Consensus Recommendations for Immunosuppressive Treatment of Dogs with Glomerular Disease Based on Established Pathology

Abstract

The purpose of this report was to provide consensus recommendations for the use of immunosuppressive therapy in dogs with active glomerular diseases. Recommendations were developed based on comprehensive review of relevant literature on immunosuppressive therapy of glomerular disease in dogs and humans, contemporary expert opinion, and anecdotal experience in dogs with glomerular disease treated with immunosuppression. Recommendations were subsequently validated by a formal consensus methodology. The Study Group recommends empirical application of immunosuppressive therapy for dogs with severe, persistent, or progressive glomerular disease in which there is evidence of an active immunemediated pathogenesis on kidney biopsy and no identified contraindication to immunosuppressive therapy. The most compelling evidence supporting active immune-mediated mechanisms includes electron-dense deposits identified with transmission electron microscopic examination and unequivocal immunofluorescent staining in the glomeruli. For diseases associated with profound proteinuria, attendant hypoalbuminemia, nephrotic syndrome, or rapidly progressive azotemia, single drug or combination therapy consisting of rapidly acting immunosuppressive drugs is recommended. The Study Group recommends mycophenolate alone or in combination with prednisolone. To minimize the adverse effects, glucocorticoids should not be used as a sole treatment, and when used concurrently with mycophenolate, glucocorticoids should be tapered as quickly as possible. For stable or slowly progressive glomerular diseases, the Study Group recommends mycophenolate or chlorambucil alone or in combination with azathioprine on alternating days. Therapeutic effectiveness should be assessed serially by changes in proteinuria, renal function, and serum albumin concentration. In the absence of overt adverse effects, at least 8 weeks of the rapidly acting nonsteroidal drug therapy and 8-12 weeks of slowly acting drug therapy should be provided before altering or abandoning an immunosuppressive trial.

ACVIM consensus update on Lyme borreliosis in dogs and cats

“…No experimental model for Lyme nephritis is available, and it is difficult to study treatment protocols. Recommendations are based on antimicrobial treatment and standard diagnostic and treatment protocols for ICGN and PLN, as recommended by the IRIS Canine Glomerulonephritis Study Group . Proteinuria concurrent with seropositivity for an infectious agent with the potential to incite glomerular disease does not necessarily document a cause and effect relationship, even if clinical signs (eg, lameness) are seen.…”

“…No experimental model to study its pathogenesis, treatment, and prevention in over‐represented (retriever) breeds has been developed, and no validated staining techniques are available to prove that glomerular immune‐complexes are Lyme‐specific in kidney biopsy specimens from living dogs. Despite these limitations, strategies for empirical management of Lyme nephritis are given, as recently offered by the International Renal Interest Society (IRIS) Glomerular Disease Study Group …”

Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone

“…The prodrug mycophenolate mofetil (MMF) has been shown to be a promising drug for the treatment of autoimmune diseases in dogs and cats (Ackermann, May, & Frank, ; Bacek & Macintire, ; Machka et al., ; Segev, Cowgill, Heiene, Labato, & Polzin, ; Yau & Bianco, ).…”

Management of Proteinuria in Dogs and Cats with Chronic Kidney Disease

“…Empirical administration of immunosuppressive or anti-inflammatory therapy has been recommended for dogs that have no known contraindications for the specific drugs being considered and have severe, persistent, or progressive glomerular disease in which there is renal biopsy-supported evidence of immune-mediated pathogenesis (Segev et al, 2013). Dogs with more severe disease or rate of progression should be treated more aggressively than those with more stable disease.…”

“…Dogs with more severe disease or rate of progression should be treated more aggressively than those with more stable disease. Single agent or combination therapy for rapid onset of immunosuppression should be considered in dogs with high magnitude proteinuria with hypoalbuminemia, NS, or rapidly progressive azotemia (Segev et al, 2013).…”