Dataset Information

Crescents formations are independently associated with higher mortality in biopsy-confirmed immunoglobulin A nephropathy.

ABSTRACT:

Background and objectives

Immunoglobulin A Nephropathy (IgAN) is the most common type of glomerulonephritis with variable renal outcome. The association between IgAN and patient survival is limited. The effect of crescents on patient survival was never studied.

Materials

We conducted a retrospective cohort study between January 2003 and December 2013. All patients with the biopsy-proved IgAN was enrolled for the analysis of patient survival and renal survival. Cox regression model was used analyze the associated factors for patient survival.

Results

All 388 participants with IgAN were enrolled, in which 45 patients with crescents. The mean percentage of glomeruli involvement was 23±18.9%. After long-term follow-up, crescents group had both worse renal (p = 0.034) and patient survivals (p = 0.016). In univariate Cox regression model, the age (HR = 1.08, 95% CI = 1.05-1.12, p<0.001), crescents (HR = 3.93, 95% CI = 1.18-13.07, p = 0.025), serum albumin (HR = 0.023, 95%CI = 0.11-0.50, p<0.001), blood total protein (HR = 0.46, 95%CI = 0.28-0.75, p = 0.002), HDL (HR = 0.95, 95%CI = 0.91-0.99, p = 0.009), daily urine protein (HR = 1.14, 95%CI = 1.01-1.29, p = 0.038), urine PCR (HR = 1.07, 95%CI = 1.02-1.12, p = 0.003), serum IgM (HR = 0.98, 95%CI = 0.96-1.00, p = 0.036), BUN (HR = 1.02, 95%CI = 1.01-1.02, p = 0.005), and eGFR (HR = 0.097, 95%CI = 0.94-0.99, p = 0.0011) were associated with patient survival. After multivariate Cox regression analysis, age (HR = 1.08, 95%CI = 1.01-1.13, p = 0.013), crescents (HR = 5.57, 95%CI = 1.14-29.05, p = 0.034), and HDL (HR = 0.94, 95%CI = 0.90-0.99, p = 0.026) were associated with patient survival. Crescents IgAN is with the highest risk (up to 5.75 of HR) for patient mortality.

Conclusions

The major strengths of the present study is that crescents IgAN had worse patient survival compared to non-crescents IgAN. Clinicians should be more careful to care patients with crescents IgAN.

SUBMITTER: Chen CH

PROVIDER: S-EPMC7394392 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Crescents formations are independently associated with higher mortality in biopsy-confirmed immunoglobulin A nephropathy.

Chen Cheng-Hsu CH Wu Ming-Ju MJ Wen Mei-Chin MC Tsai Shang-Feng SF

PloS one 20200731 7

<h4>Background and objectives</h4>Immunoglobulin A Nephropathy (IgAN) is the most common type of glomerulonephritis with variable renal outcome. The association between IgAN and patient survival is limited. The effect of crescents on patient survival was never studied.<h4>Materials</h4>We conducted a retrospective cohort study between January 2003 and December 2013. All patients with the biopsy-proved IgAN was enrolled for the analysis of patient survival and renal survival. Cox regression model ...[more]

PMID: 32735632

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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: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:ObjectivePopulation-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).DesignThis nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.ResultsOver a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).ConclusionAll NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.

Dataset Information

Crescents formations are independently associated with higher mortality in biopsy-confirmed immunoglobulin A nephropathy.

Background and objectives

Materials

Results

Conclusions

Publications

Crescents formations are independently associated with higher mortality in biopsy-confirmed immunoglobulin A nephropathy.

Similar Datasets

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