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The prevalence of immune-complex glomerulonephritides in dogs | VETgirl Veterinary Continuing Education Podcasts

In this VETgirl online veterinary continuing education podcast, we discuss the prevalence of immune-complex glomerulonephritis (ICGN) in dogs. Is it always due to glomerulonephritis? Or is it due to amyloidosis? Why should we care? First, we should care as glomerular injury is common to many renal diseases. Both primary and secondary glomerular disease is commonly seen in dogs. Primary glomerular disease refers to diseases where the glomerulus suffers the initial injury, while secondary glomerular disease refers to those diseases in which the glomerulus is secondarily injured. Based on the ongoing WSAVA Renal Standardization Project, primary glomerular disease in dogs is divided into 3 main groups: immune-complex glomerulonephritis, amyloidosis, and non-immune-complex glomerulonephritis. You can download the guidelines here, btw. Non-immune-complex glomerulonephritis is a diagnosis of exclusion, if neither immune complexes nor amyloid is demonstrated, but primary pathology is noted in the glomerulus.

So, Schneider et al wanted to evaluate the prevalence of immune-complex glomerulonephritides (and specifically, glomerulonephritis) in dogs of having suspected glomerular disease. They evaluated 501 dogs that had renal biopsies performed; all biopsies were submitted to the Texas Veterinary Renal Pathology Service. Inclusion criteria included dogs that had a clinical history suggesting nephritic syndrome, nephrotic syndrome, or glomerulonephritis as a recommendation for the reason for biopsy; dogs that had a urine protein: creatinine (UPC) value of > 2; or dogs that had a persistent and unexplained renal proteinuria. All renal biopsy samples were evaluated with light microscopy (LM), immunofluorescence (IF) and electron microscopy (TEM).

So what’d they find in this study? The average age of all dogs was 6.8 years (range 4 months to 14 years), and females (n=283) slightly outnumbered males (n=218). The majority of dogs were neutered or spayed. Dogs with glomerular disease came from all geographic areas in North America, with the greatest numbers from the Midwest (27.3%) and the Northeast (26.3%). This is interesting since VETgirl is from the Midwest and makes me unofficially hypothesize and worry that this is due to the prevalence of Lyme disease in these reported areas.

Although 52.9% of the cases were from a variety of breeds, a number of breeds were overrepresented for glomerular disease: Labrador retriever (10.4%), Golden Retriever (7.6%), Yorkshire terrier (5.8%), and other breeds at 2-3% each (e.g., Beagle, Miniature Schnauzer, Shetland Sheepdog, Boxer, Cocker Spaniel, Doberman Pinscher, Soft-Coated Wheaton Terrier, English Bulldog, and Standard Poodle). Also important to note that the Labrador retriever and Golden retriever are the top two breeds that develop Lyme nephritis also!

In almost all of the cases (95.6%, n=479/501), the UPC was > 2. In the remaining 22 dogs or 4.4%, persistent renal proteinuria was present with a UPC of < 2. In 48% of the cases, immune-complex glomerulonephritis was confirmed by immunofluorescence and electron microscopy. Amyloidosis was seen in 15.2% of cases, based on apple-green birefringence noted under polarized light. Non-immune-complex glomerulonephritis causes such as glomerulosclerosis was detected in 20.6% of biopsies and other non-immune-complex glomerulopathy was seen in 9.0% of biopsies. Non-immune-complex nephropathy was seen in 4.8%, in which chronic changes were noted in both the tubules and the glomeruli but it was unclear which was the primary insult. Lastly, primary tubulointerstitial disease was only seen in 2.4% of cases. When looking specifically at the the median urine protein: creatinine in the majority of cases, the immune-complex glomerulonephritis biopsies had a median UPC of 8.3; amyloidosis biopsies had a median UPC of 10.3; glomerulosclerosis biopsies had a median UPC of 6.0; non-immune-complex glomerulopathy biopsies had a UPC of 5.4; non-immune-complex nephropathy biopsies had a UPC of 3.4; and primary tubulointerstitial disease had a median UPC of 3.9. Of the 22 dogs had a UPC < 2, the following diagnoses were made based on renal biopsy: immune-complex glomerulonephritis (6/22), non-immune-complex glomerulonephritis (15/22) and amyloidosis (1/22). This finding is significant since glomerular disease is often thought to have UPC > 2 or 3, and obvious pathology was seen with a low UPC.

So, what do we take from this VETgirl podcast? First, this was a great study to evaluate the prevalence of immune-complex glomerulonephritides in dogs. One of the reasons why this paper was so important is because previously, immune-complex glomerulonephritis was considered to be the most common among glomerular disease in the dog. Apparently not! Based on this study, immune-complex glomerulonephritis wasn’t present in 51.9% of the dogs, reiterating the importance of renal biopsy in dogs! Given that some types of immune-complex glomerulonephritis may respond to immunomodulatory medications, this study underscores the necessity of obtaining a specific diagnosis (e.g., get a biopsy!) prior to using immunosuppressives in dogs with glomerular disease.

Another important consideration from this paper? Depending on who you are submitting your renal biopsies to, it’s important that you keep in mind that MORE than just light microscopy has to be performed with these renal biopsies! Additional testing such as immunofluorescent microscopy, electron microscopy, etc., must be done to rule out other non-immune complex glomerulonephritis causes. Biopsy samples evaluated with only light microscopy may give an erroneous diagnosis or may not be able to adequately confirm immune-complex glomerulonephritis alone.

Lastly, a UPC >0.5 indicates clinical relevant proteinuria. Often we consider a UPC > 2 or 3 suggestive of glomerular disease. This study may make us reconsider this, as some of the dogs with UPC < 2.0 in fact had glomerular disease. Some of the dogs with UPC > 2 had primary tubulointerstitial disease, including one with UPC of 8.6. So when in doubt, work up, diagnose and treat any case with a UPC > 0.5!

References:
1. Schneider SM, Cianciolo RE, Nabity MB, et al. Prevalence of immune-complex glomerulonephritides in dogs biopsies for suspected glomerular disease: 501 cases (2007-2012). J Vet Intern Med 2013;27: S67-S75.

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