Clinicopathological Characteristics and Influencing Factors of Renal Vascular Lesions in Anti-neutrophil Cytoplasmic Autoantibody-Related Renal Vasculitis

The purpose of this study was to evaluate the clinicopathological features of different degrees of extraglomerular renal vascular lesions (RVLs) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis and explore their clinical determinants. This is a retrospective study of 186 patients with ANCA-associated renal vasculitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. The patients who met the inclusion criteria were divided into non-renal RVLs, mild RVLs, moderate RVLs, and severe RVLs. It was found that there were significant differences in serum creatinine (SCR), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), high-density lipoprotein (HDL), systolic blood pressure (SBP), the prevalence rate of hypertension, the proportion of normal glomeruli, and the proportion of sclerotic glomeruli and interstitial fibrosis integral. SCR and ESR are independent risk factors for RVLs. The participants were followed up for 1 year, and the progression to end-stage renal disease (ESRD) and death was defined as endpoint events. We found that the survival rate of patients without RVLs was significantly higher than that of patients with RVLs and that the RVLs were an independent risk factor for ESRD or death. Early intervention in the progression of RVLs can improve the prognosis.

Reduced Regime of Glucocorticoids and Cyclophosphamide for Mild ANCA-Associated Renal Vasculitis May Delay Deterioration of Renal Function

ObjectivesTo compare the efficacy and safety of initial reduced-dose glucocorticoids combined with reduced-frequency cyclophosphamide and to determine risk predictors of end-stage renal disease in ANCA-associated vasculitis（AAV）patients with renal involvement which BVAS was less than 20.MethodsThis is a single-center retrospective cohort study that involved 58 patients who were newly diagnosed with ANCA-associated renal vasculitis. The efficacy and safety of reduced-frequency cyclophosphamide combined with initial reduced-dose glucocorticoids were compared using chi-square test. The cumulative probability to ESRD were estimated using the Kaplan–Meier method and compared using the log rank test. Potential variates were examined using multivariate Cox proportional hazard models to determine the risk predictors of end-stage renal disease.ResultsA total of 35 patients in the standard-dose glucocorticoids group and 23 in the reduced-dose glucocorticoids group were included. The average age of the included patients was 62.45±12.70 years, and the baseline serum creatinine was 251.35[155.53, 445] μmol/L. Nine patients (15.52%) developed ESRD within 24 months (7 Standard vs. 2 Reduced, P=0.035). Multivariate Cox regression model analysis proved that baseline serum creatinine (HR: 0.007, 95%CI: 2.48-39.48, P=0.014), infection rate within first 3 months (HR: 2.28, 95% CI: 2.14 45.27, P=0.003), persistent hematuria for more than 6 months (HR: 1.723, 95%CI: 0.043-0.738, P=0.017) were risk predictors of end-stage renal disease in ANCA-associated renal vasculitis.ConclusionThe regime of initial reduced-dose glucocorticoids combined with reduced-frequency cyclophosphamide is not inferior to the standard regimen in AAV patients with renal involvement which BVAS score was less than 20，and meantime the incidence of infection was significantly lowered. Patients had infection within first 3 months were at higher risk in development of ESRD. To reduce the incidence of infection and thus delay deterioration of renal function, the reduced-dose regime may be more appropriate than standard-dose regimen and can be used as an option in mild patients.

The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop glomerulonephritis, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (sCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade urinary sCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and 10 controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, urinary sCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic acute kidney injury. Urinary sCD163's specificity declined in AAV patients with nephrotic-range proteinuria and in primary podocytopathy, with 62% of nephrotic patients displaying a "positive" urinary sCD163. In AAV patients with significant proteinuria, urinary sCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions Urinary sCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates urinary sCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

544 Vasculitic Subglottic Stenosis: A Question of Immunosuppression?

Introduction Subglottic stenosis (SGS) is the commonest manifestation of tracheobronchial disease in granulomatosis with polyangiitis (GPA) and carries a high degree of morbidity. Management of SGS-GPA is a double-edged sword. Delayed treatment may cause respiratory compromise and infectious complications. However, aggressive surgical management may initiate a systemic inflammatory response, reactivating the vasculitic cascade and potentially lead to long-term complications including renal vasculitis and consequential end-stage renal failure. There is currently no internationally agreed management strategy for this disease. Method This retrospective review was undertaken to analyse our unique combination of surgical dilatations and immunosuppressive-focused adjuvant management strategy between years 2011-2020. Results Sixteen of our one hundred and nine GPA patients (14.7%) had SGS and were included in our analysis. Whilst three patients (18.8%) improved solely on medical treatment, thirteen (81.3%) required combined surgery and immunosuppression (consisting of cyclophosphamide or Rituximab regimens). Thirty-nine surgical dilatations and two tracheostomies were performed over a mean 53-month follow-up period, with a calculated mean procedure rate of one every 24.8 months (2.7 - 89 months). Conclusions Our current management strategy affords a lower procedure rate at every 24.8 months compared to other published studies with combined procedure rate at every 14.9 months.

ANCA-associated renal vasculitis is associated with rurality but not seasonality or deprivation in a complete national cohort study

BackgroundSmall studies suggest an association between ANCA-associated vasculitis (AAV) incidence and rurality, seasonality and socioeconomic deprivation. We examined the incidence of kidney biopsy-proven AAV and its relationship with these factors in the adult Scottish population.MethodsUsing the Scottish Renal Biopsy Registry, all adult native kidney biopsies performed between 2014 and 2018 with a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were identified. The Scottish Government Urban Rural Classification was used for rurality analysis. Seasons were defined as autumn (September–November), winter (December–February), spring (March–May) and summer (June–August). Patients were separated into quintiles of socioeconomic deprivation using the validated Scottish Index of Multiple Deprivation and incidence standardised to age. Estimated glomerular filtration rate and urine protein:creatinine ratio at time of biopsy were used to assess disease severity.Results339 cases of renal AAV were identified, of which 62% had MPA and 38% had GPA diagnosis. AAV incidence was 15.1 per million population per year (pmp/year). Mean age was 66 years and 54% were female. Incidence of GPA (but not MPA) was positively associated with rurality (5.2, 8.4 and 9.1 pmp/year in ‘urban’, ‘accessible remote’ and ‘rural remote’ areas, respectively; p=0.04). The age-standardised incidence ratio was similar across all quintiles of deprivation (p=ns).ConclusionsSeasonality and disease severity did not vary across AAV study groups. In this complete national cohort study, we observed a positive association between kidney biopsy-proven GPA and rurality.

Clinicopathological characteristics and outcomes of anti-neutrophil cytoplasmic autoantibody-related renal vasculitis with hyperuricemia: a retrospective case-control study

The objective of the study was to evaluate the clinicopathological characteristics and investigate the clinical determinants of patient and renal survival in the first 12 months after diagnosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis (AAV) patients with hyperuricemia. This was a retrospective case-control study in patients with AAV-related renal injury in the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. Patients who met the study criteria were divided into two groups: patients without hyperuricemia (n = 92) and patients with hyperuricemia (n = 55). Participants were followed-up for 12 months, and progressing to end-stage renal disease (ESRD) and death was treated as the endpoint event. We found that the level of serum creatinine was an independent risk factor for hyperuricemia, and the level of serum uric acid was an independent risk factors for renal survival and patient survival in ANCA-associated renal vasculitis patients. The crescents formation and the proportion of fibrous crescent likely contributed to severe clinical characteristics and renal pathological changes in ANCA-associated renal vasculitis patients with hyperuricemia. Hyperuricemia has an important influence on the progression of ANCA-associated renal vasculitis. A good control of serum uric acid may improve the prognosis.