Performance of clinical and histological prognostic scores for kidney survival in ANCA-associated vasculitis.

OBJECTIVES: Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV. METHODS: This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria. RESULTS: Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858), and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up. CONCLUSION: The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.

Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study.

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases was published in 2021. Since then, the pace of drug development for glomerular diseases has accelerated, due in large part to rapidly accumulating insights into disease pathogenesis from genetic and molecular studies of afflicted patients. To keep the Glomerular Diseases Guideline as current as possible, KDIGO made a commitment to the nephrology community to provide periodic updates, based on new developments for each disease. After the 2021 guideline was published, two novel drugs received regulatory approval for the management of lupus nephritis, leading to the first KDIGO guideline update. Herein, an executive summary of the most important guideline changes from the Lupus Nephritis chapter is provided as a quick reference.

Kidney involvement in systemic lupus erythematosus: From the patient assessment to a tailored treatment.

In the last few years, several studies have provided new evidence for the diagnosis, management, and follow-up of patients with lupus nephritis. Evidence showing dissociation between clinical and histological findings has prompted reevaluation of the role of the kidney biopsy as a tool for diagnosis and follow-up. In therapeutics, four immunosuppressive schemes now have supporting evidence for use as initial therapy. Current challenges include individualized selection of the best immunosuppressive regimen, an unmet need for non-invasive biomarkers of disease activity to inform treatment responses and guide subsequent therapy, holistic patient management in this complex, multisystem disease, and ultimately the development of more targeted therapies directed at specific effector pathways driving glomerular inflammation and damage in order to improve treatment response. In this communication, we review the diagnostic and therapeutic approach to lupus nephritis, as well as evaluation of response to therapy and disease control.

Acute Kidney Injury in Critical Care COVID-19 Patients on Invasive Mechanical Ventilation: The Potential Preventive Role of Dexamethasone

Abstract Background: A high incidence of acute kidney injury (AKI) has been reported in coronavirus disease 2019 (COVID-19) patients in critical care units and those undergoing invasive mechanical ventilation (IMV). The introduction of dexamethasone (DXM) as treatment for severe COVID-19 has improved mortality, but its effects in other organs remain under study. Objective: The objective of this study was to evaluate the association between DXM and AKI in COVID-19. Methods: In this prospective observational cohort study, we evaluated the incidence of AKI in critically ill COVID-19 patients undergoing mechanical ventilation, and the association of DXM treatment with the incidence, severity, and outcomes of AKI. The association between DXM treatment and AKI was evaluated by multivariable logistic regression. The association of the combination of DXM treatment and AKI on mortality was evaluated by Cox-regression analysis. Results: We included 552 patients. AKI was diagnosed in 311 (56%), of which 196 (63%) corresponded to severe (stage 2 or 3) AKI, and 46 (14.8%) received kidney replacement therapy. Two hundred and sixty-seven (48%) patients were treated with DXM. This treatment was associated to lower incidence of AKI (Odds Radio 0.34, 95% Confidence intervals [CI] 0.22-0.52, p < 0.001) after adjusting for age, body mass index, laboratory parameters, SOFA score, and vasopressor use. DXM treatment significantly reduced mortality in patients with severe AKI (HR 0.63, 95%CI 0.41-0.96, p = 0.032). Conclusions: The incidence of AKI is high in COVID-19 patients under IMV. DXM treatment is associated with a lower incidence of AKI and a lower mortality in the group with severe AKI.

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

A risk score to predict admission to the intensive care unit in patients with Covid-19: the ABC-GOALS score / Puntaje de riesgo para predecir el ingreso a una unidad de cuidados intensivos en pacientes con Covid-19: puntaje ABC-GOALS

Abstract: Objective: To develop a score to predict the need for intensive care unit (ICU) admission in Covid-19. Materials and 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-GOALScland ABC-GOALSclxoutperformed 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.

Resumen: Objetivo: Desarrollar un puntaje predictivo de la necesidad de ingreso a una unidad de cuidados intensivos (UCI) en Covid-19. Material y métodos: Se evaluaron pacientes ingresados por Covid-19 en México. Se dividieron en un grupo que requirió ingreso a UCI y un grupo que nunca lo requirió. Se derivaron modelos predictivos incluyendo variables clínicas, de laboratorio e imagen y se integraron en el puntaje ABC-GOALS. Resultados: Se incluyeron 329 y 240 pacientes en cohortes de desarrollo y validación, respectivamente. Ciento quince pacientes de cada cohorte requirieron ingreso a UCI. Las áreas bajo la curva de los modelos clínico (ABC-GOALSc), clínico+laboratorio (ABC-GOALScl), clínico+laboratorio+imagen (ABC-GOALSclx) fueron 0.79 (IC95%=0.74-0.83) y 0.77 (IC95%=0.71-0.83); 0.86 (IC95%=0.82-0.90) y 0.87 (IC95%=0.83-0.92); 0.88 (IC95%=0.84-0.92) y 0.86 (IC95%=0.81-0.90) en las cohortes de derivación y validación, respectivamente. El desempeño del ABC-GOALS fue superior a otros puntajes de riesgo. Conclusión: ABC-GOALS es una herramienta para predecir oportunamente la necesidad de ingreso a UCI en Covid-19.