High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease.
BACKGROUND
In earlier studies we found that a high-fat, high-energy diet (HFED) attenuates proteinuria, azotemia and lipid accumulation in the remnant kidney of rats subjected to 5/6 nephrectomy. This study was conducted to explore the mechanism of the salutary effect of HFED in association with moderate protein restriction in this model.


METHODS
The 5/6 nephrectomized male rats were randomized to receive regular rat chow (CRF group, n = 6) or HFED diet (CRF + HFED, n = 7) for 12 weeks. Sham-operated rats served as controls (n = 6).


RESULTS
The CRF group exhibited azotemia, hypertension, proteinuria, diminished body weight, oxidative stress, glomerulosclerosis, tubulo-interstitial inflammation and upregulation of pro-oxidant [NAD(P)H oxidase], pro-inflammatory (NF-κB activation, increased MCP-1, lipoxygenase, ICAM-1, VCAM-1), pro-fibrotic (TGF-β, CTGF) and pro-apoptotic pathways (Bax, caspase-3) in the remnant kidney. Consumption of the HFED resulted in a 66% increment in lipid intake, 8% increment in carbohydrate intake and a 24% reduction in protein intake. The CRF + HFED group gained weight normally, had increments in leptin and adiponectin levels, and despite increments in plasma cholesterol and fatty acids, showed significant attenuation of oxidative stress, proteinuria and inflammation, and partial reversal of the remnant kidney upregulation of pro-oxidant, pro-inflammatory, pro-fibrotic and pro-apoptotic pathways.


CONCLUSIONS
Consumption of high-energy diet in association with mild protein restriction results in suppression of upregulated pathways that drive progression of renal injury in the remnant kidney model. These findings may have relevance in the management of chronic kidney disease in humans.
Kim
Hyun Ju
HJ
Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, CA, USA.
Vaziri
Nosratola D
ND
Norris
Keith
K
An
Won Suk
WS
Quiroz
Yasmir
Y
Rodriguez-Iturbe
Bernardo
B
D052242:Adiponectin / Q000097:blood; D000818:Animals; D002100:Cachexia / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D018753:Diet, Protein-Restricted; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control*; D020738:Leptin / Q000097:blood; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000503:physiopathology*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D052242:Adiponectin; D004041:Dietary Fats; D020738:Leptin; D017392:Thiobarbituric Acid Reactive Substances; D051028:bcl-2-Associated X Protein; D003404:Creatinine; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3
J Am Soc Nephrol. 1998 Jun;9(6):1080-4
9621292
Hypertension. 2005 Oct;46(4):772-9
16172424
J Pharmacol Exp Ther. 2005 Oct;315(1):51-7
15951402
Am J Kidney Dis. 2001 Oct;38(4 Suppl 1):S4-7
11576913
Nephrol Dial Transplant. 2009 Aug;24(8):2328-38
19321762
Nephron Exp Nephrol. 2009;112(1):e31-42
19342872
Am J Obstet Gynecol. 1997 Dec;177(6):1315-20; discussion 1320-1
9423730
Am J Physiol Renal Physiol. 2009 Jul;297(1):F106-13
19420110
Am J Physiol Renal Physiol. 2007 Aug;293(2):F575-85
17537985
Am J Kidney Dis. 2002 Jul;40(1):104-9
12087567
Am J Physiol Cell Physiol. 2010 Sep;299(3):C638-42
20592243
Kidney Int. 1998 Aug;54(2):561-9
9690224
J Am Soc Nephrol. 1998 Dec;9(12 Suppl):S16-23
11443763
Nephrol Dial Transplant. 2002;17 Suppl 11:28-31
12386254
Kidney Int. 2004 Feb;65(2):597-605
14717930
Am J Physiol Renal Physiol. 2008 Feb;294(2):F336-44
18077597
Kidney Int. 2007 Jun;71(12):1195-7
17554349
Am J Physiol Renal Physiol. 2010 Mar;298(3):F662-71
20007347
Amino Acids. 2006 Nov;31(4):477-83
16554974
J Am Soc Nephrol. 2002 Jan;13(1):134-141
11752030
Ann Epidemiol. 2003 Feb;13(2):136-43
12559673
Clin Endocrinol (Oxf). 2005 Feb;62(2):242-9
15670203
Am J Kidney Dis. 1998 Jun;31(6):997-1006
9631845
J Nutr Biochem. 2010 Oct;21(10):999-1007
19954950
Kidney Int. 2005 Sep;68(3):1041-7
16105034
Cardiovasc Res. 2006 Jan;69(1):36-45
16324688
Endocr Rev. 2005 May;26(3):439-51
15897298
J Am Soc Nephrol. 2004 Feb;15(2):442-53
14747392
Kidney Int. 1999 Sep;56(3):1136-48
10469384
Am J Kidney Dis. 1990 May;15(5):458-82
2333868
Am J Physiol Renal Physiol. 2009 Jun;296(6):F1297-306
19357177
Kidney Int. 1999 Aug;56(2):440-51
10432382
Biochem J. 2001 Apr 15;355(Pt 2):289-96
11284714
Nephrol Dial Transplant. 2009 Dec;24(12):3626-31
19666662
Kidney Int. 2003 May;63(5):1964-76
12675893
Am J Nephrol. 2010;31(5):435-41
20389059
Am J Kidney Dis. 2005 Jun;45(6):1073-83
15957137
Nephron. 1982;31(2):103-10
7121651
Nat Clin Pract Nephrol. 2007 Jul;3(7):383-92
17592471
J Hypertens. 2005 Jan;23(1):87-96
15643129
Kidney Int. 1999 Apr;55(4):1560-7
10201023
Kidney Int. 2003 Mar;63(3):793-808
12631061
Nephrol Dial Transplant. 2001 Dec;16(12):2386-94
11733631
Am J Kidney Dis. 2003 Oct;42(4):761-73
14520627
Am J Physiol Renal Physiol. 2002 Nov;283(5):F1132-41
12372790