Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicenter real-world study.

OBJECTIVES: Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in ANCA-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement. METHODS: In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form. RESULTS: Among the 31 patients (median age 72 years), 10 had a relapsing AAV, twenty had anti-myeloperoxidase antibodies, and thirty had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2), or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favorable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73m2 [23; 45] at month 12 (p< 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration). CONCLUSIONS: The GCs' sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

Effect of steroid pulses in severe BK virus allograft nephropathy with extensive interstitial inflammation.

INTRODUCTION: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.

Urinary soluble CD163 is useful as "liquid biopsy" marker in lupus nephritis at both diagnosis and follow-up to predict impending flares.

Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC>0.972; p < 10-4 with a 100 % specificity threshold fixed at 320 ng/mmol), and for monitoring renal activity allowing prediction of impending flares and remissions in follow-up (AUC = 0.789, p < 10-4). LN-A patients with an elevated spot proteinuria/creatinuria ratio (p = 8 × 10-6) and sCD163/creatinuria ratio (p = 10-3) were at risk for developing end-stage kidney disease but sCD163/creatinuria ratio cannot substitute kidney biopsy to discriminate LN-A from other glomerulonephritis. Among serological markers (n = 14), anti-dsDNA and anti-C1q antibodies (Abs) (AUC>0.750 versus non-LN patients, and AUC>0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p < 0.001). In conclusion, and as compared to classical serological markers, the urinary sCD163/creatinuria ratio provides an additional parameter for monitoring LN patients.