高血压英文PPT精品课件TherapeuticsinRenal.ppt

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1、Therapeutics in Renal Disease,Dr Michael ClarksonConsultant Renal Physician CUH,Chronic Kidney Disease,CommonEasy to DiagnoseEffective Therapies AvailableCKD Care Suboptimal,Serum Creatinine is a Poor Marker of GFR,MDRD eGFR,MDRD equation Complex log rhythmic equationIntegrates key variables,AgeSexC

2、reatinineRace,Urea Albumin,GFR is the accepted measure of kidney functionGFR is difficult to infer from serum creatinine aloneAutomatic reporting identifies CKD patients with apparently“normal”serum creatinineReduces barrier to early detection,MDRD eGFR,Three simple tests identify CKD in adults,Dips

3、tick Urinalysis Haematuria/MacroalbuminuriaUrine PCR-Urine protein to creatinine ratio on a“spot”urine sample24-hour urine collections are NOT neededeGFR-Estimated GFR from serum creatinine using the MDRD equation,Spot Ratios!,24 hour collections cumbersomeExcretion of creatinine and protein is reas

4、onably constant throughout the dayA random urine protein:creatinine ratio has been shown to correlate with a 24-hr estimation Expressed either as mg/mg(easy)or mg/mmol(multiply x 0.0088),Spot Ratios!,24yo lady with ankle oedema,proteinuria and hypercholesterolaemiaSpot urine protein 924mg/LSpot urin

5、e creatinine 3343mol/LRatio=276mg/mmol(normal:0-45)Convert to mg/mg(276 x 0.0088)=2.4g/24hr,Identifying CKD,BISH,BASH,BOSH,Staging of Chronic Kidney Disease,StageDescriptionGFREvaluation/Plan 0At risk 90Modify risk factors 1Kidney damage/90Diagnose/Treat cause.Slownormal GFRprogression and evaluate

6、CV risk.2Mild 60-89Estimate progression 3 Moderate30-59 Evaluate and treat complications 4Severe15-29 Prepare for RRT 5ESRD15Initiate RRT,NKF,USA,Factors Mediating Evolution of CKD,Susceptibility FactorsInitiation FactorsProgression Factors,Susceptibility Factors,Male gender HypertensionAge1ml/year

7、loss normallyGenetic BackgroundACE polymorphismsReduced Nephron Mass at Birth,Diabetic Nephropathy Glomerular Disease Tubulointerstitial Disease Hypertensive Nephrosclerosis,Initiation Factors,Progression Factors,Progressive loss of renal functionwill occur even inthe absence of overt activity of th

8、e primary renal disorder,Progression Factors,HypertensionGlomerular HypertensionProteinuriaHyperlipidemiaGenetic Factors MiscellaneousExacerbating Effect of Risk Factor Clustering,Maladaptive Response to Loss of Nephron Mass,Initial Renal Insult,Loss of Nephron Mass,Compensatory Glomerular Hypertrop

9、hy/Hyperfiltration,Maximisation of GFR Intraglomerular Hypertension,Podocyte Injury/MesangialMatrix Expansion,Secondary FSGS Proteinuria/Hypertension,Hypertension and CKD,Role of Hypertension in CKD Progression,50-75%of patients with CKD have BP 140/90mmHgGoals of therapy Retard CKD progressionReduc

10、e overall cardiovascular risk,Role of Hypertension in CKD Progression,Strong association with poor renal outcomes esp.in diabetic nephropathyMicroalbuminuria progressionMorphologic injuryPredicts loss of renal function in non-diabetic glomerular disorders and in APKD.Confounding effect of proteinuri

11、a make accurate assessment of independent effect difficult,Hypertension and CKD,Target Blood Pressure,Relationship between BP Control and Rate of Decline in GFR,Bakris et al AJKD,2000.,Decline in GFR and HTN:Stratification for Proteinuria,MDRD Study:Arch Int Med,1995,Effective Control of Hypertensio

12、n in CKD:Multiple Agents Required,Bakris et alAJKD,2000,Effective Control of Hypertension Yields Major Benefit in CKD,Early treatment can make a difference,100,10,0,No TreatmentDelayedTreatmentEarly Treatment,4,7,9,14,Kidney Failure,GFR(mL/min/1.732),2,83,Blood Pressure Goals in CKD,Stratify Accordi

13、ng to ProteinuriaProteinuria 3gGoal 125/75Optimal Blood Pressure UnknownDiuretics Essential120/80?,Proteinuria and CKD,Microalbuminuria and Macroalbuminuria,MicroalbuminuriaMacroalbuminuriaDefinition30-299mg/day300mg/dayRoutine DipstickNegativePositiveRenal SignificanceRisk MarkerMarker of progressi

14、onCardiovascular RiskIncreasedIncreased,Maladaptive Response to Loss of Nephron Mass,Initial Renal Insult,Loss of Nephron Mass,Compensatory Glomerular Hypertrophy/Hyperfiltration,Maximisation of GFR Intraglomerular Hypertension,Podocyte Injury/MesangialMatrix Expansion,Secondary FSGS Proteinuria/Hyp

15、ertension,Proteinuria and CKD,Proteinuria evaluation mandatory in all patients with CKDIndependent risk factor for CKD progressionBest predictor of ESRD,Adverse Consequences of Proteinuria vs low eGFR,Hemmelgarn et al.JAMA.2010;303(5):423-429.,Proteinuria In CKD,Intervention StudiesPharmacologic App

16、roaches Dietary Approaches,Reduction in proteinuria,Reduction in proteinuria is key to successful renoprotective strategy.Anti-hypertensive regimens with better reduction in proteinuria afford greater renoprotective benefits.Benefit persists even when BP within the normal range.,Proteinuria and CKD,

17、Pharmacologic Approaches,ACE-I Decrease Proteinuria More than Conventional Anti-Hypertensive Therapy,Jafar et al,Meta AnalysisAnn Int Med2001,RAAS Blockade in CKD-Mechanism of Action,Reduction in intraglomerular hypertensionEfferent arteriolar vasodilatationImproved glomerular permselectivityAttenua

18、tion of AII-stimulated growth factor and inflammatory cytokine secretionPrevention of extracellular matrix accumulation,Afferent,Efferent,VasodilatorsProstaglandinsNitric Oxide,VasoconstrictorsEndothelinCatecholaminesAdenosine,VasoconstrictorsAngiotensin-II,Afferent,Efferent,PGc,HyperfiltrationMecha

19、nical Strain2 FSGS,Efferent,PGc,BP,Lower GFRReduction in Proteinuria,Angiotensin Recptor BlockadeMore Risk,More Benefit!,Initiation of ACE-I or ARB,“Although ACE inhibitors now have a specialised role in some forms of renal disease they also occasionally cause impairment of renal function which may

20、progress and become severe in other circumstances”BNF,Initiation of ACE-I or ARB,Case Example42 year old ladyHypertensionRecurrent UTIAtrophic left kidneyPre-eclampsia x 2BP=155/95 MAP=115SeCr=145umol/L.MDRD GFR=50ml/minUrine Protein to Creatinine ratio:1.4,Initiation of ACE-I or ARB,Initiated on Ra

21、mipril 5mg qd+low salt diet Day 7.BP=145/90 Ramipril increased to 10mg qd Day 14 BP 140/85 Repeat Creatinine=175umol/L,K+5.4mmol/L Estimated GFR=42mls/min,Initiation of ACE-I or ARB,Clinical Dilemma Substantial fall in GFR following RAAS blockadeHyperkalaemiaDo not suspect renovascular disease Withd

22、raw ACE-I/ARB?,Initiation of RAAS Blockade:Initial reduction in GFR predicts better outcome,Aperloo et al,Kid Int,1997,Initiation of ACEi/ARB,100,10,0,4,7,9,14,Kidney Failure,GFR(mL/min/1.732),2,83,Initiation of ACE-I or ARB,Continue RAAS Blockade.Accept 25%fall in GFR.Ensure it is not progressive.G

23、oal 130/80Review MedicationsDietary K+Restriction Diuretic Add second agentDiureticNon-dihydroperidine CCBBeta Blocker,Goal Proteinuria,Independent Risk MarkerTherefore Needs Independent Therapeutic Goal Irrespective of BP Control Proteinuria Dose Response to RAAS Blockade May Not Parallell That of

24、BP,Goal Proteinuria,300mg/24hours or Ratio of 0.3RAAS BlockadeBP Control Protein Restriction,Case Example,56year old Bachelor FarmerType II DMM x 2 yearsRetinopathyProteinuriaLiving aloneHigh salt intakeReferred for management of rising serum creatinine,Case Example,MedicationsBasal Bolus InsulinAml

25、odipine 10mg daily24 hour urinary sodium 160mmol/L,Case Example,Relationship between BP Control and Rate of Decline in GFR,Bakris et al AJKD,2000.,Interventions:Tight salt restriction(100mmol/5g)No added saltNo salt in cookingMinimise pre-prepared foodRamipril 5mg40/3mmHg BP drop,Case example,Case E

26、xample,Nephrology Referral,Case Example,Giving up the salt made an awful differenceSalt is a poison!By the way,Dr Horgan tells me my eyes are way better,Case example,Summary,In proteinuric CKDACE-inhibition+5g salt restrictionDiuretic(thiazide or loop eGFR)Non-dihydropyridine CCBOthersGoal 130/80mmHg at leastARB in Type II DM or if ACEi cough,Summary,In non-proteinuric CKD5g salt restrictionACE-i not mandatoryDiuretic(thiazide or loop eGFR)Non-dihydropyridine CCBOthersGoal 130/80mmHg?Beware ARVD,Questions?,