Congophilic Fibrillary Glomerulonephritis: A Case Series.

RATIONALE & OBJECTIVE: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red-positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red-negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. RESULTS: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function. LIMITATIONS: Retrospective nature. Blinded pathology evaluations were not performed. CONCLUSIONS: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.

Distribution of Biopsy-Proven Presumed Primary Glomerulonephropathies in 2000-2011 Among a Racially and Ethnically Diverse US Population.

BACKGROUND: The incidence and distribution of primary glomerulonephropathies vary throughout the world and by race and ethnicity. We sought to evaluate the distribution of primary glomerulonephropathies among a large racially and ethnically diverse population of the United States. STUDY DESIGN: Case series from January 1, 2000, through December 31, 2011. SETTING & PARTICIPANTS: Adults (aged ≥ 18 years) of an integrated health system who underwent native kidney biopsy and had kidney biopsy findings demonstrating focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and other. OUTCOMES: Rates and characteristics of the most common primary glomerulonephropathies overall and by race and ethnicity. RESULTS: 2,501 patients with primary glomerulonephropathy were identified, with a mean age 50.6 years, 45.7% women, 36.1% Hispanics, 31.2% non-Hispanic whites, 17.4% blacks, and 12.4% Asians. FSGS was the most common glomerulonephropathy (38.9%) across all race and ethnic groups, followed by MGN (12.7%), MCD (11.0%), IgAN (10.2%), and other (27.3%). The FSGS category had the greatest proportion of blacks, and patients with FSGS had the highest rate of poverty. IgAN was the second most common glomerulonephropathy among Asians (28.6%), whereas it was 1.2% among blacks. Patients with MGN presented with the highest proteinuria (protein excretion, 8.3g) whereas patients with FSGS had the highest creatinine levels (2.6mg/dL). Overall glomerulonephropathy rates increased annually in our 12-year observation period, driven by FSGS (2.7 cases/100,000) and IgAN (0.7 cases/100,000). MGN and MCD rates remained flat. LIMITATIONS: Missing data for urine albumin and sediment, indication bias in performing kidney biopsies, and inexact classification of primary versus secondary disease. CONCLUSIONS: Among a racially and ethnically diverse cohort from a single geographical area and similar environment, FSGS was the most common glomerulonephropathy, but there was variability of other glomerulonephropathies based on race and ethnicity.

Identifying Patients with Rare Disease Using Electronic Health Record Data: The Kaiser Permanente Southern California Membranous Nephropathy Cohort.

INTRODUCTION: Developing a reliable means to identify and study real-world populations of patients with membranous nephropathy (MN) using electronic health records (EHRs) would help advance glomerular disease research. Identifying MN cases using EHRs is limited by the need for manual reviews of biopsy reports. OBJECTIVE: To evaluate the accuracy of identifying patients with biopsy-proven MN using the EHR in a large, diverse population of an integrated health system. METHODS: A retrospective cohort study was performed between June 28, 1999, and June 25, 2015, among patients with kidney biopsy results (N = 4723), which were manually reviewed and designated as MN or non-MN. The sensitivity, specificity, and positive predictive value (PPV) of International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes were determined using 2 approaches: 1) clinical (MN-specific codes 581.1, 582.1, or 583.1) and 2) agnostic/data-derived (codes selected from supervised learning at the highest predictive performance). RESULTS: One year after biopsy, the sensitivity and specificity of an MN diagnosis were 86% and 76%, respectively, but the PPV was 26%. The data-driven approach detected that using only 2 codes (581.1 or 583.1) improved specificity to 94% and PPV to 58%, with a small decrease in sensitivity to 83%. When any code was reported at least 3 times, specificity was 98%; PPV, 78%; and sensitivity, 64%. DISCUSSION: Our findings suggest that ICD-9 diagnosis codes might be a convenient tool to identify patients with MN using EHR and/or administrative claims information. Codes selected from supervised learning achieved better overall performance, suggesting the potential of developing data-driven methods.

Polyoma virus nephropathy with simian virus 40 antigen-containing tubular basement membrane immune complex deposition.

Polyoma nephropathy is an increasingly prevalent complication in kidney transplant recipients. We identified tubular basement membrane immune complexes in allograft recipients with polyoma nephropathy. To evaluate this lesion, biopsies demonstrating polyoma infection over a 2-year period were assessed for the presence, localization, and composition of tubular basement membrane immune complexes including simian virus 40 (SV40) antigen and for histologic classification according to Drachenberg. Charts were reviewed for clinical information. Thirteen of 26 biopsies from 11 of 20 patients demonstrated tubular basement membrane immune complexes, all of which contained C3, immunoglobulin G, and SV40 antigen. Deposits were in all nephron segments associated with tubular cell viral infection and tubulointerstitial inflammation; no SV40 antigen was in glomeruli. The Drachenberg histologic classification tended to be more advanced in biopsies with tubular basement membrane immune complexes, but not significantly so. There were no differences in patients with and without immune complexes with respect to age, sex, time after engraftment, and plasma viral load. Tubular basement membrane immune complexes were present in 5 of 6 patients who lost renal function and in 5 of 12 with currently functioning grafts (P < .1). Polyoma-associated tubular basement membrane immune complexes seem to be a local phenomenon, likely related to viral antigen shedding. The clinical significance is uncertain but may portend a worse prognosis.

Secondary Syphilis Associated with Membranous Nephropathy and Acute Hepatitis in a Patient with HIV: A Case Report.

INTRODUCTION: We present a case of membranous nephropathy associated with a secondary syphilis infection in a patient with HIV. CASE PRESENTATION: A 37-year-old white man with HIV who was receiving highly active antiretroviral therapy presented to the Emergency Department with 6 weeks of rectal pain. He had a CD3-CD4 count of 656 cells/mm3 and an undetectable viral load. On admission, he was found to have an anal ulcer, a serum creatinine of 1.4 mg/dL (baseline 0.7 to 1.0 mg/dL), elevated transaminases, positive rapid plasmin reagin, and a urine protein/creatinine ratio revealing nephrotic-range proteinuria. Renal biopsy demonstrated membranous nephropathy with features suggestive of a secondary cause. Our patient was treated with penicillin for secondary syphilis, with normalization of renal function, resolution of the nephrotic syndrome, and improvement of his elevated transaminases. DISCUSSION: This case is a reminder that patients with HIV are not infrequently coinfected with Treponema pallidum and that secondary syphilis can have systemic manifestations, including elevated transaminases and nephrotic syndrome. Prompt diagnosis and treatment will result in resolution of these problems.

End-Stage Renal Disease and Mortality Outcomes Across Different Glomerulonephropathies in a Large Diverse US Population.

OBJECTIVE: To compare renal function decline, incident end-stage renal disease (ESRD), and mortality among patients with 5 common glomerular diseases in a large diverse population. PATIENTS AND METHODS: A retrospective cohort study (between January 1, 2000, and December 31, 2011) of patients with glomerulonephropathy using the electronic health record of an integrated health system was performed. Estimated glomerular filtration rate (eGFR) change, incident ESRD, and mortality were compared among patients with biopsy-proven focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and lupus nephritis (LN). Competing risk models were used to estimate hazard ratios for different glomerulonephropathies for incident ESRD, with mortality as a competing outcome after adjusting for potential confounders. RESULTS: Of the 2350 patients with glomerulonephropathy (208 patients [9%] younger than 18 years) with a mean follow-up of 4.5±3.6 years, 497 (21%) progressed to ESRD and 195 (8%) died before ESRD. The median eGFR decline was 1.0 mL/min per 1.73 m2 per year but varied across different glomerulonephropathies (P<.001). The highest ESRD incidence (per 100 person-years) was observed in FSGS 8.72 (95% CI, 3.93-16.72) followed by IgAN (4.54; 95% CI, 1.37-11.02), LN (2.38; 95% CI, 0.37-7.82), MN (2.15; 95% CI, 0.29-7.46), and MCD (1.67; 95% CI, 0.15-6.69). Compared with MCD, hazard ratios (95% CIs) for incident ESRD were 3.43 (2.32-5.08) and 2.35 (1.46-3.81), 1.28 (0.79-2.07), and 1.02 (0.62-1.68) for FSGS, IgAN, LN, and MN, respectively. No significant association between glomerulonephropathy types and mortality was detected (P=.24). CONCLUSION: Our findings from a real-world clinical environment revealed significant differences in eGFR decline and ESRD risk among patients with 5 glomerulonephropathies. These variations in presentation and outcomes warrant different management strategies and expectations.

Diagnosis of meningioma by time-resolved fluorescence spectroscopy.

We investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor specimens and delineation of tumor from surrounding normal tissue. Tissue autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the intensity decay profiles are recorded in the 370 to 500 nm spectral range with a fast digitizer (0.2 ns resolution). Experiments are conducted on excised specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site are used for tissue characterization. A linear discriminant analysis algorithm is used for tissue classification. Our results reveal that meningioma is characterized by unique fluorescence characteristics that enable discrimination of tumor from normal tissue with high sensitivity (>89%) and specificity (100%). The accuracy of classification is found to increase (92.8% cases in the training set and 91.8% in the cross-validated set correctly classified) when parameters from both the spectral and the time domain are used for discrimination. Our findings establish the feasibility of using TR-LIFS as a tool for the identification of meningiomas and enables further development of real-time diagnostic tools for analyzing surgical tissue specimens of meningioma or other brain tumors.

Primary herpetic peritonitis causing intestinal perforation: case report and review of the literature.

Peritonitis of viral etiology is rarely reported in the literature; a prior report described a patient undergoing continuous ambulatory peritoneal dialysis who had the disease. We report a case of primary herpetic peritonitis (the agent of which was typed by polymerase chain reaction as herpes simplex virus biotype 1), which caused intestinal perforation, and we review the current literature and provide possible pathophysiologic mechanisms.

Systemic mastocytosis presenting with acute oliguric renal failure: report of a case and review of the literature.

A 61-year old African-American woman presented with abdominal pain, tender splenomegaly, anemia, and renal insufficiency. Bone marrow biopsy demonstrated systemic mastocytosis. She was treated with mediator-specific therapy and imatinib, but her renal and hepatic function deteriorated and she required maintenance hemodialysis. Renal biopsy demonstrated interstitial infiltration with mast cells and acute tubular necrosis. Acute kidney injury in the setting of systemic mastocytosis and imatinib therapy is discussed.

Indinavir-induced nephrolithiasis three and one-half years after cessation of indinavir therapy.

Nephrolithiasis is a known side effect of indinavir sulfate, a protease inhibitor used in the treatment of human immunodeficiency virus (HIV). The duration of its side effects, however, has not been well defined. We present a case where a patient presented with symptomatic indinavir-induced nephrolithiasis 3.5 years after discontinuing indinavir. We use this case to illustrate the pathophysiology of indinavir stones and hypothesize how they can occur years after discontinuation by discussing the pharmacokinetics of the drug.