent formations. IgAN patients without detectable crescents were recruited to the C0 group. Patients with crescents in less than or more than 1/4 of all glomeruli were recruited to the C1 or C2 group, respectively. Primary outcome was defined as the time to ESRD, and the secondary outcome was defined as the time to an estimated glomerular filtration rate (eGFR) decline equal to or greater than 50% or to ESRD. RESULTS:In total, 1152 IgAN patients were recruited in this study. Among all patients, 53.7% were in the C0 group, 38.8% were in the C1 group, and 7.5% were in the C2 group. Compared to patients in the C0 group, patients in the C1 or C2 group were younger, had more urinary protein excretion and lower eGFR, and presented with more severe mesangial hypercellularity, endocapillary proliferation or tubular atrophy/interstitial fibrosis. After 45 months of follow-up, ESRD had occurred in 80 (12.9%), 46 (10.3%) and 18 (20.9%) of patients in the C0, C1 and C2 groups, respectively. By multivariable Cox regression analysis, inclusion in the C1 (HR?=?1.07, 95% CI 0.71-1.63), C2 (HR?=?0.84, 95% CI 0.41-1.73), or C1 or C2 group (HR?=?1.02, 95% CI 0.68-1.52) was not associated with a higher rate of ESRD than inclusion in the C0 group after adjusting for age, gender, eGFR, mean arterial pressure (MAP), MEST scores, and immunosuppressive treatment. However, in patients with nephrotic-range proteinuria, patients in either the C1 or C2 group had a higher rate of the primary outcome, ESRD (HR?=?2.54, 95% CI 1.14-5.66) after adjusting for age, gender, eGFR, MAP, MEST scores, and immunosuppressive treatment. Similar results were found when we evaluated the association between crescents and the secondary outcome. CONCLUSIONS:IgAN patients with crescents had more severe clinical and pathological manifestations than those without crescents. However, we failed to replicate the association between crescents and renal function progression in Chinese IgAN patients followed for more than 1 year.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5934890 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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A validation study of crescents in predicting ESRD in patients with IgA nephropathy.

Zhang Xiaoyan X Shi Sufang S Ouyang Yan Y Yang Meng M Shi Manman M Pan Xiaoxia X Lv Jicheng J Wang Zhaohui Z Ren Hong H Shen Pingyan P Wang Weiming W Zhang Hong H Xie Jingyuan J Chen Nan N

Journal of translational medicine 20180503 1

<h4>Background</h4>A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in kidney tissue predicted a worse renal outcome. However, this finding must be validated in independent cohorts before it can be widely applied to clinical practice.<h4>Methods</h4>Biopsy-proven IgAN patients were continuously recruited from two large renal centers in China from 1989 to 2014. All patients were followed for more than 1 year unless end stage renal di ...[more]

PMID: 29724226

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Project description:Crescents involving more than 50% of glomeruli in IgA nephropathy (IgAN) signify a rapid deterioration of renal function. However, little is known about the prognosis of IgAN patients presenting crescents in less than 50% of glomeruli. We aimed to investigate the clinicopathological characteristics and outcomes of IgAN patients with different proportions of crescents.From January 2000 to December 2011, biopsy-proven primary IgAN patients with histological crescents formation were enrolled in this retrospective cohort study. The patients were divided into 4 groups on the basis of crescent proportion as follows: <5%, 5% to 9%, 10% to 24%, and ≥25%. The primary endpoint was defined as the doubling of baseline serum creatinine (SCr) and/or end-stage renal disease (ESRD), and the secondary endpoint was death.A total of 538 crescent-featured IgAN patients were followed up and included in the analysis. The median crescent proportion was 8.0%. An increasing crescent proportion was associated with a reduced estimated glomerular filtration rate (eGFR), decreased level of hemoglobin, and increased amount of urine protein excretion. After a median follow-up period of 51 months (range 12-154 months), the endpoint events-free survival rate of the above 4 groups were 69.9%, 47.7%, 43.8%, and 40.6%, respectively (Log rank=13.7, P= 0.003), when we incorporated death with renal outcome as a composite endpoint. Multivariate Cox regression analyses adjusting for eGFR, hypertension, proteinuria, and the Oxford-MEST classification demonstrated the predictive significance of an increasing crescent proportion with renal survival and mortality (each increase by 5% [log-transformed]: HR=1.51, 95% CI 1.08-2.11, P = 0.02). Further comparisons of patients with small proportions of crescents (<5%) and those absent of such pathological lesion showed that the 2 groups of patients had comparable prognosis.An increasing crescent proportion was identified as an independent predictor for unfavorable clinical outcomes in IgAN. Therefore, a small proportion of crescents, over 5% particularly, should be paid more attention in clinical practice.

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:BackgroundPozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents.MethodsIn this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels).ResultsThere was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups.ConclusionsBoth the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness.Trial registrationClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.

Project description:BackgroundImmunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology.MethodsWe validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination ( RD2 ) for model fit, and the regression coefficient of the linear predictor (βPI), respectively.ResultsThe study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The RD2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported RD2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model.ConclusionsThe two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

Project description:Background and objectivesSome studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group.Design, setting, participants, & measurementsIn this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy.ResultsWe found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome.ConclusionsThe diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Project description:Background and objectivesThe International IgA Nephropathy Network recently developed and externally validated two models to predict the risk of progression of IgA nephropathy: full models without and with race. This study sought to externally validate the International IgA Nephropathy Prediction Tool in a large, independent, and contemporary cohort in China.Design, setting, participants, & measurementsWe included 1373 patients with biopsy-confirmed primary IgA nephropathy from The First Affiliated Hospital of Zhengzhou University from January 2012 to May 2018 and calculated predicted risks for each patient. The outcomes of interest were a 50% decline in eGFR or kidney failure. We assessed the performance of both models using discrimination (concordance statistics and Kaplan-Meier curves between subgroups), calibration (calibration plots), reclassification (net reclassification improvement and integrated discrimination improvement), and clinical utility (decision curve analysis).ResultsThe median follow-up was 29 months (interquartile range, 21-43 months; range, 1-95 months), and 186 (14%) patients reached the kidney outcomes of interest. Both models showed excellent discrimination (concordance statistics >0.85 and well separated survival curves). Overall, the full model without race generally underestimated the risk of primary outcome, whereas the full model with race was well calibrated for predicting 5-year risk. Compared with the full model without race, the full model with race had significant improvement in reclassification, as assessed by the net reclassification improvement (0.49; 95% confidence interval, 0.41 to 0.59) and integrated discrimination improvement (0.06; 95% confidence interval, 0.04 to 0.08). Decision curve analysis showed that both full models had a higher net benefit than default strategies, and the model with race performed better.ConclusionsIn this study, both full models demonstrated remarkable discrimination, acceptable calibration, and satisfactory clinical utility. The relatively short follow-up time may have limited the validation of these models.

Dataset Information

A validation study of crescents in predicting ESRD in patients with IgA nephropathy.

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A validation study of crescents in predicting ESRD in patients with IgA nephropathy.

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