A 28-year-old farmer with class IV lupus nephritis presented with a two-week history of a right shin lesion. The lesion was purple in color, fungating, and indurated with a focus of deep ulceration at the inferior pole and punctate, bleeding from its surface. Three months earlier, he was started on induction immunosuppression for a relapse of his lupus nephritis. Since the diagnosis of lupus nephritis, nine years previously, he had had six flares of his disease and had been treated at different time points with cyclophosphamide, rituximab, and high-dose corticosteroids, without adverse events. Laboratory investigations showed improving kidney function (chronic kidney disease [CKD] stage IV) with reducing proteinuria, on his current immunosuppressive regimen. The differential diagnosis for this lesion was calciphylaxis, pyoderma gangrenosum, vasculitic lesion, or an infection. Histology and microbiological analysis confirmed the presence of Absidia corymbifera. He was treated with a combination of isavuconazole, reduction of his immunosuppressive agents, excision of the lesion, and skin grafting.

Background and Aims The relapsing-remitting, multi-system pattern of disease in ANCA vasculitis (AAV) results in incremental tissue injury. For those with renal involvement, there is a 9-fold increased risk of end-stage kidney disease after renal relapse. Relapse is defined by the Birmingham Vasculitis Activity Score (BVAS v3) >0, particularly in the clinical trial setting. However, this metric may be missing or incorrectly scored in real world registry data, resulting in incomplete or inaccurate ascertainment of this key outcome. Our aim was the development, internal validation and evaluation of a pragmatic data-driven algorithm to automate the retrospective identification of AAV relapse in real-world data. Method The Rare Kidney Disease (RKD) Registry is a national longitudinal, multi-centre cohort study, including 663 patients with AAV, of whom those with >6 months follow up post diagnosis were eligible for inclusion. We followed five steps to develop and validate the algorithm: 1) independent expert adjudication of encounters using primary medical record information to assign the reference probability of relapse (ground truth), 2) selection of data elements and corresponding value sets using literature review, expert opinion and with a consideration of likely data availability, 3) development of a computable phenotype definition, with an embedded logistic multi-level regression model using complete case analysis, 4) internal validation, 5) development of additional models (using the same method) to account for combinations of variable missingness (models described in Fig. 1). We also developed a Shiny web application to implement the final algorithm, which determines the appropriate model based on available variables, outputting an individualised probability of relapse, with a suggested binary interpretation. Results In the first step of the algorithm, encounters with diagnostic histopathology were labelled as relapse. For encounters without histopathological confirmation, we selected five objective data elements to build the model: change in ANCA level, suggestive blood/urine tests, suggestive imaging, immunosuppressive (IS) status at the time of the encounter and the change of this IS in response (‘IS response’) (Fig. 2). Development and validation datasets comprised 1209 and 377 separate encounters, respectively. An optimal cut-point of 0.48 was determined by maximising the F1-Score (0.85) for the complete 5-variable model. Sensitivity and specificity were 0.91 and 0.95 respectively. Performance metrics were stable across fifty random-split resamples. Calibration-in-the-large was satisfied. Where ‘IS response’ was missing, ‘suggestive bloods/urine’ (Data Element [DE]2) with at least either ‘ANCA level’ (DE1) or ‘suggestive imaging’ (DE3) was required to achieve an accuracy as good as gold standard BVAS (Fig. 1). Conclusion In settings where accurate BVAS may not be available, this algorithm accurately quantifies the individualised probability of AAV relapse using objective, readily accessible registry data. In addition to our web application, the model can be directly embedded in a registry database. This framework could serve as an exemplar for other relapsing-remitting diseases and for automating the identification of other key outcomes or cohorts in registry data.

Purpose of Review: Rituximab is increasingly prescribed for glomerular diseases. However, the recently published Kidney Disease Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Glomerular Diseases lacks details on recommended dosing regimens for most individual glomerular diseases. We performed this scoping review summarizing the evidence for rituximab dosing in glomerular disease. Sources of Information: PubMed database. Methods: The PubMed search methodology was developed with a medical librarian and performed by the first, with review by a second, author. Randomized controlled trials (RCTs) and prospective cohort studies (PCSs) examining rituximab efficacy and/or safety in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), membranous nephropathy (MN), lupus nephritis (LN), or podocytopathies (minimal change disease or focal segmental glomerulosclerosis [FSGS]) were included. Fifty-three studies (14 RCTs and 39 PCSs) were included. Key Findings: We identified 16 different rituximab dosing regimens studied as induction therapy for one or more of the 5 glomerular diseases of interest. The most frequently studied rituximab induction regimens were 1000 mg as 2 doses 2 weeks apart (17 studies, 32%) and 4 doses of 375 mg/m2/week (18 studies, 33.9%). Twenty-six studies (49%) examined rituximab as monotherapy or in conjunction with corticosteroids alone, while the remaining studies examined rituximab as part of combination immunosuppression. Adapting treatment to achieve B-cell depletion, with frequent evaluation of disease-specific biomarkers, might prove the optimal approach to achieving and maintaining remission. Rituximab might also enable steroid minimization or avoidance. Limitations: Restriction of the search to a single database and to studies published in the English language, and with an accompanying abstract, could have led to selection bias. While the search was limited to prospective observational studies and RCTs, no formal assessment of study quality was performed.

Background: End-stage kidney disease is associated with a 10- to 100-fold increase in cardiovascular mortality compared with age-, sex-, and race-matched population. Cardiopulmonary resuscitation (CPR) in this cohort has poor outcomes and leads to increased functional morbidity. Objective: The aim of this study is to assess patients’ preferences toward CPR and advance care planning (ACP). Design: cross-sectional study design. Setting: Two outpatient dialysis units. Patients: Adults undergoing dialysis for more than 3 months were included. Exclusion criteria were severe cognitive impairment or non-English-speaking patients. Measurements: A structured interview with the use of Willingness to Accept Life-Sustaining Treatment (WALT) tool. Methods: Demographic data were collected, and baseline Montreal Cognitive Assessment, Patient Health Questionnaire–9, Duke Activity Status Index, Charlson comorbidity index, and WALT instruments were used. Descriptive analysis, chi-square, and t test were performed along with probability plot for testing hypotheses. Results: Seventy participants were included in this analysis representing a 62.5% response rate. There was a clear association between treatment burden, anticipated clinical outcome, and the likelihood of that outcome with patient preferences. Low-burden treatment with expected return to baseline was associated with 98.5% willingness to accept treatment, whereas high-burden treatment with expected return to baseline was associated with 94.2% willingness. When the outcome was severe functional or cognitive impairment, then 45.7% and 28.5% would accept low-burden treatment, respectively. The response changed based on the likelihood of the outcome. In terms of resuscitation, more than 75% of the participants would be in favor of receiving CPR and mechanical ventilation at their current health state. Over 94% of patients stated they had never discussed ACP, whereas 59.4% expressed their wish to discuss this with their primary nephrologist. Limitations: Limited generalizability due to lack of diversity. Unclear decision stability due to changes in health status and patients’ priorities. Conclusions: ACP should be incorporated in managing chronic kidney disease (CKD) to improve communication and encourage patient involvement.