Browsing by Author "Benediktsson, Hallgrimur"

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    A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis
    (2019-01-31) Sporinova, Barbora; McRae, Susanna A; Muruve, Daniel A; Fritzler, Marvin J; Nasr, Samih H; Chin, Alex C; Benediktsson, Hallgrimur
    Abstract Background Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30–60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as “atypical anti-GBM disease”, with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis. Case presentation A 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient’s hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient’s hemoptysis resolved with ganciclovir, though he became dialysis dependent. Conclusions This case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty.
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    Anticoagulant Related Nephropathy Induced by Dabigatran
    (2018-12-09) Sharfuddin, Nazia; Nourbakhsh, Mahra; Box, Alan; Benediktsson, Hallgrimur; Muruve, Daniel A.
    We describe a case of biopsy-proven dabigatran related nephropathy in a patient without underlying IgA nephropathy. To date, dabigatran related nephropathy was only reported in patients with concurrent or undiagnosed IgA nephropathy, suggesting that it may predispose patients to dabigatran associated injury. The patient is an 81-year-old woman with multiple medical comorbidities, including nonvalvular atrial fibrillation, who was anticoagulated with dabigatran. She presented to hospital with acute kidney injury in the setting of volume overload. Her estimated glomerular filtration rate decreased from a baseline of 57 mL/min/1.73 m2 to 4 mL/min/1.73 m2, necessitating hemodialysis. Renal ultrasound findings, fractional excretion of sodium, and urinalysis suggested acute kidney injury. Renal biopsy showed acute tubular injury, tubular red blood cell casts, and an absence of active glomerulonephritis, similar to the pathological findings of warfarin related nephropathy. A diagnosis of anticoagulant related nephropathy secondary to dabigatran was therefore established. This case demonstrates that dabigatran, like warfarin, may increase tubular bleeding risk in patients, irrespective of underlying kidney or glomerular disease.
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    The Pace of Prostatic Intraepithelial Neoplasia Development Is Determined by the Timing of Pten Tumor Suppressor Gene Excision
    (Public Library of Science, 2009) Luchman, H. Artee; Benediktsson, Hallgrimur; Villemaire, Michelle L.; Peterson, Alan C.; Jirik, Frank R.
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    Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis
    (2013-12-29) Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard
    Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor.
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    Sociodemographic associations with abnormal estimated glomerular filtration rate (eGFR) in a large Canadian city: a cross-sectional observation study
    (2018-08-09) Ma, Irene; Guo, Maggie; Muruve, Daniel; Benediktsson, Hallgrimur; Naugler, Christopher
    Abstract Background Chronic kidney disease (CKD) is often asymptomatic in its early stages but is indicated and is diagnosed with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. Certain sociodemographic groups are known to be at risk for CKD, but it is unclear if there are strong associations between these at risk groups with abnormal eGFR test results in Canada. Using only secondary laboratory and Census data, geospatial variation and sociodemographic associations with abnormal eGFR result rate were investigated in Calgary, Alberta. Methods Secondary laboratory data from all adult community patients who received an eGFR test result were collected from Calgary Laboratory Service’s Laboratory Information System, which is the sole supplier of laboratory services for the large metropolitan city. Group-level sociodemographic variables were inferred by combining laboratory data with the 2011 Canadian Census data. Poisson regression and relative risk (RR) were used to calculate associations between sociodemographic variables with abnormal eGFR. Geographical distribution of abnormal eGFR result rates were analyzed by geospatial analysis using ArcGIS. Results Of the 346,663 adult community patients who received an eGFR test result, 28,091 were abnormal (8.1%; eGFR < 60 ml/min/1.73m2). Geospatial analysis revealed distinct geographical variation in abnormal eGFR result rates in Calgary. Women (RR = 1.11, P < 0.0001), and the elderly (age ≥ 70 years; P < 0.0001) were significantly associated with an increased risk for CKD, while visible minority Chinese (RR = 0.73, P = 0.0011), South Asians (RR = 0.67, P < 0.0001) and those with a high median household income (RR = 0.88, P < 0.0001) had a significantly reduced risk for CKD. Conclusions Presented here are significant sociodemographic risk associations, and geospatial clustering of abnormal eGFR result rates in a large metropolitan Canadian city. Using solely publically available secondary laboratory and Census data, the results from this study aligns with known sociodemographic risk factors for CKD, as certain sociodemographic variables were at a higher risk for having an abnormal eGFR test result, while others were protective in this analysis.
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    The biobank for the molecular classification of kidney disease: research translation and precision medicine in nephrology
    (2017-07-26) Muruve, Daniel A; Mann, Michelle C; Chapman, Kevin; Wong, Josee F; Ravani, Pietro; Page, Stacey A; Benediktsson, Hallgrimur
    Abstract Background Advances in technology and the ability to interrogate disease pathogenesis using systems biology approaches are exploding. As exemplified by the substantial progress in the personalized diagnosis and treatment of cancer, the application of systems biology to enable precision medicine in other disciplines such as Nephrology is well underway. Infrastructure that permits the integration of clinical data, patient biospecimens and advanced technologies is required for institutions to contribute to, and benefit from research in molecular disease classification and to devise specific and patient-oriented treatments. Methods and results We describe the establishment of the Biobank for the Molecular Classification of Kidney Disease (BMCKD) at the University of Calgary, Alberta, Canada. The BMCKD consists of a fully equipped wet laboratory, an information technology infrastructure, and a formal operational, ethical and legal framework for banking human biospecimens and storing clinical data. The BMCKD first consolidated a large retrospective cohort of kidney biopsy specimens to create a population-based renal pathology database and tissue inventory of glomerular and other kidney diseases. The BMCKD will continue to prospectively bank all kidney biopsies performed in Southern Alberta. The BMCKD is equipped to perform molecular, clinical and epidemiologic studies in renal pathology. The BMCKD also developed formal biobanking procedures for human specimens such as blood, urine and nucleic acids collected for basic and clinical research studies or for advanced diagnostic technologies in clinical care. The BMCKD is guided by standard operating procedures, an ethics framework and legal agreements with stakeholders that include researchers, data custodians and patients. The design and structure of the BMCKD permits its inclusion in a wide variety of research and clinical activities. Conclusion The BMCKD is a core multidisciplinary facility that will bridge basic and clinical research and integrate precision medicine into renal pathology and nephrology.