Bio

Bio


Dr. Michelle O'Shaughnessy specializes in the treatment of kidney disease and hypertension. She practiced Internal Medicine and Nephrology for 4 years in Ireland before coming to Stanford in 2013 to complete a 3-year Clinical Research Fellowship in nephrology. Dr. O'Shaughnessy has a special interest in treating and studying patients with glomerular diseases i.e. those diseases that affect the glomerulus (or filtering portion) of the kidney.

Clinical Focus


  • Nephrology

Academic Appointments


Professional Education


  • Fellowship:Stanford University Nephrology FellowshipCA
  • Board Certification: Nephrology, Royal College of Physicians of Ireland
  • Board Certification: Internal Medicine, Royal College of Physicians of Ireland
  • Fellowship:Royal College of Physicians in Ireland (2013) Ireland
  • Residency:Mayo Clinic Graduate Medical Education (2009) MN
  • Residency:National University of Ireland Galway (2008) Ireland
  • Medical Education:National University of Ireland Galway School of Medicine (2005) Ireland

Publications

All Publications


  • Prevalence of Cardiovascular Disease Risk Factors in Childhood Glomerular Diseases. Journal of the American Heart Association Ashoor, I. F., Mansfield, S. A., O'Shaughnessy, M. M., Parekh, R. S., Zee, J., Vasylyeva, T. L., Kogon, A. J., Sethna, C. B., Glenn, D. A., Chishti, A. S., Weaver, D. J., Helmuth, M. E., Fernandez, H. E., Rheault, M. N., CureGN Consortium 2019; 8 (14): e012143

    Abstract

    Background Cardiovascular disease is a major cause of morbidity and mortality in children with chronic kidney disease. We sought to determine the prevalence of cardiovascular risk factors in children with glomerular disease and to describe current practice patterns regarding risk factor identification and management. Methods and Results Seven-hundred sixty-one children aged 0 to 17years with any of 4 biopsy-confirmed primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy/vasculitis) were enrolled at a median of 16months from glomerular disease diagnosis in the multicenter prospective Cure Glomerulonephropathy Network study. Prevalence of traditional (hypertension, hypercholesterolemia, and obesity) and novel (proteinuria, prematurity, and passive smoke exposure) cardiovascular risk factors were determined at enrollment and compared across glomerular disease subtypes. Frequency of screening for dyslipidemia and prescribing of lipid-lowering or antihypertensive medications were compared across glomerular disease subtype, steroid exposure, and remission status groups. Compared with the general population, all traditional risk factors were more frequent: among those screened, 21% had hypertension, 51% were overweight or obese, and 71% had dyslipidemia. Children who were not in remission at enrollment were more likely to have hypertension and hypercholesterolemia. Fourteen percent of hypertensive children were not receiving antihypertensives. Only 49% underwent screening for dyslipidemia and only 9% of those with confirmed dyslipidemia received lipid-lowering medications. Conclusions Children with primary glomerular diseases exhibit a high frequency of modifiable cardiovascular risk factors, particularly untreated dyslipidemia. Lipid panels should be routinely measured to better define the burden of dyslipidemia in this population. Current approaches to screening for and treating cardiovascular risk factors are not uniform, highlighting a need for evidence-based, disease-specific guidelines.

    View details for DOI 10.1161/JAHA.119.012143

    View details for PubMedID 31286821

  • Grading cardiac response in AL amyloidosis: implications for relapse and survival BRITISH JOURNAL OF HAEMATOLOGY Eckhert, E., Witteles, R., Kaufman, G., Lafayette, R., Arai, S., Schrier, S., O'Shaughnessy, M., Liedtke, M. 2019; 186 (1): 144–46

    View details for DOI 10.1111/bjh.15717

    View details for Web of Science ID 000472576700020

  • Health-related quality of life in glomerular disease KIDNEY INTERNATIONAL Canetta, P. A., Troost, J. P., Mahoney, S., Kogon, A. J., Carlozzi, N., Bartosh, S. M., Cai, Y., Davis, T., Fernandez, H., Fornoni, A., Gbadegesin, R. A., Herreshoff, E., Mahan, J. D., Nachman, P. H., Selewski, D. T., Sethna, C. B., Srivastava, T., Tuttle, K. R., Wang, C., Falk, R. J., Gharavi, A. G., Gillespie, B. W., Greenbaum, L. A., Holzman, L. B., Kretzler, M., Robinson, B. M., Smoyer, W. E., Guay-Woodford, L. M., Reeve, B., Gipson, D. S., Ahn, W., Appel, G. B., Babayev, R., Batal, I., Bomback, A. S., Brown, E., Campenot, E. S., Canetta, P., Carlassara, L., Chan, B., Chatterjee, D., D'Agati, V. D., Delbarba, E., Dogra, S., Foroncewicz, B., Ghiggeri, G., Hines, W. H., Husain, S., Jain, N. G., Khairallah, P., Kil, B., Kiryluk, K., Jeyabalan, A., Lau, W. L., Lin, F., Lugani, F., Marasa, M., Markowitz, G., Mohan, S., Mu, X., Mucha, K., Nickolas, T. L., Piva, S., Radhakrishnan, J., Rao, M. K., Renu, R., Sanna-Cherchi, S., Santoriello, D., Shirazian, S., Stokes, M. B., Uy, N., Valeri, A. M., Al-Uzri, A., Ambruzs, J., Ashoor, I., Aviles, D., Baracco, R., Barcia, J., Bartosh, S., Belsha, C., Bowers, C., Braun, M. C., Chernitskiy, V., Chishti, A., Claes, D., Clark, K., Cramer, C., Davis, K., Erkan, E., Feig, D., Freundlich, M., Gaut, J., Gbadegesin, R., Hanna, M., Hidalgo, G., Hooper, D., Hunley, T. E., Jain, A., Kallash, M., Kamel, M., Khalid, M., Klein, J. B., Kump, T., Lane, J. C., Liapis, H., Mahan, J., Mathews, N., Nester, C., Pan, C., Patterson, L., Patel, H., Raad, A., Revell, A., Rheault, M. N., Silva, C., Sreedharan, R., Steinke, J., Sumner, S., Twombley, K., Wenderfer, S. E., Vasylyeva, T. L., Weaver, D. J., Wong, C. S., Yin, H., Achanti, A., Almaani, S., Ayoub, I., Budisavljevic, M., D'Angelo, M., Fatima, H., Falk, R., Fogo, A., Gibson, K., Glenn, D., Hogan, S., Jennette, J., Julian, B., Kidd, J., Laurin, L., Massey, H., Mottl, A., Murphy, S., Nachman, P., Nadasdy, T., Novak, J., Parikh, S., Poulton, C., Powell, T., Renfrow, M., Reynolds, M., Rizk, D., Rovin, B., Royal, V., Sanghani, N., Self, S., Adler, S., Alachkar, N., Alpers, C., Matar, R., Avila-Casado, C., Bagnasco, S., Brede, E., Brown, E., Cattran, D., Choi, M., Dell, K. M., Dewalt, D., Denburg, M., Dukkipati, R., Fervenza, F. C., Gadegbeku, C., Gipson, P., Gonzalez-Zea, A., Hasely, L., Hendren, E., Hingorani, S., Hladunewich, M., Hogan, J., Hou, J., Jefferson, J., Jhaveri, K., Johnstone, D. B., Kaskel, F., Kogan, A., Kopp, J., Lafayette, R., Lemley, K., Malaga-Dieguez, L., Meyers, K., Neu, A., O'Shaughnessy, M., O'Toole, J. F., Oliverio, A., Palmer, M., Parekh, R., Pitter, R., Reich, H., Reidy, K., Rondon, H., Sambandam, K. K., Sampson, M., Sedor, J. R., Schelling, J., Sperati, J. C., Swiatecka-Urban, A., Trachtman, H., Waldman, M., Weisstuch, J., Wiggins, R., Williams, D., Winkler, C., Vento, S., Young, E., Zhdanova, O., Barisoni, L., Beil, C., Eikstadt, R., Gillespie, B., Graff, J., Hewitt, S., Hill-Callahan, P., Helmuth, M., Lienczewski, C., Mansfield, S., Mariani, L., McCullough, K., Moore, N., Nast, C. C., Sexton, M., Troost, J., Wladkowski, M., Zee, J., Zinsser, D., CureGN Consortium 2019; 95 (5): 1209–24

    Abstract

    There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

    View details for DOI 10.1016/j.kint.2018.12.018

    View details for Web of Science ID 000465213400024

    View details for PubMedID 30898342

  • Controversies in Clinical Nephrology: Long-term low-dose corticosteroids for maintenance of remission in ANCA vasculitis: Friend or foe? CLINICAL NEPHROLOGY O'Shaughnessy, M. M. 2019; 91 (4): 195–99

    View details for DOI 10.5414/CN109566

    View details for Web of Science ID 000461758300001

    View details for PubMedID 30821686

  • Cause of kidney disease and cardiovascular events in a national cohort of US patients with end- stage renal disease on dialysis: a retrospective analysis EUROPEAN HEART JOURNAL O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2019; 40 (11): 887-+
  • Preeclampsia and Preterm Birth Risk in Women Receiving Dialysis During Pregnancy: A Population-Based Cohort Study. Do, S. C., O'Shaughnessy, M. M., Mayo, J., Girsen, A. I., Shaw, G. M., Stevenson, D. K., Druzin, M. L. SAGE PUBLICATIONS INC. 2019: 178A–179A
  • Confidence in Women's Health: A Cross Border Survey of Adult Nephrologists. Journal of clinical medicine Hendren, E. M., Reynolds, M. L., Mariani, L. H., Zee, J., O'Shaughnessy, M. M., Oliverio, A. L., Moore, N. W., Hill-Callahan, P., Rizk, D. V., Almanni, S., Twombley, K. E., Herreshoff, E., Nester, C. M., Hladunewich, M. A. 2019; 8 (2)

    Abstract

    A range of women's health issues are intimately related to chronic kidney disease, yet nephrologists' confidence in counseling or managing these issues has not been evaluated. The women's health working group of Cure Glomerulonephropathy (CureGN), an international prospective cohort study of glomerular disease, sought to assess adult nephrologists' training in, exposure to, and confidence in managing women's health. A 25-item electronic questionnaire was disseminated in the United States (US) and Canada via CureGN and Canadian Society of Nephrology email networks and the American Society of Nephrology Kidney News. Response frequencies were summarized using descriptive statistics. Responses were compared across provider age, gender, country of practice, and years in practice using Pearson's chi-squared test or Fisher's exact test. Among 154 respondents, 53% were women, 58% practiced in the US, 77% practiced in an academic setting, and the median age was 41⁻45 years. Over 65% of respondents lacked confidence in women's health issues, including menstrual disorders, preconception counseling, pregnancy management, and menopause. Most provided contraception or preconception counseling to less than one woman per month, on average. Only 12% had access to interdisciplinary pregnancy clinics. Finally, 89% felt that interdisciplinary guidelines and/or continuing education seminars would improve knowledge. Participants lacked confidence in both counseling and managing women's health. Innovative approaches are warranted to improve the care of women with kidney disease and might include the expansion of interdisciplinary clinics, the development of case-based teaching materials, and interdisciplinary treatment guidelines focused on this patient group.

    View details for PubMedID 30717445

  • CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease AMERICAN JOURNAL OF KIDNEY DISEASES Mariani, L. H., Bomback, A. S., Canetta, P. A., Flessner, M. F., Helmuth, M., Hladunewich, M. A., Hogan, J. J., Kiryluk, K., Nachman, P. H., Nast, C. C., Rheault, M. N., Rizk, D., Trachtman, H., Wenderfer, S. E., Bowers, C., Hill-Callahan, P., Marasa, M., Poulton, C. J., Revell, A., Vento, S., Barisoni, L., Cattran, D., D'Agati, V., Jennette, J., Klein, J. B., Laurin, L., Twombley, K., Falk, R. J., Gharavi, A. G., Gillespie, B. W., Gipson, D. S., Greenbaum, L. A., Holzman, L. B., Kretzler, M., Robinson, B., Smoyer, W. E., Guay-Woodford, L. M., Ahn, W., Appel, G. B., Babayev, R., Batal, I., Brown, E., Campenot, E. S., Canetta, P., Carlassara, L., Chan, B., Chatterjee, D., D'Agati, V. D., Delbarba, E., Dogra, S., Fernandez, H., Foroncewicz, B., Ghiggeri, G., Hines, W. H., Husain, S., Jain, N. G., Khairallah, P., Kil, B., Jeyabalan, A., Lau, W. L., Lin, F., Lugani, F., Markowitz, G., Mohan, S., Mu, X., Mucha, K., Nickolas, T. L., Piva, S., Radhakrishnan, J., Rao, M. K., Regunathan-Shenk, R., Sanna-Cherchi, S., Santoriello, D., Shirazian, S., Stokes, M. B., Yu, N., Valeri, A. M., Zviti, R., Al-Uzri, A., Ambruzs, J., Ashoor, I., Aviles, D., Baracco, R., Barcia, J., Bartosh, S., Belsha, C., Braun, M. C., Cai, Y., Chernitskiy, V., Chishti, A., Claes, D., Clark, K., Cramer, C., Davis, K., Dutcher, A., Erkan, E., Feig, D., Freundlich, M., Gaut, J., Gbadegesin, R., Hanna, M., Hidalgo, G., Hooper, D., Hunley, T. E., Jain, A., Kallash, M., Kamel, M., Khalid, M., Kump, T., Lane, J. C., Liapis, H., Mahan, J., Mathews, N., Nester, C., Pan, C., Patterson, L., Patel, H., Raad, A., Silva, C., Sreedharan, R., Srivastava, T., Steinke, J., Sumner, S., Vasylyeva, T. L., Wang, C., Weaver, D. J., Wong, C. S., Yin, H., Achanti, A., Almaani, S., Ayoub, I., Budisavljevic, M., D'Angelo, M., Derebail, V., Fatima, H., Falk, R., Fogo, A., Gibson, K., Glenn, D., Hogan, S., Jain, K., Julian, B., Kidd, J., Massey, H., Mottl, A., Murphy, S., Nadasdy, T., Novak, J., Parikh, S., Poulton, C., Powell, T., Reeve, B., Renfrow, M., Reynolds, M., Rizk, D., Rovin, B., Royal, V., Saha, M., Sanghani, N., Self, S., Adler, S., Alachkar, N., Alpers, C., Matar, R., Avila-Casado, C., Bagnasco, S., Brede, E., Brown, E., Cattran, D., Choi, M., Contreras, G., Dell, K. M., Dewalt, D., Denburg, M., Dukkipati, R., Fervenza, F. C., Fornoni, A., Gadegbeku, C., Gipson, P., Gonzalez-Zea, A., Hasely, L., Hendren, E., Hingorani, S., Hladunewich, M., Hogan, J., Hou, J., Jefferson, J., Jhaveri, K., Johnstone, D. B., Kaskel, F., Kogan, A., Kopp, J., Lafayette, R., Lemley, K., Malaga-Dieguez, L., Meyers, K., Neu, A., O'Shaughnessy, M., O'Toole, J. F., Oliverio, A., Palmer, M., Parekh, R., Pitter, R., Reich, H., Reidy, K., Rondon, H., Sambandam, K. K., Sampson, M., Sedor, J. R., Selewski, D. T., Sethna, C. B., Schelling, J., Sperati, J. C., Swiatecka-Urban, A., Tuttle, K. R., Waldman, M., Weisstuch, J., Wiggins, R., Williams, D., Winkler, C., Young, E., Zhdanova, O., Beil, C., Eikstadt, R., Gillespie, B., Graff, J., Hewitt, S., Herreshoff, E., Lienczewski, C., Mansfield, S., Mariani, L., McCullough, K., Moore, N., Robinson, B. M., Sexton, M., Troost, J., Wladkowski, M., Zee, J., Zinsser, D., CureGN Consortium 2019; 73 (2): 218–29

    Abstract

    Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death.Multicenter prospective cohort study.Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded.Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year.Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events.The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year.Current follow-up can only detect large differences in ESKD and death outcomes.Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

    View details for PubMedID 30420158

  • Renal Complications inPregnancy Preceding Glomerulonephropathy Diagnosis. Kidney international reports Oliverio, A. L., Zee, J., Mariani, L. H., Reynolds, M. L., O'Shaughnessy, M., Hendren, E. M., Alachkar, N., Herreshoff, E., Rizk, D. V., Nester, C. M., Steinke, J., Twombley, K. E., Hladunewich, M. A. 2019; 4 (1): 159–62

    View details for PubMedID 30596179

  • Grading cardiac response in AL amyloidosis: implications for relapse and survival. British journal of haematology Eckhert, E., Witteles, R., Kaufman, G., Lafayette, R., Arai, S., Schrier, S., O'Shaughnessy, M., Liedtke, M. 2018

    View details for PubMedID 30569572

  • Graded Cardiac Response Correlates with Relapse and Survival in AL Amyloidosis Eckhert, E., Witteles, R., Kaufman, G., Lafayette, R., Arai, S., Schrier, S., O'Shaughnessy, M., Liedtke, M. AMER SOC HEMATOLOGY. 2018
  • Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study KIDNEY INTERNATIONAL REPORTS Selewski, D. T., Ambruzs, J. M., Appel, G. B., Bomback, A. S., Matar, R., Cai, Y., Cattran, D. C., Chishti, A. S., D'Agati, V. D., D'Alessandri-Silva, C. J., Gbadegesin, R. A., Hogan, J. J., Iragorri, S., Jennette, J., Julian, B. A., Khalid, M., Lafayette, R. A., Liapis, H., Lugani, F., Mansfield, S. A., Mason, S., Nachman, P. H., Nast, C. C., Nester, C. M., Noone, D. G., Novak, J., O'Shaughnessy, M. M., Reich, H. N., Rheault, M. N., Rizk, D., Saha, M. K., Sanghani, N. S., Sperati, C., Sreedharan, R., Srivastava, T., Swiatecka-Urban, A., Twombley, K., Vasylyeva, T. L., Weaver, D. J., Yin, H., Zee, J., Falk, R. J., Gharavi, A. G., Gillespie, B. W., Gipson, D. S., Greenbaum, L. A., Holzman, L. B., Kretzler, M., Robinson, B. M., Smoyer, W. E., Flessner, M., Guay-Woodford, L. M., Kiryluk, K., CureGN Consortium 2018; 3 (6): 1373–84

    Abstract

    The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001).This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

    View details for PubMedID 30450464

  • A large, international study on post-transplant glomerular diseases: the TANGO project BMC NEPHROLOGY Uffing, A., Jose Perez-Saez, M., La Manna, G., Comai, G., Fischman, C., Farouk, S., Manfro, R., Bauer, A., Lichtenfels, B., Mansur, J. B., Tedesco-Silva, H., Kirsztajn, G. M., Manonelles, A., Bestard, O., Riella, M., Hokazono, S., Arias-Cabrales, C., David-Neto, E., Ventura, C., Akalin, E., Mohammed, O., Khankin, E. V., Safa, K., Malvezzi, P., O'Shaughnessy, M., Cheng, X. S., Cravedi, P., Riella, L. V. 2018; 19: 229

    Abstract

    Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy.The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies.Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

    View details for PubMedID 30208881

  • Cause of kidney disease and cardiovascular events in a national cohort of US patients with end-stage renal disease on dialysis: a retrospective analysis. European heart journal O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2018

    Abstract

    Aims: End-stage renal disease (ESRD) is a strong cardiovascular risk factor. We aimed to determine the extent to which cause of kidney disease independently contributes to this risk.Methods and results: Using a national US ESRD registry, we selected patients with eight different causes of ESRD who initiated dialysis 1997-2014. We used proportional sub-distribution hazard models, with non-cardiovascular death or kidney transplantation as competing risks, to estimate hazard ratios (HRs) for a first composite cardiovascular event (myocardial infarction, ischaemic stroke, or cardiovascular or cerebrovascular death), by cause of ESRD. The population was restricted to those using Medicare insurance at Day 91 after dialysis initiation (when most patients become Medicare eligible). Outcomes were ascertained from Medicare claims or Death Notifications. Among the 658168 patients identified, composite event rates ranged from 3.5/100 person-years in IgA nephropathy to 14.6/100 person-years in diabetic nephropathy (DN). After adjusting for demographics, socioeconomic factors, comorbidities, dialysis modality, and laboratory values, cardiovascular event HRs differed significantly by cause of ESRD. Comparing to IgA nephropathy, the adjusted HR was highest for DN [aHR=2.97, 95% confidence interval (CI) 2.77-3.20], next highest for lupus nephritis (aHR=1.86, 95% CI 1.71-2.03), and thereafter ranged from 1.29 (95% CI 1.19-1.39) in autosomal dominant polycystic kidney disease to 1.67 (95% CI 1.52-1.83) in membranous nephropathy.Conclusion: High cardiovascular event rates in dialysis patients vary considerably by cause of ESRD. Determining underlying reasons for these differences might provide new insights in to cardiovascular disease mechanisms as well as inform future drug development and clinical trial design.

    View details for PubMedID 30085056

  • Glomerular disease frequencies by race, sex and region: results from the International Kidney Biopsy Survey NEPHROLOGY DIALYSIS TRANSPLANTATION O'Shaughnessy, M. M., Hogan, S. L., Thompson, B. D., Coppo, R., Fogo, A. B., Jennette, J. 2018; 33 (4): 661–69

    Abstract

    Large-scale studies comparing glomerular disease frequencies across continents are lacking.We surveyed 29 nephropathology laboratories in four continents using a standardized data collection form. We obtained recent consecutive kidney biopsy diagnosis frequencies at each center and summary demographics for each diagnosis. This report focuses on glomerular disease frequencies by region and race/ethnicity.Among 42 603 glomerular disease diagnoses reported (median age 47 years, 52% male, 57% white), from a total of 60 340 diagnoses, glomerular disease subtype frequencies differed considerably by continent. Diabetic glomerulosclerosis (GS; 19.1%) and focal segmental glomerulosclerosis (FSGS; 19.1%) predominated in North America; lupus nephritis (38.1%) and FSGS (15.8%) predominated in Latin America; IgA nephropathy (IgAN; 22.1%) and FSGS (14.9%) predominated in Europe; and IgAN (39.5%) and lupus nephritis (16.8%) predominated in Asia. After stratifying by race, diabetic GS (17.4% versus 4.3%, P < 0.001) and FSGS (17.3% versus 11.8%, P < 0.001) were more, and lupus nephritis less (15.8% versus 45.6%, P < 0.001), frequent among Latinos in North versus Latin America; FSGS was more (13.1% versus 7.1%, P < 0.001), and IgAN less (27.4% versus 40.5%, P < 0.001), frequent among Asians in North America versus Asia; and FSGS (18.9% versus 13.5%, P < 0.001) and diabetic GS (18.7% versus 6.5%, P < 0.001) were more, and IgAN less (14.4% versus 25.4%, P < 0.001), frequent among whites in North America versus Europe.We determined that glomerular disease frequencies differed by continent, even among patients of similar race/ethnicity. Regional environmental and lifestyle factors, and local biopsy policies, might influence glomerular disease epidemiology independently of race/ethnicity.

    View details for PubMedID 29106637

  • Agreement Between Renal Prescribing References and Determination of Prescribing Appropriateness in Hospitalised Patients with Chronic Kidney Disease. QJM : monthly journal of the Association of Physicians O'Shaughnessy, M., Allen, N., O'Regan, J., Payne-Danson, E., Mentre, L., Davin, D., Lavin, P., Grimes, T. 2017

    Abstract

    Chronic kidney disease (CKD) is a risk factor for adverse drug events. The clinical significance of discordance between renal prescribing references is unknown.We determined the prevalence of potentially inappropriate prescribing (PIP) in CKD, measured agreement between two prescribing references, and assessed potential for harm consequent to PIP.Single-centre observational study.A random sample of hospitalised patients with CKD were grouped according to baseline CKD stage (3, 4, or 5). Prescriptions requiring caution in CKD were referenced against the Renal Drug Handbook (RDH) and British National Formulary (BNF) to identify PIP (non-compliance with recommendations). Inter-reference agreement was measured using percentage agreement and Kappa coefficient. Potential for harm consequent to PIP was assessed by physicians and pharmacists using a validated scale. One-year mortality was compared between patients with or without PIP during admission.Among 119 patients (median age 73 years, 50% male), 136 cases of PIP were identified in 78 (65.5%) patients. PIP prevalence, per patient, was 64.7% using the BNF and 28.6% using the RDH (fair agreement, Kappa 0.33, p < 0.001). The majority (63.2%) of PIP cases detected exclusively by the BNF carried minimal or no potential for harm. PIP was not significantly associated with one-year mortality (34.7% versus 21.1%, p = 0.14).PIP was common in hospitalised patients with CKD. Substantial discordance between renal prescribing references was apparent. The development of universally-adopted, evidence-based, prescribing guidelines for CKD might optimise medications safety in this vulnerable group.

    View details for DOI 10.1093/qjmed/hcx086

    View details for PubMedID 28431157

  • Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986-2015 CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY O'Shaughnessy, M. M., Hogan, S. L., Poulton, C. J., Falk, R. J., Singh, H. K., Nickeleit, V., Jennette, J. C. 2017; 12 (4): 614-623

    Abstract

    Large-scale, contemporary studies exploring glomerular disease epidemiology in the United States are lacking. We aimed to determine 30-year temporal and demographic trends in renal biopsy glomerular disease diagnosis frequencies in the southeastern United States.In this cross-sectional, observational study, we identified all patients with a native kidney biopsy specimen showing one of 18 widely recognized glomerular disease diagnoses referred to the University of North Carolina Chapel Hill Division of Nephropathology between 1986 and 2015. Biopsy era (1986-1995, 1996-2005, and 2006-2015) and demographics (age, sex, and race) were our primary and secondary predictors, respectively, and the relative frequency of each glomerular disease diagnosis was our primary outcome.Among 21,374 patients (mean age =48.3±18.3 years old; 50.8% men; 56.8% white; 38.3% black; 2.8% Latino; 1.4% Asian; 0.8% other), the frequency of diabetic glomerulosclerosis in renal biopsy specimens increased dramatically over the three decades (5.5%, 11.4%, and 19.1% of diagnoses, respectively; P for trend <0.001). The frequency of FSGS initially increased but then declined (22.6%, 27.2%, and 24.7%, respectively; P for trend =0.64). The frequencies of other common glomerular disease subtypes remained stable (IgA nephropathy and ANCA/pauci-immune GN) or declined (minimal change disease, membranous nephropathy, membranoproliferative GN, and lupus nephritis). These temporal trends were largely preserved within all demographic subgroups, although cross-sectional frequency distributions differed according to age, sex, and race.We identified significant changes in relative renal biopsy frequencies of many glomerular disease subtypes over three decades. Temporal trends were consistently observed within all major demographic groups, although relative predominance of individual glomerular disease subtypes differed according to patient age, sex, and race. We propose that exploration of behavioral and environmental exposures that likely underlie these findings should be the focus of future hypothesis-driven research.

    View details for DOI 10.2215/CJN.10871016

    View details for Web of Science ID 000398646800011

    View details for PubMedID 28325866

  • Kidney Transplantation Rates Across Glomerulonephritis Subtypes in the United States. Transplantation O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2017

    Abstract

    Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown.Using the US Renal Data System, we identified all adult patients with ESRD attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios [HRs (95% confidence intervals)] for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization (OPO).Among 718,480 patients studied, unadjusted and multivariable-adjusted transplant rates differed considerably across GN subtypes. Adjusted transplant rates were highest for patients with IgA nephropathy (IgAN, referent) and lower for all other groups: focal segmental glomerulosclerosis, HR=0.80 (0.77-0.82); membranous nephropathy, HR=0.88 (0.83-0.93); membranoproliferative GN, HR=0.84 (0.76-0.92); lupus nephritis, HR=0.69 (0.66-0.71); vasculitis, HR=0.66 (0.61-0.70); DN, HR=0.50 (0.47-0.52); ADPKD, HR=0.85 (0.82-0.88). Reduced kidney transplantation rates among comparator groups were driven more so by lower rates of waitlisting [HRs, vs. IgAN, ranged from 0.49 for DN to 0.92 for membranous nephropathy or ADPKD] than by lower rates of deceased donor kidney transplantation after waitlisting [rates were only significantly lower, vs. IgAN, for those with secondary GN subtypes: lupus nephritis, HR=0.91 (0.86-0.97), vasculitis, HR=0.85 (0.76-0.94); DN, HR=0.73 (0.69-0.77)].Identifying underlying reasons for apparent disease-specific barriers to kidney transplantation might inform center-specific transplant candidate selection procedures, along with national organ allocation policies, leading to more equitable patient care and improved patient outcomes.

    View details for DOI 10.1097/TP.0000000000001657

    View details for PubMedID 28207635

  • Kidney Transplantation Outcomes across GN Subtypes in the United States JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lenihan, C. R., Lafayette, R. A., Winkelmayer, W. C. 2017; 28 (2): 632-644

    Abstract

    Differences in kidney transplantation outcomes across GN subtypes have rarely been studied. From the US Renal Data System, we identified all adult (≥18 years) first kidney transplant recipients (1996-2011) with ESRD attributed to one of six GN subtypes or two comparator kidney diseases. We computed hazard ratios (HRs) for death, all-cause allograft failure, and allograft failure excluding death as a cause (competing risks framework) using Cox proportional hazards regression. Among the 32,131 patients with GN studied, patients with IgA nephropathy (IgAN) had the lowest mortality rates and patients with IgAN or vasculitis had the lowest allograft failure rates. After adjusting for patient- and transplant-related factors, compared with IgAN (referent), FSGS, membranous nephropathy, membranoproliferative GN, lupus nephritis, and vasculitis associated with HRs (95% confidence intervals) for death of 1.57 (1.43 to 1.72), 1.52 (1.34 to 1.72), 1.76 (1.55 to 2.01), 1.82 (1.63 to 2.02), and 1.56 (1.34 to 1.81), respectively, and with HRs for allograft failure excluding death as a cause of 1.20 (1.12 to 1.28), 1.27 (1.14 to 1.41), 1.50 (1.36 to 1.66), 1.11 (1.02 to 1.20), and 0.94 (0.81 to 1.09), respectively. Considering external comparator groups, and comparing with IgAN, autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy associated with higher HRs for mortality [1.22 (1.12 to 1.34) and 2.57 (2.35 to 2.82), respectively], but ADPKD associated with a lower HR for allograft failure excluding death as a cause [0.85 (0.79 to 0.91)]. Reasons for differential outcomes by GN subtype and cause of ESRD should be examined in future research.

    View details for DOI 10.1681/ASN.2016020126

    View details for Web of Science ID 000393017600025

    View details for PubMedID 27432742

  • Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina. American journal of nephrology O'Shaughnessy, M. M., Jobson, M. A., Sims, K., Liberty, A. L., Nachman, P. H., Pendergraft, W. F. 2017; 45 (5): 442-451

    Abstract

    Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center.All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes.Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS.Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

    View details for DOI 10.1159/000471894

    View details for PubMedID 28445873

  • Corticosteroids for IgA Nephropathy: TESTING for Benefit, Discovering Harm. JAMA O'Shaughnessy, M. M., Lafayette, R. A. 2017; 318 (5): 429–31

    View details for PubMedID 28763530

  • Differences in Initial Hemodialysis Vascular Access Use Among Glomerulonephritis Subtypes in the United States. American journal of kidney diseases O'Shaughnessy, M. M., Montez-Rath, M. E., Zheng, Y., Lafayette, R. A., Winkelmayer, W. C. 2016; 67 (4): 638-647

    Abstract

    The type of vascular access used for hemodialysis affects patient morbidity and mortality. Whether vascular access types differ by glomerulonephritis (GN) subtype in the US hemodialysis population has not been investigated.Cross-sectional observational study.We identified all adult (aged ≥ 18 years) patients within the US Renal Data System who initiated hemodialysis therapy from July 2005 through December 2011 with a diagnosis of end-stage renal disease attributed to any of 4 primary (focal segmental glomerulosclerosis, immunoglobulin A nephropathy [reference group], membranous nephropathy, and membranoproliferative GN) or 2 secondary (lupus nephritis and vasculitis) GN subtypes.GN subtype.ORs with 95% CIs for arteriovenous fistula versus central venous catheter (CVC) use and for arteriovenous graft versus CVC use were computed using multinomial logistic regression, with adjustment for demographic, socioeconomic, comorbidity, and duration of nephrology care covariates.Among 29,015 patients, CVC use at initiation of hemodialysis therapy was substantially higher in patients with lupus nephritis (89.2%) or vasculitis (91.2%) compared with patients with primary GN subtypes (72.7%-79.8%). After adjustment and compared with patients with immunoglobulin A nephropathy, patients with lupus nephritis or vasculitis were as likely to have used an arteriovenous graft (ORs of 0.94 [95% CI, 0.70-1.27] and 0.80 [95% CI, 0.56-1.13], respectively) but significantly less likely to have used an arteriovenous fistula (ORs of 0.66 [95% CI, 0.57-0.76] and 0.54 [95% CI, 0.45-0.63], respectively), whereas patients with any comparator primary GN subtype were at least as likely to have used either of these 2 access types.Potential misclassification of exposure; residual confounding by unmeasured covariates; inability to determine causes of observed associations; lacking longitudinal data for vascular access use.Significant differences in vascular access distributions at initiation of hemodialysis therapy are apparent among GN subtypes. The unacceptably high use of CVCs in patients with lupus nephritis and vasculitis is particularly concerning. Further studies are needed to identify any potentially modifiable factors underlying these findings.

    View details for DOI 10.1053/j.ajkd.2015.11.019

    View details for PubMedID 26774466

  • Differences in initial treatment modality for end-stage renal disease among glomerulonephritis subtypes in the USA. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association O'Shaughnessy, M. M., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2016; 31 (2): 290-298

    Abstract

    Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), while peritoneal dialysis affords certain benefits over hemodialysis. Distributions and determinants of first ESRD treatment modality have not been compared across glomerulonephritis (GN) subtypes.We identified all adult (18-75 years) patients with ESRD attributed to any of six GN subtypes [focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), membranous nephropathy (MN), membranoproliferative GN (MPGN), lupus nephritis (LN) and vasculitis] who were first registered in the US Renal Data System (USRDS) between 1996 and 2011. We used multinomial logistic regression-adjusting for temporal, geographic, demographic, socioeconomic and comorbid factors-to determine odds ratios (ORs) with 95% confidence intervals (CIs) for transplantation versus hemodialysis, and for peritoneal dialysis versus hemodialysis, comparing other GN subtypes to IgAN.Among the 75 278 patients studied, patients with comparator GN subtypes were significantly less likely than those with IgAN to receive either transplantation or peritoneal dialysis. After adjusting for potentially confounding covariates, patients with comparator primary GN subtypes (FSGS, MN, MPGN) were at least as likely to receive transplantation [FSGS OR 0.98 (95% CI 0.93-1.15), MN OR 1.19 (95% CI 1.01-1.39), MPGN OR 1.08 (95% CI 0.93-1.26)] or peritoneal dialysis [FSGS OR 1.05 (95% CI 0.98-1.12), MN OR 1.30 (95% CI 1.18-1.43), MPGN OR 0.95 (95% CI 0.85-1.06)] as patients with IgAN. Conversely, patients with the secondary GN subtypes LN and vasculitis remained significantly less likely to receive either modality [transplantation OR 0.49 (95% CI 0.43-0.56) for LN and 0.27 (95% CI 0.22-0.34) for vasculitis, peritoneal dialysis OR 0.76 (95% CI 0.70-0.82) for LN and 0.54 (95% CI 0.48-0.60) for vasculitis].Significant differences in ESRD treatment practice patterns are apparent among GN subtypes. To ensure equitable care for all patients, regardless of GN subtype, reasons for observed disparities should be elucidated and-if appropriate-eliminated.

    View details for DOI 10.1093/ndt/gfv386

    View details for PubMedID 26610594

  • Distinguishing the Signals From the Noise: Can Epidemiologic Studies Inform Our Understanding of Glomerular Disease? American journal of kidney diseases : the official journal of the National Kidney Foundation O'Shaughnessy, M. M., Hogan, S. L. 2016; 68 (4): 503–7

    View details for PubMedID 27664473

  • Measuring Comorbidity in Patients Receiving Dialysis: Can We Do Better? AMERICAN JOURNAL OF KIDNEY DISEASES O'Shaughnessy, M. M., Erickson, K. F. 2015; 66 (5): 731-734

    View details for DOI 10.1053/j.ajkd.2015.07.001

    View details for Web of Science ID 000363489600009

    View details for PubMedID 26210068

  • Patient Characteristics and Outcomes by GN Subtype in ESRD. Clinical journal of the American Society of Nephrology O'Shaughnessy, M. M., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2015; 10 (7): 1170-1178

    Abstract

    Outcomes-based research rarely focuses on patients with ESRD caused by GN. The hypotheses were that the GN subtype would clinically discriminate patient groups and independently associate with survival after ESRD therapy initiation.Data were extracted from the US Renal Data System for adult patients with incident (1996-2011) ESRD attributed to six GN subtypes: FSGS, IgA nephropathy (IgAN), membranous nephropathy, membranoproliferative glomeruonephritis, lupus nephritis (LN), and vasculitis. ESRD attributed to diabetes and autosomal dominant polycystic kidney disease served as non-GN comparators. Unadjusted and adjusted mortality hazard ratios (aHRs) with 95% confidence intervals (95% CIs) were estimated using Cox regression (reference, IgAN). Models sequentially adjusted for sociodemographic (model 2), comorbidity/laboratory (model 3), and ESRD treatment modality (model 4) variables.Among 84,301 patients with ESRD attributed to GN, the median age ranged from 39 (LN) to 66 (vasculitis) years, male sex ranged from 18% (LN) to 68% (IgAN), and black race ranged from 7% (IgAN) to 49% (LN). Patients with IgAN had the fewest comorbidities and lowest use of hemodialysis (70.1%). After a median follow-up of 2.5 (interquartile range, 1.0-4.9) years, crude mortality was lowest in IgAN (3.7 deaths/100 person years). Compared to IgAN, adjusted mortality was highest in LN (model 4 aHR=1.75; 95% CI, 1.68 to 1.83) and in diabetes (aHR=1.73; 95% CI, 1.67 to 1.79), and was also higher in all other GN subtypes (membranous nephropathy: aHR=1.23; 95% CI, 1.17 to 1.29; FSGS: aHR=1.37; 95% CI, 1.32 to 1.42; membranoproliferative GN: aHR=1.38; 95% CI, 1.31 to 1.45; vasculitis: aHR=1.51; 95% CI, 1.45 to 1.58) and in autosomal dominant polycystic kidney disease (aHR=1.22; 95% CI, 1.18 to 1.27).This study exposes substantial heterogeneity across GN subtypes at ESRD therapy initiation and identifies independent associations between GN subtype and post-ESRD mortality. These survival discrepancies warrant further study, and the utility of current research practice to group GN subtypes together when evaluating ESRD outcomes should be questioned.

    View details for DOI 10.2215/CJN.11261114

    View details for PubMedID 26092830

    View details for PubMedCentralID PMC4491300

  • Familial MPGN - a case series: a clinical description of familial membranoproliferative glomerulonephritis amongst three Irish families RENAL FAILURE Redahan, L., Doyle, R., O'Shaughnessy, M., Dorman, A., Little, M., Conlon, P. 2014; 36 (8): 1333-1336

    Abstract

    Genetic factors have been implicated in the pathogenesis of certain cases of MPGN. Familial cases of all three histological subtypes have been described. Genetic defects in the control of complement pathways appear to be at the root of many hereditary forms of MPGN. Here we describe a series of three families with familial MPGN. We have identified 3 individuals with a diagnosis of idiopathic MPGN, each with a sibling with the same diagnosis. Data collected included age at presentation, histological findings and age at commencement of renal replacement therapy. A family pedigree was generated for each family as well as a description of the long-term clinical course and transplant outcomes of affected individuals. We have identified male and female affected individuals in this series of three families. The progression to end-stage kidney disease was universal amongst affected individuals. The majority of cases were successfully transplanted. Recurrence in a transplanted kidney occurred in only one individual. This series of familial MPGN provides further evidence for a genetic basis for the disease. Additional studies on these three families will further our knowledge of the underlying mutations in hereditary MPGN and contribute to the understanding of complement-mediated renal disease.

    View details for DOI 10.3109/0886022X.2014.931681

    View details for Web of Science ID 000341298100026

    View details for PubMedID 24975727

  • C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Medjeral-Thomas, N. R., O'Shaughnessy, M. M., O'Regan, J. A., Traynor, C., Flanagan, M., Wong, L., Teoh, C. W., Awan, A., Waldron, M., Cairns, T., O'Kelly, P., Dorman, A. M., Pickering, M. C., Conlon, P. J., Cook, H. T. 2014; 9 (1): 46-53

    Abstract

    The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome.All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model.Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD.Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.

    View details for DOI 10.2215/CJN.04700513

    View details for Web of Science ID 000329364700009

    View details for PubMedID 24178974

  • Prevention of sudden cardiac death in hemodialysis patients. Cardiovascular & hematological disorders drug targets O'Shaughnessy, M. M., O'Regan, J. A., Lavin, P. J. 2014; 14 (3): 195-204

    Abstract

    One quarter of all hemodialysis patients will succumb to sudden cardiac death (SCD), a rate far exceeding that observed in the general population. A high prevalence of atherosclerotic coronary artery disease amongst patients with end-stage kidney disease (ESKD) partly explains this exaggerated risk. However, uremia and dialysis related factors are also of critical importance. Interventions aimed at preventing SCD have been inadequately studied in patients with ESKD. Data extrapolated from non-renal populations cannot necessarily be applied to hemodialysis patients, who possess relatively unique risk factors for SCD including "uremic cardiomyopathy", electrolyte shifts, fluctuations in intravascular volume and derangements of mineral and bone metabolism. Pending data derived from proposed randomized controlled clinical trials, critical appraisal of existing evidence and the selective application of guidelines developed for the general population to dialysis patients are required if therapeutic nihilism, or excessive intervention, are to be avoided. We discuss the evidence supporting a role for medical therapies, dialysis prescription refinements, revascularization procedures and electrical therapies as potential interventions to prevent SCD amongst hemodialysis patients. Based on current best available evidence, we present suggested strategies for the prevention of arrhythmia-mediated death in this highly vulnerable patient population.

    View details for PubMedID 24720456

  • BLOOD PRESSURE MEASUREMENT IN PERITONEAL DIALYSIS: WHICH METHOD IS BEST? PERITONEAL DIALYSIS INTERNATIONAL O'Shaughnessy, M. M., Durcan, M., Kinsella, S. M., Griffin, M. D., Reddan, D. N., Lappin, D. W. 2013; 33 (5): 544-551

    Abstract

    The optimal approach to monitoring blood pressure (BP) in the peritoneal dialysis (PD) population is unclear. Ambulatory BP monitoring reliably predicts prognosis, but can be inconvenient. The accuracy of home BP monitoring in this population is unproven. The automated BpTRU device (BpTRU Medical Devices, Coquitlam, BC, Canada), which provides an average of up to 6 successive in-office BP measurements, has not been studied in this patient group.We studied 17 patients (average age: 54 ± 12 years; 12 men, 5 women; 94% on automated PD) attending a single center. All patients underwent office, home, BpTRU, and ambulatory BP measurement. The reference standard for analysis was daytime ambulatory BP. Correlation between the referent method and each comparator method was determined (Pearson correlation coefficient), and Bland-Altman scatter plots depicting the differences in the BP measurements were constructed.Mean office BP (126.4 ± 16.9/78.8 ± 11.6 mmHg) and BpTRU BP (123.8 ± 13.7/80.7 ± 11.1 mmHg) closely approximated mean daytime ambulatory BP (129.3 ± 14.8/78.2 ± 7.9 mmHg). Mean home BP (143.8 ± 15.0/89.9 ± 28.1 mmHg) significantly overestimated mean daytime systolic BP by 14.2 mmHg (95% confidence interval: 4.3 mmHg to 24.1 mmHg; p = 0.008). Bland-Altman plots demonstrated poorest agreement between home BP and daytime ambulatory BP. No patient had "white-coat hypertension," and only 1 patient had false-resistant hypertension. Most patients showed abnormal nocturnal dipping patterns (non-dipping: n = 11; reverse-dipping: n = 5; normal dipping: n = 1).We report a novel finding that BP measurement using the BpTRU device is more accurate than home BP measurement in a PD population. Potential explanations for this observation include poor home BP measurement technique, use of poorly validated home BP measurement devices, or a reduced prevalence of white-coat effect among PD patients. Our study also confirms that, in the PD population, BP measurements vary considerably with patient location, time of day, and measurement technique.

    View details for DOI 10.3747/pdi.2012.00027

    View details for Web of Science ID 000325804800016

    View details for PubMedID 23547279

  • Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy. Clinical kidney journal O'Shaughnessy, M. M., O'Regan, J. A., Murray, F. E., Connell, J. A., Duffy, M. P., Francis, V. M., Dwyer, S., Thornton, L. M., Conlon, P. J. 2012; 5 (3): 250-253

    Abstract

    We report the case of a 45-year-old haemodialysis patient who achieved a sustained virological response (SVR) following pegylated interferon therapy for hepatitis C virus (HCV) genotype 2 infection. He was subsequently cohorted with other HCV-infected dialysis patients and became re-infected with HCV genotype 3a. Epidemiological and molecular investigations identified a highly viraemic HCV genotype 3a-infected dialysis patient as the likely source of this infection. This critical incident informed a revision to local and national infection control policy regarding the dialysis management of patients who achieve an SVR following anti-viral treatment.

    View details for DOI 10.1093/ckj/sfs040

    View details for PubMedID 26069778

  • Sudden Cardiac Death in Dialysis: Do Current Guidelines for Implantable Cardioverter Defibrillator Therapy Apply to Patients with End-stage Kidney Disease? SEMINARS IN DIALYSIS O'Shaughnessy, M. M., Lappin, D. W., Reddan, D. N. 2012; 25 (3): 272-276

    Abstract

    Arrhythmic mechanisms account for one in four deaths in end-stage kidney disease. Large-scale randomized controlled trials have demonstrated a mortality benefit from implantable cardioverter defibrillator therapy in carefully selected patient groups at high risk for sudden cardiac death. Unfortunately, patients with end-stage kidney disease were systematically excluded from these trials. Consequently, the applicability of American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines on implantable cardioverter defibrillator therapy to dialysis patients remains uncertain. Observational data suggest that secondary preventative implantable cardioverter defibrillator therapy following resuscitated cardiac arrest prolongs the lives of dialysis patients. This intervention may also offer a survival advantage as a primary preventative strategy in end-stage kidney disease. However, competing risk from co-morbidity can negate any perceived benefit. Device-related complications also negatively impact outcome. The recommendation that primary preventative device implantation be reserved for patients with severely impaired left ventricular function may be excessively restrictive in this high-risk population. Trials of implantable cardioverter defibrillator therapy that include dialysis patients are required to validate existing device eligibility criteria in this unique population. Novel indications for this intervention in dialysis patients should also be identified.

    View details for DOI 10.1111/j.1525-139X.2012.01067.x

    View details for Web of Science ID 000304190200005

    View details for PubMedID 22452711

  • In-office assessment of blood pressure in chronic kidney disease: usual measurement versus automated BpTRU measurement BLOOD PRESSURE MONITORING O'Shaughnessy, M. M., Newman, C. A., Kinsella, S. M., Reddan, D. N., Lappin, D. W. 2011; 16 (3): 124-128

    Abstract

    The automated BpTRU device has been shown to improve the accuracy of in-office blood pressure assessment in hypertensive populations. We aimed to determine whether this was also true for patients with chronic kidney disease.We recorded the blood pressure of 80 hypertensive outpatients with chronic kidney disease by usual automated measurement and BpTRU automated measurement. We established whether there were any statistically significant differences in the absolute blood pressure values measured by either method and whether these differences had any impact on the assessment of blood pressure control.Systolic and diastolic blood pressures were significantly lower by BpTRU measurement than by usual measurement, by 10.1±12.2 mmHg (95% confidence interval: 7.4-12.8 mmHg, P<0.001) and 2.8±10.6 mmHg (95% confidence interval: 0.4-5.1 mmHg, P=0.02), respectively. Significantly, more patients achieved their blood pressure target of 130/80 mmHg or less by BpTRU measurement than by usual measurement (72.5 vs. 48.8% for systolic blood pressure, P<0.001; 68.8 vs. 61.3% for diastolic blood pressure, P=0.02). Systolic blood pressures remained significantly lower by BpTRU measurement than by usual measurement in all predefined study subgroups (estimated glomerular filtration rate <30 vs ≥30 ml/min/1.73m; transplant vs. nontransplant). We detected more hypotension by BpTRU measurement than by usual measurement.Our study suggests that the BpTRU device can negate white coat effect in patients with chronic kidney disease. The use of this device in routine clinical practice could improve the overall accuracy of in-office blood pressure assessment in this high-risk population, minimizing the potential for undertreatment and overtreatment of hypertension.

    View details for DOI 10.1097/MBP.0b013e328346e0db

    View details for Web of Science ID 000290433700004

    View details for PubMedID 21562454