开同专家会议

IntroductionCRFresultsinnumerousmetabolicdisorderswhichaccountforseverecomplicationsresponsibleformajormorbidityandmortalitycondition.PreventionofthesecomplicationsshouldbetheaimwhilemanagingCKDpatientsinordertoimproveausuallypooroutcome.第一页，共51页。PhysiopathologyofmetabolicdisordersinCRF°Accumulationofwasteproductsusuallyexcretedbythekidneys:-nitrogenouswasteproducts,H+ions,phosphate….°Iontransportabnormalities

°Decreasedhormoneproduction:-EPO,calcitriol°Decreasedhormoneclearance:-insulin,glucagon,leptin°Inflammation第二页，共51页。WhybeneficialeffectsonmetabolicdisorderscanbeexpectedfromSVLPD

SVLPDpermitstherestrictionoftheintakeoroftheproductionofnitrogenouswasteproducts,phosphate,inorganicionsandhydrogenions.SVLPDimprovesNa+K+ATPaseactivityinCRFpatientsLastly,itislikelythatSVLPDiseffectiveincorrectinginflammationassuggestedbyrecentnutritionalinterventionsusingaconventionalLPDorMediterranean-stylediet第三页，共51页。Caloricsupply

(kcal/kgbw/day)30-35%fromcarbohydrates67%fromlipids30%fromproteins

3Proteincontent

(g/kgbw/day)0.3-0.4(max.0.6)Phosphoruscontent

(mg/kgbw/day)5-7Supplementedwith:Calcium(g/day)VitaminD(IU/day)1,000Iron(mg/day)100mg/kgbw/day10-15DietarymanagementinCKDCompositionofaKetoAcidTherapyKA/AA(Ketosteril®)第四页，共51页。EffectsofSVLPDon

carbohydratemetabolismdisorders

第五页，共51页。InsulinresistanceinCKDpatients

OccursearlyinthecourseofCRFandispresentinmorethan50%ofCKDpatients.Isfavouredby:-accumulationofproteinwasteproducts-metabolicacidosis-inflammation-2ndHPT第六页，共51页。InsulinresistanceinCKDpatientseffectsoncarbohydratemetabolismInsulinresistance:-decreasedglucosestorage-decreasedglucoseoxidation-increasedendogenousglucoseproduction

-

decreasedmetabolicclearancerateofinsulin-elevatedfastingglucoseandinsulinlevels

第七页，共51页。Insulinresistancein

typeIIdiabetesandinCRFtypeIIdiabetesCRFglycemia+++insulinlevels++++glucosestorage----glucoseoxidation--EGP++++第八页，共51页。Invivoexploration

ofglucosemetabolism:thetoolsOralglucosetolerancetest:overallglucosemetabolismHyperinsulinemiceuglycemicclamp:insulinsensitivity,MCRofexogenousinsulinConcomitantuseofindirectcalorimetry:oxidativeandnonoxidativepathwayofglucoseIsotopicallylabeledglucose:endogenousglucoseproduction

第九页，共51页。PlasmaglucoseandInsulinafteroralglucoseloadbeforeandafter3monthsonSVLPDL.Bailletetcol.,Metabolism2001第十页，共51页。EvolutionoftheinsulinlevelandoftheamountglucoseinfusedduringtheeuglycemichyperinsulinclampinnondiabeticuremicpatientsbeforeandafterSVLPDAparicioM.etal.KidneyInt,1989第十一页，共51页。KetoAcidsTherapyimprovesthemetabolicclearancerateofinsulinandreduceshyperinsulinemiawhichisassociatedwithmultipleriskfactorsforatherosclerosis

GINH.etalAm.J.Clin.Nutr.1994

KetoAcidTherapyImprovementofinsulinclearancerate第十二页，共51页。SVLPDandsubstrateoxidationrate

RigalleauKidneyInt.1997

baselinemonth3glucoseoxidationmg/kg/min1.46+/-0.311.71+/-0.28lipidoxidationmg/kg/min0.79+/-0.081.02+/-0.01proteinoxidationmg/kg/min0.29+/-0.060.07+/-0.01energyproductioncal/kg/min15.72+/-0.4817.16+/-0.67第十三页，共51页。REEandSVLPDinuremiaRigalleauKidneyInt.1997第十四页，共51页。SVLPDandendogenousglucose

production(EGP)baselinemonth3insulinMCR(mL/min)803+/-2041149+/-284EGP(mg/kg/min)0.90+/-0.310.30+/-0.17第十五页，共51页。Insulinresistance:othereffects

IndependentCVriskfactor:-endothelialdysfunction(decreasedendothelialNOsynthesis),improvementinIRimprovesendothelialfunction-atherosclerosisProteinmetabolism:-increasedskeletalmuscleproteinbreakdown(UPP)Inflammation:-subclinicalinflammationispartofIRsyndrome第十六页，共51页。Copyright©2002AmericanSocietyofNephrologyShinohara,K.etal.JAmSocNephrol2002;13:1894-1900InsulinresistanceandoutcomeofESRDpatients第十七页，共51页。Mechanismsofimprovementof

insulinresistancebySVLPDDecreasedaccumulationofnitrogenouscompoundsactingasinhibitorsofglucoseutilization

ImprovementofmetabolicacidosisImprovementof2ndHPTDirectbeneficialeffectofproteinrestrictiononglucosemetabolismwhenproteincaloriesaremadeupbycarbohydratecalories第十八页，共51页。EffectsofSVLPDon

secondaryhyperparathyroidism第十九页，共51页。Factorsof2ndHPTHyperphosphatemiaDecreasedcalcitriolsynthesisNegativecalciumbalanceMetabolicacidosis第二十页，共51页。PCaHighphosphatelevelsLowcalciumlevelsPhosphate-CalciummetabolismdisordersinCKD第二十一页，共51页。Consequencesof2ndHPT

andhyperphosphatemiaOsteodystrophyCardiovascularcalcificationSofttissuecalcificationRefractoryanemiaInflammationIncreaseintherelativeriskofdeath第二十二页，共51页。*p<0.05Design:No.ofpatients:n=17(GFR20ml/min) Duration: 12months Diet: 0.3gprotein/kgbw/d+1tabl.Ketosteril®/5kgbw/d +1gCaCO3

+1,000IUvitaminD2LAFAGEetal.(1992):KidneyInt,42,1217-1225KetoAcidTherapyPhosphate-Calciummetabolismdisordersp<0.01*第二十三页，共51页。Parameters(mean+SD)NormalrangeBeforethedietAfter12monthsofdietCalcium(mmol/l)2.1-2.652.29±0.152.32±0.16Phosphate(mmol/l)0.8-1.451.54±0.421.30±0.28(a)Bicarbonate(mmol/l)24-3023.1±4.627.6±3(c)IntactPTH(µg/ml)10-60168±10183±68(b)Alk.Phophatase(IU/l)30-12088±4586±38Osteocalcin(µg/ml)3.7-6.940±2931±251-25OHVitaminD(pg/ml)12.-3215.3±6.817.5±6.9LAFAGEetal.(1992):KidneyInt,42,1217-1225Resultsareexpressedasmean+SD:(a)p<0.05;(b)p<0.01;(c)p<0.001KetoAcidTherapyPhosphate-Calciummetabolismdisorders第二十四页，共51页。第二十五页，共51页。Design:No.ofpatients:n=21 Creatinineserum:>6.5mg/dl Diet: VLPD(0.3g/kgbw/d)+AA/KA+2-4gCaCO3 Duration: 42monthsPTHlevelcanbereducedby49%duetothedietarytherapy.BARSOTTIetal.(1998):sHPTinsevereCRFiscorrectedbyvery-lowdietaryphosphateintakeandcalciumcarbonatesupplementation.Nephron,79,137-141*p<0.001*p<0.001KetoAcidTherapyPhosphate-Calciummetabolismdisorders第二十六页，共51页。KetoAcidTherapyPhosphate-Calciummetabolismdisorders第二十七页，共51页。Improvementinosteofibroticandosteomalacicchangesafter

12monthsoftreatmentwithaKetoAcidTherapy.

M.HLafageetal.KidneyInt.1992KetoAcidTherapyPhosphate-Calciummetabolismdisorders第二十八页，共51页。Evolutionofhistologicaldata

after12monthsonSVLPD

M.H.Lafageetal.KidneyInt.1992Mixedosteopathy(n=4):-mineralizationrate(u/d):0.32+/-0.15to0.67+/-0.02-osteoidthickness(u):13+/-2.5to8+/-2-BFR(u3/u2/d):0.005+/-0.006to0.044+/-0.02Osteitisfibrosa(n=9):-osteoblasticsurface(%):8.4+/-2.6to6+/-3.1-osteoclasticsurface(%):7.7+/-2.8to3.1+/-2.2-BFR(u3/u2/d):0.087+/-0.43to0.044+/-0.03第二十九页，共51页。第三十页，共51页。第三十一页，共51页。Mechanismsofimprovementof

2ndHPTbySVLPDReducedphosphateintake(1gprotein=13mgP)ImprovementofmetabolicacidosisCasaltsofketoacids:-increasedCaintake-actasphosphatebinders第三十二页，共51页。EffectsofSVLPDonmetabolicacidosis第三十三页，共51页。FixedacidproductionApproximately1mmolacid/kgbodyweightisgeneratingeverydaybyadultseatinga«

regulardiet

»Fish,meat,grainproductsandcheeseshaveahighpotentialrenalacidload.Incontrast,fruitsandvegetablessupplyalkali-ash第三十四页，共51页。MetabolicacidosisinCRFpathogenesisDecreasedabilitytoexcretenonvolatilacidsReducedrenalsynthesisofbicarbonate第三十五页，共51页。MetabolicacidosisinCRF

consequences-I-Nutritionalstatus:-increasedproteincatabolism-decreasedmuscleproteinandalbuminsynthesis-negativenitrogenandtotalbodyproteinbalanceBonemetabolism:-inhibitionofosteoblastandstimulationofosteoclastfunction-releaseofcalciumandphosphatetobufferH+ions第三十六页，共51页。第三十七页，共51页。第三十八页，共51页。MetabolicacidosisinCRF

consequences-II-InducesinsulinresistanceImpairstriglyceridesutilization第三十九页，共51页。PlasmabicarbonatelevelsanddeathrateinHDpatientsLowrie-LewAJKD1990

第四十页，共51页。KetoAcidTherapyCorrectionofmetabolicacidosis第四十一页，共51页。Correlationbetweenthechangesinbicarbonatelevelsandthechangesofthemineralappositionrate

M.H.LafageKidneyInt.1992

第四十二页，共51页。EffectsofSVLPDonlipiddisorders第四十三页，共51页。°HYPERTRIGLYCERIDAEMIA

(duetotheimpairmentoftriglyceridehydrolysis)°DYSLIPOPROTEINAEMIA-DecreaseinHDL-cholesterol

(mostimportantantiatherogenicfactor)-IncreaseofapolipoproteinCIII-DecreaseinapolipoproteinAI(integralpartofHDL)°

NEPHROTICSYNDROME

-IncreaseintotalandLDL-cholesterol1)BERNARDetal.(1996):MinerElectrolyteMetab,22,143-146;2)CIARDELLAetal.(1988):Nephron,42,196-199;3)ATTMANandALAUPOVIC(1991):Nephron,51,401-410LipidmetabolismdisordersinCKD第四十四页，共51页。Dyslipidemiamayhavearoleinthecardiovasculardiseasewhichisresponsibleof50%ofdeathsafterinitiatingmaintenancedialysistherapySeveralreportshavesuggestedthatdyslipidemiamightfavourtheprogressionofrenalfailureConsequencesoflipiddisordersinCRF第四十五页，共51页。Significantimprovementoftheserumlipidprofile

-Correctionofhypertriglyceridaemia(211+/-139vs.154+/-102mg/dl;p<0.05)Ciardellaetal.Nephron1986

-IncreaseinserumapolipoproteinAI(1.73+/-0.05vs.1.82+/-0.06g/l;p<0.025)Bernardetal.Miner.ElectrolyteMetab.1996-IncreaseinHDL-cholesterol(35.1+/-8.1vs.45.7+/-12.2mg/dl;p<0.005)AttmanandAlaupovicNephron1991

-Decrease

intotalcholesterol(5.9+/-1.4vs5.2+/-1.2mmol/L;p<0.01)KetoAcidTherapyOverallimprovementoflipidmetabolism第四十六页，共51页。Outcomeofproteinuriaaccordingtobaselinevalues

allpatientsn=781-3g/24hn=56>3g/24h