Progress 07/01/07 to 06/30/11
Outputs
OUTPUTS: The specific objectives of this study were to: 1. Use a feline model to evaluate the relationship of fish oil omega-3 fatty acids, EPA and DHA, and inflammation in chronic renal failure 2. Examine the relationship of fish oil omega-3 fatty acids and malnutrition:inflammation syndrome in chronic kidney disease 3. Examine the relationship of fish oil omega-3 fatty acids and serum albumin, hemoglobin and hematocrit and body condition score as markers of nutritional status. 63 client owned feline patients, mean age 14.04 + 3.86 years, with diagnosed stage 2 and 3 chronic kidney disease (mean BUN 58.08 + 24.15 mg/dl; creatinine 17.02 +.0), seen at the Colorado State University Veterinary Teaching Hospital, completed the study. Dietary intake of omega-3 DHA and EPA were analyzed by diet record. Omega-3 DHA and EPA status was evaluated by measurement of erythrocyte membrane fatty acids. Markers of inflammation, serum amyloid A (SAA) and the longer reacting mediator, alpha-1 acid glycoprotein (AAG) were correlated with clinical response variables, serum albumin, body condition score, hemoglobin, hematocrit and Urine protein:creatinine ratio. PARTICIPANTS: Mary Harris, PhD,RD (Department of Food Science and Human Nutrition) and Kathryn Lunn, DVM (Voss Veterinary Teaching Hospital) were co-principal investigators ont he project. Jessica Quimby, DVM and PHd candidate recurited subjects and colllected medical data for the study. Two graduate students in Food science and Human Nutrition, Christopher Mulligan, PHD candidate and SUsan Kim, MS candidate provided laboratory analysis. TARGET AUDIENCES: This study was designed to provide knowledge of the effectiveness of omega-3 DHA and EPA (fish oil fatty acids) in the control of inflammation and the prevention of malnutrition:inflammation in chronic kidney disease. A feline model was used to provide information to be used to inform diet formularion for cats with chronic kidney disease. Additionally, the data may provide evidence for the protective effect of n-3 DHA and EPA in malnutrition:inflammation syndrome in humans with chronic kidney disease. PROJECT MODIFICATIONS: None since previous report.
Impacts
This study examined the relationship of dietary omega-3 (n-3)fatty acid intake on erythrocyte fatty acid composition and inflammatory markers (SAA and A1G) and malnutriton in stage 2 and 3 chronic kidney disease (CKD). The diet recommended for cats with CKD is a specialty diet which is low in protein and provides adequate energy. A variety of dry, semi-moist and canned foods are available, all of which began to be supplemented with n-3 fish oil during the study period. Many cats will not eat these specialty diets resulting in a large variation in n-3 DHA and n-3 EPA intake among this study group. Mean intakes of n-3 DHA and EPA were 42.77 + 74.34 and 36.02+ 69.74 mg/day, respectively. Mean RBC n-6 Arachidonic Acid and n-3 DHA were 12.18 + 5 and 1.02 + 0.77 % total fatty acids, respectively. BCS was correlated with DHA intake (r=.299, p=.05) when controlling for age , gender and indicators of chronic kidney disease (BUN, calcium, Hct, potassium and bicarbonate). Mean AGP was 446.98 + 220.48 ug/ml (range 140 - 1460) and mean SAA was 11.75 +25.78 ug/ml (range 0.1 - 151). Mean serum albumin was 3.5 +.35 g/dl, Protein:creatinine ratio was .42 + .63 and Hct was 29.87 +5.99. Serum albumin was inversely correlated with AGP (r=-.321, p=.01). The negative association between serum albumin and SAA was approaching significance (r=-.219, p=.08). The protein:creatinine ratio was positively and highly correlated with SAA (r=.338, p=.008) and approaching significance with AGP (r=.237, p=.06). Hemoglobin and hematocrit was negatively and highly correlated with both AGP (p=.000) and SAA (p=.04). The results indicate that DHA status may decrease inflammation in chronic kidney disease and that higher DHA intakes may protect against malnutrition:inflammation syndrome as indicated by higher body condition scores and serum albumin in felines with stage 2 and 3 chronic kidney failure. Elevation of inflammatory markers is associated with risk for malnutrition as indicated by lower serum albumin and progression of kidney disease as indicated by greater protein loss in the urine. The data have been submitted for presentation at the 2012 Experimental Biology Meeting.
Publications
- No publications reported this period
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: This study examined the relationship of dietary omega-3 fatty acids intake on erythrocyte fatty acid composition and inflammatory markers (SAA and A1G) in stage 3 and 4 chronic kidney disease (CKD). The diet recommended for cats with CKD is a specialty diet which is low in protein and provides adequate energy. A variety of dry, semi-moist and canned foods are available, all of which began to be supplemented with n-3 fish oil during the study period. Many cats will not eat these specialty diets resulting in a large variation in n-3 DHA and EPA dietary intake among this study group. The study data are collected and the data are in final analysis. PARTICIPANTS: Mary Harris,PhD,RD, BC-ADM Kathryn Lunn, DVM Jessica Quimby, DVM, PhD candidate Susan Kim, BS Masters degree candidate TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Omega-3 fish oil fatty acid intake is expected to decrease inflammation and improve disease status as measured by inflammatory markers and clinical measure including blood pressure and creatinine. To date, omega-3 intake and fatty acid status, SAA and A1G have been analyzed in 62 cats with stage 3 and 4 CKD. Dietary intake of n-3 is being estimated from diet records and GC analysis of each cat food reported in the records. There is a wide range of n-3 contribution from the diets which we are in the process of correlating with outcome variables (inflammatory markers and clinical outcome data). RBC fatty acid composition expressed as % Total Fatty acids (average and range) 16:0 = 17.42 + 2.29, 18:0=24.49 + 1.48, 18:1 = 14.95+ 3.52, 18:2n6 (LA)= 21.65 + 20:3n6 = 1.02+0.27, 20:4n6 (AA)= 16.74+ 3.55, 20:5n3 (EPA)=0.41+ 0.20 and 22:6n3 (DHA)= 1.42+0.66. Associations among dietary omega-3 intake and inflammatory markers and clinical status are currently being examined.
Publications
- No publications reported this period
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: This study originally supplemented a small number of cats to examine the effect of dietary omega-3 (n-3) fish oil fatty acids, EPA and DHA, on inflammatory markers (SAA and A1G) in stage 3 and 4 chronic kidney disease (CKD). Cats identified with CKD during the early recruitment process were largely disqualified due to preexisting conditions/comorbidities including cardiovascular disease, cancer and gastrointestinal disorders and secondary hyperparathyroidism. The diet recommended for cats with CKD is a specialty diet which is low in protein and provides adequate energy. A variety of dry, semi-moist and canned foods are available, all of which began to be supplemented with n-3 fish oil during the study period. Many cats will not eat these specialty diets resulting in a large variation in n-3 DHA and EPA dietary intake among this study group. These changes necessitated changes in the original study protocol. The study has been expanded to include cats in all stages of CKD and the design has been modified to examine the association of varying dietary EPA and DHA dose on inflammatory markers in CKD, markers of oxidative damaage and clinical parameters as modified by the severity of kidney disease and co-morbidities which exist in most of the animals presenting with kidney disease (cardiovascular disease, hyperparathyroidism and/or cancer). To the best of our knowledge, no other dose response study has been published on the effect of n-3 fish oil fatty acids on inflammatory markers or oxidative damage in cats with CKD. The present study will include evaluation of the effect of fish oil containing diets on inflammatory markers (alpha-1 glycoprotein, serum amyloid A and measures of oxidative damage (TBARS) and clinical parameters associated with health in cats with CKD(urine protein:creatinine ratio, Serum parathyroid hormone, calcium, phosphate, potassium, creatinine, urea nitrogen), indicators of nutritional status(weight, serum albumin, hemoglobin and hematocrit) and erythrocyte EPA and DHA as an indicator of n-3 fatty acids status and plasma EPA and DHA as an indicator of n-3 intake. Diet intake is obtained and feeds are analyzed for fatty acid content to determine dose. Control variables are age, medications, blood pressure, gender (to control for muscle mass)and study site. PARTICIPANTS: M. Harris, PHD,RD,BC-ADM (Department of Food Science and Human Nutrition, Colorado State University)and K. Lunn, DVM (Dept. of Clinical Science,James L. Voss Veterinary Teaching Hospital,Colorado State University)are the PI's on the study. Training was provided for two REsearch Associates: Christopher Mulligan, MS (PhD candidate,Department of Food Science and Human Nutrition) and Susi Bennett, Research Associate, Dept. of Clinical Science,Colorado State University. Collaboration with Jessica Quimby, DVM, DACVIM (Small Animal Internal Medicine,James L. Voss Veterinary Teaching Hospital,Colorado State University). TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: No major changes in this reporting period.
Impacts
Omega-3 (n-3)fish oil fatty acid intake is expected to decrease inflammation and improve disease status as measured by inflammatory markers and measures of oxidative damage and clinical parameters
Publications
- No publications reported this period
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: This study supplemented a small number of cats to study the effect of dietary n-3 fish oil fatty acid, EPA and DHA, on inflammatory markers (SAA and A1G) in stage 3 and 4 chronic kidney disease (CKD). Cats identified with CKD during the early recruitment process were largely disqualified due to preexisting conditions/comorbidities including cardiovascular disease, cancer and gastrointestinal disorders and secondary hyperparathyroidism. The diet recommended for cats with CKD is a specialty diet which is low in protein and provides adequate energy. A variety of dry, semi-moist and canned foods are available, all of which began to be supplemented with n-3 fish oil during the study period. Many cats will not eat these specialty diets resulting in a large variation in n-3 DHA and EPA dietary intake among this study group. These changes have necessitated changes in the original study protocol (see below). PARTICIPANTS: Mary Harris, PhD, Rd, BC-ADM co-PI; Chris Mulligan, MS laboratory assistant; Kathy Lunn, BVMS, MS, PhD, MRCVS co-PI. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Changes in specialty diets and the existanc of comorbidities in the majority of cats with chronic kidney diesae (CKD)have necessitated development of a new model to study the effect of n-3 fish oil fatty acids on inflammatory markers and nutritional status in cats with CKD. The study will be expanded to include cats in all stages of CKD and the design has been modified to examine the assocaition of varying dietary EPA and DHA dose on inflammatory markers in CKD, as modified by the severity of kidney disease and co-morbidities which exist in most of the animals presenting with kidney disease (cardiovascular disease, hyperparathyroidism and/or cancer). To the best of our knowledge, no other dose response study has been published on the effect of n-3 fish oil fatty acids on inflammatory markers in cats with CKD. Although CKD specialty feeds are now adding n-3 fish oil to the chronic kidney disease diets, there is in sufficient evidence of efficacy other than the observation that diets with the greatest beneficial effect on survival time had the highest EPA content. The present study will include evlaulate the effect of fish oil containing diets on inflammatory markers (alpha-1 glycoporotein, serum amyloid A and laboratory parameters associated with health in cats with CKD(urine protein: creatinine ratio, Serum parathyroid hormone, calciuim, phosphate, potassium, creatinine, urea nitrogen), indicators of nutritional status(weight, serum albumin, hemoglobin and hematocrit) and erythrocyte EPA and DHA as an indicator of n-3 fatty acids status and plamsa EPA and DHA as an indicator of n-3 intake. Diets will be analyyzed for fatty acid content. Control variables will be age, medications, blood pressure, gender (to control for muscle mass)and study site.
Impacts
This is an ongoing study with an anticipated outcome to provide evidence linking n-3 EPA and DHA to decreased inflammation and improved nutritional status by in an animal model of human disease. . A modification to the original randomized double blind design was necessitated because specialty renal diets are now being fortified with DHA, ahead of the scientific evidence. The efficacy of added n-3 fish oil fatty acids to specialty diets for cats with chronic kidney disease has not been adequately studied. The current study will examine the effect of n-3 fish oil fatty acid intake on nutritional status and health parameters of cats with CKD over a range of dietary intakes. Additionally, the data may substantiate the added cost of adding fish oil n-3 fatty acids to specialty feeds for animals with CKD.
Publications
- No publications reported this period
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Progress 01/01/07 to 12/31/07
Outputs
This project is a two year randomized double blind controlled clinical trial of DHA supplementation using patient cats at the Colorado State University Veterinary Teaching Hospital with chronic kidney failure as a model for human disease. It is in the recruitment phase. No data will be available until the code is broken at the end of the study.
Impacts
A significant number of human and feline patients in end-stage renal failure present with chronic low levels of serum albumin, regardless of protein intake. This is in part due to proteinuria, but in humans with stable proteinuria, malnutrition is often associated with inflammation. In inflammatory states in humans, serum albumin levels are decreased. Since serum albumin is a marker for immune system function, raising albumin is an important dietary goal in patients with CKD. This study addresses the use of a functional nutrient to decrease inflammation and reverse malnutrition in this population. Today, many chronic diseases including Cardiovascular disease are associated with inflammatory processes which may play pathological roles.
Publications
- No publications reported this period
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