VETcpd - Feline Peer Reviewed

How to diagnose and manage in Feline Chronic Disease

Chronic kidney disease is commonly diagnosed in older cats. Following diagnosis, staging by serum creatinine and substaging by protein creatinine ratio and systolic blood pressure are important for appropriate monitoring and treatment. Proteinuria is a negative prognostic indicator in cats with CKD and multiple studies have demonstrated that the magnitude of proteinuria is inversely proportional to survival. Identifying and managing proteinuria is therefore important. Assessment of proteinuria involves identification of its localisation, persistence and magnitude. Dr Evelyn Maniaki DVM The origin of proteinuria can be pre-renal, renal or post-renal and it is considered CertAVP PgCertVPS MRCVS persistent if detected at least three times, two weeks apart. Urine protein creatinine Evelyn graduated from University of (UPC) ratio is the gold standard method of confirming and quantifying the Thessaly, Greece in 2009 and worked magnitude of proteinuria. Treatment is indicated in cats with a UPC>0.4 and in a busy small animal hospital in centres on inhibition of the activated renin angiotensin aldosterone system using an Athens before moving to the UK in angiotensin converting enzyme inhibitor (benazepril) or an angiotensin receptor 2013. She completed a Clinical blocker (telmisartan). Systemic hypertension should also be treated if present. Training Scholarship in Small Animal Key words: proteinuria, UPC, feline chronic kidney disease, CKD, hypertension Medicine and Surgery at Langford Vets, University of Bristol in 2016 and was awarded the RCVS Certificate in Introduction Advanced Veterinary Practice and the Chronic kidney disease (CKD) is one of normal hydration status and stable renal Postgraduate Certificate in Veterinary the most commonly diagnosed diseases function by measuring fasting serum/ Professional Studies in 2017. Evelyn plasma creatinine concentration (Table 1). has recently been appointed as the in cats, the prevalence of which increases Zoetis Feline Scholar at the University with advancing age, ranging from 31% to Substaging is performed for urine protein of Bristol where she is investigating 81% in geriatric populations, (Brown et creatinine ratio (UPC; Table 2) and “The impact of feline degenerative joint al. 2016). systolic blood pressure (SBP; Table 3). disease on mobility and quality of life Diagnostic investigation should be in cats” using data from the Bristol Cats performed in the presence of history and Assessment of Proteinuria Study for her MSc project. She is also clinical findings suggestive of CKD and It is estimated that 50-60% of cats with involved in additional feline projects generally includes blood and urine testing, CKD are non-proteinuric, whilst overt within the Bristol Cats Study and blood pressure measurement and imaging. proteinuria (UPC >0.4) is seen in undertakes a range of clinical, teaching Typical presenting signs are lethargy, inap- approximately 20% of cats with CKD and laboratory duties within University petence, weight loss dehydration (Figure (Syme et al. 2006; King et al. 2007; Sparkes of Bristol. 1), polyuria/polydipsia, altered kidney size, et al. 2016). Recognition and management E-mail: [email protected] systemic hypertension and isosthenuria of proteinuria is of paramount importance since proteinuria has been strongly (USG typically 1.008-1.012). associated with CKD progression and CKD management consists of dietary survival (Syme et al. 2006). Assessment of modification, treatment of systemic proteinuria includes identification of its hypertension and proteinuria, as well as localisation, persistence and magnitude. supportive care on a case by case basis. Although there is no cure for CKD, early Localisation diagnosis and disease management in con- The origin of proteinuria can be pre- junction with home monitoring, result in renal, renal or post-renal. It is important delay of disease progression and, ultimately, to establish the cause of proteinuria as improved prognosis and quality of life. the treatment differs markedly depending on localisation. Diagnosis and • Pre-renal proteinuria is caused by Staging of CKD an excess of low molecular weight Subscribe to VetCPD Journal Following diagnosis, staging is performed proteins produced as a result of systemic according to the International Renal disease. The protein involved is either Call us on 01225 445561 Interest Society (IRIS) guidelines. It haemoglobin (intravascular haemolysis), or visit www.vetcpd.co.uk is important to note that staging can (rhabdomyolysis) or only be undertaken in patients with immunoglobulin (plasma cell neoplasia

Page 16 - VETcpd - Vol 6 - Issue 1 Table 1: IRIS Staging based on fasting blood creatinine concentration

Stage Creatinine (µmol/l) Clinical Comments

How to diagnose and manage At risk < 140 At risk of developing CKD based on history (age, breed, drugs) Proteinuria in Feline Chronic Stage 1 < 140 Non-azotaemic. Other renal abnormalities, such as low USG, renal proteinuria etc. present. Stage 2 140 – 250 Mild renal azotaemia. Mild clinical signs (PU/PD) or absent. Kidney Disease Stage 3 251 – 440 Moderate renal azotaemia. Many renal and extra-renal signs. Stage 4 > 440 Severe renal azotaemia. Increased risk of systemic signs and uraemic crisis.

Table 2: IRIS Substaging Table 3: IRIS Substaging by Systolic Blood Pressure by Proteinuria (UPC) Systolic Blood Risk of Future Target Substage Substage UPCa Pressure (mmHg) Organ Damage Normotensive < 150 Minimal Non proteinuric <0.2 Borderline Hypertensive 150 – 159 Low Borderline proteinuric 0.2-0.4 Hypertensive 160 – 179 Moderate Proteinuric >0.4 Severely Hypertensive ≥ 180 High aNormal intact male cats can have a UPC ≤ 0.6

e.g. multiple myeloma). The protein culture. In cats with CKD, it is important is filtered by the glomerulus (as in to exclude post renal proteinuria as the healthy animal) and exceeds the urinary tract infections are common. reabsorptive capacity of the proximal tubule. As well as urinalysis, haematology Persistence and serum biochemistry, specific Proteinuria is considered persistent if diagnostics such as serum protein detected at least three times, two or more electrophoresis may be indicated for the weeks apart. investigation of pre-renal proteinuria. Magnitude • Renal proteinuria can be functional Different methods can be used to assess the or pathological. Functional renal magnitude of proteinuria. These are either Figure 1: Cats with CKD often present with proteinuria is transient and can be dehydration manifested as skin tenting. Note that semi-quantitative, such as the “dipstick” skin elasticity is reduced in older cats making this a seen as a result of fever, seizures or or the sulfosalicylic acid turbidimetric less sensitive test and mucous membranes should strenuous exercise, although this is method (SSA), or quantitative, such as also be evaluated. rarely recognised in cats. Pathological UPC and urine albumin. Proteinuria renal proteinuria is permanent and detected via dipstick or SSA should always can be the result of damage to the be interpreted in relation to the urine glomerulus (glomerular proteinuria) specific gravity and sediment examination. or the renal tubules and interstitium • Reagent pad colorimetric method (tubulointerstitial proteinuria). UPC The reagent pad colorimetric method, can be used to determine if renal also known as “dipstick” (Figure 2), proteinuria is glomerular or tubular primarily detects albumim and is less in origin. Primary glomerular disease sensitive to globulins. Although it is is much less common in cats than widely available and easy to use, false dogs but a UPC of >2.0 is highly positive and false negative readings suggestive of a glomerular rather than can occur when urine is highly tubulointerstitial cause. In cats with concentrated, strongly acidic or alkaline, CKD, systemic hypertension results or pigmented. In the cat, sensitivity is in secondary glomerular damage and 90% and specificity is only 11% treatment of hypertension may resolve (Lyon et al. 2010). resultant proteinuria. • The Sulfosalicylic acid turbidimetric • Post-renal proteinuria occurs as a method (SSA): Specificity and positive result of exudative or haemorrhagic predictive values are higher for SSA Figure 2: Urine dipsticks are a convenient, semi processes affecting the lower urinary or than dipsticks; however, SSA cannot quantitative method of detection of proteinuria. Persistently positive dipstick results should be genital tract e.g. . be run in-house and false positives or confirmed and quantified at an external laboratory This can be excluded by performing negatives can still occur. Dipstick is via assessment of urine protein: creatinine ratio. urine sediment examination and/or therefore used more commonly.

VETcpd - Vol 6 - Issue 1 - Page 17