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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
Veterinary Clinics of North America: Small Animal Practice
Management of Proteinuria in Dogs and Cats with Chronic Kidney Disease
Section snippets
Key points
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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Cited by (37)
Chronic Renal Failure-Causes, Clinical Findings, Treatments and Prognosis
2022, Veterinary Clinics of North America - Equine PracticeEvaluation of the progression of non-azotemic proteinuric chronic kidney disease in dogs
2021, Research in Veterinary ScienceCitation Excerpt :Hence, proteinuria is relatively common in dogs with CKD. In addition, many studies in humans, dogs, and cats have demonstrated that proteinuria is associated with progression of CKD (Erkan, 2013; Gorriz and Martinez-Castelao, 2012; Vaden and Elliott, 2016). Especially, a urine protein:creatinine ratio (UPC) ≥1.0 at the time of diagnosis is associated with a higher risk of developing uremic crisis, CKD progression, and death in CKD dogs with serum creatinine concentrations of 177–707 μmol/L (Jacob et al., 2005).
The Effect of Intermittent Hemodialysis on the Hematological and Serum Biochemistry Profile in Dogs With Chronic Kidney Disease
2020, Topics in Companion Animal MedicineCitation Excerpt :Both findings are explained by the intense proteinuria observed in both groups which often accompanies CKD, and are intensified by the malabsorption syndrome and by the catabolism caused by prolonged anorexia. Additionally, proteinuria is also an indicator of unfavorable prognosis for the disease.15,24 As was the case with anemia, plasma hypoproteinemia was significant in the CG on T1 and T2, but this parameter is often misinterpreted after hydration due to the negative effect of hemoconcentration and the superhydration of recently admitted patients.16
Evaluation of serum symmetric dimethylarginine as a biomarker of kidney disease in canine leishmaniosis due to Leishmania infantum
2020, Veterinary ParasitologyCitation Excerpt :On a comparative basis, Pardo-Marín et al. (2017) did not find an association between sSDMA and Up/c, while Torrent et al. (2018), found a numerical (not statistical) higher prevalence of increased sSDMA in proteinuric (47 %) versus non-proteinuric dogs with CanL, but the median sSDMA was not different. This discrepancy may be attributed to the fact that glomerulopathy may unpredictably precede, follow or proceed concurrently with the renal excretory impairment in canine CKD (Wehner et al., 2008; Vaden and Elliott, 2016; Torrent et al., 2018). In CanL, the prevalence of proteinuria may be as high as 70 %, as a result of the severe glomerular pathology (Plevraki et al., 2006; Petanides et al., 2008; Torrent et al., 2018).
Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study
2019, Experimental ParasitologyCitation Excerpt :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.
Novel renal injury markers in dogs with ehrlichiosis
2023, PLoS ONE
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.