Introduction

There are various renal diseases and extrarenal diseases with detrimental effects on renal function. By the time a clinical diagnosis is made, damage is often presumed to be permanent and progressive. However, there is a considerable variety in renal diseases and their therapeutic options; prognosis can range from only days to many years of survival with a good quality of life.

With routinely available diagnostics such as urinalysis, serum chemistry and imaging, it is possible to determine the severity of renal failure and monitor it over time. Unfortunately, these are generally insufficient to identify the specific nature of renal damage, to adequately underpin the therapeutic options or to predict any remaining regenerative capacity.

Especially in the early stages, a precise description of the histological features combined with clinical data offer insight into the pathogenesis and provide guidelines for appropriate therapy. This is in contrast to patients with long-standing, advanced chronic kidney disease where secondary changes are abundant and the focus is usually on symptomatic treatment and timely detection of treatable complications.

Although adequate characterisation of glomerular disease has long proven its value in human medicine and has led to a classification system used to standardise treatment protocols and improve outcome, this is still lacking in veterinary medicine.

Standardisation of Renal Diseases

Along the lines of the Hepatic and Gastrointestinal Standardization Groups, an international consortium with an interest in renal pathology from veterinary and human medicine was brought together to work on setting up a renal classification system. Contrary to these already standardised organ system diseases, retrospective development of a renal standardisation system proved to be difficult because of insufficient numbers of adequately assessable veterinary patient material. This was mainly due to absence of diagnostic centres that offer a full renal biopsy service on a routine base.

Classification of Canine Glomerular Diseases

Under the auspices of the World Small Animal Veterinary Association and with the generous support of Bayer Healthcare-Animal Health and Hill's Pet Nutrition, the Renal Standardization Group was initiated to start the prospective study to develop a classification system for veterinary renal diseases. As glomerular diseases are a leading cause of renal disease in dogs, initial emphasis was placed on dogs with persisting renal proteinuria that had not progressed to end-stage renal failure.

To accommodate the specific needs of this project an international group was put together consisting of:

 Clinicians. Clinical study group: C. Brovida (Italy), L.D. Cowgill (USA), A.M. van Dongen (NL), J. Elliott (UK), R. Heiene (N), D. Polzin (USA), H. Syme (UK) and S. Vaden (USA)

 Pathologists. Pathology study group: L. Aresu (Italy), B. Berridge (USA), C. Brown (USA), R. Cianciolo (USA), F. Clubb (USA), R. Goldschmeding (NL), C. James (UK), J. Jansen (N), G. Lees (USA), J. van der Lugt (NL), C. Mohr (USA), B. Spangler (USA)

 A statistician. P. Kass (USA).

Two diagnostic renal pathology centres were established to provide routinely a high quality, standardised renal biopsy service including light microscopy (LM) examination, immunofluorescence (IF) and transmission electron microscopy (TEM):

 Diagnostic renal pathology centres: Texas Veterinary Renal Pathology Service (G.Lees@cvm.tamu.edu) and Utrecht Veterinary Nephropathology Service (Kidney.VPDC@uu.nl).

By means of a digital pathology system these images could be made electronically available, which greatly improved their accessibility and enhanced possibilities for individual annotation. In addition, a web-based infrastructure was developed to collect and store comprehensive clinical data as well as the digitalised histopathological images. These on-line technologies not only facilitated a convenient and worldwide access, they also allowed for an efficient and thorough evaluation of incorporated case material.

During regular on-line meetings, collaborative reviews contributed to integration of the different disciplines. Renal biopsy features were defined and illustrated to ensure continuity. To reach a consensus opinion, all pathologists scored each case in a qualitative and quantitative way. Similarly, clinicians reviewed history, results of physical examination as well as laboratory data and scored relevant findings in a numerical way for statistical purposes.

Results

Results so far confirm that combining clinical data with imaging does improve diagnosis. They also revealed some remarkable differences in prognosis emphasising the value of a correct diagnosis for individual patients (and their owners). Moreover, canine glomerular diseases are more complex than previously recognised and it appears that routine pathological nomenclature may not suffice to accurately characterise glomerular pathogenesis and direct therapy. In the proposed classification system, disease categories are therefore based on lesion analysis and clinical variables rather than historical nomenclature.

Future Aims

Additional cases will become available in time. These will be vital to validate this classification system. Follow-up information will be actively pursued as it is needed to elucidate clinical course including outcome of the different disease categories. These data and the developed infrastructure will hopefully also provide a positive stimulus for future efforts towards multicentre clinical trials in an effective and practical way.