Survival of cats with naturally occurring chronic renal failure: effect of dietary management

Fifty cats with naturally occurring stable chronic renal failure (CRF) were entered into a prospective study on the effect of feeding a veterinary diet restricted in phosphorus and protein with or without an intestinal phosphate binding agent on their survival from initial diagnosis. Twenty-nine cats accepted the veterinary diet, whereas compliance (due to limited intake by the cats or owner resistance to diet change) was not achieved in the remaining 21. At diagnosis, both groups of cats were matched in terms of age, bodyweight, plasma creatinine, phosphate, potassium and parathyroid hormone (PTH) concentrations, packed cell volume and urine specific gravity. Feeding the veterinary diet was associated with a reduction in plasma phosphate and urea concentrations and prevented the increase in plasma PTH concentrations seen in cats not receiving the diet. Cats fed the veterinary diet survived for longer when compared with those that were not (median survival times of 633 versus 264 days). These data suggest that feeding a diet specifically formulated to meet the needs of cats with CRF, together with phosphate binding drugs if required, controls hyperphosphataemia and secondary renal hyperparathyroidism, and is associated with an increased survival time.     

Assessment of acid-base status of cats with naturally occurring chronic renal failure

Metabolic acidosis is reported to be a common complication of feline chronic renal failure (CRF) but acid-base status of feline patients with this disease is rarely assessed by general practitioners. A cross-sectional study involving 59 cases of naturally occurring feline CRF was conducted to determine the prevalence of acid-base disturbances. Cases were categorised on the basis of their plasma creatinine concentrations as mild, moderate or severe. A group of 27 clinically healthy, age-matched cats was assessed for comparison. A low venous blood pH (<7.270) was found in 10 of the 19 severe cases (52.6 per cent), three of the 20 moderate cases (15 per cent) and none of the 20 mild cases. Acidaemia was associated with an increased anion gap contributed to by both low plasma bicarbonate and low chloride ion concentrations. Biochemical analysis of urine samples showed urine pH to decrease with increasing severity of renal failure. Urinary loss of bicarbonate was not associated with the occurrence of acidaemia and there was a tendency for urinary ammonium ion excretion to decrease as the severity of renal failure increased. Cats with naturally occurring CRF do not show plasma biochemical evidence of acid-base disturbances until the disease is advanced.     

Prevalence of systolic hypertension in cats with chronic renal failure at initial evaluation

OBJECTIVE: To determine prevalence of systolic hypertension and associated risk factors in cats with chronic renal failure evaluated in first-opinion practice. DESIGN: Prospective study. ANIMALS: 103 cats with chronic renal failure. PROCEDURE: Systolic arterial blood pressure (SABP) was measured with a noninvasive Doppler technique, and cats that had SABP > 175 mm Hg on 2 occasions or that had SABP > 175 mm Hg and compatible ocular lesions were classified as hypertensive. Information from the history (previous treatment for hyperthyroidism, age), physical examination (sex, body weight), routine plasma biochemical analyses (creatinine, cholesterol, potassium, sodium, chloride, and calcium concentrations), and thyroid status were evaluated as potential risk factors for systolic hypertension. Variables associated with systolic hypertension were evaluated by use of logistic regression. RESULTS: 20 (19.4%; 95% confidence interval, 13 to 28%) cats had systolic hypertension. Plasma potassium concentration was significantly and inversely associated with systolic hypertension. CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of systolic hypertension, although clinically important, was lower than that reported previously. The cause of the inverse association between systolic hypertension and plasma potassium concentration is not yet known.     

Generalised amyloidosis in two Siamese cats: spontaneous liver haemorrhage and chronic renal failure

Two cases are reported, illustrating the antemortem diagnosis of systemic amyloidosis in Siamese cats. A cat presenting with inappetence and depression was diagnosed as having systemic amyloidosis with spontaneous haemorrhage from the liver. In another cat from the same breeding cattery, chronic renal failure due to systemic amyloidosis was an incidental finding. Little treatment was possible in either case and both were later euthanased. The two cats had similar renal and hepatic pathology but different signs of disease.     

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.     

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.     

Acute renal failure in four cats treated with paromomycin

Acute renal failure was diagnosed in 4 cats receiving paromomycin orally for treatment of infectious enteritis. All 4 cats responded to fluid therapy and recovered normal or near-normal renal function; however, 3 of the cats subsequently became deaf and developed cataracts. Toxicoses were attributed to a combination of an excessive dosage of paromomycin and absorption of the drug across injured intestinal mucosal epithelium. Pharmacokinetic studies are needed to further define the disposition of paromomycin after oral administration to cats.     

Hypertensive encephalopathy in cats with reduced renal function

The clinical, hemodynamic, and pathologic features of hypertensive encephalopathy in two cats with reduced renal mass are described. The cats developed a progressive syndrome of lethargy, ataxia, blindness, stupor, and seizures following an abrupt increase in blood pressure associated with a surgical reduction in renal mass. The cats had severe gross brain edema, evidenced by cerebellar changes of caudal coning and cranial displacement over the corpora quadrigemina and cerebral changes of widening and flattening of the gyri. Histologically, interstitial edema was most pronounced in the cerebral white matter. Hypertensive vascular lesions were present as hyaline arteriolosclerosis in one cat and hyperplastic arteriolosclerosis in the other. Rare foci of parenchymal microhemorrhages and necrosis were also observed. Systemic hypertension (especially severe or rapidly developing) accompanied by neurologic signs and the pathologic findings of diffuse brain edema with cerebral arteriolosclerosis are consistent with an etiologic diagnosis of hypertensive encephalopathy.     

Expression of alpha-smooth muscle actin and fibronectin in tubulointerstitial lesions of cats with chronic renal failure

OBJECTIVE: To examine renal expression of alpha-smooth muscle actin (alpha-SMA) and fibronectin in cats with tubulointerstitial nephritis (TIN) for use in predicting progression to renal fibrosis. ANIMALS: 19 cats with TIN and 9 cats without nephritis. PROCEDURE: Serum creatinine and BUN concentrations were measured. Indices for glomerular extra-cellular matrix (ECM), tubular injury (TI), and fibronectin were determined in renal specimens to quantify the extent of injury and fibrotic lesions. Expression of alpha-SMA in renal tissue was immunohistochemically detected, and correlations were evaluated between the alpha-SMA index and other histologic and clinical variables. RESULTS: The alpha-SMA index in tubulointerstitial areas (1.63 +/- 0.78) was significantly higher in cats with TIN, especially in the periglomerular and peritubular areas, than in cats without nephritis (0.20 +/- 0.14). The alpha-SMA index was significantly associated with the TI index (r2 = 0.70), fibronectin index (r2 = 0.95), BUN concentration (r = 0.64), and serum creatinine concentration () = 0.66). Of special interest was that interstitial alpha-SMA expression appeared evident in the kidneys at an early stage of TIN, prior to the onset of ECM deposition. CONCLUSION AND CLINICAL RELEVANCE: Analysis of results of histologic and clinical examinations revealed that interstitial alpha-SMA expression may have clinical importance and may be a useful early histologic marker for development of chronic renal failure in cats. An immunohistochemical examination for fibrogenic molecules (such as alpha-SMA expression) may provide fundamental information on the pathogenesis of early-stage renal disease and aid clinical management of cats with chronic renal failure, including TIN.     

Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria

BACKGROUND: Tubulointerstitial kidney disease is a common cause of illness and death in pet cats and is typically not associated with overt proteinuria. HYPOTHESIS: Proteinuria would be independently related to survival in cats with renal failure, with or without hypertension. ANIMALS: The study included 136 client-owned cats; 28 apparently normal, 14 hypertensive but not azotemic, 66 azotemic but not hypertensive, and 28 both hypertensive and azotemic. METHODS: Cox's proportional hazards model was used to determine the influence of initial plasma creatinine concentration, proteinuria (urine protein-to-creatinine ratio or albumin-to-creatinine ratio), age, and systemic hypertension on the risk of death or euthanasia during the follow-up period. Multivariable linear regression was used to determine the relation between severity of proteinuria and predictive variables, including age, plasma creatinine concentration, systolic blood pressure, sex, and urine specific gravity. RESULTS: Plasma creatinine concentration and proteinuria were very highly related to survival. The hazard ratio (95% confidence intervals) for death or euthanasia was 2.9 (1.4-6.3) and 4.0 (2.0-8.0) for urine protein-to-creatinine ratio 0.2-0.4 and >0.4, respectively, compared with the baseline group with a urine protein-to-creatinine ratio of <0.2 and were 2.4 (1.2-4.8) and 4.9 (2.3-10.2) for an albumin-to-creatinine ratio of 30-82 mg/g and <82 mg/g, respectively, compared with a baseline group with albumin-to-creatinine ratio of <30 mg/g. Treated hypertensive cats did not have reduced survival, although systolic blood pressure, together with plasma creatinine concentration was positively related to the magnitude of proteinuria. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the relatively low concentrations of proteinuria typical of chronic renal disease in cats, this measurement is of prognostic significance.     

Renal clearance studies in cats with chronic renal disease: Dietary implications

Renal clearance studies were undertaken on 15 cats, 10 with mild chronic renal disease (CRD) and five with severe CRD. Plasma creatinine concentration and urinary specific gravity measurements in the mild and severe CRD cats were significantly different (P < 0–05) and were 131 ± 26-7 umol/litre and 1–034 ± 0–016, and 392 ± 117-3 nmol/litre and 1–015 ± 0–002, respectively. Endogenous creatinine clearance in the mild and severe CRD cats were significantly different (P < 0–01) and were 2–3 ± 0–58 and 0–62 ± 0–230 ml/min/kg bodyweight, respectively. Hypokalemia was present in one cat but it was not associated with hypercalcinuria. Two cats with mild CRD had hypophosphataemia, hypercalcaemia and hyperphosphaturia which was suggestive of primary hyperparathyroidism, while two cats with severe CRD had hyperphosphataemia and hyperphosphaturia which was indicative of renal secondary hyperparathyroidism. Eight of the 15 cats were subsequently necropsied and were found to have segmental atrophic nephropathy.     

Diet and lifestyle variables as risk factors for chronic renal failure in pet cats

A case-control study examining diet and lifestyle variables to generate hypotheses of potential risk factors for chronic renal failure in pet cats was conducted in five private practices in Texas, USA and at the Texas A&M University Veterinary Medical Teaching Hospital. A telephone questionnaire was used to gather information from owners of 38 cats newly diagnosed with CRF between December 1994 and 1995 and from owners of 56 control cats. Factor analysis was used to determine whether composite variables should be constructed to summarize the nutritional predictors adequately. The composite variables and other lifestyle variables were analyzed with logistic-regression. Three final exploratory models were developed: ad libitum feeding with fiber; ad libitum with Factor-2 (a composite variable composed of fiber, magnesium, protein, sodium and ash); and fiber alone. Ad libitum feeding and increased ash intake were associated with increased odds of CRF; increased dietary fiber, magnesium, protein and sodium were associated with decreased odds of CRF.     

Effects of methimazole on renal function in cats with hyperthyroidism

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.     

Evaluation of hepatic and renal function in cats with chediak-higashi syndrome

Cats with the Chediak-Higashi Syndrome (CHS) have partial oculocutaneous albinism, a bleeding tendency, and enlarged cytoplasmic granules in many cell types including those in the liver and kidney. Hepatic and renal function was evaluated in six CHS and six age-matched control cats to determine if the functions of these organs were compromised by the CHS trait. Serum concentrations of alanine aminotransferase, alkaline phosphatase, and total bilirubin were determined to assess the status of the liver. Sulfobromophthalein retention tests were also performed. Renal function was evaluated by determination of (14)C-inulin clearance; blood urea nitrogen and serum creatinine concentrations; 24-hour protein/creatinine ratios, percent clearance ratios of calcium, phosphorus, sodium, potassium and chloride; and urinalysis values. The CHS cats were not significantly (P > 0.05) different from the control cats in any of the above tests. Use of a non-parametric statistical test did reveal a mild difference (P = 0.047) in 24-hour protein excretion between CHS and control cats. Complete blood counts were performed, and the packed cell volume and hemoglobin concentrations were significantly lower (P< 0.05) in the CHS cats than in the control cats.     

Comparison of fractional excretion and 24-hour urinary excretion of sodium and potassium in clinically normal cats and cats with induced chronic renal failure.

The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P less than 0.0001) and sodium (P less than 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats.     

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.     

Tumoral calcinosis in a dog with chronic renal failure

A 2-year-old male German shepherd dog in poor bodily condition was evaluated for thoracic limb lameness due to a large, firm mass medial to the left cranial scapula. Radiography revealed several large cauliflower-like mineralized masses in the craniomedial left scapula musculature, pectoral region and bilaterally in the biceps tendon sheaths. Urinalysis, haematology and serum biochemistry showed that the dog was severely anaemic, hyperphosphataemic and in chronic renal failure. The dog was euthanased and a full post mortem performed. A diagnosis of chronic renal failure with secondary hyperparathyroidism was confirmed. The mineralised masses were grossly and histopathologically consistent with a diagnosis of tumoral calcinosis. Tumoral calcinosis associated with chronic renal failure that does not involve the foot pads is rarely seen.