scholarly journals AB0400 URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITISIN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1228-1228
Author(s):  
S. Hakroush ◽  
B. Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Urinary Albumin ◽  
Histopathological Diagnosis ◽  
Creatinine Ratio ◽  
Short Term ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies ◽  
Severe Deterioration

Background:Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death.Objectives:We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV.Methods:A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study.Results:Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria. Severe deterioration of kidney function requiring RRT within 30 days after admission was associated with elevated levels of nonselective proteinuria, mostly attributed to albuminuria (uACR). Because we have previously shown that histologically confirmed ANCA GN with glomerular crescents and necrosis is associated with AKI and requirement of RRT during short-term disease course and elevated uACR levels were equally associated with AKI and requirement of RRT during the short-term course after disease onset, we next analyzed the association between uACR measurements at admission and histopathological findings within renal biopsies performed thereafter. Severely increased uACR levels >300 mg/g correlated with reduction of normal glomeruli, attributed to increased glomerular crescents and necrosis. By contrast, no such association was observed for global sclerotic glomeruli, revealing that uACR reflects crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. Since uACR levels could reflect both, either a specific renal involvement with necrotizing and crescentic ANCA GN or severity of systemic AAV disease, we next correlated uACR levels assessed at admission with extrarenal disease manifestation. We observed no association between uACR levels and extrarenal manifestation of AAV disease including pulmonary hemorrhage, skin involvement and BVAS assessment, suggesting that uACR levels reflected specific renal involvement in AAV. These observations were further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease.Conclusion:Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.Disclosure of Interests:None declared

MO303URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS IN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Clinical Importance ◽  
Kidney Injury ◽  
Histopathological Diagnosis ◽  
Intermediate Risk ◽  
Creatinine Ratio ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies

Abstract Background and Aims Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV. Method A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Results Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria predominated by albumin (uACR). Severely increased uACR levels >300 mg/g correlated with reduction of normal glomeruli (P<0.001), attributed to increased glomerular crescents (P<0.001) and necrosis (P=0.008). By contrast, no such association was observed for global sclerotic glomeruli (P=0.58), revealing that uACR reflects necrotizing and crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. These findings were additionnaly bolstered by histopathological subgrouping and ARRS: patients with uACR levels >300 mg/g were classified either into Berden’s crescentic class (P=0.002) or ANCA renal risk score (ARRS) high/intermediate risk (P=0.003). No association between uACR levels and extrarenal manifestation of AAV disease could be observered, suggesting that uACR levels reflected specific renal involvement with ANCA GN and further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease. In summary, uACR measurements at admission were associated with renal biopsy findings thereafter. Levels of uACR >300 mg/g were more frequently observed in necrotizing and crescentic ANCA GN with classification either into Berden’s crescentic class or ARRS high/intermediate risk and specific for renal involvement in AAV. Conclusion Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.

MO083SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Björn Tampe ◽  
Samy Hakroush
Keyword(s):  
High Risk ◽  
Immunosuppressive Therapy ◽  
Kidney Function ◽  
Current Knowledge ◽  
Renal Involvement ◽  
Remission Induction ◽  
Tubulointerstitial Injury ◽  
Short Term ◽  
Tubulointerstitial Lesions ◽  
Renal Biopsies

Abstract Background and Aims Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously reported that severe deterioration of kidney function is associated with necrotizing and crescentic ANCA glomerulonephritis (GN), classified into Berden’s crescentic class or ANCA renal risk score (ARRS) high risk. However, tubulointerstitial inflammation associated with either histopathological subgrouping or ARRS remains elusive. Furthermore, clinical and laboratory markers of AAV disease severity or deterioration of kidney function in association with inflammatory findings in the kidney have not been described yet. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, we here aimed to expand our current knowledge with regard to histopathological classification of tubulointerstitial injury and inflammatory findings analogous to the Banff classification. Method A total number of 50 renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Renal biopsies were evaluated for either focal, crescentic, mixed or sclerotic class (according to Berden et al.) and ARRS low, intermediate or high risk (according to Brix et al.). Inflammatory and fibrotic tubulointerstital alterations were evaluated analogous to Banff scoring system for allograft pathology. Results We here show that distinct inflammatory lesions are associated with glomerular findings classified into either histopathological subgrouping or ARRS. Furthermore, interstitial inflammation and tubulitis correlate with disease severity and decline of kidney function in AAV. Finally, we provide data that tubulointerstitial injury and inflammatory findings correlate with short-term outcome in response to aggressive immunosuppression and remission induction therapy. Conclusion In summary, we here provide evidence that a systematic scoring of inflammatory and degenerative tubulointerstitial lesions correlate with severe renal impairment and short-term response to remission induction therapy. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, systematic histopathological scoring of tubuloinsterstital lesions could further improve our current knowledge of ANCA GN progression.

scholarly journals Glucocorticoid maintenance therapy and severe infectious complications in ANCA-associated vasculitis: a retrospective analysis

2020 ◽  
Author(s):  
Claudius Speer ◽  
Christine Altenmüller-Walther ◽  
Jan Splitthoff ◽  
Christian Nusshag ◽  
Florian Kälble ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Kidney Function ◽  
Patient Survival ◽  
Disease Onset ◽  
Infectious Complications ◽  
Physical Damage ◽  
Anca Associated Vasculitis ◽  
Time To Relapse ◽  
The Impact ◽  
Patient Survival Time

AbstractTo study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme (< 7.5 mg) or patients treated with glucocorticoids ≥ 7.5 mg after 6 months. Compared to patients receiving < 7.5 mg glucocorticoids after 6 months, patients receiving $$\ge $$ ≥ 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p < 0.001), including urinary tract infection (p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 − 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with $$\ge $$ ≥ 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.

scholarly journals The role of urinary renalase on early-stage renal damage in Chinese adults with primary hypertension

2020 ◽  
Vol 245 (6) ◽  
pp. 576-582
Author(s):  
Na-Na You ◽  
Wei-Hong Jiang ◽  
Ming-Yuan Lin ◽  
Xiao-Gang Li ◽  
Yu-Yan Wu ◽  
...  
Keyword(s):  
Kidney Function ◽  
Renal Injury ◽  
Renal Damage ◽  
Early Stage ◽  
Urinary Albumin ◽  
Primary Hypertension ◽  
Enzyme Linked Immunosorbent Assay ◽  
Creatinine Ratio ◽  
Clinical Value ◽  
Predictive Index

It would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Previous findings have shown renalase not only plays an important role in hypertension but also closely correlates with kidney function. The purpose of this study is to investigate whether urinary renalase could be used as a predictive index of early-stage renal damage in patients with primary hypertension. Urinary albumin to creatinine ratio (UACR) was used to divide subjects with primary hypertension into two groups: a no renal damage (NRD) group (UACR <30 mg/g) and an early-stage renal damage (RD) group (UACR >30 mg/g). Subjects with normal examination results were randomly included in a healthy control (HC) group. Urinary renalase was determined through an enzyme-linked immunosorbent assay (ELISA). Urinary renalase continued to reduce among the HC (n = 81), NRD (n = 84) and RD group (n = 80), while systolic blood pressure (SBP) increased. Urinary renalase was negatively correlated with SBP in all the groups. Among the subjects with stage 1 primary hypertension, urinary renalase in the RD group was lower than the NRD group, while the UACR was higher, and urinary renalase was negatively correlated with the UACR. A multiple linear stepwise regression analysis showed that there was a linear regression relationship between the increase of the UACR and urinary renalase, heart rate (HR), SBP and serum creatinine. In addition, the standardized partial regression coefficient of urinary renalase was the highest. The performance of urinary renalase as a marker for the diagnosis of early-stage renal damage in patients with primary hypertension was 0.968 with a cut off value of 2.01 µg/ml. Taken together, urinary renalase was further decreased in patients with early-stage renal damage and primary hypertension, and consequently, it could be used as a predictive index. Impact statement In patients with early-stage kidney damage of primary hypertension, there are no obvious structural or functional changes, which leads to a high level of diagnostic omissions. Therefore, it would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Urinary albumin to creatinine ratio (UACR) is a classic indicator used in early-stage renal damage, but it is affected by many factors. Renalase, a protein discovered by Xu in 2005, not only plays an important role in hypertension but also closely correlates with kidney function. In our study, we found that urinary renalase was further decreased in patients with early-stage renal damage in primary hypertension, and it could be used as a predictive index. This finding could help to diagnose the early-stage renal damage in primary hypertension much earlier and improve the prognosis of these patients.

scholarly journals Transtubular potassium gradient predicts kidney function impairment after adrenalectomy in primary aldosteronism

2020 ◽  
Vol 11 ◽  
pp. 204062232094479
Author(s):  
Hung-Wei Liao ◽  
Shuo-Meng Wang ◽  
Chieh-Kai Chan ◽  
Yen-Hung Lin ◽  
Po-Chih Lin ◽  
...  
Keyword(s):  
Left Ventricular Mass ◽  
Kidney Function ◽  
Primary Aldosteronism ◽  
Organ Damage ◽  
Left Ventricular ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
End Organ Damage ◽  
Function Impairment ◽  
Potassium Gradient

Background: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. Methods: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass. Results: In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. Conclusions: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

scholarly journals Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis

2021 ◽  
Vol 10 (12) ◽  
pp. 2682
Author(s):  
Samy Hakroush ◽  
Désirée Tampe ◽  
Peter Korsten ◽  
Philipp Ströbel ◽  
Björn Tampe
Keyword(s):  
Medical Center ◽  
Renal Involvement ◽  
Disease Onset ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Small Vessel Vasculitis ◽  
Glomerular Sclerosis ◽  
Tubular Injury ◽  
Injury Patterns ◽  
Renal Biopsies ◽  
Glomerular Lesions

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.

FC 032THE EFFECT OF AVACOPAN, A COMPLEMENT C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS WITH RENAL DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
David Jayne ◽  
Peter Merkel ◽  
Pirow Bekker ◽  
Jeffrey McMahon ◽  
Thomas J Schall ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Renal Involvement ◽  
Creatinine Ratio ◽  
Rapid Improvement ◽  
Phase 3 ◽  
C5a Receptor ◽  
Anca Associated Vasculitis ◽  
Stage 4 ◽  
Similar Decrease

Abstract Background and Aims Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life- or organ-threatening condition in which patients experience severe inflammation of small arteries. Renal involvement is common in ANCA-associated vasculitis and is correlated with high morbidity and mortality. Current treatment regimens have limited efficacy for renal disease in patients presenting with organ- or life-threatening ANCA-associated vasculitis. Avacopan, a novel orally-administered antagonist of the complement fragment C5a receptor (C5aR), was evaluated through a Phase 3 trial in patients with ANCA vasculitis. Efficacy and safety results have been previously reported; this abstract provides details of the effects on renal function in patients with renal involvement. Method The ADVOCATE trial was a randomized, double-blind, active controlled, double-dummy, 52-week treatment Phase 3 trial of 331 patients with ANCA-associated vasculitis. Patients were randomized 1:1 and received either a standard daily prednisone dosing with taper (i.e., starting at 60 mg / day tapered to 0 mg by Week 21), or daily avacopan. Background therapy included either: a) cyclophosphamide (oral or IV) followed by azathioprine, or, b) rituximab (four IV infusions). Patients with active glomerulonephritis at baseline were included in this analysis. Kidney function was analyzed based on the following parameters, which were assessed at pre-specified time-points: changes in the urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and Urinary Monocyte Chemoattractant Protein-1 (MCP-1):Creatinine ratio. Results At the baseline visit, 265 patients had renal disease. eGFR improved more in the avacopan group (n=131) compared to the prednisone group (n=134). At Week 26, eGFR increased 5.8 mL/min/1.73 m2 (from a baseline of 44.6 mL/min/1.73 m2), compared to 2.9 mL/min/1.73 m2 in the prednisone group (from a baseline of 45.6 mL/min/m2), P=0.046. At Week 52, the increases in eGFR were 7.3 mL/min/1.73 m2 and 4.1 mL/min/1.73 m2, respectively, P=0.029. The improvement was most prominent in subjects with Stage 4 kidney disease at baseline (eGFR &lt; 30 mL/min/1.73 m2), in whom eGFR improved 13.7 mL/min/1.73 m2 at Week 52 in the avacopan group (from a baseline of 21.1 mL/min/1.73 m2) compared to 8.2 mL/min/1.73 m2 in the prednisone group (from a baseline of 21.6 mL/min/1.73 m2), P=0.005. In addition to the differences in eGFR, a more rapid decrease in UACR was observed with avacopan; by Week 3 this difference was statistically significant, and at Week 4, a 40% decrease from baseline occurred in the avacopan group vs no change from baseline in the prednisone group (P&lt;0.0001). By Week 52, both groups showed a similar decrease in UACR from baseline. The urinary MCP-1:creatinine ratio decreased 59% in the avacopan group by Week 13 vs 52% in the prednisone group, P=0.03, but there was a similar decrease in the two treatment groups by Week 52. Conclusion Treatment with avacopan in patients with ANCA-associated vasculitis with renal disease led to greater recovery in eGFR when compared to standard prednisone therapy, especially in patients with Stage 4 kidney disease (eGFR &lt;30 mL/min/1.73 m2). Avacopan also led to more rapid improvement in the UACR and urinary MCP-1:creatinine ratio than prednisone. Since albuminuria is an independent risk factor for progression of renal disease (in addition to eGFR decline), the more rapid improvement in albuminuria with avacopan may also provide long-term benefit. These findings have important implications for the health of patients with ANCA-associated vasculitis.

scholarly journals Meta-analyses identify DNA methylation associated with kidney function and damage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pascal Schlosser ◽  
Adrienne Tin ◽  
Pamela R. Matias-Garcia ◽  
Chris H. L. Thio ◽  
Roby Joehanes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Kidney Function ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Urinary Albumin ◽  
Creatinine Ratio

AbstractChronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

scholarly journals P0444SEASONALITY HAS NO ASSOCIATION WITH TIMING OF DIAGNOSIS OF RENAL ANCA ASSOCIATED VASCULITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marina Frleta-Gilchrist ◽  
Oshorenua Aiyegbusi ◽  
Malcolm MacKinnon ◽  
Jamie Traynor ◽  
Emily McQuarrie ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Seasonal Variation ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Renal Involvement ◽  
Disease Onset ◽  
Seasonal Incidence ◽  
Anca Associated Vasculitis ◽  
Significant Difference

Abstract Background and Aims Seasonal variation of ANCA associated vasculitis (AAV) and a possible link to extrinsic infective triggers is predominantly based on single centre epidemiological data. Despite frequent confounding factors including difficulty in identifying the precise time of disease onset, seasonality may be associated with the type of vasculitis and may impact the incidence of renal involvement. Therefore, the aim of this study was to explore if there is an association between seasonality, severity and incidence of biopsy-proven renal vasculitis in the Scottish population. Method Using the Scottish renal biopsy registry, we identified all adult native renal biopsies performed across Scotland between 2014 and 2018 with a diagnosis of AAV, including microscopic polyangiitis (MPA) and granulomatosis with polyangitis (GPA). Demographic data including ANCA antibody status, histological diagnosis, estimated glomerular filtration rate (eGFR) and proteinuria at presentation were recorded. Seasons were defined as autumn (September – November), winter (December-February), spring (March – May) and summer (June - August). Statistical analysis was performed using multivariate ANOVA analysis and Student’s t-test in parametric data. Results 339 cases of biopsy proven AAV were identified and included in the analysis. In this cohort, 53% were female with mean patient age of 65.6 years (± 13). Mean estimated glomerular filtration rate (eGFR) at the time of diagnosis of AAV was 32 (± 27.2) mL/min/1.73m2 and median urinary protein creatinine ratio (uPCR) was 146mg/mmol (IQR 79.8 – 271.3). Diagnosis of MPA n=209(62%) was more common than GPA n=130(38%) and patients with MPA were significantly younger at presentation (63.5 ± 13.6 ‘vs’ 67 ± 12.7 years, p = 0.017). Otherwise, these groups did not differ in mean eGFR (MPA 29.6 ± 25.7 ‘vs’ GPA 34.8 ± 27.6 mL/min/1.73m2) or median uPCR (MPA 147, IQR 78.6 – 286.5 ‘vs’ GPA 139, IQR 80.5 – 261 mg/mmol) at onset. We observed a mean of 3.5 (± 1) new cases of MPA and 2.1 (± 0.7) new cases of GPA per month, with no significant difference observed in month-to-month comparison. Seasonal analysis showed mean occurrence of 11.4 (± 4.5) cases of MPA in autumn, 11.2 (± 4.9) in winter, 10.6 (± 1.5) in spring and 8.6 (± 1.9) in summer months. In GPA, mean 6.6 (±2.7) cases occurred each autumn, 5.4 (± 3) in winter, 7.2 (± 2.9) in spring and 6.4 (± 0.9) in summer months. Overall, no significant differences in monthly or seasonal incidence across 5 years of monitoring were detected. Similarly, we observed no difference in renal function at presentation during different seasons for MPA (mean eGFR range 21.8 – 37.6 mL/min/1.73m2, uPCR median range 112 – 167.5 mg/mmol) or GPA (mean eGFR range 32-37 mL/min/1.73m2; uPCR median range 110 – 244 mg/mmol). Conclusion Our data suggest that there is no seasonal variation in the incidence of AAV diagnosed on kidney biopsy in patients living in Scotland. Additionally, patients present with similar levels of kidney function regardless of season. Thus traditional holiday periods i.e. Easter/Christmas do not seem to lead to a delay in diagnosis. This is the first study to consider seasonality in a complete national cohort and suggests that seasonal extrinsic factors do not play a major role in the pathogenesis leading to AAV onset.

scholarly journals AB0497 RENAL INVOLVEMENT IN ANCA-ASSOCIATED VASCULITIS: DO THE PRESENCE OF ANCA AND THEIR TYPE MATTER?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1546.2-1547
Author(s):  
N. Bulanov ◽  
E. Stolyarevich ◽  
A. Zykova ◽  
E. Safonova ◽  
E. Shchegoleva ◽  
...  
Keyword(s):  
Risk Score ◽  
Renal Involvement ◽  
Survival Rates ◽  
Disease Onset ◽  
Morphological Features ◽  
Renal Survival ◽  
Research Support ◽  
Anca Associated Vasculitis ◽  
Kaplan Meier ◽  
Significant Difference

Background:The role of ANCA type is well established for the risk of relapses of ANCA-associated vasculitis (AAV). However their association with renal involvement and its outcomes is less well understood.Objectives:To assess clinical and morphological features of ANCA-associated glomerulonephritis (ANCA-GN) and renal survival in ANCA-negative patients, proteinase-3-ANCA (pr3-ANCA) positive and myeloperoxidase-ANCA (MPO-ANCA) positive patients.Methods:We enrolled 53 patients with AAV, diagnosed according to Chapel Hill Consensus Conference (2012) definition and/or ACR (1990) criteria, with histologically proven renal involvement. There were 13 (24.5%) males, median age at onset was 48 (33; 57) years. Seven patients were ANCA-negative (13.3%), 17 (32.0%) patients were pr-3-ANCA positive and 29 (54.7%) patients were MPO-ANCA-positive. ANCA-associates glomerulonephritis (ANCA-GN) class was established according to Berden et al classification.1We retrospectively assessed ANCA renal risk score (ARRS) at disease onset.2Twelve patients (22.6%) developed end-stage renal disease (ESRD) after a median of 12 (6.5; 28) months. Renal survival rates were assessed by Kaplan-Meier method and compared by log-rank test.Results:The only significant difference was median BVAS score which was significantly higher in pr3-ANCA-positive (18 (17;20)) than in MPO-ANCA positive patients (15 (12; 18), p=0.012). Creatinine levels, eGFR, percentage of glomeruli with crescents, global sclerosis, and interstitial fibrosis and tubular atrophy didn’t depend on the presence of ANCA or type of the antibodies. The proportion of patients with focal, crescentic, mixed of sclerotic class of ANCA-GN was similar in all groups. There was no significant difference in the numbers of patients with low, medium or high risk of ESRD according to ARRS. One- and three-year renal survival rates were similar in ANCA-negative (81.7% and 60.0% respectively) and ANCA-positive patients (84.2% and 74.6% respectively, Figure 1A). One-year and three-year survival rates were higher in MPO-ANCA-positive (84.4% and 84.4% respectively) than in pr3-ANCA-positive patients (73.1% and 50.1% respectively), however the difference was not statistically significant (Figure 1B).Figure 1.Kaplan-Meier curves showing renal survival in ANCA-positive and ANCA-negative patients (A), and pr3-ANCA-positive and MPO-ANCA-positive patients (B)Conclusion:Our small study indicates that clinical and morphological features of renal involvement, as well as renal survival are similar in ANCA-negative and ANCA-positive patients and don’t depend on the type of ANCA.References:[1]Berden AE, Ferrario F, Hagen EC, et al. Histopathologic Classification of ANCA-Associated Glomerulonephritis. J Am Soc Nephrol. 2010;21(10):1628–1636.[2]Brix RB, Noriega M, Tennstedt P, et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 2018;94(6):1177-1188.Disclosure of Interests: :Nikolai Bulanov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Ekaterina Stolyarevich: None declared, Anastasiia Zykova: None declared, Elizaveta Safonova: None declared, Elena Shchegoleva: None declared, Ekaterina Kuznezova: None declared, Mayra Bulanova: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow

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