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J Vet Intern Med 2013;27:S2–S4
Development of Clinical Guidelines for Management of Glomerular
Disease in Dogs
D.J. Polzin and L.D. Cowgill
Key words: Canine; Glomerulonephritis; Nephrotic syndrome; Formal consensus.
Scope and Clinical Significance of Glomerular
Disease in Dogs
lomerular disease (GD) in dogs has recently experienced a rising profile among veterinarians in
part attributable to enhanced efforts to facilitate early
recognition, diagnosis, and treatment of kidney disease
and particularly proteinuric kidney diseases in dogs.
One of the primary goals in developing the IRIS CKD
Staging systema was to increase early recognition of
kidney disease with the belief that early diagnosis
would improve overall management of dogs and cats
with chronic kidney disease (CKD). Furthermore,
inclusion of proteinuria as one of the core descriptors
of the IRIS CKD Stage has emphasized the importance of proteinuria and glomerular injury. Over the
past 6 years, the WSAVA Renal Standardization
Projectb has been operating with the goal of developing a unique classification system for canine GD based
on light, electron, and immunofluorescent microscopic
imaging of the glomerular pathology. The outcome of
this study has the potential to advance our understanding of GD in dogs to a new level, potentially
opening many new options for improving our ability
to diagnose and manage GD in dogs. The apparent
association between GD and infectious diseases, such
as borreliosis in selected areas within North America
and leishmaniasis in the Mediterranean area of Europe, has also enhanced awareness of the importance of
GD and potential value of proteinuria as a sentinel for
certain infectious diseases.1,2
Although an accurate measure of the prevalence of
GD in dogs has not been established, veterinarians
generally recognize it as an important cause of morbidity and mortality in dogs. Although not always recognized as such, GD may present as several renal
syndromes in dogs, including CKD, acute kidney
G
From the Department of Veterinary Clinical Sciences, College
of Veterinary Medicine, University of Minnesota, St Paul, MN
(Polzin); and the Department of Medicine and Epidemiology,
School of Veterinary Medicine, University of California-Davis,
Davis, CA (Cowgill). Co-Chairs – IRIS Glomerular Disease
Study Group (Polzin, Cowgill).
Corresponding author: D. Polzin, Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, University of
Minnesota, 1352 Boyd Ave, Room 432 VMC, St. Paul, MN
55108; e-mail: [email protected].
Submitted September 12, 2013; Revised September 12,
2013; Accepted September 12, 2013.
Copyright © 2013 by the American College of Veterinary Internal
Medicine
10.1111/jvim.12225
Abbreviations:
GD
CKD
NS
IRIS
glomerular disease
chronic kidney disease
nephrotic syndrome
International Renal Interest Society
injury, nephrotic syndrome (NS), or isolated proteinuria. Of these syndromes, the best-defined population
data are available for CKD. The prevalence of CKD
in dogs has been estimated to be as high as 1.5% of
dogs presented in general veterinary practice.3 Based
on renal pathology findings, it has been estimated that
GD may account for over 50% of cases of CKD in
dogs.4 Extrapolating from these data, it may be estimated that the prevalence of GD in dogs may be in
excess of 0.75% of dogs seen in general practice.
Of particular concern is the observation that many
dogs with GD have seemingly poor outcomes when
treated with current therapies.5,6 A recent study
reported that median survival time for dogs with NS
was 12.5 days, although survival among nonsurvivors
ranged as high as 2,783 days.5 In this same study,
median survival for dogs with non-nephrotic GD was
104.5 days with survival ranging up to 3,124 days. The
presence of NS and azotemia, in particular, portended
especially poor outcomes in dogs with GD. Nonazotemic dogs with NS had significantly shorter survival
times (median of 51 days; mean of 390 days) than nonazotemic dogs with non-nephrotic GD (median of
605 days; mean of 71 days). In contrast, survival for
azotemic dogs with NS (median of 10 days; mean of
316 days) and non-nephrotic GD (median of 45 days;
mean of 390 days) was particularly grave and not significantly different. Clearly, we need to seek ways to
improve our therapeutic success in these dogs. Many
of the therapeutic recommendations found in the
guidelines provided in this supplement issue are aimed
specifically at improving outcomes among dogs with
the gravest prognoses.
Need for Treatment Guidelines
In human medicine, therapeutic guidelines are
viewed as an important clinical tool in enhancing the
overall quality of patient care.7 Ideally, recommendations provided through clinical guidelines are based on
high-quality evidence. However, despite the increased
recognition of the importance of GD in dogs, only a
few select studies provide high-grade evidence on
which to base treatment recommendations. Even the
Developing Clinical Guidelines
“standard therapy” recommended for dogs with GD,
which typically includes an angiotensin converting
enzyme inhibitor, diet, and aspirin therapy, has little
convincing evidence supporting their effectiveness in
improving clinical signs or extending survival times.
Obviously, when high-quality evidence is available,
developing treatment guidelines is very straight forward and largely noncontroversial. In contrast, developing guidelines absent strong clinical studies to
support that the recommendations is challenging.
Although one option would be to choose not to make
recommendations in the absence of firm evidence, it is
often in the areas of greatest uncertainty, and in which
the evidentiary base is incomplete, that guidelines are
needed most.8 Clearly, the current state of affairs for
treatment guidelines for GD in dogs is of the latter
type, and yet the veterinary profession needs guidance
in how to manage these difficult cases.
Clinical practice guidelines for managing dogs with
GD are needed to improve clinical outcomes. In
response to this need, the International Renal Interest
Society (IRIS) appointed a 20-member international
work group (the IRIS Glomerular Disease Study
Group) and charged them with developing clinical
guidelines for managing dogs with GD. This charge
was made with the understanding that while the limited literature available in dogs with GD will provide
underpinning for some recommendations, most recommendations will reflect consensus of opinion based on
the literature, review of case material, and the clinical
experience of the members of the Study Group. It is
our belief that these clinical guidelines are a starting
point in the journey to improve the treatment of dogs
with GD. They should not be viewed as the final word
in management of dogs with GD, and the guidelines
should be regularly revisited, reviewed, tested, and
updated as new scientific evidence is acquired.
The clinical guidelines presented herein are intended
to provide counsel on how to approach diagnosis and
treatment as recommended by established experts in
the field of veterinary nephrology. The recommendations have been written primarily for an expected audience of veterinary internal medicine specialists, but it
is our hope that other veterinarians involved in the
management of dogs with GD will also find it useful.
However, these guidelines are not intended to replace
the veterinarian’s own clinical judgment in the application of these recommendations. Application of the recommendations should meet each individual dog’s
needs and circumstances.
Methodology for Guideline Development
The clinical guidelines provided here were developed
by the IRIS GN Study Group, a group composed of
20 veterinarians with expertise in canine GD and
nephrology (Table 1). From this larger group, five subgroups were formed to develop proposed clinical
guidelines for (1) diagnostic investigation of dogs with
suspected GD; (2) standard therapy for dogs with GD;
(3) immunosuppressive treatment of dogs with GD
S3
based on established pathology findings; (4) immunosuppressive treatment of dogs with GD absent a pathologic diagnosis; and (5) treatment for dogs with GD
that are also serology positive for an infectious agent
possibly responsible for the GD. Each subgroup performed a literature search, and reviewed any unpublished clinical material available, appropriate and
relevant to their topic. Each subgroup (topic steering
committee) met as needed by online conferencing to
develop recommendations and rationale for each
recommendation.
Because much of the evidence available to support
recommendations on management of canine GD is
limited, inconsistent, indirect, or of poor quality, a formal consensus method was used to validate the recommendations. This approach is particularly useful when
available evidence fails to provide a clear path to a
recommendation. Specifically, the formal consensus
method is particularly useful for developing recommendations when a clear evidence-based recommendation is not available. The formal consensus method
involves iterations of independent anonymous voting
on draft recommendations and subsequent revisions.8,9
Members of the IRIS Glomerular Disease Study
Group and the IRIS Board (Tables 1, 2) voted on all
recommendations and provided comments on the recommendations and their rationale. Participants were
asked to identify their level of support with the recommendations using a scale of “strongly agree,” “agree,”
“neutral,” “disagree,” or “strongly disagree.” Anonymity of the voting and submitted comments was maintained by submission of ballots and comments to a
disinterested third party who forwarded the masked
ballots and comments to one of the co-chairs (djp) for
counting and reporting to the subgroups. To achieve a
consensus, a minimum of 75% of the voting participants must choose either “strongly agree” or “agree.”
The percentage of those supporting the recommendation and the percentage of supporters that voted
“strongly agree” are provided as assessments of
the strength of consensus for the recommendation. If
the recommendation did not achieve consensus after
the first vote, the recommendation was returned to the
subcommittee with the voter comments for rewriting
or reconsideration. If a modified recommendation was
Table 1. Members of the IRIS Glomerular Disease
Study Group.
Claudio Brovidaa
Larry Cowgill (co-chair) a
Mª Josefa Fernandez del Palacioa
Thierry Francey
Richard Goldstein
Reidun Heinea
Cathy Langston
Meryl Littman
Barrak Pressler
Shelly Vaden
Andrea Zatelli
a
Members of the IRIS Board.
Scott Browna
Sylvie Daminet
Jonathan Elliota
Bernard Gerber
Greg Grauera
Mary A. Labato
George Lees
David Polzin (co-chair)
Gilad Segev
Astrid van Dongena
a
S4
Polzin and Cowgill
Table 2. Members of the International Renal Interest
Society (IRIS) Board.
Claudio Brovida (Italy)
Scott Brown (President, IRIS Board, USA)
Larry Cowgill (co-chair; USA)
Jonathan Elliot (UK)
Mª Josefa Fern
andez del Palacio (Spain)
Greg Grauer (USA)
Mary A. Labato (USA)
Herve P. Lefebvre (France)a
Xavier Roura L
opez (Spain)a
Alexander H€
uttig (Germany)
Reidun Heine (Norway)
David Polzin (co-chair; USA)
Jean-Louis Pouchelon (France)a
Astrid van Dongen (Netherlands)
Toshifume Watanabe (Japan)
David Watson (Australia)a
humans. Such a database would facilitate performing
large observational studies on the guidelines developed
here and provide a tool for recognizing changing
trends in spontaneous GD.
Footnotes
a
b
www.iris-kidney.com
The WSAVA RSP is supported by grants from the Hill’s Pet
Food Company and Bayer Animal Health
Acknowledgment
In addition to members of the IRIS GN Study Group, members of the IRIS Board not on the IRIS GN Study Group also
voted on the recommendations.
The authors and IRIS GN Study Group thank the
International Renal Interest Society (IRIS) for their
charge and guidance in the development of these
recommendations.
Conflict of Interest Declaration: Authors disclose no
conflict of interest.
developed by the subcommittee, it was subjected to a
second round of voting and comment. If a recommendation failed on the second vote, no recommendation
was made.
References
a
Where Do We Go From Here?
The Clinical Guidelines provided herein are intended
to help veterinarians develop diagnostic and therapeutic plans that reflect the opinion of the majority of
experts participating in this exercise. Although it is our
hope that veterinarians find these guidelines helpful
and that they will improve the care of dogs with GD,
these guidelines are not intended to be the final statements on managing canine GD. Further studies are
needed to confirm or reject these recommendations
based on higher levels of evidence such as randomized
clinical trials or large observational studies. Ideally,
clinical trials will focus on treatments for specific
glomerulopathies based on renal biopsy findings. However, even in humans, GD is sufficiently uncommon
that it is considered difficult to perform randomized
clinical trials to define optimal treatment for many specific glomerulopathies.7 As a result, multicenter studies
are likely to be necessary for future trials to be
successful. In addition, perhaps the profession should
consider developing a veterinary nephrology database
similar to The United States Renal Data System, a
national data system that collects, analyzes, and distributes information about end-stage renal disease in
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