exercise, postural changes, volume depletion, or acute illnesses should be reevaluated during stable conditions. The typical annual rates of progression of DKD from the diagnosis of DM to microalbuminuria, macroalbuminuria, and then to advanced CKD or ESRD are 2.0%, 2.8%, and 2.3%, respectively. DM and microalbuminuria represent independent risk factors for CVD. In addition, nearly 70–80% of diabetic CKD patients are hypertensive. Thus, routine screening for DKD is recommended for diabetic patients as follows: a) annual testing of urinary albumin excretion by “spot” UACR and eGFR in type 1 diabetic patients with 5 yr duration of DM and b) annual testing of all type 2 diabetic patients from the time of diagnosis. Because several factors may cause transient increases in microalbuminuria, the diagnosis requires at least 2 serial first-morning urine specimens over 2–3 weeks. Occasionally, proteinuria in DM may herald other possible causes of CKD, particularly glomerular disorders as described above. Suspect other causes when one or more of the following is present: a) absence of diabetic retinopathy or neuropathy b) presence of low or rapidly decreasing GFR c) presence of rapidly increasing proteinuria or nephrotic syndrome d) refractory hypertension e) active (blood and protein) urinary sediment f) manifestations of other systemic disease g) presence of >30% reduction in GFR within 2–3 months of the initiation of anti-renin–angiotensin–aldosterone system (RAAS) therapy. The rate of improvement in renal function following this initial expected physiologic decline in eGFR will depend on several patient-related factors, such as disease severity and ethnicity. For example, African Americans typically display earlier and more rapid declines in renal function. The presence of one or more of these clinical scenarios should prompt urgent patient referral to a nephrologist for confirmatory and/or additional diagnoses. Clinical remission of renal disease has taken place when proteinuria declines to 1 or UACRs are >300 mg/g. African Americans also tend to respond less well than Caucasian patients to monotherapy with beta blockers (BBs), ACEIs (angiotensin-converting–enzyme inhibitors) and/or ARBs (angiotensin–receptor blockers). However, ethnicity-related differences in therapeutic response are usually nullified by concomitant diuretic therapy. For example, the response to combined thiazide diuretic-ACEI/ARB therapy is equivalent among the various ethnicities. Therefore, no particular agent should be avoided in patients of African American ethnicity. Since non-diabetic CKD patients have equivalent or greater risk for the development of CVD as diabetic patients without CKD, cardiovascular protective measures in addition to antihypertensive therapy must always be considered. Since a given individual’s BP response to high sodium intake (salt sensitivity) is not predictable, sodium restriction should generally be enforced in all CKD patients, ie, 55 mmHg). Either the SBP or pulse pressure may be increased in hypervolemic/edematous individuals who must often be treated with diuretics. Proteinuria Evaluation for and quantitation of albuminuria/proteinuria is recommended when there is a family history of CKD or the eGFR is 1–2 g/d proteinuria, the risk for progressive CKD rises steeply after SBP 130 mmHg. All of the antirenin–angiotensin–aldosterone system (anti-RAAS) agents are anti-fibrogenic, including aldosterone receptor antagonists (ARAs). Patients with a SBP of 115–130 mmHg and proteinuria 1 g/d, a SBP of 120–130 mmHg is recommended. Overall, HTN control in CKD patients is suboptimal with less than one-half of patients achieving target BP levels. In the majority of such cases, the blood pressure regimen can be improved. JNC 7 COMPELLING INDICATIONS HYPERTENSION TREATMENT Indication Treatment Chronic kidney disease ACEI, ARB Diabetes mellitus ACEI, ARB, BB, CCB* Heart failure ACEI, ARB, BB, ARA, thiazide High CAD risk ACEI, thiazide, BB, CCB* Post-MI ACEI, BB, ARA Primary stroke prevention Secondary stroke prevention ARB (losartan, LIFE Trial) ACEI Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta blocker; CCB, calcium channel blocker; ARA, aldosterone receptor antagonist (epleronone, spironolactone). *Selection of a non-dihydropyridine CCB is preferred in CKD patients with proteinuria. 21 Therapeutic Targets BP 20 mL/min/1.73 m2 ACEI or ARB Most CKD patients with HTN require 2 or more antihypertensive medications Second and Third Line Agents GFR 40 mL/min/1.73 m2 Add thiazide and/or CCB, if anti-RAAS agent is first-line GFR 80 bpm Beta blocker or alpha/beta blocker HR 80 bpm Consider adding ARA (spironolactone or eplerenone), if proteinuria present Specific Clinical Situations Diabetes ACEI or ARB for type 1 diabetes ARB or ACEI for type 2 diabetes CAD Beta blocker, CCB, alpha/beta blocker, eg, labetalol BPH Alpha-1 blocker, eg, prazosin, terazosin, doxazosin Thiazide-resistant HTN Amiloride or ARA Primary aldosteronism ARA Orthostatic hypotension Target 2-min standing SBP (>120 mmHg) Stage 2 Hypertension (uncontrolled) SBP 150 mmHg on 2 occasions, separated by 2 d DBP 90 mmHg on 2 occasions, separated by 2 d COMMENTS • Anti-RAAS therapy: SCr increases are common and can often be tolerated.