A Case Control on the Intake of Polyunsaturated Fatty Acids
and Chronic Renal Failure in Cats
Esther A. Plantinga
Anton C. Beynen
Department of Nutrition, Faculty of Veterinary Medicine
Utrecht University, The Netherlands
Source: The Journal of Applied Research in Veterinary Medicine. Vol 1, No. 2, Spring 2003, 127-132
Abstract
Background: A Case-control study was carried out to determine the association between chronic renal failure(CRF) and polyunsaturated fatty acid (PUFA) intake in cats.
Methods: Thirty-six cats, newly diagnosed with CRF, were matched to 35 controls. Plasma cholesteryl-ester (CE) fatty acid composition, in combination with a food intake questionnaire, was used to assess fatty acid intake.
Results: The cases had a significantly higher relative percentage arachidonic acid (AA) and a significantly lower percentage of linoleic acid in plasma CEs that the control cats (P<0.01). Linoleic acid intake was significantly lower in cases than in controls.
Conclusions: It is suggested that high AA intake might be a risk factor of CRF in cats.
Introduction
Chronic renal failure (CRF) is a common clinical problem in cats, affecting u[ to 30% of all animals above 15 years of age.1
Affected cats have a poor prognosis because the renal dysfunction frequently progresses to end-stage renal failure.2 The pathogenesis of CRF in general is not yet fully understood, but people risk factors such a systemic hypertension, high dietary protein intake, and, hyperlipidemia have been identified.3
The type of polyunsaturated fatty acids (PUFA) in the diet might be important in relation to chronic renal failure. Studies with dogs and rats show that supplementation with n-3 PUFA might delay and that supplemental with n- PUFA might accelerate the progression of CRF.4-6 The possible protective effect of polyunsaturated fatty acids might relate to the role of these fatty acids as precursors of eicosanoids. A predominance of n-6 fatty acids in the diet, linoleic acid being the most important n-6 fatty acid, will lead to a higher percentage of arachidonic acid (AA) in the cellular membranes, which can result in a proinflammatory status as a result of the production of prostaglandins of the 2 series and leukotrienes of the 4 series. As the relative dietary intake n-3 fatty acids increases, more prostaglandins 3 series an leukotrines of the 5 series are being considered to reduce inflammation. 7-9 The anti-inflammatory effects of n-3 fatty acids can also be explained by another mechanism as the principles, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are competitive inhibitors of AA conversion into eicosanoids.10
One important difference between cats and other mammalian species is that cats are not or are only marginally capable of desaturating and elongating linoleic acid into AA, because they lack the necessary enzymes.11 This means not only that AA in tissues reflects the intake of this fatty aid, but also that feeding of extra linoleic acid to cats will not lead to an increase in arachidonic acid and thus might not result in a n increase of proinflammatory eicosanoids.
To find out whether PUFA play a role in the development of renal disease in cats, a case-control study was carried out. The intake of the major n-6 PUFA, linoleic acid, was assessed on the basis of food intake questionnaires. In addition, the percentage of linoleic acid in plasma cholesterol esters (CEs)was used as a biomarker of the intake of this fatty acid. A controlled dietary trail with cats has shown that an increased intake of linoleic acid is associated with an increased in its content in the plasma CEs.12
Materials and Methods
Cats
From Mat to September 2001, 36 cats, newly diagnosed with CRF, and 35 healthy
control animals were obtained with the help of various Dutch veterinary clinics
and the Faculty of Veterinary medicine, Utrecht University. Control cats were
matched to the cases n the basis of age, breed and gender. The characteristics
of the cats are given in Table 1.
The majority of the cats (93%) were European Shorthairs. The rest consisted of Siameses and Persian cats.
The diagnosis of CRF was made on the basis of clinical signs of CRF (polyuria/polydipsia, vomiting, weight loss, anorexia) and the elevation of the plasma urea and cretinine concentrations. Only cases with a plasma creatinine above 175 mol/L were considered eligible for this study. CRF diagnosis was based on a single measurement of urea and creatinine, which might have led to some of the cats being wrongly categorized.13 The observed contrast between cases and controls could thus be smaller than the true contrast.
Food Intake Questionnaire
A questionnaire was used to estimate the dietary intake of the cats. Part of the questionnaire had questions about the brand and the quantity of the commercial cat foods that were given to the cats. The remainder of the questionnaire consisted of 26 food items that are frequently used to feed cats, such as milk, fish, fresh meat and cooked rice. The owners were asked to fill out whether they used each food item, and if they did, the amounts they used. The food intake data were converted into nutrients using cat food analysis data as provided by the various manufacturers, and standard food tables were used for the composition of the other foods.14
The intake of linoleic acid was expressed as a percentage of total fatty acids or as a percentage of dietary metabolizable energy. Total dietary fatty acids were calculated as 95% of total dietary crude fat. It was assumed that, on a weight basis, linoleic acid and crude fat provide identical amounts of metabolizable energy. To calculate the metabolizable energy content of the diets, the following conversion factors were used: 1 g crude protein = 17kJ, 1 g carbohydrates (nitrogen-free extract) = 16 kJ, and 1 g crude fat = 37 kJ.
Blood Sampling and Analysis
Blood samples were taken after the cats had been fasted for 8 to 12 hours before sampling. Sampling was undertaken by jugular venipuncture into tubes containing lithium haparin. The blood was immediately centrifuged and the plasma harvested and stored at -20 degrees C for further analysis. Plasma urea and creatinine were measured at the clinical laboratory of the Faculty of Veterinary Medicine in Utrecht, The Netherlands, using standard autonanalyzer techniques (Beckman).
Fatty acid analysis was performed by capillary gas chromatography using a flame ionization detector, a Chromopack column (Fused silica, no. 7485, CP.FFAPBC 25mx 0.32 mm., Chromopack, Middleburg, The Netherlands) and H2 as a carrier gas. Plasma total lipids were extracted according to the method of Wang and Frank.15 The CEs were isolated with prepacked silica Sep-Pak columns (3 ml/500 mg, Varian Bond Elut 1210-2041, Allech Associates Inc. Deerfiled, IL) using the method of Hamilton and Comai.16 The cholesteryl-ester methylation occurred as described by Metcalfe et al.17
Statistical Analysis
Pearson's correlation coefficients between the fatty acid intake questionnaires and the CE fatty acid measurements were computed with the help of the SPSS 9.0 for Windows statistical program (SPSS Inc. Chicago, IL). Furthermore, the statistical significance of the differences between the cases and controls were evaluated with an independents sample t test.
Results
The fatty acid compositions of the plasma CE in the cases and the controls are expressed in Table 2.
The cases had a significantly lower content of linoleic acid (C18:2 n-6) and a higher level of AA (c20:4 n-6). Table 3 shows nutrient intake of both cases and controls.
The cases has a significantly lower intake of linoleic acid. There was a significant correlation between linoleic acid intake and the linoleic acid content of the plasma CE: the linear correlation coefficient was 0.376 for the cases and 0.62 for the controls (P<0.05). The relationship between the linoleic acid content of the diet and that of the plasma CE of controls and cases combined is shown in figure 1.
Discussion
The purpose of this study was to determine whether there exists an association between PUFA intake and the risk of CRF in cats. The CE fatty acid composition was used to assess the dietary fatty acid intake. However, CE fatty acid composition only reflects the pervious intake of fatty acids for a period u[ to 1 month.18-19 A food intake questionnaire was also used as an estimate of the fatty acid intake. However, the PUFA content of most commercial cat foods is unknown, with the exception of linoleic acid. Figure 1 shows a statistically significant correlation between linoleic acid in CEs and linoleic acid intake which supports our controlled feeding trial 12 and indicates that the CE composition can be used as a biomarker for fatty acid intake.
As based on the CE data, the results indicate that the cases had a significantly higher intake of AA compared with the control cats. This might apply that high intake of AA is a risk factor in the development of CRF in cats. Furthermore, the cases has a significantly lower intake of linoleic acid, suggesting that low linoleic acid intake could also be a risk factor. However, based on studies conducted with other mammalian species, it was expected that low linoleic acid intake would be protective rather than a risk factor.4-6 Cats have a limited capacity to convert linoleic acid into AA, the main precursor of proinflammitory eicosanoids in the body. Thus, in cats the source of AA is the diet A high AA intake could lead to a higher level of this fatty acid in membranes and consequently to a relatively higher proinflammitory status.7-9
The significance of the low linoleic acid intake in the cases is the unknown. High levels of linoleic acid typically occur in plant oils, whereas AA only occurs in foodstuffs of animal origin. Possibly, in the diet of the cats, the contents of linoleic acid in AA were inversely related.
The cases and controls had similar relative percentages of both ?-linolenic acid (C18:3 n-3) and EPA in plasma CEs, which points at similar intakes of each of these n-3 PUFA. Thus, the results of this study specifically indicate that a high AA intake might be a risk factor in the development of renal failure. Further controlled research in this field is necessary to clarify the role of the various PUFA in CRF in cats.
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