Angiotensin Converting Enzyme (ACE) inhibitors and Anogiotensin II Receptor Blockers (ARBs)S Ahmedpressure which contributes to their beneficial effect ofslowing the progression of kidney disease.2. ACEI& ARBs reduce proteinuria:Proteinuria is associated with faster progression ofkidney disease. In controlled trial in CKD, ACE /
Journal of Bangladesh College of Physicians and Surgeons Vol. 22, No. 3, <strong>September</strong> <strong>2004</strong>in patients with diabetes. ACEI have shown to delayrenal decline in patients with type I diabetes, whereasprotective effect with type II diabetes is less clear.The ARBs have shown to provide significant benefitswith type II diabetes, both early (microalbuminuria)and late (proteinuria) stages of renal decline. In theIrbesartan Diabetic Nephropathy Trial (IDNT) andthe reduction of end points in NIDDM with theangiotensin II antagonist losartan(RENNAL) study,ARB therapy significantly reduced the progression ofovert nephropathy (composite of doubling of serumcreatinine, ESRD and death) benefit that has not beenshown for ACE inhibitor.Addition of ARB with maximized ACE inhibitorProlonged angiotensin coverting enzyme ACEinhibitors therapy lead to angiotensin I accumulationwhich may escape ACE inhibition generateangiotensin II, stimulate angiotensin II subtype AT,receptor and exerts deleterious renal effects in patientwith chronic renal disease like vasoconstriction, saltretension, inflammation and fibrosis and enhance theactivity of central & peripheral sympathetic activity.Furthermore, pathway other than ACE may beresponsible for angiotensin II generation particularlyin tissues of blood vessels. ARBs can overcome theseshortcomings of ACEI by antagonizing the AT1receptors.In addition, because AT2 receptor mediate thebeneficial effects of angiotensin II, by blocking ATIreceptors with ARBs, angiotensin II would beavailable to stimulate the AT2 receptors 24 .Combination treatment with ACEI & ARBs safelyretards progression of non diabetic renal diseasecompared with monotherapy of each drug at itsmaximum dose 25 . The benefit of combination therapyof its antiproteinuric effect was different between1gA and diabetic nephropathy over the 12 weeks trial.24 hours urinary total protein excretion rate wassignificantly reduced by combination therapy inpatients with IgA nephropathy but no reduction withdiabetic nephropathy with combination therapy 26however, one study showed dual blockade of reninangiotensin system is superior to maximalrecommended dose of ACE inhibitions with regard tolowering of albuminuria and blood pressure in type Ipatients with diabetic nephropathy. Another studysuggests that combined antihypertensive therapy witheither a calcium channel blocker (CCB) plus an ARBor an ACEI plus ARB exerts an antiproteinuric effectin patients with type II diabetic nephropathy withmild renal impairment. ACEI and ARB combinationhad more profound effect, but it was associated withincrease in serum potassium concentration andworsening of renal anaemia. Thus, combination ofCCB and ARB should be first line forantihypertensive therapy in those overt type 2diabetic nephropathy 28 . To sumerise the combinationtherapy ACEI & ARBs showed benefical effect inboth non diabetic and type I diabetic nephropathypatients. In type II diabetic nephropathy ARB plusCCB combination is better option of combinationtreatment.Patient treated with ACE inhibitor & ARBsPatient treated with ACEI & ARBs should bemonitored for hypertension, decrease GFR andhyperkalaemia 15 . At initiation and increase in dose ofACE inhibition or ARB, the level of blood pressure,GFR and serum potassium should be measured toestablish a "baseline" or "new baseline". Transientabrupt decrease in blood pressure occur in about 2.5%of patients. Clinician should be cautious to lowersystolic blood pressure below 110 mm Hg. Causes ofhypotension in CKD are excessive dose ofantihypertensive agents, extracellular fluid depletion(diuretics), cardiovascular diseases (myocardialinfarction, heart failure, arrhythmia, valvular disease,pericarditis), neurological diseases, liver disease,haemorrhage & sepsis 15 .An early decrease in GFR is defined as a decrease inGFR by more than 15% from baseline within 4 weeksafter initiation of ACEI or ARB. The reportedincidence varies from 4% to 17% and most commoncauses are ECF volume depletion, excessive dose ofACEIs or ARBs and concomitant use of diuretics orNSAIDs 15 . If GFR decreases by more than 30% overbase line, the dose of ACEI or ARB may be reducedand GFR reassessed. If GFR does not return tobaseline within appropriate interval ACEI or ARBsshould be discontinued with alternativeantihypertensive agents. Hyperkalaemia is definedwhen single measurement of serum potassium > 5mEq/1, > 6 mEq/L, or persistant or single increase of108
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