Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Low-level proteinuria, characterized by a urinary protein:creatinine ratio (UPC) between 0.2 and 1, commonly affects cats with chronic kidney disease (CKD) and is mainly associated with primary tubulointerstitial lesions. Despite its mild severity, it is an important prognostic factor and therapeutic target.1-3 In contrast, marked proteinuria and primary glomerular disease are uncommon in cats with CKD.
Proteinuria contributes to progressive renal injury as it induces tubular and mesangial damage and toxicity, as well as an inflammatory response.4 In addition, proteinuria is negatively associated with survival time of cats with CKD.2,3 Further, determination of UPC is an integral part of the IRIS staging system of cats with CKD.5 Thus, quantifying and longitudinal monitoring of proteinuria is very important in all cats with CKD.
Of the existing routine methods to evaluate cats for proteinuria (dipstick, sulfosalicylic acid precipitation test, UPC), the UPC is the only reliable method to determine its clinical implications. The urinary albumin:creatinine ratio has also been investigated in cats, but does not provide any benefit over UPC.2,6 Cats should be classified as (overt) proteinuric (UPC >0.4), borderline proteinuric (UPC 0.2–0.4) or non-proteinuric (UPC <0.2).7 The clinical significance of borderline proteinuria and the reliability of UPC assays warrant further investigation because a large proportion of healthy cats, including juvenile cats, had borderline proteinuria that could not be explained by CKD in all of them.8,9
It is important to realize that proteinuria may be of prerenal, renal or postrenal origin and only persistent renal proteinuria indicates CKD. A stepwise diagnostic approach must be followed to eliminate prerenal (e.g., hemoglobinuria, myoglobinuria, Bence-Jones proteinuria), postrenal urinary (e.g., urolithiasis, cystitis, ureteritis, bladder or urethral neoplasia) and postrenal extraurinary (e.g., genital tract inflammation) proteinuria. The severity of proteinuria may help to localize renal proteinuria: UPC values above 2 are likely glomerular, but lower values might be glomerular, tubular or interstitial in origin. Although less frequently in cats than in dogs, kidney biopsies after excluding extrarenal causes need to be considered in cats with severe proteinuria or protein-losing nephropathy.5,7
Treatment of proteinuria is highly recommended because control of the factors associated with disease progression might promote longevity of cats with CKD. Current guidelines recommend treatment in cats with UPC values that persistently exceed 0.4, regardless of the IRIS stage.5 Management of proteinuria focuses primarily on interfering with the renin-angiotensin-aldosterone system (RAAS) resulting in reduced glomerular capillary pressures. This can be achieved by using angiotensin-converting enzyme (ACE) inhibitors, or angiotensin-receptor blockers (ARBs). RAAS-blockade should be advised in well-hydrated cats with stable CKD and initial monitoring is recommended after 5–7 days. ARBs have the theoretical advantages to act selectively on the angiotensin II type 1 receptor while leaving beneficial effects of the angiotensin II type 2 receptor, and to avoid ACE-escape mechanisms that may occur with chronic use of ACE-inhibitors. Recent studies in feline medicine confirm the antiproteinuric effect of the ACE-inhibitor benazepril and the ARB telmisartan.1,10 Despite the antiproteinuric effect of telmisartan that appeared to be more pronounced, superiority of telmisartan over benazepril was not confirmed.10 Also, whether RAAS- blockade slows down CKD progression or improves survival time, has yet to be proven in cats.
Next to interfering with the RAAS system, other strategies may be beneficial to control proteinuria. In canine models of glomerular disease, dietary protein restriction and supplementation with n-3 polyunsaturated fatty acids (PUFA) may offer renoprotection. Because feline proteinuria is mostly associated with CKD, feeding a protein-restricted diet (renal diet) should be part of the treatment plan. Whether feeding diets with a reduced n-6/n-3 PUFA ratio should be recommended is currently uncertain in cats. Further, factors that contribute to proteinuria, such as hypertension, should be corrected. Finally, if identified, correction or treatment of the underlying disease etiology might significantly reduce proteinuria.
References
1. King JN, Gunn-Moore DA, Tasker S, et al. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med. 2006;20:1054–1064.
2. Syme HM, Markwell PJ, Pfeiffer D, Elliott J. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med. 2006;20:528–535.
3. King JN, Tasker S, Gunn-Moore DA, et al. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med. 2007;21:906–916.
4. Chakrabarti S, Syme HM, Elliott J. Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med. 2012;26:275–281.
5. International Renal Interest Society (IRIS). IRIS staging of CKD (modified 2015). Available from: www.iris-kidney.com/pdf/003-5559.001-iris-website-staging-of-ckd-pdf_220116-final.pdf (VIN editor: link updated 10/10/2017).
6. Jepson RE, Brodbelt D, Vallance C, et al. Evaluation of predictors of the development of azotemia in cats. J Vet Intern Med. 2009;23:806–813.
7. Lees GE, Brown SA, Elliott J, et al. Assessment and management of proteinuria in dogs and cats: 2004 ACVIM forum consensus statement (small animal). J Vet Intern Med. 2005;19:377–385.
8. Paepe D, Verjans G, Duchateau L et al. Routine health screening. findings in apparently healthy middle-aged and old cats. J Feline Med Surg. 2013;15:8–19.
9. Paepe D, Bavegems V, Combes A, et al. Prospective evaluation of healthy ragdoll and control cats for chronic kidney disease by routine laboratory parameters and ultrasonography. J Feline Med Surg. 2013;15:849–857.
10. Sent U, Gössl R, Elliott J, et al. Comparison of efficacy of long-term oral treatment with telmisartan and benazepril in cats with chronic kidney disease. J Vet Intern Med. 2015;29:1479–1487.