The Detrimental Impact of End-Stage Kidney Disease Is Not Reflected in Autopsy Reports.

CONTEXT.­: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease. OBJECTIVE.­: To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report. DESIGN.­: Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings. RESULTS.­: One hundred sixty decedents with documented ESKD and premortem dialysis who underwent autopsy assessment were identified. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions. CONCLUSIONS.­: The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases.

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 conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy.

Primary membranous nephropathy is a leading cause of adult nephrotic syndrome. The field took a major step forward with the identification of phospholipase A2 receptor (PLA2R) as a target antigen in the majority of cases and with the ability to measure circulating autoantibodies to PLA2R. Since then, the existence of additional target antigens such as thrombospondin type-1 domain-containing 7A, exostosin 1 and 2, neural EGFL like 1, and semaphorin 3B has been demonstrated. The ability to detect and monitor levels of circulating autoantibodies has opened a new window onto the humoral aspect of primary membranous nephropathy. Clinicians now rely on clinical parameters such as proteinuria, as well as levels of circulating autoantibodies against PLA2R and the results of immunofluorescence staining for PLA2R within kidney biopsy tissue, to guide the management of this disease. The relationship between immunologic and clinical disease course is consistent, but not necessarily intuitive. In addition, kidney biopsy provides only a single snapshot of disease that needs to be interpreted in light of changing clinical and serological findings. A clear understanding of these dynamic parameters is essential for staging, treatment, and management of this disease. This review aims to shed light on current knowledge regarding the development and time course of changes in the serum levels of autoantibodies against PLA2R, proteinuria, and histological findings that underlie the pathophysiology of primary membranous nephropathy.

Polypharmacy and risk of falls and fractures for patients with HIV infection and substance dependence.

Although people with HIV infection (PLWH) are at higher risk of polypharmacy and substance use, there is limited knowledge about potential harms associated with polypharmacy such as falls and fractures in this population. The study objective was to determine whether polypharmacy, as measured by the number and type of medication, is associated with falls and fractures among PLWH and DSM-IV substance dependence in the past year or ever injection drug use (IDU). We identified the number of medications by electronic medical record review in the following categories: (i) systemically active, (ii) non-antiretroviral (non-ARV), (iii) sedating, (iv) non-sedating as well as any opioid medication and any non-opioid sedating medication. Outcomes were self-reported (1) fall/accident requiring medical attention and (2) fracture in the previous year. Separate logistic regression models were fitted for medications in each category and each outcome. Among 250 participants, the odds of a fall requiring medical attention were higher with each additional medication overall (odds ratio [OR] 1.12, 95% Confidence Interval [CI] = 1.05, 1.18), each additional non-ARV medication (OR 1.13, 95%CI = 1.06, 1.20), each additional sedating medication (OR 1.36, 95%CI = 1.14, 1.62), and a non-opioid sedating medication (OR 2.89, 95%CI = 1.06, 7.85) but not with an additional non-sedating medication or opioid medication. In receiver operating characteristic (ROC) curve analyses, optimal cutoffs for predicting falls were: ≥8 overall and ≥2 sedating medications. Odds ratios for fracture in the previous year were OR 1.05, 95%CI = 0.97, 1.13 for each additional medication overall and OR 1.11, 95%CI = 0.89, 1.38 for each additional sedating medication. In PLWH and substance dependence or ever IDU, a higher number of medications was associated with greater odds of having a fall requiring medical attention. The association appeared to be driven largely by sedating medications. Future studies should determine if reducing such polypharmacy, particularly sedating medications, lowers the risk of falls.

Polypharmacy and risk of non-fatal overdose for patients with HIV infection and substance dependence.

INTRODUCTION: People living with HIV (PLWH) are at risk of both polypharmacy and unintentional overdose yet there are few data on whether polypharmacy increases risk of overdose. The study objective was to determine if the number and type of medication (e.g., sedating) were associated with non-fatal overdose (OD) among PLWH with past-year substance dependence or a lifetime history of injection drug use. MATERIALS AND METHODS: This was a longitudinal study of adults recruited from two urban, safety-net HIV clinics. Outcomes were i) lifetime and ii) past-year non-fatal OD assessed at baseline and a 12-month follow-up. We used logistic regression to examine the association between each outcome and the number of medications (identified from the electronic medical record) in the following categories: i) overall medications, ii) non-antiretroviral (non-ARV), iii) sedating, iv) non-sedating, as well as any vs no opioid medication and any vs no non-opioid sedating medication. Covariates included demographics, medical comorbidities, depressive and anxiety symptoms, and substance use. RESULTS: Among 250 participants, 80% were prescribed a sedating medication, 50% were prescribed an opioid; 51% exceeded risky drinking limits. In the past month, 23% reported illicit opioid use and 9% illicit opioid sedative use; 37% reported lifetime non-fatal OD and 7% past-year non-fatal OD. The median number (interquartile range) of total medications was 10 (7, 14) and 2 (1, 3) sedating. The odds of lifetime non-fatal OD were significantly higher with each additional sedating medication (OR 1.26, 95% CI 1.08, 1.46) and any opioid medication (OR 2.31; 95% CI 1.37, 3.90), but not with each overall, non-ARV, or non-sedating medication. The odds of past year non-fatal OD were greater with each additional sedating medication (OR 1.18; 95% CI 1.00, 1.39, p=0.049), each additional non-ARV medication (OR 1.07; 95% CI 1.00, 1.15, p=0.048), and non-significantly for any opioid medication (OR 2.23; 95% CI 0.93, 5.35). CONCLUSIONS: In this sample of PLWH with substance dependence and/or injection drug use, number of sedating medications and any opioid were associated with non-fatal overdose; sedating medications were prescribed to the majority of patients. Polypharmacy among PLWH and substance dependence warrants further research to determine whether reducing sedating medications, including opioids, lowers overdose risk.