Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis
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SUBMITTER: Chen X
PROVIDER: S-EPMC10953224 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis.MethodsWe retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68-78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event.ResultsThe median serum creatinine concentration at diagnosis was 300 (202-502) µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6-20.0) in the medium-risk group and 44.0% (29.0-58.0) in the high-risk group (P < .001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58-0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80-0.90) when dialysis status at diagnosis was included.ConclusionThe ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement-especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS.
| S-EPMC11483564 | biostudies-literature
Project description:BackgroundThe incidence of venous thromboembolism (VTE) is increased in ANCA-associated vasculitis (AAV). We assessed the frequency of VTE observed among patients with AAV evaluated at our center and identified risk factors.MethodsPatients from the Johns Hopkins Vasculitis Center cohort who were evaluated between 1998 and 2018 and had a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were eligible for analysis. Baseline demographics and clinical and serologic data were extracted. Univariate and multivariate analyses were performed to identify factors associated with VTE in AAV.ResultsA total of 162 patients with AAV were identified, 105 (65%) with GPA; 22 (14%) of these patients had a recorded VTE with a median time to VTE of 1 month. The mean (SD) age in the VTE versus non-VTE groups was 54±20 versus 55±17 years (P=0.99), 64% versus 60% female (P=0.93), 82% versus 49% PR3-ANCA positive (P=0.01), with a total mean BMI of 33.3±5.7 versus 28.3±6.1 kg/m2, (P<0.001) respectively. The median Birmingham Vasculitis Activity Score (BVAS version 3) was 19 versus 14 (P=0.02). Univariate analyses identified PR3-ANCA, rapidly progressive GN (RPGN), and hypoalbuminemia. In multivariate analysis, the significant associations with VTE included PR3-ANCA (OR, 4.77; P=0.02), hypoalbuminemia (OR, 4.84; P=0.004), and BMI (OR, 1.18; P<0.001).ConclusionsVTE is a surprisingly common complication of AAV. PR3-ANCA and hypoalbuminemia are risk factors for developing VTEs. Further studies are needed to confirm these findings.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_04_30_KID0000572019.mp3.
| S-EPMC8809268 | biostudies-literature
Project description:Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.
| S-EPMC5156375 | biostudies-literature
Project description:BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.
| S-EPMC9437287 | biostudies-literature
Project description:Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m(2) × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.
| S-EPMC4378104 | biostudies-literature
Project description:Activin A, a member of the transforming growth factor-beta superfamily, is a critical modulator of inflammation and plays a key role in controlling the cytokine cascade that drives the inflammatory response. However, the role of activin A in inflammatory kidney diseases remains unknown. To address this issue, we examined here whether activin A can be detected in the kidney and/or urine from patients with antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV). Fifty-one patients who had been diagnosed with AAV and were treated in our department between November 2011 to March 2018 were included in this study. Forty-one patients had renal complications (renal AAV). Serum and urinary activin A levels were measured by enzyme-linked immunosorbent assay. Correlation of urinary activin A concentration with clinical parameters was analyzed. Urinary activin A was undetectable in healthy volunteers. In contrast, urinary activin A concentration was significantly increased in patients with renal AAV but not in those with non-renal AAV. Urinary activin A concentration decreased rapidly after immunosuppressive treatment. There was a significant correlation of urinary activin A level with urinary protein, L-FABP, and NAG. Histologic evaluation revealed that urinary activin A levels were significantly higher in patients with cellular crescentic glomeruli than in those lacking this damage. In situ hybridization demonstrated that the mRNA encoding the activin A βA subunit was undetectable in normal kidneys but accumulated in the proximal tubules and crescentic glomeruli of the kidneys of patients with renal AAV. Immunostaining showed that activin A protein also was present in the proximal tubules, crescentic glomeruli, and macrophages infiltrating into the interstitium in the kidneys of patients with renal AAV. These data suggested that urinary activin A concentration reflects renal inflammation and tubular damage in AAV and may be a useful biomarker for monitoring renal AAV.
| S-EPMC6793943 | biostudies-literature
Project description:ObjectiveThis study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsAnalysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease-specific and non-disease-specific damage scores built from VDI and AVID items.ResultsAnalysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3-ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA (P < 0.001) except the disease-specific damage score, which did not differ (P = 0.44). For EGPA, VDI scores increased with age at diagnosis (P < 0.009), whereas all other scores were not significantly different.ConclusionAge at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non-disease-specific damage items.
| S-EPMC10782596 | biostudies-literature
Project description:Background and objectivesThe significance of persistent hematuria or proteinuria in patients with ANCA-associated vasculitis who are otherwise in clinical remission is unclear.Design, setting, participants, & measurementsA post hoc analysis was conducted using participants enrolled in two randomized, placebo-controlled clinical trials who had active GN due to ANCA-associated vasculitis, had positive ANCA, and achieved remission by month 6. Dipstick and microscopic urinalyses were performed at each visit. Persistent hematuria or proteinuria for at least 6 months and the cumulative duration of hematuria were examined. Renal relapse was defined as new or worsening red blood cell casts and/or worsening kidney function according to the Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis.ResultsThere were 149 patients included in this study: 42% had persistent hematuria, and 43% had persistent proteinuria beyond 6 months. Persistent hematuria was associated with a significantly higher risk of relapse, even after adjusting for potential confounders (subdistribution hazard ratio, 3.99; 95% confidence interval, 1.20 to 13.25; P=0.02); persistent proteinuria was not associated with renal relapse (subdistribution hazard ratio, 1.44; 95% confidence interval, 0.47 to 4.42; P=0.53). Furthermore, greater cumulative duration of hematuria was significantly associated with a higher risk of renal relapse (adjusted subdistribution hazard ratio, 1.08 per each month; 95% confidence interval, 1.03 to 1.12; P<0.01). The median time to renal relapse was 22 months.ConclusionsIn patients with ANCA-associated vasculitis and kidney involvement who achieve remission after induction therapy, the presence of persistent hematuria, but not proteinuria, is a significant predictor of future renal relapse.
| S-EPMC5967421 | biostudies-literature
Project description:Background and objectivesThis study evaluated predictors for patient and renal survival in patients with ANCA-associated vasculitis (AAV) with and without renal involvement.Design, setting, participants, & measurementsThere were 273 consecutive AAV patients from January 1990 until December 2007 who were followed until death, loss to follow-up, or December 2010. Based on organ involvement, patients were divided into renal (n=212) and nonrenal groups (n=61). The primary end point was ESRD requiring renal replacement therapy (RRT) or renal transplantation or death.ResultsPatient survival was significantly better in the nonrenal group compared with the renal group (hazard ratio, 0.55; 95% confidence interval, 0.33 to 0.92; P=0.02). In the renal group, renal survival was significantly worse in MPO-ANCA-positive patients (n=65) compared with PR3-ANCA-positive patients (n=138) (hazard ratio, 2.1; 95% confidence interval, 1.11 to 3.8; P=0.01). Of 48 patients who needed RRT at diagnosis, 11 patients (23%) died within 6 months and 14 patients (29%) did not regain renal function. Of all 23 patients who regained renal function after RRT, 7 patients (30%) were temporarily dialysis independent and needed dialysis later (range, 13-63 months). Five patients had a renal relapse in the 6 months before restart of RRT. Of all 203 PR3-ANCA-positive and MPO-ANCA-positive patients with renal involvement, 12 patients (6%) developed ESRD during follow-up. These patients were classified as CKD stage 4 or 5 after initial treatment and eight patients had a renal relapse before becoming dialysis dependent.ConclusionsAAV patients with renal involvement who needed RRT had the worst survival probability. In multivariate analysis, the only major determinants for long-term renal survival were renal function at 6 months and renal relapses.
| S-EPMC3789333 | biostudies-literature
Project description:The prognosis of patients with ANCA-associated vasculitis has improved over the past decades, but overall survival rates are still unsatisfactory. Recent research has focused on complications of immunosuppressive measures and comorbidities of ANCA-associated vasculitis. This review focuses on thromboembolic and cardiovascular events. A considerably increased risk of thromboembolic events has been reported, which is associated with active disease and impaired coagulation factors. There is mounting evidence that a hypercoagulable state is present even in patients in remission, and studies investigating the impact of tailored anticoagulation are needed to reduce the burden of thromboembolism. Cardiovascular mortality is one of the leading causes of death and accelerated atherosclerosis is frequently observed in patients with ANCA-associated vasculitis. A high frequency of patients develops hypertension, diabetes mellitus and hypercholesterolaemia, either as a consequence of immunosuppression or associated with the underlying disease. The current control of modifiable cardiovascular risk factors is insufficient and thorough reviews should be performed periodically. Treatment of these risk factors should be adopted according to current recommendations related to individual cardiovascular risk prediction.
| S-EPMC7190116 | biostudies-literature