Diagnosis of hypertension and proteinuria
Current recommendations are that blood pressure be measured in a quiet area prior to performing a physical examination on
the patient, typically after a five- to 10-minute period of acclimation to the hospital setting. The ACVIM Panel on Hypertension
suggests discarding the first measurement, then obtaining a minimum of three, preferably five to seven, consecutive measurements
with less than 10 percent to 20 percent variability in systolic blood pressure. The animal's disposition, cuff size, measurement
site, as well as all measured values, should be entered in the medical record. Many suggest that hypertension be documented
on more than one occasion before accepting the diagnosis.
Diagnosis and management of proteinuria in dogs with CKD should be accomplished in a step-wise fashion.
The specificity of the dipstick screening test for proteinuria is poor, and therefore confirmation of traditional dipstick-positive
proteinuria should be accomplished with a more specific follow-up test, such as the sulfo-salicylic acid (SSA) turbidimetric
test, urine protein/creatinine ratio (UP/C) or species-specific albuminuria assay (e.g., quantitative ELISA or ERD® test).
The second step in assessment of proteinuria is to determine its origin. Proteinuria of renal origin can adversely affect
the prognosis of dogs with CKD and, therefore, physiologic or benign proteinuria and pre- and post-renal proteinuria should
be ruled out. Subsequently, via serial monitoring, it should be determined if the proteinuria is persistent or transient and,
if persistent, is the magnitude stable, increasing, or decreasing over time?
Persistent proteinuria is defined as at least two positive tests at two-week intervals. Renal proteinuria is persistent and
most commonly associated with a normal urine sediment (although hyaline casts may be observed).
Renal proteinuria in dogs with CKD appears to be a negative predictor of survival. For example, in 45 client-owned dogs with
spontaneous CKD, the relative risk of uremic crises and mortality was approximately three times higher in dogs with UP/C >
1.0 (n=25) compared with dogs with UP/C < 1.0 (n=20).
In addition, the risk of adverse outcomes was approximately 1.5 times greater for every one-unit increase in UP/C ratio. The
decline in renal function, as measured by serum creatinine concentration, also was greater in dogs with higher UP/C ratios
(Jacob, Am J Vet Res 226:393-400, 2005).
Gradual reduction of dietary salt often is recommended as the first line of treatment for hypertension. Renal failure diets
have reduced sodium content; however, there are no studies that document the efficacy of this treatment.
In many cases, vasodilators are necessary to control systemic hypertension. Initial treatment with an angiotensin-converting
enzyme inhibitor (ACEI) is appropriate in dogs with CKD because of the beneficial effects on intraglomerular pressure and
In those cases where systemic hypertension persists after initiation of ACEI treatment, or is initially > 180 mm Hg, a calcium-channel
antagonist (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 <150 mm Hg.
Direct-acting vasodilator drugs like ACEI and CCA are the most successful in achieving acute reduction of blood pressure,
but sympathetic nervous system-mediated increases in heart rate and aldosterone-mediated sodium and water retention may modulate
the effects of the vasodilation over time.
Combining antihypertensive treatments with different modes of action may block the compensatory effects caused by one medication
when used alone. For example, diuretics, aldosterone antagonists and beta-blockers, which may have minimal antihypertensive
effect alone, may produce additive effects when given in combination with ACEI or CCA.
A UP/C > 0.5 in azotemic dogs or a UP/C > 1.0 in non-azotemic dogs should be treated with an ACEI and/or dietary protein reduction.
A follow-up UP/C test should be performed in 30 days.
A positive response to treatment is a 50 percent reduction in the baseline UP/C. If after 30 days there is a less than 50
percent decrease in the UP/C, the dose of the ACEI can be increased.
Clinical trials have demonstrated the utility of ACEI and/or dietary treatment in dogs and found that benefits of treating
with this combination have included decreased proteinuria, lowered systolic blood pressure, improved renal excretory function,
decreased glomerular basement membrane splitting, improved outcome and prolonged survival.
(Effects of enalapril vs. placebo as a treatment for canine idiopathic glomerulonephritis, Grauer, J Vet Intern Med 14:526-533,
2000) (Treatment of X-linked hereditary nephritis in Samoyed dogs with angiotensin-converting enzyme inhibitor, Grodecki,
J Comp Pathol 117, 209-225, 1997).