Acid-base balance of cats with chronic renal failure: effect of deterioration in renal function

In a previous cross-sectional study of feline chronic renal failure (CRF), metabolic acidosis was identified in 52.6 per cent of animals with severe renal failure (plasma creatinine concentration >400 micromol/litre). The aim of this longitudinal study was to determine whether metabolic acidosis preceded or accompanied a deterioration in renal function in cats with CRF. Data were analysed from 55 cats with CRF that had been followed longitudinally for at least four months. Twenty-one cases showed deterioration in renal function over the period of the study, as evidenced by significant rises in their plasma creatinine concentrations and decreases in bodyweight. In five of the 21 cases, acidaemia accompanied the deterioration in renal function. Only one of these cats had evidence of metabolic acidosis before renal function deterioration. One other case developed metabolic acidosis without a rise in plasma creatinine concentration. These data suggest that biochemical evidence of metabolic acidosis does not generally occur until late in the course of feline CRF.     

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.     

Association between initial systolic blood pressure and risk of developing a uremic crisis or of dying in dogs with chronic renal failure

OBJECTIVE: To determine whether high systolic blood pressure (SBP) at the time of initial diagnosis of chronic renal failure in dogs was associated with increased risk of uremic crisis, risk of dying, or rate of decline in renal function. DESIGN: Prospective cohort study. ANIMALS: 45 dogs with spontaneous chronic renal failure. PROCEDURE: Dogs were assigned to 1 of 3 groups on the basis of initial SBP (high, intermediate, low); Kaplan-Meier and Cox proportional hazards methods were used to estimate the association between SBP and development of a uremic crisis and death. The reciprocal of serum creatinine concentration was used as an estimate of renal function. RESULTS: Dogs in the high SBP group were more likely to develop a uremic crisis and to die than were dogs in the other groups, and the risks of developing a uremic crisis and of dying increased significantly as SBP increased. A greater decrease in renal function was observed in dogs in the high SBP group. Retinopathy and hypertensive encephalopathy were detected in 3 of 14 dogs with SBP > or = 180 mm Hg. Systolic blood pressure remained high in 10 of 11 dogs treated with antihypertensive drugs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that initial high SBP in dogs with chronic renal failure was associated with increased risk of developing a uremic crisis and of dying. Further studies are required to determine whether there is a cause-and-effect relationship between high SBP and progressive renal injury and to identify the risks and benefits of antihypertensive drug treatment.     

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.     

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.     

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.     

Effect of control of systolic blood pressure on survival in cats with systemic hypertension

BACKGROUND: Systemic hypertension is a common clinical problem, often occurring in association with renal disease in cats. Limited information is available to assess the effect of blood pressure and the treatment of hypertension on survival. HYPOTHESIS: That adequacy of blood pressure control is associated with the duration of survival in cats with systolic hypertension. ANIMALS: One hundred and forty-one client-owned cats with systolic hypertension. METHODS: Hypertensive cats were treated with amlodipine besylate and were followed until death or the study end point. Time-averaged systolic blood pressure (SBPOT) after implementation of antihypertensive medication and stabilization of systolic blood pressure (SBP) was calculated by using the equation (area under the curve/survival [days]). Cats were divided into quartiles based on their SBPOT, representing varying levels of blood pressure control (median [25th, 75th percentile]: Q1 = 137 [132, 141] mm Hg, Q2 = 148 [145, 151] mm Hg, Q3 = 157 [155, 158] mm Hg, Q4 = 170 [164, 175] mm Hg). Survival and clinical variables were compared between the quartiles. Cox proportional hazard regression analysis was used to determine the association of age, renal function, proteinuria, SBPOT, and the presence of hyperthyroidism on survival. Urine protein to creatinine ratio (UP:C) was compared at diagnosis of hypertension and after initiating treatment. RESULTS: Only UP:C and SBP at diagnosis differed significantly between SBPOT quartiles. Proteinuria was the only variable significantly related to survival in hypertensive cats. A significant decline in UP:C was found in cats treated with amlodipine besylate. CONCLUSIONS AND CLINICAL IMPORTANCE: Proteinuria before and after treatment of hypertension is strongly associated with survival in cats with systolic hypertension. Treatment with amlodipine besylate can result in a significant reduction in UP: C.     

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.     

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 systemic hypertension with renal injury in dogs with induced renal failure

Systemic hypertension is hypothesized to cause renal injury to dogs. This study was performed on dogs with surgically induced renal failure to determine whether hypertension was associated with altered renal function or morphology. Mean arterial pressure (MAP), heart rate (HR), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) were measured before and after surgery. Glomerular filtration rate (GFR) and urine protein:creatinine ratios (UPC) were measured at 1, 12, 24, 36, and 56-69 weeks after surgery, and renal histology was evaluated terminally. The mean of weekly MAP, SAP, and DAP measurements for each dog over the 1st 26 weeks was used to rank dogs on the basis of MAP, SAP, or DAP values. A statistically significant association was found between systemic arterial pressure ranking and ranked measures of adverse renal responses. When dogs were divided into higher pressure and lower pressure groups on the basis of SAP, group 1 (higher pressure, n = 9) compared with group 2 (lower pressure, n = 10) had significantly lower GFR values at 36 and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, and fibrosis. When dogs were divided on MAP and DAP values, group 1 compared with group 2 had significantly lower GFR values at 12, 24, 36, and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, fibrosis, and cell infiltrate. These results demonstrate an association between increased systemic arterial pressure and renal injury. Results from this study might apply to dogs with some types of naturally occurring renal failure.     

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.     

Shear wave elastography evaluation of cats with chronic kidney disease

Chronic kidney disease (CKD) is a major health condition in cats that can lead to poor quality of life and financial implications for therapy. Currently staging and identification of CKD is limited by diagnostic testing such as creatinine and urine-specific gravity, which do not change until late in the disease course. Other methods to evaluate CKD would be valuable in the clinical setting. Shear wave elastography is one novel ultrasound method, which has shown promise in identifying increases in tissue stiffness and identifying CKD in people. As CKD is often histologically characterized by tubulointerstitial fibrosis, shear wave elastography has the potential to identify CKD and differentiate between stages of CKD in cats. This prospective observational case-control study with 78 cats found no difference in shear wave velocities between groups (P = 0.33), a contradictory finding to one prior publication. There was no effect of weight (P = 0.65), nor the presence of mineralization (P = 0.31) or infarction (P = 0.52) on cortical shear wave velocities. There was a significant effect of age on shear wave velocity (P = 0.018) where velocities increased with age. The intraclass correlation coefficient was only moderate (0.62). Possible reasons for the difference in results between our work and that published prior, include differences in methodology and differences in instrumentation. Variability in measurements in our population may be due to the effects of respiratory motion or limitations in shear wave elastography software. As such, shear wave elastography is not currently recommended as a tool to evaluate CKD in cats and further work is necessary.     

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.