Publications by authors named "Appel G"

Article Synopsis
  • IgA vasculitis (IgAV) is a pediatric disease characterized by skin and systemic symptoms, and researchers conducted comprehensive studies involving genome, transcriptome, and proteome analyses on a large cohort of IgAV patients and controls to better understand the disease mechanisms.* -
  • Significant associations were found with specific genetic risk factors, including two novel non-HLA loci linked to IgA receptor functioning, which may contribute to disease development through altered immune responses.* -
  • Systems biology approaches helped identify key regulatory networks and master regulators in myeloid cells, along with 21 genetic loci that overlap with IgA nephropathy, suggesting shared pathways in these related conditions.*
View Article and Find Full Text PDF

Purpose: During the third-year emergency medicine (EM) clerkship, medical students are immersed in traumatic incidents with their patients and clinical teams. Trauma-informed medical education (TIME) applies trauma-informed care (TIC) principles to help students manage trauma. We aimed to qualitatively describe the extent to which students perceived the six TIME domains as they navigated critical incidents during their EM clerkship.

View Article and Find Full Text PDF

Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression.

View Article and Find Full Text PDF

Key Points: Lademirsen, an anti–microRNA-21 therapy, was generally well-tolerated in adults with Alport syndrome at risk of rapid disease progression. There were no significant differences between lademirsen-treated and placebo-treated participants in eGFR at any timepoint. The proportions of participants with prespecified reductions in eGFR at weeks 24 and 48 were not significantly different for lademirsen versus placebo.

View Article and Find Full Text PDF

To produce a qualitative description of the impact of moral injury on medical providers during the COVID-19 pandemic. A convergent mixed-methods study design was used to explore experiences of health care workers during the first 12 months of the COVID-19 pandemic. Participants completed the Moral Injury Symptom Scale-HP (MISS-HP) and a 60-minute interview, in which they described their work experiences from March 2020 through January 2021.

View Article and Find Full Text PDF

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

View Article and Find Full Text PDF

Fibronectin glomerulopathy is a rare inherited kidney disease, characterized by abnormal accumulation of fibronectin in the glomeruli. We report an exceptional case of recurrent fibronectin glomerulopathy first diagnosed in the kidney allograft. The presence of IgA staining in the native kidney biopsy and the reported family history of IgA nephropathy had led to initial pretransplant diagnosis of IgA nephropathy.

View Article and Find Full Text PDF

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

View Article and Find Full Text PDF

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

View Article and Find Full Text PDF

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

View Article and Find Full Text PDF
Article Synopsis
  • Proteinuric kidney diseases, particularly focal segmental glomerulosclerosis (FSGS), are difficult to diagnose and manage, and genetic testing is often too late for timely action.
  • A study was conducted on 10 patients with FSGS or minimal change disease to see if rapid genome sequencing (GS) could be incorporated into standard nephrology appointments, achieving an average result turnaround of 21.8 days.
  • Results showed that GS helped diagnose genetic forms of kidney disease in half the patients, changed treatment plans, and improved transplant evaluation, indicating that real-time GS can enhance outpatient kidney care, though more research is needed on its broader benefits and costs.
View Article and Find Full Text PDF

Background: The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (PLA2R) antibody levels as a marker of treatment response in membranous nephropathy; however, the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown.

Methods: We used a cohort of 85 patients from the Membranous Nephropathy Trial Of Rituximab (MENTOR) with anti-PLA2R antibodies ≥14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab. Three landmark times were considered: at baseline and after 3 and 6 months of treatment.

View Article and Find Full Text PDF
Article Synopsis
  • IgA nephropathy (IgAN) is a serious kidney disease linked to IgA buildup, and a large study identified 30 genetic risk factors associated with it.
  • Fourteen new loci were discovered that suggest a connection between genetic influences and abnormal IgA levels.
  • The research highlights inflammation-related pathways and potential drug targets, revealing that higher genetic risk scores are tied to earlier kidney failure.
View Article and Find Full Text PDF

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min per 1.

View Article and Find Full Text PDF

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.

View Article and Find Full Text PDF

Patients with co-occurring substance use disorders and borderline personality disorder have high rates of morbidity, mortality, and utilization of medical services. Their acute symptoms present complex challenges to clinical staff in the medical emergency department related to both logistics and management of countertransference. This article examines patterns in countertransference and proposes application of psychodynamically informed principles and strategies to facilitate safety and enhance communication during fraught clinical encounters.

View Article and Find Full Text PDF

Significance Statement: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years.

View Article and Find Full Text PDF

Background: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope.

View Article and Find Full Text PDF

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage.

View Article and Find Full Text PDF