2 Introduction loss of nephrons Renal disease Systemic hypertension ProteinuriaProgressivedeclinein GFR
3 CKD: Common pathway in disease progression RENAL INJURYNephron massGlomerular capillary hypertensionGlomerular permeability to macromoleculesFiltration of plasma proteins ProteinuriaExcessive tubular protein reabsorbtionTubulo-interstitial inflammationSYSTEMICHYPERTENSIONRENAL SCARRING
4 CKD: Common pathway in disease progression Therapeutic intervention inhibiting this common pathway may succeed in slowing the rate of progression of CRF irrespective of the initiating cause
5 How important is systemic blood pressure control? Relative risk of ESRD according to quintile BPMRFIT studyN= 332,544 men
6 What should be the treatment goal? Treatment goal for hypertension in the general population has remained relatively the same for the last decade.GuidelinesBP targetBritish Hypertension Society (2004)< 140/85Malaysian Hypertension Society<140/90JNC VII (2003)
7 What should be the treatment goal for renal disease?Should be lower than the general populationShould be tailored according to :the severity of renal failurethe severity of the proteinuria
8 Proteinuria and target BP control Aggressive BP control to 125/75 mmHg showed better preservation of GFR for those with proteinuria >3g/day.No additional benefit if proteinuria is < 1g/dayKlahr S, Levey AS: NEJM 1994; 330:877
9 What should be the treatment goal for renal disease?GuidelinesTarget BPBritish Hypertension Society (2004)<130/80Malaysian Hypertension SocietyJNC VII (2003)
10 What should be the treatment goal for non diabetic renal disease? Treatment goal should depend on the severity of proteinuriaProteinuria (g/d)BP target (mm Hg)>1125/75<1130/80
11 ProteinuriaThere is indisputable evidence from animal, laboratory and clinical studies that proteinuria per se contributes to progressive renal injury
13 Proteinuria and renal disease progression REIN SUBSTUDY : Progression of renal diseaseaccording to severity of proteinuria
14 Proteinuria and renal disease progression It is now clear that different classes of antihypertensive agents have different antiproteinuric capacityACEI and ARB have been showed to exhibit the highest capacity to diminish protein excretion in urine
15 ACE Inhibitors In Nephropathy REIN Study : KIDNEY SURVIVAL
17 ACEI, ARB and combination treatment in Nephropathy COOPERATE STUDY: Median urinary protein excretion
18 ACEI, ARB and combination treatment in Nephropathy COOPERATE STUDY: proportion reaching endpoints
19 Choice of antihypertensive agent for non diabetic renal disease ACEI or ARB should be the first choice antihypertensive agent in patient with significant proteinuria.
20 Choice of antihypertensive agent for non diabetic renal disease Dose of ACEI or ARB should be titrated to achieve both target BP and the disappearance of proteinuria
21 Choice of antihypertensive agent for non diabetic renal disease If target blood pressure is not achieved and especially in the presence of persistent proteinuria, an ARB should be added.
22 Precautions when starting ACEI or ARB Check Cr and K+ within 7-14 days after starting treatment especially in the presence of renal impairmentAn acute rise in Cr of 30% should be tolerated if BP is adequately reduced (<140/90), hyperkalaemia is absent and the patient is euvolaemicIf Cr continues to rise, or hyperkalaemia persist, stop drugs; assess for bilateral RAS
23 Choice of antihypertensive agent for non diabetic renal disease Choice of combination antihypertensive agents depend on the existing comorbidity
24 Drug(s) for the compelling indication DiureticB-blockerACE IARBCCBAldosterone antagonistHeart failurePost-myocardial infarctionHigh coronary riskDiabetesChronic Kidney DiseaseRecurrent stroke prevention
25 Choice of Anti-Hypertensive drugs in patient with concomitant disease DiureticsB-blockersACEICa channel blockerAlpha- blockerARBDiabetesCarefulcarefulyesGoutNoYesYes/noHyperlipidaemiaIHDHeart FailureAsthmaPVDRenal ImpairmentRenal A StenosisElderly with no co morbid cond.
26 Choice of antihypertensive agent for non diabetic renal disease Since studies have demonstrated that most hypertensive patients will require multiple drugs to achieve target BP, the argument about which one is superior has become almost irrelevantWe must provide all of the drugs needed to achieve maximal protection with the fewest adverse effects
27 Summary Control Blood Pressure Proteinuria (g/d) BP target (mm Hg) >1125/75<1130/80