the abcs of micronutrients in dialysis patients
TRANSCRIPT
![Page 1: The ABCs of Micronutrients in Dialysis Patients](https://reader036.vdocuments.net/reader036/viewer/2022082719/5750763f1a28abdd2e9d9f0f/html5/thumbnails/1.jpg)
M(ppbtmrtlibta
rdicocepdhtcnMbhcadi
msmctanctvn
A
The ABCs of Micronutrients in Dialysis Patients
mlcmDasCaniatlwi
atomprtTdhilt(taRhsmpplrti
KW
Related Article, p. 513
uch attention has rightly been focused onproviding adequate protein and calories
macronutrients) to dialysis patients in an effort torevent development of malnutrition. A state ofrotein-energy wasting (PEW) can be diagnosedy low circulating levels of albumin and/or choles-erol, in conjunction with reduced total body anduscle mass.1 In most cases, the diagnosis of PEW
epresents a complex readout on several concomi-ant biological processes that include hypercatabo-ism, poor protein and calorie intake, and activenflammation. Study of the PEW syndrome haseen emphasized in dialysis patients due to associa-ion with higher rates of morbidity and mortality,long with diminished quality of life.
Comparatively less attention has been paid inecent years to the possibility that micronutrienteficiencies can also contribute to poor outcomesn dialysis patients. Yet micronutrients, such asoenzyme Q10, L-carnitine, taurine, and a varietyf water- and fat-soluble vitamins, are essentialofactors that provide the necessary cellular machin-ry for energy transfer and the maintenance ofhysiological energy homeostasis. Micronutrienteficiency may be particularly important in theuman heart.2 Described as a metabolic omnivore,3
he heart must constantly convert a huge amount ofhemical energy into mechanical energy, and thuseeds a steady stream of nutrients to function well.oreover, provision of adequate micronutrients may
e especially important in the setting of the failingeart, in order to prevent myocyte death and restoreompromised function. Micronutrient deficiency islso emerging as a potential contributor to cognitiveysfunction, also a commonly observed complicationn patients with advanced kidney disease.4
The general teaching regarding vitamin supple-entation in hemodialysis patients is that water-
oluble vitamins (such as the B vitamins and vita-in C [ascorbate]) are dialyzed and blood
oncentrations tend to be low without supplementa-ion, while fat-soluble vitamins such as vitamin Are not dialyzed and blood levels are usually eitherormal or elevated without supplementation.5 As aonsequence, several studies have focused atten-ion on supplementation with either B vitamins oritamin C in dialysis patients. The primary ratio-
ale for investigating aggressive B vitamin supple-merican Journal of Kidney Diseases, Vol 56, No 3 (September),
entation has been to exploit their homocysteine-owering properties, in an effort to reduceardiovascular risk. Unfortunately, the HOST (Ho-ocysteinemia in Kidney and End-stage Renalisease) trial, which compared the use of folic
cid, vitamin B6, and vitamin B12 to placebo,upported the null hypothesis.6 Studies of vitamin, an important antioxidant, have focused on allevi-ting the increased oxidative stress that accompa-ies kidney disease, and on increasing iron availabil-ty to promote erythropoeisis and treat refractorynemia.7 While pilot studies have been promising,he use of aggressive vitamin C supplementation isimited by accumulation of the metabolite oxalate,hich may lead to calcium oxalate supersaturation
n blood vessels of uremic patients.8
The potential for toxicity of vitaminAhas gener-lly precluded its use in kidney failure. However,he antioxidant potential of retinol, the active formf vitamin A, requires a review of this topic anday warrant closer examination in hemodialysis
atients. Plasma concentration of retinol has beeneported to be elevated in both adults and childrenreated by hemodialysis and peritoneal dialysis.9-13
he dialysis procedure is not associated with anyecrease in plasma retinol concentration and thereas been concern about risk for vitamin A toxicityn dialysis patients. Retinol is synthesized and re-eased from the liver and circulates in blood boundo retinol binding protein (RBP) and transthyretinTTR).14 The binding with carrier proteins ensureshe appropriate delivery and availability of retinolt the tissue level. When complexed with retinol,BP and TTR are not filtered by the glomeruli;owever, after the tissue delivery of retinol, themaller size of noncomplexed RBP allows for glo-erular filtration followed by absorption in the
roximal tubules through the megalin-cubulin com-lex. Eventually, retinol is catabolized by the tubu-ar epithelia.15 Thus, kidney function plays a vitalole in vitamin A metabolism, and in kidney failurehe plasma concentration of both retinol and RBPncreases, paralleling the rise in creatinine concen-
Address correspondence to Jonathan Himmelfarb, MD,idney Research Institute, 325 9th Ave, Box 359606, Seattle,A 98104-2499. E-mail:[email protected].© 2010 by the National Kidney Foundation, Inc.0272-6386/10/5603-0003$36.00/0
doi:10.1053/j.ajkd.2010.07.0042010: pp 431-433 431
![Page 2: The ABCs of Micronutrients in Dialysis Patients](https://reader036.vdocuments.net/reader036/viewer/2022082719/5750763f1a28abdd2e9d9f0f/html5/thumbnails/2.jpg)
ttrrs
otssfaacrvipsretpe
tcHisa
wiedprIspr(vtm
i
c ked tob ), hypo
Ahmad and Himmelfarb432
ration.11 In addition to reduced glomerular filtra-ion, impaired activity of enzymatic conversion ofetinol to retinoic acid in kidney failure has beeneported, which may also contribute to the ob-erved elevation of plasma retinol levels.16,17
The article in this issue of the American Journalf Kidney Diseases by Kalousová et al18 evaluatedhe role of retinol, RBP, �-tocopherol, zinc, andelenium on mortality in 261 prevalent hemodialy-is patients. Similar to previous reports, the studyound elevated plasma concentrations of retinolnd RBP. However Kalousová et al made the novelnd surprising observation that lower plasma con-entrations of retinol (and a lower retinol to RBPatio) were strong predictors of overall and cardio-ascular mortality. That a lower retinol to RBP ratios a predictor of poor outcome has not been re-orted before. These data can be interpreted asuggesting that there is a lower bioavailability ofetinol at the cellular and tissue level, despite el-vated plasma concentration. This is analogous tohe carnitine “insufficiency” described in dialysisatients with lower free to acyl-carnitine ratio (or
Figure 1. Cellular oxidation pathways and antioxidaarotenoids (CAR), ROO represents either an alkyl chain linut could equally be a radical formed from a hydroxyl (OH�
levated acyl to free carnitine ratio). It is interesting v
hat Abahusain and Al-Nahedh19 reported an in-reased retinol to RBP ratio in patients on dialysis.owever, these authors also observed that the ratio
ncreased with time, suggesting that ongoing dialy-is is not associated with progressive reduction invailability of retinol.
Retinol is derived from dietary carotenoids,hich are important constituents of cell membrane,
nfluence DNAstructure, and have antioxidant prop-rties. Increased oxidative stress has been wellocumented in dialysis patients20,21 and it maylay an important role in increased cardiovascularisk, the leading cause of death in this population.n vitro tests under appropriate conditions havehown that carotenoids have important antioxidantroperties, and can neutralize superoxides or, throughedox activity, act on other free radical compoundsFig 1). However the efficacy of these compounds inivo is far from clear, particularly since their concen-ration in human tissue is much lower and conditionsay differ substantially from in vitro experiments.Retinol is a known antioxidant, although its role
n humans does not appear to be as strong as that of
the equations listing the antioxidant activities of thea peroxyl radical (ie, -C-O-O.) or an alkoxyl radical (-C-O.),chlorite (OCl�), or toxic nitrogen derivative (NOO�).
nts. In
itamin E and vitamin C.22 In 1 trial, supplemen-
![Page 3: The ABCs of Micronutrients in Dialysis Patients](https://reader036.vdocuments.net/reader036/viewer/2022082719/5750763f1a28abdd2e9d9f0f/html5/thumbnails/3.jpg)
tdavnhonpnilso
Khlakrk
n
peI
dC
b1
o
IP
har
aa
tcA
a1
ti
Mts
s
lrd
r
efi
cN
SK
rlt
ssJ
ia
sa
rip
afi
r
Editorial 433
ary vitamin A and other nutrients in malnourishedialysis patients had a positive effect on serumlbumin levels.23 Trials using supplements in indi-iduals without kidney failure have either showno effect of vitamin A or even some potentialarmful effects, including activation of proto-ncogenes, with an associated increase in risk ofeoplasia. Similarly, the data on the markers of lipideroxidation, malondialdehyde (MDA), aminolevuli-ate dehydratase (ALA-D), and retinol concentrationsn 29 hemodialysis patients revealed a positive corre-ation between retinol and MDA,24 findings whichuggest that retinol may paradoxically have pro-xidant properties in some circumstances.
Like other such studies, the article fromalousová et al has raised more questions than itas answered. What is clear is that there is a generalack of available data regarding whether vitamin And many other micronutrients are friend or foe inidney failure. When it comes to understanding theole of micronutrient deficiencies in patients withidney disease, we need to go back to the ABCs.
Suhail Ahmad, MDJonathan Himmelfarb, MD
University of WashingtonSeattle, Washington
ACKNOWLEDGEMENTSFinancial Disclosure: The authors declare that they have
o relevant financial interests.
REFERENCES1. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A
roposed nomenclature and diagnostic criteria for protein-nergy wasting in acute and chronic kidney disease. Kidneynt. 2008;73(4):391-398.
2. Soukoulis V, Dihu JB, Sole M, et al. Micronutrienteficiencies: an unmet need in heart failure. J Am Collardiol. 2009;54(18):1660-1673.3. Taegetmeyer H. Energy metabolism of the heart: from
asic concepts to clinical applications. Curr Probl Cardiol.994;19(2):59-113.4. Gómez-Pinilla F. Brain foods: the effects of nutrients
n brain function. Nat Rev Neurosci. 2008;9(7):568-578.5. Kopple JD. Trace elements and vitamins. In: Mitch WE,
kizler TA, eds, Handbook of Nutrition and the Kidney, 6th edition.hiladelphia, PA: Lippincott Williams & Wilkins; 2010:163-176.6. Jamison RL, Hartigan P, Kaufman JS, et al. Effect of
omocysteine lowering on mortality and vascular disease indvanced chronic kidney disease and end-stage renal disease: a
andomized controlled trial. JAMA. 2007;298(1):1163-1170. p7. Deved V, Poyah P, James MT, et al. Ascorbic acid fornemia management in hemodialysis patients: a systematic reviewnd meta-analysis. Am J Kidney Dis. 2009;54(6):1089-1097.
8. Canavese C, Petrarulo M, Massarenti P, et al. Long-erm, low-dose, intravenous vitamin C leads to plasmaalcium oxalate supersaturation in hemodialysis patients.m J Kidney Dis. 2005;45(3):540-549.9. Zima T, Janebová M, Nemecek K, Bártová V. Retinol
nd alpha-tocopherol in hemodialysis patients. Ren Fail.998;20(3):505-512.10. Smith FR, Goodman DS. The effects of diseases of
he liver, thyroid, and kidneys on the transport of vitamin An human plasma. J Clin Invest. 1971;50(11):2426-2436.
11. Rock CL, Jahnke MG, Gorenflo DW, Swartz RD,essana JM. Racial group differences in plasma concentra-
ions of antioxidant vitamins and carotenoids in hemodialy-is patients. Am J Clin Nutr. 1997;65(3):844-850.
12. Ono K. HypervitaminosisAtoxicity in regular hemodialy-is patients. Trans Am Soc Artif Intern Organs. 1984;30:40-43.
13. Vannucchi MT, Vannuchi H, Humphreys M. Serumevels of vitamin A and retinol binding protein in chronicenal patients treated by continuous ambulatorial peritonealialysis. Int J Vitam Nutr Res. 1992;62(2):107-112.14. Britton G. Structure and properties of carotenoids in
elation to function. FASEB J. 1995;9(15):1551-1558.15. Jaconi S, Rose K, Hughes GJ, Saurat JH, Siegenthal-
rl G. Characterization of two post-translationally processedorms of human serum retinol-binding protein: altered ratiosn chronic renal failure. J Lipid Res. 1995;36(6):1247-1252.
16. Ono K, Waki Y, Takeda K. Hypervitaminosis A: aontributing factor to anemia in regular dialysis patients.ephron. 1984;38(1):44-47.17. Fishbane S, Frei GL, Finger M, Dressler R, Silbiger
. Hypervitaminosis A in two hemodialysis patients. Am Jidney Dis. 1995;25(2):346-349.18. Kalousová M, Kubena AA, Koštírová M, et al. Lower
etinol levels as an independent predictor of mortality inong-term hemodialysis patients: a prospective observa-ional cohort study. Am J Kidney Dis. 2010;56(3):513-521.
19. Abahusain MA, Al-Nahedh NN. The biochemicaltatus of vitamin A and alpha-tocopherol during differenttages of renal disease and its relationship to diabetes. SaudiKidney Dis Transpl. 2002;13(1):18-23.20. Descamps-Latscha B, Drüeke T, Witko-Sarsat V. Dialysis-
nduced oxidative stress: biological aspects, clinical consequences,nd therapy. Semin Dial. 2001;14(3):193-199.
21. Sawant JM, Nair A, Redkar NN. Oxidative stress anderum paraoxonase activity in patients on maintenance hemodi-lysis. Internet J Nephrol. April 1 2010;6/1(0-13):15402665.
22. Komindr S, Puchaiwatananon O,Thirawitayakom J, Dom-ongkitchaiporn S, Songchitsomboon S. Effects of dietary counsel-ng on vitaminA, B-1, B-2 and zinc status of chronic hemodialysisatients. J Med Assoc Thai. 1997;80(11):724-730.
23. Kalantar-Zadeh K, Braglia A, Chow J, et al. Annti-inflammatory and antioxidant nutritional supplementor hypoalbuminemic hemodialysis patients: a pilot/feasibil-ty study. J Ren Nutr. 2005;15(3):318-331.
24. Roehrs M, Valentini J, Bulcão R, et al. The plasmaetinol levels as pro-oxidant/oxidant agents in hemodialysis
atients. Nephrol Dial Transplant. 2009;24(7):2212-2218.