-
1.
The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.
Bate, S, McGovern, D, Costigliolo, F, Tan, PG, Kratky, V, Scott, J, Chapman, GB, Brown, N, Floyd, L, Brilland, B, et al
Journal of the American Society of Nephrology : JASN. 2024;(3):335-346
Abstract
SIGNIFICANCE STATEMENT Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
-
2.
ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review.
Faz-Muñoz, D, Hinojosa-Azaola, A, Mejía-Vilet, JM, Uribe-Uribe, NO, Rull-Gabayet, M, Muñoz-Castañeda, WR, Vargas-Parra, NJ, Martín-Nares, E
Immunologic research. 2022;(4):550-559
-
-
Free full text
-
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are infrequent autoimmune diseases characterized by inflammation of the walls of small vessels leading to tissue and endothelial damage. On the other hand, IgG4-related disease is a fibroinflammatory disease characterized histologically by lymphoplasmacytic infiltrates with IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis that may affect nearly every organ of the body. There are similarities in clinical, serological, radiological, and histopathological features between both diseases, and hence, they usually mimic each other complicating the differential diagnosis. Furthermore, reports of patients with the coexistence of both conditions (overlap syndrome) have been reported. We herein report a patient with an unequivocal diagnosis of ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (posterior uveitis, polyneuropathy, pauci-immune glomerulonephritis with crescent formation and granulomas, and MPO-ANCA positivity) and IgG4-related disease (thoracic aortitis, tubulointerstitial nephritis with prominent IgG4+ plasma cell infiltration, fibrosis, and obliterative arteritis, high levels of serum IgG4, and eosinophilia) overlap syndrome.
-
3.
Voclosporin: a novel calcineurin inhibitor for the management of lupus nephritis.
Mejía-Vilet, JM, Romero-Díaz, J
Expert review of clinical immunology. 2021;(9):937-945
Abstract
INTRODUCTION Kidney survival rates in lupus nephritis (LN) remain suboptimal, with 10-20% of patients progressing to end-stage kidney disease by 10-20 years. Recently, the landscape of LN management has changed with the advent of new molecules that have demonstrated safety and efficacy in clinical trials. AREAS COVERED In this review, we approach the current state of LN management, the unmet therapeutic needs, and deep dive into voclosporin, a novel calcineurin inhibitor (CNI) that has demonstrated improved efficacy when added to a mycophenolate mofetil (MMF) and glucocorticoid regimen, without an increase in adverse events. We focus on the characteristics of this new CNI and the studies that led to its approval by the US FDA. EXPERT OPINION Voclosporin adds to therapeutic options for LN. This drug offers potential advantages over other CNIs. The addition of voclosporin to a standard-of-care regimen of MMF/glucocorticoids demonstrated higher and faster response rates. As other regimens, a combination of CNI, MMF, and glucocorticoids must be individualized and is not appropriate for all patients. Some questions remain to be answered for this regimen, such as the length of treatment, the tapering schedule, and its long-term safety and efficacy for preserving kidney function.
-
4.
Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases.
Rovin, BH, Adler, SG, Barratt, J, Bridoux, F, Burdge, KA, Chan, TM, Cook, HT, Fervenza, FC, Gibson, KL, Glassock, RJ, et al
Kidney international. 2021;(4):753-779
Abstract
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
-
5.
The Use of Glucocorticoids in Lupus Nephritis: New Pathways for an Old Drug.
Mejía-Vilet, JM, Ayoub, I
Frontiers in medicine. 2021;:622225
Abstract
Glucocorticoids therapy has greatly improved the outcome of lupus nephritis patients. Since their discovery, their adverse effects have counterbalanced their beneficial anti-inflammatory effects. Glucocorticoids exert their effects through both genomic and non-genomic pathways. Differential activation of these pathways is clinically relevant in terms of benefit and adverse effects. Ongoing aims in lupus nephritis treatment development focus on a better use of glucocorticoids combined with immunosuppressant drugs and biologics. Newer regimens aim to decrease the peak glucocorticoid dose, allow a rapid glucocorticoid tapering, and intend to control disease activity with a lower cumulative glucocorticoid exposure. In this review we discuss the mechanisms, adverse effects and recent strategies to limit glucocorticoid exposure without compromising treatment efficacy.
-
6.
A Risk Score to Predict Admission to the Intensive Care Unit in Patients with COVID-19: the ABC-GOALS score.
Mejía-Vilet, JM, Córdova-Sánchez, BM, Fernández-Camargo, DA, Méndez-Pérez, RA, Morales-Buenrostro, LE, Hernández-Gilsoul, T
Salud publica de Mexico. 2020;(1, ene-feb):1-11
Abstract
OBJECTIVE To develop a score to predict the need for ICU admission in COVID-19. METHODS We assessed patients admitted to a COVID-19 center in Mexico. Patients were segregated into a group that required ICU admission, and a group that never required ICU admission. By logistic regression, we derived predictive models including clinical, laboratory, and imaging findings. The ABC-GOALS was constructed and compared to other scores. RESULTS We included 329 and 240 patients in the development and validation cohorts, respectively. One-hundred-fifteen patients from each cohort required ICU admission. The clinical (ABC-GOALSc), clinical+laboratory (ABC-GOALScl), clinical+laboratory+image (ABC-GOALSclx) models area under the curve were 0.79 (95%CI=0.74-0.83) and 0.77 (95%CI=0.71-0.83), 0.86 (95%CI=0.82-0.90) and 0.87 (95%CI=0.83-0.92), 0.88 (95%CI=0.84-0.92) and 0.86 (95%CI=0.81-0.90), in the development and validation cohorts, respectively. The ABC-GOALScl and ABC-GOALSclx outperformed other COVID-19 and pneumonia predictive scores. CONCLUSION ABC-GOALS is a tool to timely predict the need for admission to ICU in COVID-19.
-
7.
Validation of a renal risk score in a cohort of ANCA-associated vasculitis patients with severe kidney damage.
Mejía-Vilet, JM, Martín-Nares, E, Cano-Verduzco, ML, Pérez-Arias, AA, Sedano-Montoya, MA, Hinojosa-Azaola, A
Clinical rheumatology. 2020;(6):1935-1943
Abstract
OBJECTIVE To validate the renal risk score in a cohort of patients with advanced kidney damage. METHODS A total of 72 patients with biopsy-proven ANCA glomerulonephritis with >12 months of follow-up were studied. The renal risk score was calculated and evaluated by survival analysis for time of renal survival. Cohort-specific clinical, histopathologic, and post-treatment factors associated with renal survival were determined by Cox regression analysis. RESULTS Kidney biopsies were classified as focal, crescentic, mixed, and sclerotic classes in 6 (8%), 4 (6%), 25 (35%), and 37 (51%) patients, respectively. The 1-, 3-, and 5-year renal survival rates were 79%, 73%, and 68%, respectively. Patients were segregated by the risk score in low- (18%), medium- (47%), and high-risk (35%) groups. Patients in the low-risk group had 36-, 60-, and 84-month renal survival of 100%; those in the medium risk 85% (95% CI 72-92), 81% (95% CI 66-95), and 76% (95% CI 60-92), respectively; and those in the high risk 37% (95% CI 17-57), 26% (95% CI 7-45), and 18% (95% CI 1-36), respectively. Six (43%) of the 14 patients in the high-risk group recovered renal function after the initial episode, and 2 (14%) remained dialysis-free. Other parameters associated with renal survival included age, proteinuria, general symptoms, cellular crescents, glomerulosclerosis, tubulointerstitial lesions, best post-treatment eGFR, and renal relapses. CONCLUSIONS We validated the renal risk score as a prognostic tool in a cohort with predominantly mixed and sclerotic histologic categories. Since patients in the high-risk group still benefited from immunosuppressive therapy, this score should be used in conjunction with other predictive parameters to aid therapeutic decisions.Key Points• The ANCA renal risk score is validated in a cohort with advanced kidney damage.• Patients in the high-risk group still benefited from immunosuppressive therapy.• Parameters not included in the risk score are associated with renal survival and may be useful.
-
8.
Immunosuppressive treatment for pure membranous lupus nephropathy in a Hispanic population.
Mejía-Vilet, JM, Córdova-Sánchez, BM, Uribe-Uribe, NO, Correa-Rotter, R
Clinical rheumatology. 2016;(9):2219-27
Abstract
Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19-16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08-5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010-1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.