Immunoglobulin-Negative Fibrillary Glomerulonephritis Masked in Diabetic Nephropathy: A Case Report and Discussion of a Diagnostic Pitfall.

Introduction: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease with poor prognosis, characterized by deposition of randomly arranged fibrillar material measuring 10-30 nm in diameter. This diagnosis is confirmed with DNAJB9 immunohistochemistry as well as ultrastructural examination. Ultrastructurally, the fibrillary material seen in this entity may be confused with diabetic fibrillosis occurring in diabetic nephropathy. Case Presentation: We present a case of a 63-year-old African American male with remote hepatitis C virus (HCV) infection and type II diabetes mellitus who presented with chronic kidney disease and nephrotic range proteinuria. A kidney biopsy revealed PAS-positive mesangial matrix expansion consistent with diabetic nephropathy and focal randomly oriented fibril deposition on ultrastructural examination. Immunofluorescence for immunoglobulin G and light chains was negative by both routine and paraffin immunofluorescence. Immunohistochemistry for DNAJB9 was diffusely positive, confirming co-existing FGN. Discussion/Conclusion: Patients with diabetic nephropathy and FGN have similar clinicopathologic presentations with a slowly progressive onset of kidney failure and proteinuria. In diabetic patients with fibrillary deposits under ultrastructural examination, concurrence of these disease entities must be considered. In this patient with remote HCV infection that was successfully treated years before, it is possible that in the absence of an FGN trigger, there was a loss of antigenicity with a loss of immunoglobulin staining. Therefore, we recommend DNAJB9 immunostaining for patients with remote HCV infection to avoid this diagnostic pitfall. Further studies are needed to determine the potential role of HCV infection in the initiation and etiopathogenesis of FGN.

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

Abridged mindfulness intervention to support wellness in first-year medical students.

BACKGROUND: Medical students experience a high burden of stress and suffer elevated rates of depression, burnout, and suicide compared to the general population, yet there is no consensus on how to address student wellness. PURPOSES: The purpose of this study was to determine whether an abridged mindfulness based stress reduction (MBSR) intervention can improve measures of wellness in a randomized sample of 1st-year medical students. METHODS: Fifty-eight participants were randomized to control or 8-week MBSR intervention and then invited to participate in the study. All participants were assessed using the Perceived Stress Scale (PSS), the Resilience Scale (RS), and Self-Compassion Scale (SCS) at 3 separate time points: baseline, at the conclusion of the study intervention (8 weeks), and at 6 months after the conclusion of the intervention. The intervention consisted of 75 minutes of weekly class time, suggested meditation at home, and a half-day retreat in the last week. RESULTS: The intervention group achieved significant increase on SCS scores both at the conclusion of the study (0.58, p=.002), 95% confidence interval (CI) [0.23, 0.92], and at 6 months (0.56, p=.001), 95% CI [0.25, 0.87]. PSS scores achieved significant reduction at the conclusion of the study (3.63, p=.03), 95% CI [0.37, 6.89], but not at 6 months poststudy (2.91, p=.08), 95% CI [-0.37, 6.19]. The study did not demonstrate a difference in RS after the intervention, though RS was significantly correlated with both SCS and PSS. CONCLUSIONS: An abridged MBSR intervention improves perceived stress and self-compassion in 1st-year medical students and may be a valuable curricular tool to enhance wellness and professional development.

Short course induction immunosuppression with thymoglobulin for renal transplant recipients.

BACKGROUND: The aim of this study was to demonstrate that 3-days of induction immunosuppression with thymoglobulin was as effective and safe as a 7-day course and reduced initial hospitalization after transplantation. METHODS: This was a prospective, nonrandomized trial of 40 consecutive patients receiving thymoglobulin induction for 3 days and followed for 1 year. An historical group of 48 patients that received 7 days of thymoglobulin served as controls. RESULTS: At 1 year, acute rejection (5 vs. 4%), graft survival (95 vs. 98%) and patient survival were similar; a composite end point of freedom from death, rejection, or graft loss, the event-free graft survival, was similar as was the safety profile. In the 3-day group, lymphocyte depletion was more sustained and initial hospitalization was significantly shorter (6 vs. 8 days). CONCLUSION: Three-day induction with thymoglobulin is as effective and safe as seven days, decreases initial hospitalization and causes more sustained lymphocyte depletion.

In vitro T cell proliferation from kidney allograft biopsies with unremarkable pathology: new strategies for an old problem.

Acute rejection of renal allografts is mediated by infiltrating alloreactive T cells. The goals of this study were to correlate T cell proliferation with rejection and to determine whether T cell proliferation in the absence of rejection would predict future rejection episodes. Toward this, kidney biopsies (n=100) were cultured in the presence of interleukin-2. Cultures were examined at 4, 24, and 48 hr for T cell proliferation. A strong correlation was observed between T cell proliferation at any time point and rejection. There was not a significant correlation between T cell proliferation in biopsies with no rejection and the occurrence of a rejection episode within 2 months. However, T cell proliferation after 4 hr was a better predictor of the occurrence of rejection within 2 months compared with observations after 24 and 48 hr. Therefore, a subgroup of patients with unremarkable biopsies but T cell proliferation may be at risk for rejection and warrant closer observation and possible tailoring of immunosuppression.