Medical Renal Biopsy / Electron Microscopy Center of Excellence

Faculty

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Clinical Work

The Medical Renal Biopsy / Electron Microscopy Center of Excellence is based at UPMC Presbyterian Hospital, and is focused on providing diagnostic excellence in medical renal disease for patient care. We work closely with nephrologists, rheumatologists, and other clinical physicians throughout the UPMC Health System and outside of the network of UPMC hospitals, providing comprehensive diagnostic interpretation of medical renal biopsies utilizing light microscopy with histochemical and immunohistochemical stains, immunofluorescence, electron microscopy, and in selected cases flow cytometry, molecular diagnostics, and proteomics. We also provide diagnostic interpretations of non-renal biopsies that require immunofluorescence or electron microscopy, including assessment of poorly differentiated neoplasms, neuromuscular disorders, metabolic storage disorders, and congenital anatomic disorders (e.g. immotile cilia syndrome).

Toluidine-blue stained slide showing zebra bodies in a Fabry disease case
Our division evaluates approximately 400 native renal biopsies per year, and the Transplant Pathology Division assesses over 600 renal allograft biopsies. Our Electron Microscopy laboratory serves as a reference laboratory, providing ultrastructural evaluation for hospital networks outside of Southwestern Pennsylvania. We use state of the art digital imaging for electron microscopy, with images accessible remotely on a HIPPA compliant shared drive through UPMC servers. We will soon be performing whole slide imaging of immunofluorescence slides, with images to be made available remotely, also. COE faculty members have served on the International Banff Panel that standardizes nomenclature in allograft pathology. They have also worked with major pharmaceutical companies (Wyeth-Ayerst, Novartis, and LifeCycle Pharmaceuticals) as the central pathologist in international clinical trials of modern immunosuppressive agents. Other service assignments include chairmanship of the Special Emphasis Panel on Urologic and Kidney Development and Genitourinary Diseases Study Section, and membership of the Transplantation Tolerance and Tumor Immunology Study Section, the Cardiovascular and Renal Drugs Advisory Committee at the Food and Drug Administration, the AST Transplant Diagnostics Community of Practice, the AST Infectious Disease Community of Practice, and the Task Force on Expanded Criteria Donors convened by the Center for Organ Recovery and Education.

Research

Research in Nephropathology at UPMC Presbyterian Hospital COE involves several areas. The division is a participant in the P30 O’Brien Kidney Research Center, which is part of a multicenter group NIH grant to investigate kidney diseases. The Renal Pathology COE is part of the morphology core. We collaborate with other researchers on a variety of projects in the following broad areas:
  • clinicopathologic correlation studies in human medical renal disorders
  • allograft – related renal disorders
  • pathologic assessment in animal models of renal disorders
Some clinicopathologic projects involving native kidney disorders have included:
  • role of serum and tissue C4d in lupus nephritis and scleroderma renal crisis
  • IgG4 related renal disease, hepatitis C and cryoglobulinemia
  • cholesterol atheroembolic renal disease
  • renal disorders complicating diabetic nephropathy
Our Transplant Renal Pathology group has active investigation in several areas. This group serves as the Kidney Pathology Core for the Immune Tolerance Network. The syndrome of Polyomavirus nephropathy in the era of modern immunosuppression was defined as a result of studies conducted by faculty members associated with this COE. These studies were supported by more than 4.5 million dollars in NIH grant money that was intended to stimulate the development of better laboratory diagnostic tests, vaccines, and drugs for this viral infection. Data generated from the research laboratories has helped formulate the American Society of Transplantation guidelines for monitoring BK virus infection in kidney transplant recipients.

Other areas of active research by the Transplant Pathology faculty include the role of C4d in humoral rejection, immune rejection / tolerance, and post-transplant lymphoproliferative disorder. Collaborative projects with researchers investigating animal models of renal disease include pharmacologic manipulations in rat strains with spontaneous diabetes, obesity, and hypertension, mechanism of interstitial fibrosis, renal effects of cigarette smoking in mice, modulation of lymphocyte receptors using adenovirus vectors in a mouse model with spontaneous lupus nephritis, and several knock-out mouse models associated with renal disease.

Training

EM image of permeation of the glomerular basement membrane
The UPMC Presbyterian Renal / EM COE participates in the second year medical school renal course each year in October. The students receive lectures supplemented by small group sessions covering glomerular, tubulointerstitial, and vascular disorders of the kidney. The instruction is provided by pathology faculty, residents, and fellows. Medical students may choose to spend elective time in the Renal / EM COE providing the opportunity to learn how medical kidney biopsies are processed and evaluated, and to learn how to use the immunofluorescence and electron microscopes. Renal pathology didactic training is provided to pathology residents and nephrology fellows via didactic lectures presented in respective lecture series, and unknown slide conferences are provided to pathology residents. Renal pathology continuing education is provided to nephrologists within and outside of UPMC via renal biopsy conferences. On a national level, COE faculty have delivered educational lectures in renal pathology at the American Society of Nephrology, the American Society of Transplantation (AST), and the United States and Canadian Academy of Pathology. They have served on the AST Educational Committee and the AST Expert Faculty Resource Service as Charter Speaker.

Pathology residents at UPMC Presbyterian Hospital have a three-week rotation in Medical Renal Biopsy / EM after the PGY-1 year. They receive training in the evaluation of native and allograft renal biopsies including interpretation of light microscopy and ancillary stains, immunofluorescence, and electron microscopy, and correlation of the pathology with the clinical findings. During the second and third weeks of the rotation, residents discuss the provisional pathology findings with the attending nephrologist on the day following the biopsy, and dictate the pathology reports. Three one-hour sessions / week are provided by the Electron Microscopy Laboratory staff, in which residents learn how to use the dissecting microscope to assess adequacy and divide renal biopsies, process biopsies for immunofluorescence and electron microscopy, and use the transmission electron microscope and digital image system. Residents have access to light microscopy and electron microscopy teaching sets, providing the opportunity to see a variety of classic and unusual renal disorders. Residents are encouraged to contribute one electronic case report to the department website. Training in nephropathology is also available to the Transplant Pathology and Nephropathology fellows.