Preface

This Atlas of Renal Lesions in Proteinuric Dogs is a seminal work that is the product of a huge amount of effort by a dedicated cadre of veterinary pathologists and nephrologists. However, it is noteworthy that it has only recently become possible to prepare such an atlas because during the last decade veterinary pathologists have had the opportunity to routinely evaluate appropriate specimens from proteinuric dogs using adequate methods of examination. This opportunity occurred because of the confluence of 3 important trends: (1) increased availability of informative specimens, (2) greater ability to perform adequately revealing tissue examinations, and (3) improved integration of the clinical and pathologic findings to better support clinical decision-making.

Several key factors contributed to the increased availability of informative specimens. One of these was the emergence of a heightened clinical awareness of the potential value of detecting and managing proteinuria and hypertension, which are common clinical manifestations of canine glomerular diseases. Publication of ACVIM Forum Consensus Statements regarding proteinuria (in 2004) and hypertension (in 2007) both reflected this heightened awareness and armed clinicians with specific guidelines for diagnosis and treatment of these problems. Another key factor contributing to greater availability of informative specimens was increased use of renal biopsy to obtain an antemortem diagnosis and guide therapeutic decisions. Increased emphasis on detecting proteinuria no doubt led to more frequent identification of appropriate indications for renal biopsy.  In addition, renal specimens obtained by biopsy are diagnostically more informative than postmortem samples. The first of these is that biopsy specimens frequently exhibit earlier stages in the pathogenesis of the animal’s nephropathy, which makes it easier for the pathologist to discern the fundamental nature of the initial abnormality. Second, biopsy specimens typically are relatively small pieces of tissue that are, when handled properly and promptly placed in appropriate fixatives / preservatives, devoid of artifacts, which makes it possible for the pathologist to confidently identify even very subtle lesions that might otherwise be obscured by or confused with postmortem changes.

A pivotal event that enabled veterinary renal pathology to evolve to its present state of maturation was the development of veterinary Diagnostic Renal Pathology Centers (DRPCs), which provided the ability to routinely perform adequately revealing tissue examinations. From a laboratory perspective, processing renal specimens for the kinds of examinations that are required for excellent diagnostic evaluation are highly specialized and demanding tasks. Moreover, developing and maintaining a high degree of technical competence in performing these tasks requires a fairly steady supply of cases to maintain proficiency. Beginning in 2005, DRPCs were established first at Texas A&M University in the USA and subsequently (in 2008) also at Utrecht University in the Netherlands. Each of these DRPCs functioned to:

1. Provide guidance and support for clinicians seeking to submit renal specimens and providing, upon request, Renal Biopsy Kits that contain the materials and instructions needed to properly submit optimum specimens.
2. Routinely perform specialized tissue examinations, including:
   1. Light microscopy with tissue sections cut at 3 micron thickness and routine use of a panel of histochemical stains.
   2. Immunostaining of cryosections cut at 3 to 5 micron thickness with routine use of fluorescent antibody probes for immunoglobulins and complement components.
   3. Transmission electron microscopy
3. Utilize digital pathology technologies to capture digital images of all microscopic specimens in formats that were suitable for viewing with sufficient magnification and clarity to permit astute diagnostic evaluation.
4. Accumulate all evaluated cases in a searchable, web-based archive that includes:
   1. The clinical information provided when the samples were submitted
   2. Digital images of the microscopic specimens
   3. Descriptions of all microscopic findings
   4. Interpretive comments offered by the pathologists
   5. Any follow-up clinical information that is made available

The searchable, web-based archive created by operations of veterinary DRPCs since their inception now (January, 2018) contains ~2,000 cases, the majority of which are evaluations of biopsy specimens obtained from proteinuric dogs in North America.

The third, and possibly most important, element contributing to the current relevance of renal pathology to contemporary veterinary nephrology practice has been greatly improved processes for integrating the findings and expertise of renal pathologists with the findings and expertise of clinical nephrologists. One of the first uses of the archive (database) was to serve as the substrate for a WSAVA-sponsored project to establish appropriate diagnostic criteria for canine glomerular diseases. Prior to this initiative, canine glomerular diseases were most often classified according to criteria for human diseases, which was tantamount to making diagnoses of human diseases in dogs. The objective of this project was to establish standardized, objective species-specific criteria for classifying canine glomerular diseases. The project, the results of which have been published (Vet Pathol 2016:53:113-135), was accomplished in a highly collaborative fashion using a digital pathology platform to review cases in the web-based archive during online meetings. These meetings fostered a culture of clinician-pathologist collaboration that is essential for optimum use of renal biopsy findings to support clinical decision-making for the benefit of patients. The nature and importance of this clinician-pathologist relationship is aptly conveyed by the following statements:

“The correct diagnosis requires a well-trained renal pathologist with thorough knowledge not only of renal pathology but also renal medicine in order to correlate intricate tissue derived information with detailed and sometimes subtle clinical data to provide the best possible clinicopathologic diagnosis.”

Walker PD, et al: Practice guidelines for the renal biopsy.

Mod Pathol 2004;17:1555-1563.

“Getting high value from a renal biopsy requires a well-trained clinician with thorough knowledge not only of renal medicine but also of renal pathology to correlate detailed and sometimes subtle clinical data with intricate tissue-derived information to obtain the best possible clinicopathologic diagnosis and provide optimum patient care.”

A corollary statement made in a presentation by George Lees

25th ACVIM Forum; June, 2007; Seattle, WA

The accomplishments of the International Renal Pathology Initiative over the last 13 years have constructed a solid foundation for continued progress in veterinary nephrology and renal pathology. Renal biopsy is now well established as a productive diagnostic procedure in large part because of the ready availability of excellent tissue analysis combined with expert, clinically-relevant interpretation of the findings by experienced veterinary renal pathologists. The infrastructure and procedures needed to reliably deliver renal pathology services in a timely manner have been developed and have withstood the test of time. A growing cohort of clinicians and pathologists is being trained to perform and evaluate renal biopsies as a collaborative enterprise focused on optimizing patient care. There is, of course, much that is yet to be learned; however, the necessary resources now exist and the future of veterinary renal pathology is exciting to contemplate.

George E. Lees, DVM, MS

Diplomate, ACVIM (Small Animal Internal Medicine)

Diplomate, ACVP (Honorary)

Emeritus Professor

Department of Small Animal Clinical Sciences

College of Veterinary Medicine and Biomedical Sciences

Texas A&M University