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Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs

      Abstract

      Dietary supplementation with polyunsaturated fatty acids (PUFAs) alters the course of experimental kidney disease in dogs. In particular, supplementation with ω-6 PUFAs hastens the decline of kidney function, and ω-3 PUFAs are renoprotective. We investigated the early stages of renal insufficiency to determine whether PUFA supplementation altered the magnitude of hypercholesterolemia or glomerular hemodynamics. Two months after 11/12 nephrectomy, dogs were randomly divided into three groups of 6 animals each. Each group of dogs was then fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources were rich in ω-3 PUFAs (menhaden fish oil, group FO), ω-6 PUFAs (safflower oil, group SO), or saturated fatty acids (beef tallow, group C). Early in renal insufficiency, before significant kidney damage, group FO had a lower (P <.05) serum cholesterol concentration and tended to have a lower urinary prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) excretion than group C. In contrast, group SO had a higher mean glomerular capillary pressure (P <.05) and more glomerular enlargement (P <.05) and tended to have higher eicosanoid excretion rates than group C. These differences in lipid metabolism, glomerular hypertension and hypertrophy, and urinary eicosanoid metabolism could explain, in part, the beneficial effects of ω-3 PUFAs and the detrimental effects of ω-6 PUFAs when administered on a long-term basis in this model of renal insufficiency. (J Lab Clin Med 2000;135:275-86)

      Abbreviations:

      BUN (blood urea nitrogen), CCr (urinary clearance of exogenously administered creatinine), FF (renal filtration fraction), FO (menhaden fish oil), GBF (single glomerular blood flow), GFR (glomerular filtration rate (urinary clearance of inulin)), GPF (single glomerular plasma flow), Hct (hematocrit), HDL cholesterol (cholesterol contained in high-density lipoprotein particles), Kf (glomerular ultrafiltration coefficient), ΔP (glomerular transcapillary hydraulic pressure gradient), MAP (mean systemic arterial pressure), PGE2 (prostaglandin E2), PCP (peritubular capillary hydraulic pressure), PGC (glomerular capillary pressure), PSF (proximal tubular stop-flow pressure), πa (arterial colloid osmotic pressure), πe (glomerular efferent colloid osmotic pressure), PUFA (polyunsaturated fatty acid), RA (pre-glomerular vascular resistance), RBF (renal blood flow), RE (post-glomerular vascular resistance), RPF (renal plasma flow), RT (total renal vascular resistance), SCr (plasma concentration of creatinine), SNGFR (single nephron glomerular filtration rate), SO (safflower oil), TxB2 (thromboxane B2 (the stable metabolite of thromboxane A2))
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      References

        • Polzin DL
        • Leininger JR
        • Osborne CA
        • Jeraj K.
        Development of renal lesions in dogs after 11/12 reduction of renal mass.
        Lab Invest. 1988; 58: 172-183
        • Brown SA
        • Crowell WA
        • Barsanti JA
        • White JV
        • Finco DR.
        Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass.
        J Am Soc Nephr. 1991; 1: 1169-1179
        • Finco DR
        • Brown SA
        • Crowell WA
        • Groves CA
        • Duncan JR
        • Barsanti JA.
        Effects of phosphorus/calcium-restricted and phosphorus/calcium-replete 32% protein diets in dogs with chronic renal failure.
        Am J Vet Res. 1992; 53: 157-163
        • Finco DR
        • Brown SA
        • Crowell WA
        • Duncan JR
        • Barsanti JA
        • Bennett SE.
        Effects of dietary phosphorus and protein in dogs with chronic renal failure.
        Am J Vet Res. 1992; 53: 2264-2271
        • Brown SA
        • Brown CA
        • Crowell WA
        • Barsanti JA
        • Allen T
        • Cowell C
        • et al.
        Beneficial effects of chronic administration of dietary ω-3 polyunsaturated fatty acids in dogs with renal insufficiency.
        J Lab Clin Med. 1997; 131: 447-455
        • Bovee KC
        • Abt DA
        • Kronfeld DS.
        The effects of dietary protein intake on renal function in dogs with experimentally reduced renal function.
        Invest Urol. 1979; 15: 9-16
        • Robertson JL
        • Goldschmidt M
        • Kronfeld DS
        • Tomaszewski JE
        • Hill S
        • Bovee KC.
        Long-term renal responses to high dietary protein in dogs with 75% nephrectomy.
        Kidney Int. 1986; 29: 511-519
        • Brown SA
        • Finco DR
        • Crowell WA
        • Choat DC
        • Navar LG.
        Single-nephron adaptations to partial renal ablation in the dog.
        Am J Physiol. 1990; 258: F495-F503
        • Brown SA
        • Finco DR
        • Crowell WA
        • Navar LG.
        Dietary protein intake and the glomerular adaptations to partial nephrectomy in dogs.
        J Nutr. 1991; 121: S125-S127
        • Polzin DJ
        • Osborne CA
        • Hayden DW
        • Stevens JB.
        Influence of reduced protein diets on morbidity, mortality, and renal function in dogs with induced chronic renal failure.
        Am J Vet Res. 1983; 45: 506-517
        • Brown SA
        • Walton CA
        • Crawford P
        • Bakris GL.
        Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria.
        Kidney Int. 1993; 43: 1210-1218
        • Gaber L
        • Walton C
        • Brown S
        • Bakris G.
        Effects of antihypertensive agents on the morphologic progression of diabetic nephropathy in dogs.
        Kidney Int. 1994; 46: 161-169
        • Nath K
        • Chmielewski D
        • Hostetter T.
        Regulatory role of prostanoids in glomerular microcirculation of remnant nephrons.
        Am J Physiol. 1987; 252: F829-F837
        • Forpomes O
        • Combe C
        • Cambar J
        • Aparicio M.
        Cyclosporin-A and angiotensin-II-induced vasoreactivity in isolated glomeruli and cultured mesangial cells, 4 and 24 h after renal mass reduction: role of vasodilatory prostaglandins.
        Nephron. 1997; 76: 337-344
        • DeRubertis FR
        • Craven PA.
        Eicosanoids in the pathogenesis of the functional and structural alterations of the kidney in diabetes.
        Am J Kidney Dis. 1993; 22: 727-735
        • Kelefiotis D
        • Bresnahan BA
        • Stratidakis I
        • Lianos EA.
        Eicosanoid-induced growth and signaling events in rat glomerular mesangial cells.
        Prostaglandins. 1995; 49: 269-283
        • Nakahama K
        • Morita I
        • Murota S.
        Effects of endogenously produced arachidonic acid metabolites on rat mesangial cell proliferation.
        Prostaglandins Leukot Essent Fatty Acids. 1994; 51: 177-182
        • Spurney RF
        • Ruiz P
        • Albrightson CR
        • Pisetsky DS
        • Coffman TM.
        Fish oil feeding modulates leukotriene production in murine lupus nephritis.
        Prostaglandins. 1994; 48: 331-348
        • Chandrasekar B
        • Fernandes G.
        Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by omega-3 lipids in murine nephritis.
        Biochem Biophys Res Commun. 1994; 200: 893-898
        • Finco DR
        • Brown SA
        • Crowell WA
        • Barsanti JA.
        Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass.
        Am J Vet Res. 1991; 52: 1029-1032
        • Williams RH
        • Thomas C
        • Bell D
        • Navar LA.
        Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique.
        Am J Physiol. 1977; 233: F282-F289
        • Brun C.
        A rapid method for the determination of para-aminohippuric acid in kidney function tests.
        J Lab Clin Med. 1951; 37: 955-958
        • Bradford MM.
        A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
        Anal Biochem. 1976; 72: 248-254
        • Thomas CE
        • Bell PD
        • Navar LG.
        Glomerular filtration dynamics in the dog during elevated plasma colloid osmotic pressure.
        Kidney Int. 1979; 15: 502-512
        • Thomas CE
        • Ott CE
        • Bell PD
        • Knox FG
        • Navar LG.
        Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog.
        Am J Physiol. 1983; 244: F606-F611
        • Navar LG
        • Bell PD
        • White RW
        • Williams RL.
        Evaluation of the single nephron glomerular filtration coefficient in the dog.
        Kidney Int. 1977; 12: 137-149
        • Finco DR
        • Coulter DB
        • Barsanti JA.
        Procedure for a simple method of measuring glomerular filtration rate in the dog.
        J Am Anim Hosp Assoc. 1982; 18: 804-806
        • Brenner BM
        • Meyer TW
        • Hostetter TH.
        Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease.
        N Engl J Med. 1982; 307: 652-659
        • Hostetter TH
        • Olson JL
        • Rennke HG
        • Venkatachalam MA
        • Brenner BM.
        Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation.
        Am J Physiol. 1981; 241: F85-F92
        • Anderson S
        • Meyer TW
        • Rennke HG
        • Brenner BM.
        Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.
        J Clin Invest. 1985; 76: 612-619
        • Yoshida T
        • Fogo A
        • Ichikawa I.
        Glomerular hemodynamic changes vs hypertrophy in experimental glomerular sclerosis.
        Kidney Int. 1989; 35: 654-660
        • Doi T
        • Quaife C
        • Conti F
        • Palmiter R
        • Behringer R
        • Brinster R
        • et al.
        Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor I.
        Am J Pathol. 1988; 131: 398-403
        • Miller PL
        • Rennke HG
        • Meyer TW.
        Glomerular hypertrophy accelerates hypertensive glomerular injury in rats.
        Am J Physiol. 1991; 261: F459-F465
        • Clark WF
        • Parbtani A
        • Huff MW
        • Reid B
        • Holub BJ
        • Falardeau P.
        Omega-3 fatty acid dietary supplementation in systemic lupus erythematosus.
        Kidney Int. 1989; 36: 653-660
        • Kaisiske B
        • O'Donnell M
        • Cleary M
        • Keane WF
        Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats.
        Kidney Int. 1988; 33: 667-672
        • Guijarno C
        • Keane WF.
        Lipid-induced glomerular injury.
        Nephron. 1994; 67: 1-6
        • Keane WF
        • Kasiske BL
        • O'Donnell MP
        Hyperlipidemia and the progression of renal disease.
        Am J Clin Nutr. 1988; 47: 157-160
        • Wanner C
        • Kramer-Guth A
        • Nauck M
        • Quaschning T
        • Pavenstadt H
        • Schollmeyer P.
        Cholesterol metabolism in glomerular cells: effect of lipoproteins from nephrotic patients.
        Miner Electrolyte Metab. 1996; 22: 39-46
        • Schlondorff D.
        Cellular mechanisms of lipid injury in the glomerulus.
        Am J Kidney Dis. 1993; 22: 72-82
        • Bank N.
        Renal hemodynamic consequences of hyperlipidemia.
        Miner Electrolyte Metab. 1993; 19: 165-172
        • Schmitz PG
        • O'Donnell MP
        • Kasiske BL
        • Keane WF
        Glomerular hemodynamic effects of dietary polyunsaturated fatty acid supplementation.
        J Lab Clin Med. 1991; 118: 129-135
        • Neumayer HH
        • Heinrich M
        • Schmissas M
        • Haller H
        • Wagner K
        • Luft FC.
        Amelioration of ischemic acute renal failure by dietary fish oil administration in conscious dogs.
        J Am Soc Nephr. 1992; 3: 1312-1320
        • Abdel-Gayoum AA
        • Bashir AA
        • el-Fakhri MM.
        Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat.
        Hum Exp Toxicol. 1995; 14: 884-888
        • Kasiske BL
        • O'Donnell MP
        • Lee H
        • Kim Y
        • Keane WF
        Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats.
        Kidney Int. 1991; 39: 1125-1134
        • Rahman MA
        • Sauter DC
        • Young MR.
        Effects of fish oil on the induction of experimental membranous nephropathy in the rat.
        Lab Invest. 1991; 64: 371-376
        • Shimamura T
        • Wilson AC.
        Influence of dietary fish oil on the aortic, myocardial, and renal lesions of SHR.
        J Nutr Sci Vitaminol. 1991; 37: 581-590
        • Wheeler DC
        • Nair DR
        • Persaud JW
        • Jeremy JY
        • Chappell ME
        • Varghese Z
        • et al.
        Effects of dietary fatty acids in an animal model of focal glomerulosclerosis.
        Kidney Int. 1991; 39: 930-937
        • Robinson DR
        • Xu LL
        • Tateno S
        • Guo M
        • Colvin RB.
        Suppression of autoimmune disease by dietary n-3 fatty acids.
        J Lipid Res. 1993; 34: 1435-1444
        • Weise WJ
        • Natori Y
        • Levine JS
        • O'Meara YM
        • Minto AW
        • Manning EC
        • et al.
        Fish oil has protective and therapeutic effects on proteinuria in passive Heymann nephritis.
        Kidney Int. 1993; 43: 359-368
        • Chandrasekar B
        • Troyer DA
        • Venkatraman JT
        • Fernandes G.
        Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression.
        J Autoimmun. 1995; 8: 381-393
        • Burgess NA
        • Reynolds TM
        • Williams N
        • Pathy A
        • Smith S.
        Evaluation of four animal models of intrarenal calcium deposition and assessment of the influence of dietary supplementation with essential fatty acids on calcifications.
        Urol Res. 1995; 23: 239-242
        • Goldstein DJ
        • Wheeler DC
        • Sandstrom DJ
        • Kawachi H
        • Salant DJ.
        Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis.
        J Am Soc Nephrol. 1995; 6: 1468-1475
        • Clark WF
        • Parbtani A
        • Philbrick DJ
        • Spanner E
        • Huff MW
        • Holub BJ.
        Dietary protein restriction versus fish oil supplementation in the chronic remnant nephron model.
        Clin Nephrol. 1993; 39: 295-304
        • Scharschmidt LA
        • Gibbons NB
        • McGarry L
        • Berger P
        • Axelrod M
        • Janis R
        • et al.
        Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy.
        Kidney Int. 1987; 32: 700-709
        • Logan JL
        • Michael UF
        • Benson B.
        Dietary fish oil interferes with renal arachidonic acid metabolism in rats: correlations with renal physiology.
        Metabolism. 1992; 41: 382-389
        • Aukema HM
        • Ogborn MR
        • Tomobe K
        • Takahashi H
        • Hibino T
        • Holub BJ.
        Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease.
        Kidney Int. 1992; 42: 837-842
        • Donadio JV
        • Bergstralh EJ
        • Offord KP
        • Spencer DC
        • Holley KE.
        A controlled trial of fish oil in IgA nephropathy.
        N Engl J Med. 1994; 331: 1194-1199
        • Homan JJ
        • Biol HJ
        • Donker AJ
        • Wilmink JM
        • Sluiter WJ
        • Tegzess AM.
        The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients.
        Transplantation. 1992; 54: 257-263
        • Clark WF
        • Parabtani A
        • Naylor CD
        • Levinton CM
        • Muirhead N
        • Spanner E
        • et al.
        Fish oil in lupus nephritis: clinical findings and methodological implications.
        Kidney Int. 1993; 44: 75-86
        • Clark WF
        • Parbtani A
        • Philbrick DJ
        • Holub BJ
        • Huff MW.
        Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model.
        J Am Soc Nephrol. 1991; 1: 1343-1353
        • National Research Council
        Nutrient requirements of domestic animals. Nutrient requirements of dogs.
        National Academy Press, Washington, DC1985
        • Prickett JD
        • Robinson DW
        • Steinberg AD.
        Effects of dietary enrichment with eicosapentaenoic acid upon autoimmune nephritis in female NZB X NZW/P1 mice.
        Arthritis Rheum. 1983; 26: 133-139
        • Donadio JV.
        Omega-3 polyunsaturated fatty acids: a potential new treatment of immune renal disease.
        Mayo Clin Proc. 1991; 66: 1018-1028
        • Boutard V
        • Fouqueray B
        • Philippe C
        • Perez J
        • Baud L.
        Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages.
        Kidney Int. 1994; 46: 1280-1286
        • Collie-Duguid ES
        • Wahale KW.
        Inhibitory effect of fish oil n-3 polyunsaturated fatty acids on the expression of endothelial cell adhesion molecules.
        Biochem Biophys Res Commun. 1996; 220: 969-974
        • Barcelli U
        • Glass-Greenwalt P
        • Pollak VE.
        Enhancing effects of dietary supplementation with omega-3 fatty acids on plasma fibrinolysis.
        Thromb Res. 1985; 39: 307-312
        • Clark WF
        • Parbtani A
        • Philbrick D
        • McDonald JW
        • Smallbone B
        • Reid B
        • et al.
        Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion.
        Clin Nephrol. 1990; 33: 25-34
        • Radack K
        • Deck C
        • Huster G.
        The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects.
        Arch Intern Med. 1991; 151: 1173-1180
        • Morris MC
        • Sacks F
        • Rosner B.
        Does fish oil lower blood pressure?.
        Circulation. 1993; 88: 523-533
        • Mills DE
        • Ward RP
        • McCutcheon D
        • Dixon H
        • Ly H
        • Scholey J.
        Attenuation of cyclosporine-induced hypertension by dietary fatty acids in the borderline hypertensive rat.
        Transplantation. 1992; 53: 649-654
        • Kimura S
        • Minami M
        • Saito H
        • Kobayashi T
        • Okuyama H.
        Dietary docosahexaenoic acid (22:6n-3) prevents the development of hypertension in SHRSP.
        Clin Exp Pharmacol Physiol. 1995; 22: S308-S309
        • Bidani A
        • Mitchell K
        • Schwartz MM
        • Navar LG
        • Lewis EJ.
        Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model.
        Kidney Int. 1990; 38: 28-38
        • Panzetta O
        • Cominacini L
        • Garbin U
        • Fratta A
        • Gammaro L
        • Bianco F
        • et al.
        Increased susceptibility of LDL to in vitro oxidation in patients on maintenance hemodialysis: effects of fish oil and vitamin E administration.
        Clin Nephrol. 1995; 44: 303-309