Systemic hypertension is often observed in dogs and cats with chronic kidney disease, forming a complex cause-and-effect relationship. As kidney disease is often associated with disturbances of neuroendocrine factors and body fluid balance, most surveys have identified systemic hypertension in a majority of cats and dogs affected with kidney disease. High blood pressure can produce intrarenal baro-trauma, completing the self-perpetuating cycle of renal failure leading to systemic hypertension.

Capillary hydrostatic pressure has complex effects on kidney function:

• A minimal level of capillary blood pressure is required in order to assure adequacy of renal blood flow and glomerular filtration for extracellular fluid volume regulation and nitrogenous waste removal. Excess pressure within the glomerular capillary bed, termed glomerular capillary hypertension, leads to nephron hyperfunction and hypertensive damage of glomerular and vascular elements of the kidney and proteinuria. Secondary tubulointerstitial damage may follow. A low capillary pressure can reduce GFR and be associated with renal ischemia.
  
• Excessively high peritubular capillary pressure inhibits tubular reabsorption of sodium and water. Peritubular capillary hypotension has the opposite effect.

In dogs with acute or chronic kidney disease, kidney function and glomerular pressure vary directly with blood pressure , and autoregulatory function is compromised. Consequently, it is likely that the afferent arteriole is not able to autoregulate glomerular capillary pressure. Any increase in blood pressure is likely to be transmitted to the glomerular capillary bed which can lead to hypertensive glomerular damage and protenuria or microalbuminuria. This produces an interesting paradox in a hypertensive animal with kidney disease. A clinician may interpret a rising GFR—noted clinically as a falling serum creatinine or blood urea nitrogen concentration—as a beneficial effect. However, it is important to recognize that high intracapillary pressures within the glomerulus may be slowly destroying renal tissue.

By contrast, cats with mild to moderate kidney disease still retain some autoregulatory efficiency. The feline renal afferent arteriole retains a remarkable degree of function, and is better at autoregulatory control than that of any other species studied. This likely explains why many cats with high systemic arterial blood pressure have only modest proteinuria and stable kidney function for prolonged periods of time.

Elevated pressure leads to proteinuria, increased shear stress and local production of cytokines and growth factors which ultimately cause progressive renal injury.

The kidney has complex effects on blood pressure:

• Through control of body sodium and water content, the kidney regulates vascular volume, cardiac output, and blood pressure. In every animal with systemic hypertension the kidney plays either a permissive or a causative role or both.
  
• High systemic arterial blood pressure inhibits tubular reabsorption of sodium and water.

In renal insufficiency, the most frequently recommended antihypertensive agents are vasodilators because of their important dilating effects on intrarenal arterioles. Two classes of agents have proven renoprotective effects in rodents and people: angiotensin converting enzyme inhibitors (ACEI) and calcium channel antagonists (CCA).

Angiotensin Converting Enzyme Inhibitors (ACEI) inhibit formation of angiotensin II. Angiotensin II is a potent vasoconstrictor, particularly of the efferent arteriole. ACEIs (e.g., benazepril, enalapril, ramipril, or spirapril) will lower blood pressure by producing systemic vasodilation in many hypertensive dogs. In cats, the role of the renin-angiotensin system in maintenance of systemic hypertension has been questioned, although ACEI may still prove efficacious because of specific intrarenal effects. These drugs are also anti-proteinuric and interfere with the profibrotic effects of the intrarenal renin-angiotensin system. Alternative methods of interfering with the renin-angiotensin-aldosterone system, including aldosterone and angiotensin antagonists have not been fully evaluated in veterinary medicine.

Calcium Channel Antagonists (CCA) reduce total peripheral resistance, leading to a decrease in blood pressure. CCAs also have non-hemodynamic effects that may offer renoprotection. Amlodipine besylate, a long-acting dihydropyridine CCA, has been used effectively in hypertensive cats. However, CCA may also promote renal injury and/or proteinuria by preferentially dilating preglomerular (afferent) arterioles. Currently, the coadministration of CCA and ACEI is in favor as this may reduce systemic arterial blood pressure, equally dilate both sets of renal arterioles, and decrease the magnitude of proteinuria, thereby producing a balanced renoprotective effect on GFR and glomerular capillary pressure.

References: References: Brown S, Brown C, Hendi R. Proc, ACVIM 2000, Seattle, 728A; Elliott J, Barber PJ, Syme HM et al. J Small Anim Pract 42:122-129, 2001; Syme HM, Barber PJ, Markwell PJ et al. J Am Vet Med Assoc 220:1799-1804, 2002; Brown SA, College Vet Med Univ Georgia, Athens, GA; sbrown@vet.uga.edu