Drug Topics - January 14, 2008 - (Page 34) 34 DRUG TOPICS JANUARY 14, 2008 www.drugtopics.com CONTINUING EDUCATION ally asymptomatic. Target organ damage (eyes, heart, kidney, etc.) occurs when blood pressure is elevated, or uncontrolled, for long periods of time. Target organ damage can occur throughout the body with complications such as left ventricular failure, MI, cerebral hemorrhage, renal failure, or damage to the retina of the eye. The practitioner should be trained to recognize the symptoms subjectively such as chest pains, unilateral weakness, headaches, and blurred vision. Hypertension is diagnosed using the ausculatory method, which includes the use of a sphygmomanometer. Elevated blood pressure readings >140/90mmHg on two separate office visits are required for diagnosis of hypertension. Normal blood pressure is a systolic blood pressure (SBP) <120mmHg and diastolic blood pressure (DBP) 160mmHG or DBP >100mmHg. When determining BP, the practitioner must consider many variables that may cause transient elevation of BP. The patient must have been sitting relaxed for at least five minutes with feet flat on the floor and should not have consumed any caffeine, nicotine, alcohol, or have exercised within 30 minutes of the BP check. In the event of white coat hypertension, the patient should receive ambulatory blood pressure monitoring to obtain an accurate diagnosis of hypertension. Persistent proteinuria is considered to be the principal marker for kidney damage, so monitoring proteins in the urine helps to monitor progression and severity of CKD. It is recommended to test for proteinuria in patients with hypertension, known vascular disease, diabetes, and family history of chronic kidney disease. As previously mentioned, there are three types of presentation, which include glomerular, tubular, and overflow. The tubular type cannot be diagnosed with the urine dipstick because the size and the amount of the proteins are too small. For the purposes of monitoring proteins in cardiovascular disease, glomerular proteinuria is the main focus because it deals with macromolecules. Proteinuria should be assessed as a measure of albumin because it is the most sensitive marker for CKD due to hypertension, diabetes, and glomerular diseases. Albumin can be detected in the urine with the use of a dipstick. The urine dipstick analysis allows a qualitative assessment for the presence of proteins in the urine. This test has high specificity and low sensitivity, meaning that there are few false positive results. However, the urine dipstick may not be sensitive enough to detect CKD in the early stages. The dipstick is impregnated with a dye that detects proteins with color changes on the strip. The color yellow indicates there is not a detectable amount of proteins in the urine (negative). A green color on the strip indicates that proteins are present in the urine and is graded as follows: trace (15-30mg/dl), 1+ (30-100mg/dl), 2+ (100300mg/dl), 3+ (300-1000mg/dl), 4+ (>1000mg/dl). Standard dipstick analysis can detect the presence of proteins in quantities greater than 10-20 mg/dl. Average albumin excretion for adults is usually less than 10mg/dl. Upon obtaining a positive result with the dipstick analysis of 1+ or greater, a quantitative analysis should be done within three months. According to the CARI guidelines, the current gold standard for quantitative analysis is the 24-hour urine collection. But the 24-hour collection has become the least desirable method due to different amounts of patient activity throughout the day, poor collection technique, improper timing, and missed samples. An overnight timed collection can be done, instead of the 24-hour collection, but this also can become inconsistent due to poor collection technique. A more widely accepted method is collecting a protein:creatinine ratio or albumin:creatinine ratio via random spot collection. The albumin:creatinine ratio is superior to protein:creatinine ratio in that albuminuria is a more sensitive marker than proteinuria for CKD caused by hypertension, diabetes, and glomerular diseases. Obtaining a result of < 30mg/g albumin:creatinine is considered normal, 30-299mg/g albumin:creatinine is microalbuminuria, and ≥ 300mg/g albumin:creatinine is albuminuria. Current pharmacologic therapy Drug therapy for hypertension complicated with proteinuria targets lowering blood pressure and preserving renal function. In a patient with hypertension and proteinuria, controlling blood pressure mitigates the effect of proteinuria. Reducing proteinuria has shown to reduce the progression of renal disease. Pharmacologic agents that act at the RAAS in particular have consistently shown to be the most effective antiproteinuric agents and are effective for preserving renal function in diabetic and non-diabetic patients. The benefit provided by these antihypertensive agents is independent from BP lowering. Other agents exhibit their antiproteinuric effect by decreasing BP alone. The antihypertensive agents that will be discussed are angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), diuretics, non-dihydropyridine calcium channel blockers, and beta-blockers (cardioselective or with alpha blocking activity). Individual agents may be seen in Table 1. Some agents such as direct vasodilators of dihydropyridine calcium channel blockers do not provide any benefit on hypertension with proteinuria, and are not recommended over the agents listed above. Angiotensin converting enzyme inhibitors (ACEIs) ACEIs are the standard antihypertensives to reduce proteinuria and blood pressure, as well as preserve kidney function. Other compelling indications for the use of ACEIs are congestive heart failure (CHF), status post myocardial infarction (MI), or cerebrovascular disease (CVA). The beneficial effect ACEI therapy has on the kidney function is greater with higher levels of proteinuria. ACEIs reduce proteinuria by slowing down the rise of albumin excretion. These drugs are beneficial in delaying progression to microalbuminuria as well as from microalbuminuria to macroalbuminuria in diabetic nephropathy or non-diabetic kidney disease. The antiproteinuric effect of ACEI therapy is drug specific, dependent on sodium restriction, and independent of blood pressure levels. ACEIs block the conversion of angiotensin I to angiotensin II. Angiotensin II, as mentioned earlier, is a potent vasoconstrictor and stimulates the release of aldosterone, which causes sodium and water retention. These drugs also block the degradation of bradykinin via ACE inhibition. Bradykinin promotes vasodilation of the blood vessels and natriuresis in the kidneys. Excessive amounts of angiotensin II will lead to http://www.drugtopics.com
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