Management of Proteinuria in Dogs and Cats with Chronic Kidney Disease

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Key points

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    Proteinuria is a negative prognostic for chronic kidney disease and is associated with degree of functional impairment, the risk of uremic crisis, progressive worsening of azotemia, or death.

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    Normal dogs and most normal cats should have a urine protein:creatinine ratio that is less than 0.4 and less than 0.2, respectively; persistent proteinuria above this magnitude warrants attention.

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    Administration of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is considered a

Proteinuria as a prognostic indicator in chronic kidney disease

Proteinuria is a negative prognostic indicator for both dogs and cats with chronic kidney disease. In dogs with chronic kidney disease, an initial urine protein:creatinine ratio (UPC) of greater than 1.0 was associated with a threefold greater risk of developing a uremic crisis and death.1 The relative risk of adverse outcomes increased 1.5 times for every increase in the UPC by 1. In another canine study, proteinuria correlated with the degree of functional impairment, as measured by

Normal renal handling of protein

The glomerulus is a complex structure that functions as a filter, across which an ultrafiltrate of the plasma is formed. This filtration system, made up of the fenestrated endothelium, glomerular basement membrane, and visceral epithelial cells (podocytes), is freely permeable to water and small dissolved solutes but retains cells and most macromolecules, such as proteins. The podocyte is the most differentiated cell in the glomerulus and is essential to the filtration unit.6 In addition to

Laboratory tests for urine protein

The urine dipstick, the sulfosalicylic turbidimetric test (SSA, Bumin test), or the UPC can be used to measure total urine protein. The urine dipstick is the most readily available test of urine protein, but is also the least reliable. Both false positives and false negatives occur. The sensitivity and specificity of the urine protein dipstick are as low as 54% and 69%, respectively, in the dog and 60% and 31%, respectively, in the cat.10 Although the urine dipstick primarily detects albumin,

Clinical assessment of proteinuria

Accurate assessment of proteinuria involves 3 key elements: persistence, localization, and magnitude.11 Persistent proteinuria is defined as proteinuria that has been detected on 3 or more occasions, 2 or more weeks apart. Persistent proteinuria should be localized as being prerenal, postrenal, or renal (Table 2). Identifying the cause of proteinuria in an affected dog or cat is important so that appropriate therapeutic measures can be implemented. Renal proteinuria that is glomerular or

Inhibition of the renin–angiotensin–aldosterone system to manage proteinuria

Hemodynamic forces influence the transglomerular movement of proteins, and it follows that altering renal hemodynamics would be effective in reducing proteinuria.13 The renin–angiotensin–aldosterone system (RAAS) has been the major target system for this approach to reducing proteinuria (Fig. 1). Agents that target RAAS include the angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and aldosterone receptor antagonists (Table 3). Although renin inhibitors are

Management of hypertension

The kidney is one of the target organs for hypertensive damage and sustained hypertension may lead to an increased magnitude of proteinuria, rate of decline of renal function, frequency of uremic crises, and mortality.3, 38, 39 The goal of antihypertensive therapy is to reduce the blood pressure so the risk of continued target organ damage is minimized (Table 4). Inhibitors of RAAS are generally only weak antihypertensive agents, leading to a reduction in blood pressure by only about 10% to

Diet

In animal models of chronic kidney disease, the magnitude of proteinuria can be reduced by dietary modification, specifically by modifying the polyunsaturated fatty acid ratio and protein content.13 Dietary supplementation with n-3 polyunsaturated fatty acids or feeding a diet that has a reduced n-6/n-3 ratio that is, close to 5:1, as found in most commercially available renal diets is expected to alter the long-term course of renal injury and decrease the magnitude of proteinuria. It is

Renal biopsy

Nearly 60% of dogs with glomerular proteinuria will have either immune complex–mediated glomerulonephritis or amyloidosis,42 both of which may represent an aberrant or excessive immune or inflammatory response to an infectious, neoplastic or inflammatory condition. Cats rarely get glomerulonephritis; however, it should be anticipated that individual cats could develop glomerulonephritis secondary to a concurrent systemic disease. Therefore, in dogs or cats with glomerular proteinuria it is

Immunosuppressive agents

Empirical administration of immunosuppressive or antiinflammatory 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.44 Dogs with more severe disease or rate of progression should be treated more aggressively than those with relatively stable disease. Single agent or combination therapy

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References (46)

  • A. Singh et al.

    Glomerular endothelial glycocalyx constitutes a barrier to protein permeability

    J Am Soc Nephrol

    (2007)
  • T. Maack

    Renal handling of proteins and polypeptides

    Compr Physiol

    (2011)
  • G.F. Grauer et al.

    Comparison of conventional urine protein test strips and a quantitative ELISA for the detection of canine and feline albuminuria

    J Vet Intern Med

    (2004)
  • G.E. Lees et al.

    Assessment and management of proteinuria in dogs and cats: 2004 ACVIM forum consensus statement (small animal)

    J Vet Intern Med

    (2005)
  • Nabity MB. Urinary biomarkers of chronic kidney disease in veterinary medicine: where do we stand? Paper presented at...
  • S. Brown et al.

    Consensus recommendations for standard therapy of glomerular disease in dogs

    J Vet Intern Med

    (2013)
  • J. Tenhundfeld et al.

    A randomized controlled clinical trial of the use of benazepril and heparin for the treatment of chronic kidney disease in dogs

    J Am Vet Med Assoc

    (2009)
  • J.N. King et al.

    Tolerability and efficacy of benazepril in cats with chronic kidney disease

    J Vet Intern Med

    (2006)
  • H. Mizutani et al.

    Evaluation of the clinical efficacy of benazepril in the treatment of chronic insufficiency in cats

    J Vet Intern Med

    (2006)
  • G.F. Grauer et al.

    Effects of enalapril vs placebo as a treatment for canine idiopathic glomerulonephritis

    J Vet Intern Med

    (2000)
  • S.A. Brown et al.

    Evaluation of the effects of inhibition of angiotensin converting enzyme with enalapril in dogs with induced chronic renal insufficiency

    Am J Vet Res

    (2003)
  • S.A. Brown et al.

    Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency

    Am J Vet Res

    (2001)
  • M.J. Ryan et al.

    Elevations in serum creatinine with RAAS blockade: why isn’t it a sign of kidney injury?

    Curr Opin Nephrol Hyperten

    (2008)

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      Urine creatinine concentration was measured with a modified Jaffe reaction method (creatinine kinetic, Flowcytogen Laboratories) in samples diluted 1:20 in distilled water. Dogs were classified according to the current IRIS guidelines as non-proteinuric if UPC <0.2, borderline proteinuric if UPC = 0.2–0.5, and proteinuric if UPC >0.5 (Vaden and Elliott, 2016). For each of the dogs, possible treatment-related nephrotoxicity was considered when serum creatinine concentration increased >0.3 mg/dl from baseline (Hokamp and Nabity, 2016) or when glycosuria and/or casts were present at urinary sediment examination.

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    Dr S.L. Vaden has acted as a paid consultant for Heska Corporation and Idexx Ltd. She receives research grant funding from Morris Animal Foundation (D12CA-053) and the American Kennel Club Canine Health Foundation (01844). Dr J. Elliot has acted as a paid consultant for Bayer Animal Health, Boehringer Ingelheim, Elanco Animal Health, Idexx Ltd, CEVA Animal Health, Orion Inc, Nextvet Ltd, Waltham Centre for Pet Nutrition. He receives research grant funding from CEVA Animal Health, Elanco Animal Health, Zoetis Animal Health, Royal Canin and Waltham Centre for Pet Nutrition. Dr J. Elliot is also a member of the International Renal Interest Society, which receives financial support from Elanco Animal Health.

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