Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats

A pathogenetic role of the renin-angiotensin-aldosterone system has been implicated in cats in both systemic arterial hypertension and hypokalemic myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a cause of these conditions. To obtain appropriate reference ranges, this study included a large number (130) of healthy house cats of different breeds without a history of recent illness and plasma concentrations of urea and creatinine below the upper limit of the respective reference ranges. In addition, the pituitary-adrenocortical axis was studied by measuring plasma concentrations of adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3-3.8) were very similar to those established in the same laboratory for humans in a supine position. No breed differences were found. The ARRs in neutered cats were significantly higher than in intact cats, primarily because of low PRA in neutered cats. The ARRs of cats > or = 5 years of age were significantly higher than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha-MSH, and cortisol did not correlate significantly with PAC. Thus, although blood sampling was performed in cats in nonstandardized positions and was associated with a wide variation of stress responses, the references ranges of PAC, PRA, and ARR were similar to the relatively narrow limits established for humans under standardized conditions. The effects of neutering and aging on PRA and ARR warrant further investigation.     

Primary hyperaldosteronism: expanding the diagnostic net

PRACTICAL RELEVANCE: Primary hyperaldosteronism is probably the most common adrenocortical disorder in cats. As in humans, it is often unrecognised, which excludes a potentially large number of cats from appropriate treatment. PATIENT GROUP: Affected cats present at a median age of 13 years (range 5-20 years). A breed or sex predilection has not been documented. The excessive secretion of mineralocorticoids usually leads to hypokalaemia and/or systemic arterial hypertension. Most affected cats present with muscular weakness and/or ocular signs of arterial hypertension. DIAGNOSTICS: In any cat presenting with hypokalaemia and/or arterial hypertension, other potential causes should be excluded. The ratio of plasma aldosterone concentration to plasma renin activity (aldosterone:renin ratio) is currently the best screening test for feline primary hyperaldosteronism. Diagnostic imaging is required to differentiate between adrenocortical neoplasia and bilateral hyperplasia, and to detect any distant metastases. CLINICAL CHALLENGES: The differentiation between adrenocortical neoplasia and bilateral hyperplasia is imperative for planning optimal therapy, but the limited sensitivity of diagnostic imaging may occasionally pose a problem. For confirmed unilateral primary hyperaldosteronism, unilateral adrenalectomy is the treatment of choice, and offers an excellent prognosis, but potentially fatal intra- and postoperative haemorrhage is a reported complication and risk factors have yet to be identified. EVIDENCE BASE: Only a few case reports are available on which to base the optimal diagnostic and therapeutic approach to feline primary hyperaldosteronism. This article reviews the physiology of aldosterone production and the pathophysiology of primary hyperaldosteronism, and summarises the currently available literature on the feline disease. Practical suggestions are given for the diagnostic investigation of cats with suspected primary hyperaldosteronism.     

Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease

Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.     

Urinary aldosterone to creatinine ratio in cats before and after suppression with salt or fludrocortisone acetate

Background: The endocrine diagnosis of primary hyperaldosteronism in cats currently is based on an increased plasma aldosterone to renin ratio, which has several disadvantages for use in veterinary practice. Objectives: To establish a reference range for the urinary aldosterone to creatinine ratio (UACR) and to determine whether oral administration of either sodium chloride or fludrocortisone acetate is effective for use in a suppression test. Animals: Forty‐two healthy cats from an animal shelter and 1 cat with primary hyperaldosteronism from a veterinary teaching hospital. Methods: Morning urine samples for determination of the basal UACR were collected from 42 healthy cats. For the suppression tests, urine samples for the UACR were collected after twice daily oral administration for 4 consecutive days of either sodium chloride, 0.25 g/kg body weight (n = 22) or fludrocortisone acetate, 0.05 mg/kg body weight (n = 15). Results: The median basal UACR was 7.2 × 10^?9 (range, 1.8–52.3 × 10^?9), with a calculated reference range of <46.5 × 10^?9. Administration of sodium chloride resulted in adequate salt loading in 10 of 22 cats, but without significant reduction in the UACR. Administration of fludrocortisone resulted in a significant decrease in the UACR (median, 78%; range, 44–97%; P < .001) in healthy cats. In the cat with an aldosterone‐producing adrenocortical carcinoma, the basal UACR and the UACR after fludrocortisone administration were 32 × 10^?9 and 36 × 10^?9, respectively. Conclusions and Clinical Importance: Using the UACR for an oral fludrocortisone suppression test may be useful for the diagnosis of primary hyperaldosteronism in cats.     

Association of laboratory data and death within one month in cats with chronic renal failure

OBJECTIVES: To retrospectively compare the data taken at the first visit of 34 cats with chronic renal failure surviving more than one month (surviving group) and 16 cats dying within one month (non-surviving group). METHODS: Records were collected on cats with chronic renal failure presented to a private veterinary practice in Nagoya, Japan, from March 1996 to March 2005. All cats with chronic renal failure diagnosed on the basis of case histories, clinical signs (such as, lethargy, anorexia, loss of bodyweight and vomiting) and a high plasma creatinine (>180 micromol/l) were included in the study. RESULTS: Plasma creatinine, urea nitrogen, inorganic phosphate, packed cell volume and urine protein/creatinine ratio were significantly different between cats of the surviving and non-surviving groups. In the surviving group, survival statuses were recorded, and laboratory data was obtained within one month before death in 13 cats. In the 13 cats, plasma creatinine, packed cell volume and urine protein/creatinine ratio showed significant differences between the data taken within one month before death and that taken at first visit, and only urine protein/creatinine ratio exhibited a consistent alteration (increase) in relation to first visit data. CLINICAL SIGNIFICANCE: These results indicated that plasma creatinine, urea nitrogen, inorganic phosphate, packed cell volume and urine protein/creatinine ratio were associated with death within one month and urine protein/creatinine ratio was most likely to be associated with mortality in cats with chronic renal failure.     

Treatment of feline hyperthyroidism with radioactive iodine-131

Feline hyperthyroidism can be treated by thyroidectomy, antithyroid drugs, or radioactive iodine-131 (131I). The aim of this retrospective study was to evaluate the treatment of 83 hyperthyroid cats with 131I The dosage of 131I ranged from 4 to 6 milliCurie (mCi). Blood samples for determination of plasma concentrations of total thyroxine (TT4), urea, and creatinine were collected before, ten days after, and several months after treatment. In addition, arterial blood pressure was measured before and ten days after treatment. The median plasma TT4 concentration ten days after 131I treatment (27 nmol/L, 64 cats) was significantly lower than that before treatment (123 nmol/L). The median plasma TT4 concentration several months after 131I treatment was 22,5 nmol/L (40 cats). Ten days and several months after 131I treatment, plasma TT4 concentration had decreased below the upper limit of the reference range in 64 (77%) and 72 cats (87%), respectively. In four cats the plasma TT4 concentration had decreased below the lower limit of the reference range, but only two cats had symptoms of hypothyroidism. Plasma urea and creatinine concentrations were not increased ten days after 131I treatment, but the median plasma creatinine concentration was significantly higher several months after treatment when compared with before 131I treatment. Before treatment in 28 cats a high arterial blood pressure (> 180 mmHg) was measured, whereas after treatment in 25 cats a high arterial blood pressure was measured. The results of this study indicate that 131I treatment is an effective therapy in most cats with hyperthyroidism.     

Aldosteronoma in a dog with polyuria as the leading symptom.

In a 10-year-old castrated male shorthaired German pointer polyuria was associated with slight hypokalemia, hypophosphatemia and alkalosis, as well as elevated plasma concentrations of a glucocorticoid-inducible iso-enzyme of alkaline phosphatase. Repeated measurements of urinary corticoids and normal suppressibility of the hypothalamus-pituitary-adrenocorticial axis excluded glucocorticoid excess.Urine osmolality (Uosm) did not increase during administration of the vasopressin analogue desmopressin. At the time water deprivation had caused Uosm to rise from 300 to 788 mOsm/kg, there was also plasma hypertonicity. During hypertonic saline infusion the osmotic threshold for vasopressin release was increased.The combination of elevated plasma aldosterone concentrations and unmeasurably low plasma renin activity pointed to primary hyperaldosteronism. As initially computed tomography (CT) did not reveal an adrenocortical lesion, the dog was treated with the aldosterone antagonist spironolactone. This caused Uosm to rise in a dose-dependent manner. However, well-concentrated urine was only achieved with doses that gave rise to adverse effects.Once repeated CT, using 2-mm-thick slices, had revealed a small nodule in the cranial pole of the left adrenal, unilateral adrenalectomy was performed which resolved the polyuria completely. Also the plasma concentrations of kalium, aldosterone and renin activity returned to within their respective reference ranges. The adrenocortical nodule had the histological characteristics of an aldosteronoma, with the non-affected zona glomerulosa being atrophic.In this dog with primary hyperaldosteronism the polyuria was characterized by vasopressin resistance and increased osmotic threshold of vasopressin release, similar to the polyuria of glucocorticoid excess. The possibility is discussed that the polyuria of glucocorticoid excess is actually a mineralocorticoid effect.     

Potassium depletion in cats: renal and dietary influences

Excessive urinary potassium loss was diagnosed in 7 cats with persistent hypokalemia and high serum creatinine concentrations. Renal tubular acidosis (proximal or distal) was not evident in the affected cats. Plasma aldosterone concentrations and plasma renin activities in affected cats were not significantly different from control values. Potassium depletion and hypokalemia were attributed to the combined effects of decreased dietary potassium intake and excessive urinary potassium losses. It was concluded that increased urinary potassium excretion may represent a basic response to renal dysfunction in cats. Data suggested that dietary potassium supplementation improved renal function in most cats in this study.     

Association between urinary vascular endothelial growth factor excretion and chronic kidney disease in hyperthyroid cats

Many hyperthyroid cats develop azotaemic chronic kidney disease (aCKD) following treatment, which has led to the hypothesis that hyperthyroidism might be detrimental to renal function. Renin-angiotensin-aldosterone system (RAAS) activation occurs in hyperthyroidism, which could cause peri-tubular hypoxia, tubular damage and the development of aCKD. Urinary vascular endothelial growth factor:creatinine ratio (VEGFCR) is postulated to be a marker of tubular hypoxia. VEGFCR was correlated with plasma renin activity (PRA) and compared between hyperthyroid cats that did and did not develop aCKD following treatment (pre-azotaemic and non-azotaemic groups respectively). PRA was positively correlated with VEGFCR (r_s = 0.382; P = 0.028); however, pre-azotaemic hyperthyroid cats had significantly lower VEGFCR than non-azotaemic cats at baseline (median 122.3 fg/g versus 167.0 fg/g; P < 0.001). RAAS activation in hyperthyroidism is associated with increased VEGFCR; however, increased VEGFCR was not correlated with the development of aCKD. Therefore, tubular hypoxia may not be a mechanism for renal damage in hyperthyroid cats.     

Increased mean arterial pressure and aldosterone-to-renin ratio in Persian cats with polycystic kidney disease

Polycystic kidney disease (PKD) in Persian cats has been increasingly reported and compared to human autosomal dominant polycystic kidney disease (ADPKD) in the last decade. In cats, however, few studies have dealt with the occurrence and hormonal determinants of hypertension, one of the most common extrarenal manifestations of ADPKD in humans. The purpose of this study was to compare Persian cats >4 years old with PKD to unaffected control cats with regard to blood pressure (BP), plasma renin activity (PRA), serum aldosterone concentration, plasma atrial natriuretic peptide (ANP) concentration, and aldosterone-to-renin ratio (ARR). Three gender- and age-matched groups were studied, each consisting of 7 cats: (1) a control group without cysts, (2) a group with mild PKD, and (3) a group with severe PKD (multiple cysts and renal enlargement). Mild renal insufficiency was found in only 1 of 14 cats with PKD. Cats with PKD had a higher mean arterial pressure (P = .04) and more often had a high ARR (P = .047) than did control cats. Tendencies toward higher diastolic and systolic arterial pressures (DAPs and SAPs, respectively) and lower PRAs were observed in cats with PKD compared to controls (.05 < P < or = .1). No significant differences were found between the groups in serum aldosterone and plasma ANP concentrations. None of the cats had echocardiographic evidence of cardiac hypertrophy. In conclusion, cats with PKD had a minor increase in mean arterial pressure compared to control cats, and half of the cats had a high ARR.     

Effects of benazepril hydrochloride in cats with experimentally induced or spontaneously occurring chronic renal failure

We examined effects of an angiotensin converting-enzyme inhibitor, benazepril hydrochloride (BH), on renal hypertension and chronic renal failure (CRF) in cats. For experimental CRF, healthy cats (n=5) underwent 7/8 renal ablation. After renal insufficiency and hypertension were confirmed by blood urea nitrogen (BUN), serum creatinine, creatinine clearance and telemetric recording of systemic blood pressure, BH was administered orally once daily at 0.9 to 2.0 mg/kg/day for 2 to 3 weeks. Within 2 months after renal ablation, renal failure and hypertension developed as evidenced by significant increases in BUN, serum creatinine and systemic blood pressure (p<0.01 or 0.05) and significantly decreased creatinine clearance accompanied by elevated plasma renin activity, angiotensin I and II, and aldosterone (p<0.01 or 0.05). BH administration corrected systemic hypertension (p<0.05) and significantly reduced angiotensin II and aldosterone (p<0.05). Upon discontinuation of BH, these values returned to the pre-administration levels. Studies on spontaneous CRF enrolled 11 cats with spontaneously occurring CRF. BH was administered orally to 6 cats once daily for 24 weeks at a final dose of 1.0 mg/kg/day, while 5 cats served as control. BH administration reduced serum creatinine and urinary protein concentration in every cat. Results demonstrate that in cats, loss of renal mass leads to activation of the renin-angiotensin-aldosterone system and associated renal hypertension, and indicate that BH is effective in correcting renal hypertension and may provide renal benefits to cats with CRF.     

Effects of dilated cardiomyopathy on the renin-angiotensin-aldosterone system, atrial natriuretic peptide activity, and thyroid hormone concentrations in dogs

OBJECTIVE: To evaluate the effect of dilated cardiomyopathy (DCM) on activity of the renin-angiotensin-aldosterone system (RAAS), the N-terminal fragment of proatrial natriuretic peptide (NT-proANP), and thyroid hormone concentrations in dogs. ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs without clinical signs of DCM, and 15 age-, breed-, and sex-matched control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs, and blood and urine samples were collected. RESULTS: Plasma renin activity (PRA), plasma aldosterone concentration (PAC), urine aldosterone-to-creatinine ratio, and NT-proANP concentrations were significantly increased in dogs with clinical signs of DCM, compared with dogs without clinical signs and control dogs. Thyroid-stimulating hormone and total thyroxine concentrations did not differ significantly among groups; however, free thyroxine (FT4) concentrations were significantly decreased in dogs with clinical signs of DCM, compared with control dogs and DCM-dogs without clinical signs. Concentrations of PRA, PAC, FT4, and urine aldosterone-to-creatinine ratio were significantly correlated, whereas plasma concentrations of NT-proANP only correlated with FT4 concentration. CONCLUSION AND CLINICAL RELEVANCE: In dogs with clinical signs of DCM, increased concentrations of components of the RAAS were associated with increased concentrations of NT-proANP Analysis of the neurohormonal system may aid in identification of clinical stages of DCM for groups of dogs, but the range is too great and there are too many dogs that have neurohormonal concentrations within reference ranges to assess dogs on an individual basis.     

Evaluation of the effects of ischemic injury and ureteral obstruction on delayed graft function in cats after renal autotransplantation

OBJECTIVE: To determine the relative importance of ischemic injury to delayed graft function (DGF) in cats. STUDY DESIGN: Experimental study. ANIMALS: Six intact female cats. METHODS: Cats had renal autograft transplantation without ureteral transection and reimplantation and a contralateral nephrectomy. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured regularly and abdominal ultrasound was performed before surgery, the day after surgery and twice weekly thereafter. Ultrasound-guided renal biopsy was performed on day 7. Cats were euthanatized on day 21. Histology of the autograft, ureter, bladder, vascular anastomoses sites, and contralateral kidney were performed. Observations were compared with those from an historic group of research cats that had extravesicular ureteroneocystostomy and contralateral nephrectomy. RESULTS: Five cats completed the study. Serum creatinine and BUN concentrations increased after surgery, peaking at 3.2+/-0.8 and 77.6+/-15.9 mg/dL, respectively, 1-2 days after surgery. Serum creatinine concentration returned to the reference interval by 6 days after surgery. BUN gradually decreased in all cats but did not return to the reference interval by study end. Serum creatinine and BUN concentrations were consistently lower but not significantly so (P=.29 and .56, respectively) compared with the historic ureteroneocystostomy group. No ultrasonographic abnormalities or renal biopsy histologic abnormalities were observed. At necropsy, 1 autograft had generalized interstitial fibrosis. CONCLUSION: Harvesting the renal graft and the ischemia before revascularization causes impaired renal function after engraftment. CLINICAL RELEVANCE: The process of harvesting and reimplanting the renal graft can contribute to DGF in cats, independent of ureteral obstruction.     

Hyperaldosteronism in a cat with metastasised adrenocortical tumour

In a 12-year-old male shorthaired cat with attacks of hypokalaemic muscular weakness in spite of oral potassium supplementation, highly elevated plasma aldosterone concentrations in combination with low plasma renin activity pointed to primary hyperaldosteronism. Ultrasonography and computed tomography revealed a large left-sided adrenal tumour growing into the phrenicoabdominal vein and the caudal vena cava. The tumour and its intravascular extension were surgically removed, but the subsequent stenosis of the caudal vena cava caused congestion and renal failure. At autopsy pulmonary micrometastases of the aldosteronoma were found.     

Primary hyperaldosteronism in two cats.

A condition of primary hyperaldosteronism resulting from an adrenal tumor in two cats is presented and was characterized by hypertension, hypokalemia, inappropriate kaliuresis, low normal plasma renin activity, and markedly increased serum aldosterone concentration. One of the two cats underwent a laparotomy, and in this case hypertension and hypokalemia resolved following the removal of an adrenal tumor.     

Idiopathic hyperaldosteronism in a dog

Idiopathic hyperaldosteronism was diagnosed in an 8-year-old castrated male Yorkshire Terrier, based on increased concentration of plasma aldosterone, hypertension, hypernatremia, decreased natriuresis, hypokalemia, and hyperkaluria. Unilateral adrenalectomy was performed after visualization of a nodule on the right adrenal gland. Hyperplasia of the zona glomerulosa and increased postoperative aldosterone concentrations supported the diagnosis of idiopathic hyperaldosteronism.     

Azotemia in cats with feline hypertrophic cardiomyopathy: Prevalence and relationships with echocardiographic variables

ObjectivesThe prevalence of renal azotemia in cats with acquired heart disease is not well documented. The aims of this study were therefore (1) to determine the prevalence of azotemia within a hospital population of cats with hypertrophic cardiomyopathy (HCM), and (2) to evaluate the relationship between echocardiographic variables and plasma urea and creatinine.Animals, materials and methods134 client-owned cats were retrospectively studied including 102 cats with HCM and 32 control cats. A complete physical examination, electrocardiography, systolic arterial blood pressure measurement, thoracic radiographs, and echocardiography were performed. Plasma creatinine and urea were determined in all cats. The animal was considered azotemic if plasma creatinine was >1.8 mg/dL and/or urea >65 mg/dL (i.e. BUN> 30 mg/dL).ResultsThe prevalence of azotemia was lower in control cats (25.0%) than in cats with HCM (58.8%) (P = 0.003). No significant differences in plasma urea and creatinine were observed between the HCM and control cats. There was no effect of plasma creatinine and urea on conventional echocardiographic variables in cats with HCM.ConclusionsAzotemia is a frequent finding in cats with HCM but is not dependent on echocardiographic variables.     

Study of calcium homeostasis in feline hyperthyroidism

Thirty cats with untreated hyperthyroidism were blood sampled and their calcium homeosta-tic mechanisms and renal function assessed. The results were compared with those obtained from 38 age-matched control cats. The hyperthyroid group of cats were found to have significantly lower blood ionised calcium and plasma creatinine concentrations and significantly higher plasma phosphate and parathyroid hormone concentrations. Hyperparathyroidism occurred in 77 per cent of hyperthyroid cats, with parathyroid hormone concentrations reaching up to 19 times the upper limit of the normal range. The aetiology, significance and reversibility of hyperparathyroidism in feline hyperthyroidism remains to be established but could have important implications for both bone strength and renal function.     

Prognostic factors in cats with chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD.