Ace Inhibitors and CKD: The Good, Bad, and Ugly

By altering pre-glomerular resistance, healthy kidneys can maintain relatively stable glomerular capillary pressures despite variations in systemic blood pressure. This pressure regulatory 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 and cats 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 depending on the definition of hypertension. 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 (more common in dogs e.g., amyloidosis and 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 that can result from systemic 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. Indirect systolic blood pressure greater than 160 mmHg is often listed as the threshold for systemic hypertension in dogs and cats.