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Hypertension & Proteinuria in Feline CKD

Gregory F. Grauer, DVM, MS, Diplomate ACVIM (Small Animal Internal Medicine, and Clarke E. Atkins, DVM, Diplomate ACVIM (Small Animal Internal Medicine)

Urology & Nephrology

|December 2007|Peer Reviewed

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Systemic hypertension and proteinuria are frequently observed in cats with chronic kidney disease. It remains to be determined whether these complicating conditions are simply markers of more severe CKD or contributors to disease progression. Since systemic hypertension can damage several target organs and attenuated proteinuria is associated with prolonged survival, diagnosis of hypertension and proteinuria associated with CKD is important.

Systemic Hypertension
Systemic hypertension is relatively common in cats with CKD with prevalence ranging from 19% to 65%.

Although the exact mechanism of hypertension is not known, a combination of glomerular capillary and arteriolar scarring, decreased production of renal vasodilatory prostaglandins, increased responsiveness to normal pressor mechanisms, and activation of the reninangiotensin system secondary to impaired sodium excretion and excessive renin secretion may be involved.

Increased renin secretion leads to increased production of angiotensin II and aldosterone. In addition to its pressor effects, angiotensin II also has a direct stimulatory effect on the sympathetic nervous system, increasing vascular tone, and, in CKD, vasoconstriction of the efferent arteriole, which further contributes to the intraglomerular hypertension.

Systemic hypertension may contribute to progressive nephron loss by causing irreversible glomerular damage via increased intraglomerular pressures and glomerulosclerosis. By altering preglomerular resistance, healthy kidneys can maintain relatively static glomerular capillary pressures despite variations in systemic blood pressure. This process is termed "renal autoregulation."

Inappropriate dilation of the afferent glomerular arteriole occurs in cats with CKD and diminishes the ability of the afferent arteriole to protect the glomerulus from variations in systemic blood pressure. Angiotensin also causes the efferent glomerular arteriole to constrict, which further increases intraglomerular pressure.

The consequences of systemic hypertension usually depend on the magnitude and duration of blood pressure elevations. Acute ocular and central nervous system abnormalities can occur associated with hemorrhage or edema formation (eg, retinal hemorrhage and/or detachment, cerebral edema, and seizures). Renal damage associated with hypertension tends to be more chronic and characterized by glomerular lesions (eg, glomerulosclerosis) and proteinuria. Finally, functional/adaptive changes like ventricular hypertrophy can occur due to increased after-load in patients with hypertension. Diagnosis and treatment of hypertension in cats with CKD may prevent development of retinal lesions or may limit or slow progression of renal and cardiac lesions.

Mechanism & Consequences

Renal proteinuria associated with CKD can occur due to structural changes in the glomerular capillary wall (fusion of epithelial foot processes, increased production of mesangial matrix, hyaline accumulation, microaneurysm, etc), intraglomerular hypertension, or decreased tubular reabsorption of plasma proteins that are normally filtered through the glomerulus.

In addition to being a diagnostic marker of the severity of renal disease, it is possible that renal proteinuria is also a mediator of glomerular and tubular injury. In mice and rats, excessive protein in the glomerular filtrate can cause glomerular lesions as well as tubulointerstitial lesions, leading to loss of more nephrons. Recent findings have demonstrated that proteinuria is associated with increased risk of developing end-stage CKD in cats. In addition, studies have shown that therapies that reduce the magnitude of proteinuria are associated with prolonged survival.

Proteinuric renal disease is often associated with systemic hypertension, which can conversely exacerbate renal proteinuria and, therefore, it is difficult at times to separate the effects of high systemic and intraglomerular pressures and proteinuria. It should be noted that hypertension and proteinuria have not been proven to be mediators of progressive renal damage in cats with CKD; it is possible that hypertension and proteinuria are simply markers that CKD is more likely to be rapidly progressive.


Current recommendations are that blood pressure be measured in a quiet area prior to examining the patient, typically in the presence of the owner and after a 5- to 10-minute period of acclimation. The ACVIM Panel on Hypertension suggests discarding the first measurement, then obtaining a minimum of 3, preferably 5 to 7, consecutive measurements with less than 20% variability in systolic blood pressure. The animal's disposition and heart rate as well as the cuff size, measurement site, and all measured values should be recorded in the medical record. Many clinicians require that hypertension be documented on more than one occasion before accepting the diagnosis.

Diagnosis of proteinuria in cats with CKD should be accomplished in a stepwise fashion. The specificity of the dipstick screening test for proteinuria is poor and therefore confirmation of proteinuria should be accomplished with a more specific follow-up test such as the SSA turbidimetric test, UP/C ratio, or a feline-specific albuminuria assay.

The second step of assessment is to determine the origin: proteinuria of renal origin can adversely affect the prognosis of cats with CKD and, therefore, physiologic or benign proteinuria and pre- and postrenal proteinuria should be ruled out. Subsequently, via serial monitoring, proteinuria should be classified as persistent or transient. Proteinuria is defined as persistent after at least 2 positive tests separated by 10 to 14 days.

The final step is to quantitate the magnitude of the proteinuria using the UP/C ratio. Relatively mild proteinuria in cats with spontaneous/naturally occurring CKD appears to be a negative predictor of survival.

Persistent proteinuria of renal origin of a magnitude greater than UP/C of 0.4 in cats with CKD should be treated with an ACE inhibitor and/or dietary protein reduction. Gradual reduction of dietary salt is often recommended as the first line of treatment for hypertension; however, there are no studies that document the efficacy of this treatment. In many cases, vasodilators (ACE inhibitors and CCAs) may be necessary to control systemic hypertension.

The CCA, amlodipine, is often recommended as the first-choice antihypertensive treatment for cats. However, recent information has raised concerns that treatment with a CCA alone may activate the renin-angiotensin-aldosterone system and potentially create higher intraglomerular pressures via further efferent arteriolar vasoconstriction. Therefore, initial treatment with an ACE inhibitor may be appropriate in cats with CKD due to the beneficial effects on intraglomerular pressure and proteinuria. In those cases where systemic hypertension persists after initiation of ACE inhibitor treatment or the magnitude of the hypertension is severe, a CCA can be added. The overall risk of target organ damage to the eyes, brain, heart, and kidneys is thought to be minimal if systolic blood pressure is maintained at less than 150 mm Hg. 

Case Example

Willie, 12-year-old, neutered male, domestic shorthair

Past Pertinent History
• Recurrent feline lower urinary tract disease (treated with pain medication and canned diet)
• No recurrence for 5 years

Presenting History
• Normal; mostly indoor cat
• On monthly heartworm preventative × 2 yr
• Possible polyuria
• Soft heart murmur recently noted by referring veterinarian

Physical Examination
• Temperature: 101°F; pulse: 170 bpm; respiration: 30 rpm; weight: 6.5 kg; normal pulses and breath sound
• Mucous membrane: pink with normal CRT, hydration status normal
• Fundic exam: normal
• No palpable thyroid nodule
• Soft early to midsystolic murmur
• Systolic blood pressure: 195 mm Hg (Doppler)

Initial Diagnostic Results
• CBC: normal
• Chemistry profile and urinalysis (see Table)

Second Wave Diagnostic Results
• Urine protein by SSA turbidimetric test = 2+
• UP/C ratio = 1.1
• Urine culture = no growth
• Thoracic radiographs = mild cardiomegaly
• ECG = left ventricular hypertrophy
• Echo = left ventricular hypertrophy and mild mitral regurgitation
• Abdominal ultrasound = kidneys small, slightly irregular with increased cortical echogenicity and loss of corticomedullary differentiation; no renoliths or pyeloectasia

Treatment Plan
• Enalapril: ~ 0.5 mg/kg/day
• Amlodipine: 1.25 mg/day
• Renal diet
• Phosphate binder (Epakitin; Vetoquinol, 1 gm/5 kg with food (each meal)
• Potassium supplement (Tumil-K; Virbac, 2.2 mEq/100 Kcal intake

Follow-up Results
At one week:
• Systolic blood pressure = 160 mmHg
At one month:
• Systolic blood pressure = 145 mmHg
• Heart rate = 180 (nervous)
• CBC = normal
• Chemistry panel (see Table)
• UP/C = 0.8
• Resting T4 = 2.2


For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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