Modulating proteinuria and hypertension of chronic kidney disease (Proceedings)
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 and cats with surgically reduced renal mass. In these models, glomerular hypertension was associated with glomerular hypertrophy and sclerosis and proteinuria. Systemic hypertension is relatively common in dogs with renal disease. In a recent study of dogs with spontaneous chronic kidney disease (CKD), 29/45 (64%) had systolic blood pressure ≥ 144 mm Hg and 14/45 (31%) had systolic blood pressure ≥ 161 mm Hg. In cats with naturally-occurring CKD, systemic hypertension has been observed in 19-65% of cases.
Renal proteinuria can result from glomerular and/or tubular abnormalities in dogs and cats with CKD. Glomerular proteinuria may arise from immune complex disease or structural abnormalities involving the glomerular capillary wall (e.g., x-linked hereditary nephropathy). Protein-losing nephropathy caused by glomerular capillary wall lesions is often accompanied by systemic hypertension and glomerular proteinuria can be exacerbated by intraglomerular glomerular hypertension. Tubular proteinuria occurs when tubular reabsorption of protein from the glomerular filtrate is compromised. Whether caused by capillary wall lesions, tubular lesions, or intraglomerular hypertension, excessive quantities of protein in the glomerular filtrate may contribute to additional glomerular and tubulointerstitial lesions leading to loss of more nephrons.
HypertensionSystemic hypertension in animals has largely been thought to be secondary to another disease (e.g., renal disease and endocrinopathies), as opposed to idiopathic (primary or essential). This has recently been called into question. For example, in a report of 69 hypertensive cats, seen at North Carolina State University (NCSU) for ocular disease, revealed that at least 17%, and possibly as many as 50%, of cats had no identifiable cause for their systemic hypertension. Elliott and associates at the Royal Veterinary College in London have documented that approximately 20% of hypertensive cats, diagnosed in primary-care practices, were idiopathic. Another retrospective study, which used very strict criteria for the diagnosis of primary (essential, idiopathic) hypertension, revealed a prevalence of 11%.
Described and potential etiologies of secondary hypertension include acute and chronic renal disease, hyperthyroidism, hypothyroidism, hyperadrenocorticism, hyperaldosteronism, pheochromocytoma, diabetes mellitus, and obesity. Chronic kidney disease has the greatest association with hypertension and may often be causal. A recent report suggested approximately 29% of elderly cats with CKD were hypertensive, with the range reported in 4 studies being 19-65%. In dogs with CKD, approximately one-third will be normotensive, one-third will have borderline hypertension, and one-third will be hypertensive.
Systemic hypertension may contribute to progressive nephron loss by causing irreversible glomerular damage via increased intraglomerular pressures and glomerulosclerosis. By altering pre-glomerular resistance, healthy kidneys can maintain relatively static glomerular capillary pressures despite variations in systemic blood pressure via autoregulation. Inappropriate dilation of the afferent glomerular arteriole occurs in dogs and cats with CKD and diminishes the ability of the afferent arteriole 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-aldosterone system (RAAS) may be involved. The increased renin secretion leads to increased production of angiotensin II and aldosterone. In addition to its direct pressor effects, angiotensin II also has a 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. Finally, angiotensin and aldosterone may also stimulate renal tissue remodeling via increased matrix production and fibrosis.
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 and cats with CKD renal may prevent development of retinal lesions or may limit or slow progression of renal and cardiac lesions.