By altering pre-glomerular resistance, healthy kidneys can maintain relatively stable glomerular capillary pressures despite
variations in systemic blood pressure. This process is termed "renal autoregulation."
Autoregulation can be reduced when renal disease results in loss of nephrons. Compromised autoregulation allows high systemic
blood pressure to be transmitted to glomerular capillaries. This glomerular hypertension has been documented by micropuncture
studies in dogs with surgically reduced renal mass. In these models, glomerular hypertension was associated with systemic
hypertension, proteinuria and tubulointerstitial lesions.
Systemic hypertension is relatively common in dogs with chronic kidney disease (CKD); systemic hypertension has been observed
in as many as two-thirds of cases. In a recent study of client-owned dogs with naturally-occurring CKD, 29/45 (64 percent)
had systolic blood pressure > 144 mm Hg and 14/45 (31 percent) had systolic blood pressure > 161 mm Hg (Jacob, JAVMA 222:322-329,
Glomerular proteinuria can result from immune-mediated disease, amyloidosis or structural abnormalities involving the glomerular
capillary wall. Proteinuria associated with CKD often is accompanied by systemic hypertension. Protein leakage through the
glomerular capillary wall also can arise as a consequence of intraglomerular hypertension.
Finally, proteinuria can occur as a result of tubulointerstitial disease that compromises reabsorption of protein from the
glomerular filtrate. Whether caused by capillary wall lesions, intraglomerular hypertension or tubulointerstitial lesions,
excessive quantities of protein in the glomerular filtrate may cause additional glomerular lesions as well as downstream tubulointerstitial
lesions; both of which can lead to loss of more nephrons.
Systemic hypertension in dogs has largely been thought to be secondary to another disease, as opposed to idiopathic (primary
or essential). Described and potential etiologies of secondary hypertension include acute and chronic kidney disease, hypothyroidism,
hyperadreno-corticism, hyperaldosteronism, pheochromocytoma, diabetes melli-tus and obesity.
Of these conditions, CKD has the greatest association with systemic hypertension.
Systemic hypertension may contribute to progressive nephron loss by causing irreversible glomerular damage via increased intraglomerular
pressures and glomerulosclerosis. In dogs with CKD, autoregulation is impaired and inappropriate dilation of the afferent
glomerular arteriole occurs, which diminishes its ability to protect the glomerulus from variations in systemic blood pressure.
Although the exact mechanism of the CKD-associated 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 renin-angiotensin system secondary to impaired sodium excretion and excessive renin secretion may be
The increased renin secretion leads to increased production of angiotensin II and aldosterone. In addition to its pressor
effects, angiotensin II has a direct stimulatory effect on the sympathetic nervous system, increasing vascular tone, and resulting
in CKD vasoconstriction of the efferent arteriole, which further contributes to the intraglomerular hypertension. Angiotensin
and aldosterone also may cause tissue remodeling and fibrosis of the kidneys.
The consequences of systemic hypertension are usually dependent on the magnitude and duration of the blood pressure elevations.
Acute ocular and central nervous system abnormalities can occur associated with hemorrhage or edema formation. Renal damage
associated with hypertension tends to be more chronic and characterized by glomerular lesions (e.g., 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 dogs with CKD may prevent development of retinal lesions or
may limit or slow progression of renal and cardiac lesions.
In addition to being a diagnostic marker of the severity of renal disease, renal proteinuria may be a mediator of glomerular
and tubular injury. Recent findings have demonstrated that proteinuria is associated with increased risk of developing progressive
CKD in dogs.
In addition, studies have shown that therapies that reduce the magnitude of proteinuria often are renoprotective. 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.