High blood pressure is common in cats with chronic kidney disease (CKD) and if untreated can lead to severe end organ damage and further promote kidney damage. This complex link between hypertension and CRF suggests that therapies targeting a potential pathophysiological mechanism linking these two processes may be superior in treating feline renal hypertension. The aim of our study therefore was to validate a urotensin assay for cat plasma and determine plasma levels of urotensin-II, a potent vasoconstrictor peptide produced in the kidney, in cats with renal hypertension and in healthy controls.
Systolic blood pressure (SBP) measurements were obtained and plasma creatinine levels determined in 60 cats (xmale, xfemale, average age: 12.7±4.4 years). EDTA plasma was collected for analysis using a commercial urotensin-II (U-II) enzyme-linked immunoassay (EK-071-05, Phoenix Pharmaceuticals, Belmont, CA, USA). Assay validation examined assay specificity in cat plasma (dilutional parallelism and recovery). Cats were grouped according to their blood pressure (hypertension defined as repeated SBP measurements > 170mmHg or a single measurement combined with characteristic ocular lesions) and renal status (CKD defined as plasma creatinine persistently > 177µmol/L associated with urine specific gravity <1.035) and U-II levels compared between groups using Mann-Whitney-U or Kruskall-Wallis test (p<0.05 indicating statistical significance). Hypertensive cats with no evidence of CKD were categorised as idiopathic hypertensives (iHT).
Dilution curves of feline samples were parallel to the standard curve and recovery was greater than 70%. U-II levels were significantly lower in hypertensive cats compared to normal controls (median (25-75 percentile): 0.27ng/ml (0.23-0.61) vs. 0.35ng/ml (0.27-0.74), p=0.044). However, U-II levels were not different between normotensive and hypertensive cats with CKD (non-hypertensive and non-azotemic: 0.41ng/ml (0.24-0.65); non-hypertensive and azotemic: 0.3ng/ml (0.23-0.54); hypertensive and non-azotemic/iHT: 0.26ng/ml (0.18-0.44); hypertensive and azotemic: 0.29ng/ml (0.23-0.36); p=0.23) and no correlation observed between urotensin-II, creatinine and SBP (p=0.15/0.19 respectively).
In this study we report for the first time plasma U-II levels in the cat. Despite the reported upregulation of plasma U-II in experimental renal failure in the rat and in human patients with high blood pressure, our findings, showing strong overlap of plasma urotensin-II levels in cats with hypertension compared to normotensive controls animals, and demonstrating no significant difference in U-II between normotensive and hypertensive cats with CRF, suggest that changes in plasma levels of this vasoactive renal peptide hormone do not play a significant role in the pathogenesis of feline renal hypertension. Indeed, our results suggest urotensin production may be physiologically down-regulated in hypertensive cats.