REVIEW ARTICLE
Managing hypertension in patients with chronic kidney disease Kim Zuber, PA-C, DFAAPA; Cheryl Gilmartin, PharmD; Jane Davis, DNP
ABSTRACT Chronic kidney disease (CKD) and hypertension are intrinsically linked. Although 59% of the US population will be diagnosed with CKD during their lifetimes, mortality is usually due to a cardiovascular event. Sodium restriction and a combination of a renin-angiotensin-aldosterone medication and a calcium channel blocker are the most effective methods of managing hypertension in patients with CKD. Keywords: chronic kidney disease, hypertension, cardiovascular, BP, albuminuria, renin-angiotensin-aldosterone system
Although cardiovascular disease (CVD) was the leading cause of death in the United States in 2009, chronic kidney disease (CKD) by far creates the greatest financial burden.1 In 2012, the total medical expenditure for patients with CKD stages 1 through 4 (glomerular filtration rate of 15 to 60 mL/min/1.73m2) was estimated at $50 billion.2 This does not account for the costs incurred by patients who need dialysis. These facts become more chilling when one realizes that baby boomers are rapidly approaching middle age, and a recent study estimated that 59% of Americans would develop stage 3 to 5 CKD at some point in their lifetimes.3 When patients with CVD develop CKD, the picture becomes more complicated and the adverse reactions increase. Thus, the care of the previously straightforward patient with hypertension becomes more complicated. One example is that patients with CKD are highly sensitive to Kim Zuber practices at Metropolitan Nephrology in Alexandria, Va., and is CME chair of the National Kidney Foundation. Cheryl Gilmartin is a clinical assistant professor in the departments of pharmacy practice and nephrology at the University of Illinois Hospital and Health Sciences System in Chicago, Ill. Jane S. Davis is a nurse practitioner at the University of Alabama at Birmingham and a member of the National Kidney Foundation board. The authors have disclosed no potential conflicts of interest, financial or otherwise. Acknowledgment: The authors would like to thank Van Nguyen and Lauren Rothrock, PharmD students at the University of Illinois Hospital and Health Sciences System, for their assistance with this manuscript. DOI: 10.1097/01.JAA.0000453239.92473.41 Copyright © 2014 American Academy of Physician Assistants
JAAPA Journal of the American Academy of Physician Assistants
sodium. As the kidney continues to lose function, the sodium sensitivity becomes a larger component of BP management. This is especially true for both older adults and black patients.4 With the multiplicative effect of CKD and hypertension, hypertensive control becomes all the more critical for the practicing clinician. Now that patients are enrolling for plans under the Affordable Care Act, more patients with previously undiagnosed CKD and hypertension will be seen in primary care offices. What follows is a primer for the nonnephrology PA treating hypertension in patients with CKD. GOAL BP In 2002, the National Kidney Foundation’s (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) publication identified the stages of kidney disease as defined by the glomerular filtration rate (GFR).5 After 10 years of study and analysis, NKF revised CKD staging to better reflect patient needs and recent research findings (Figure 1).6 Proteinuria, in the form of albumin, was found to be the most predictive factor in CKD progression. CKD stage 3 was split into stages 3a and 3b because a single category was too large to be useful for medication dosing, research, and treatment. All hypertension medication class recommendations in this article use the new CKD stages. However, when the international experts of the Kidney Disease Improving Global Outcomes (KDIGO) work group published new guidelines for hypertension management in patients with CKD, the group noted that few hypertension studies reported outcomes by CKD stage.7 So although we will refer to stages of CKD, the data for choosing medications as identified by CKD stage are limited. That said, many references still refer to the choice of a particular medication by CKD stage, such as move to a loop diuretic by stage 4.8 Management of hypertension in patients with CKD depends largely on patient comorbidities. Albuminuria, especially in a patient with diabetes, poses an especially high risk.7 Diabetes is a major risk factor and can increase the risk of CVD by two to three times for every level of CKD. The risk of CVD must be treated as a multiplicative risk factor in CKD. www.JAAPA.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
37
REVIEW ARTICLE
Key points CKD and hypertension are intrinsically linked; 90% of patients with stages 4 or 5 CKD have hypertension. BP goals for patients with CKD depend on whether the patient has diabetes and/or albuminuria. Diuretics, ACE inhibitors, and ARBs are first-line medications for hypertension in patients with CKD. BP control using an RAAS agent is the most effective method to reduce BP and progression to kidney failure in patients with CKD.
With all the published data and meta-analyses unable to define the ideal BP in patients with CKD, most practitioners will aim for a BP between 130-140/80-90 mm Hg. Data are being collected in the Systolic Blood Pressure Intervention Trial (SPRINT), which has enrolled more than 9,000 patients with CKD. Patients are randomly assigned a systolic BP goal of either 120 or 140 mm Hg.16 SPRINT’s strengths are its multiyear design and large, diverse cohort. Although the choice of BP medication is important, the most important factor is the actual lowering of the BP. Kidneys are sensitive organs and increased pressure can cause irreversible damage. Patients should take the BP medication that is the most effective for their condition. Most practitioners have written a prescription and found out later that the patient never filled it due to cost or stopped taking the medication because of adverse reactions. Small differences among BP medications are less important than the interaction between the practitioner and the patient to explain the need for improved hypertension control.
BP goals are based on the presence or absence of diabetes and/or albuminuria (urine albumin excretion greater than 30 mg in 24 hours via spot urine) (Table 1). Lowering BP below a systolic pressure of 130 mm Hg may not slow CKD progression and may actually increase the incidence of serious adverse reactions.9-12 The most recent study shows that goals below 130/80 mm Hg may in fact ACE INHIBITORS AND ARBS lead to an increase in mortality in patients with CKD All classes of BP medications have a role in hypertension stages 4 and 5.13 However, that study was done in older management in patients with CKD. Diuretics and reninwhite men followed by the Los Angeles Veterans Admin- angiotensin-aldosterone-system (RAAS) blockers are the istration, and may not be pertinent to other patient most common initial medications. For patients with albupopulations. Evidence about BP goals is conflicting, and minuria, RAAS blockade is vital. Angiotensin-converting KDIGO erred on the side of safety with its recommenda- enzyme (ACE) inhibitors produce a vasodilator effect in the efferent arterioles. Every large RAAS study has shown tions (Table 1).4 A recent meta-analysis of trials of hypertension man- that the blockade of the RAAS system slows CKD progression in patients with proteinuria.7,17,18 However, due to agement involved 9,287 patients with CKD and included 14 all races, sexes, and ages, including children. Although teratogenicity, RAAS blockers are contraindicated in pregthe study authors found a decrease in CKD progression nancy and should be used cautiously in women who are with tighter BP goals, they found no effect on cardiovas- capable of conception.5 cular events or death. The results from the individual RAAS inhibition affects the changes in sodium and the trials used for the meta-analysis were inconsistent but kidneys. Healthy kidneys are extremely sensitive to sodium albuminuria was found to be a strong predictor of progression. This complicated determining whether hypertension management slowed CKD progression. The authors postulate that the proteinuric kidney, known to have high glomerular pressure, may be more sensitive to a lower BP. By the time the patient has progressed to stage 4 or 5 (GFR less than 30 mL/min/1.73m2), 90% of patients have hypertension.4 Recent recommendations from the International Society of Hypertension in Blacks aim for a BP of 135/85 mm Hg; for patients with end organ damage (including CKD), the goal BP is 130/80 mm Hg.15 However, no hard evidence supports this goal. FIGURE 1. CKD stages per KDIGO 38
www.JAAPA.com
Volume 27 • Number 9 • September 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Managing hypertension in patients with chronic kidney disease TABLE 1.
BP goals as defined by KDIGO
Diabetes
Albuminuria
Goal BP (mm Hg)
No
No
140/90
No
Yes
130/90
Yes
No
140/90
Yes
Yes
130/90
and will correct for sodium intake. However, as the kidneys fail in patients whose CKD is progressing, they become more sodium-sensitive and the RAAS system is inappropriately stimulated.4 Blockade of the RAAS system with either an ACE inhibitor or an angiotensin receptor blocker (ARB) can help shift the sensitivity of the arteriole and decrease reabsorption of sodium and water.8 A recent study in the Netherlands showed that adding dietary sodium restriction to RAAS control was more effective than dual medication blockade in patients with CKD.19 Remember, these patients, especially those who are black and/or older, are exquisitely sensitive to sodium. Up to 30% of all patients with CKD also have a genetic component that increases their sodium sensitivity.4 Lifestyle modifications can be an extremely effective treatment in these patients. A 20% to 30% increase in serum creatinine is acceptable with initiation of RAAS blockade.20 Many practitioners will recheck both serum creatinine and potassium within 4 weeks after initiation and/or dose changes and again at 2 months. Removing RAAS blockade when the patient reaches CKD stage 4 or 5 is controversial.21 Given the 20% to 30% increase in serum creatinine with RAAS as a patient progresses to kidney failure, the remaining amount of kidney function, no matter how small, may be important. Also, older patients are more susceptible to hyperkalemia and dehydration. Although prospective studies have never shown that holding an ACE inhibitor or ARB in a select patient population is productive, some nephrologists will decide to stop these medications in a very select population regardless of the dearth of data.22 Table 2 contains specific dosing and guidelines for CKD stage for RAAS blockade medications and the various classes of antihypertensives. Fosinopril is unusual among the RAAS blockade agents because it is very proteinbound, so renal dosing is not needed.23 Both fosinopril and candesartan have been shown in studies to trend toward reducing cardiovascular outcomes in patients with CKD but neither study reached statistical significance.23,24 Irbesartan has been shown to slow progression of CKD in a post hoc analysis of the Irbesartan Diabetic Nephropathy Trial.25 As to the debate whether an ACE inhibitor or an ARB is better for CKD management, KDIGO states that no head-to-head studies demonstrate either class is superior.7 When ACE inhibitors were introduced in 1977, the trials JAAPA Journal of the American Academy of Physician Assistants
were conducted in patients with type 2 diabetes. By the time ARBs were introduced in 1995, RAAS inhibition was considered standard of care for type 2 diabetes and the trial focus was shifted to patients with type 1 diabetes and CKD. Because of these design differences, comparing ACE inhibitors with ARBs is impossible. However, meta-analysis of trials using combination therapy of an ACE inhibitor and an ARB did not reveal a delay in CKD progression. The analysis demonstrated that combining an ACE inhibitor and an ARB caused more adverse reactions, including hyperkalemia, hypotension, and renal failure.26,27 Combining ACE inhibitors and ARBs is not recommended. DIURETIC DOSING Diuretics are the mainstay of hypertension management and should be prescribed to all patients with CKD. Volume expansion and sodium sensitivity are dominant components of hypertension in patients with CKD.4 A recent report concluded that furosemide actually decreased albuminuria in patients with heart failure.28 Diuretics are even useful in older adults.29 The recent Systolic Hypertension in the Elderly program showed that diuretics will decrease cardiac endpoints in older adults. The major question is then not whether to use a diuretic but when to move from a thiazidebased diuretic to a loop diuretic as CKD progresses. Thiazide diuretics are especially useful when the patient’s BP is more than 20 points above goal and the GFR is greater than 60 mL/min/1.73m2.8,30 This class of diuretics inhibits the sodium/chloride cotransport system in the distal tubules. Thiazide diuretics decrease edema, ameliorate the effects of other antihypertensives (especially ACE inhibitors and ARBs), and minimize hyperkalemia. As the GFR falls below 30 mL/min/1.73m2, thiazide diuretics are unable to reach the distal tubules and a loop diuretic may be more beneficial in managing hypertension and edema.7 Loop diuretics inhibit the sodium/potassium/chloride cotransport systems in the ascending loop of Henle.31 Loop diuretics include furosemide, bumetanide, and torsemide, and are effective at all stages of CKD. Bumetanide and torsemide have better absorption (furosemide absorption can be as low as 10%) but they are dosed differently than furosemide.31 As renal failure progresses, higher doses of furosemide are required and twice-daily dosing is usually warranted. Loop diuretics, like thiazide diuretics, reduce the risk of hyperkalemia that might occur due to reduced renal function and the concomitant use of ACE inhibitors or ARBs. Potassium-sparing diuretics include aldosterone antagonists, triamterene, and amiloride. Triamterene and amiloride are less effective in fluid removal when compared with thiazide and loop diuretics, and are contraindicated in patients with CKD because of the risk of hyperkalemia. Spironolactone, an aldosterone antagonist, reduces albuminuria when used adjunctively with ACE inhibitors or ARBs. Because ARBs, ACE inhibitors, and spironolactone www.JAAPA.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
39
REVIEW ARTICLE TABLE 2.
Hypertension medications
Medication class and typical dosing range in patients without CKD
Renal dosing, precautions, and adverse reactions
Alpha-adrenergic agonists Clonidine Oral: 0.1-0.3 mg every 12 hours Transdermal patch: 0.1-0.6 mg applied weekly Methyldopa 500-2,000 mg daily in two to four divided doses
• Adverse reactions: vasodilation; drowsiness, especially in older adults; bradycardia • Reduced adverse reactions with transdermal patch • Renally excreted—patients with CKD may respond to lower doses or experience more toxicity. • GFR >50 mL/min: dose every 8 hours • GFR 10-50 mL/min: dose every 8 to 12 hours • GFR
Managing hypertension in patients with chronic kidney disease Kim Zuber, PA-C, DFAAPA; Cheryl Gilmartin, PharmD; Jane Davis, DNP
ABSTRACT Chronic kidney disease (CKD) and hypertension are intrinsically linked. Although 59% of the US population will be diagnosed with CKD during their lifetimes, mortality is usually due to a cardiovascular event. Sodium restriction and a combination of a renin-angiotensin-aldosterone medication and a calcium channel blocker are the most effective methods of managing hypertension in patients with CKD. Keywords: chronic kidney disease, hypertension, cardiovascular, BP, albuminuria, renin-angiotensin-aldosterone system
Although cardiovascular disease (CVD) was the leading cause of death in the United States in 2009, chronic kidney disease (CKD) by far creates the greatest financial burden.1 In 2012, the total medical expenditure for patients with CKD stages 1 through 4 (glomerular filtration rate of 15 to 60 mL/min/1.73m2) was estimated at $50 billion.2 This does not account for the costs incurred by patients who need dialysis. These facts become more chilling when one realizes that baby boomers are rapidly approaching middle age, and a recent study estimated that 59% of Americans would develop stage 3 to 5 CKD at some point in their lifetimes.3 When patients with CVD develop CKD, the picture becomes more complicated and the adverse reactions increase. Thus, the care of the previously straightforward patient with hypertension becomes more complicated. One example is that patients with CKD are highly sensitive to Kim Zuber practices at Metropolitan Nephrology in Alexandria, Va., and is CME chair of the National Kidney Foundation. Cheryl Gilmartin is a clinical assistant professor in the departments of pharmacy practice and nephrology at the University of Illinois Hospital and Health Sciences System in Chicago, Ill. Jane S. Davis is a nurse practitioner at the University of Alabama at Birmingham and a member of the National Kidney Foundation board. The authors have disclosed no potential conflicts of interest, financial or otherwise. Acknowledgment: The authors would like to thank Van Nguyen and Lauren Rothrock, PharmD students at the University of Illinois Hospital and Health Sciences System, for their assistance with this manuscript. DOI: 10.1097/01.JAA.0000453239.92473.41 Copyright © 2014 American Academy of Physician Assistants
JAAPA Journal of the American Academy of Physician Assistants
sodium. As the kidney continues to lose function, the sodium sensitivity becomes a larger component of BP management. This is especially true for both older adults and black patients.4 With the multiplicative effect of CKD and hypertension, hypertensive control becomes all the more critical for the practicing clinician. Now that patients are enrolling for plans under the Affordable Care Act, more patients with previously undiagnosed CKD and hypertension will be seen in primary care offices. What follows is a primer for the nonnephrology PA treating hypertension in patients with CKD. GOAL BP In 2002, the National Kidney Foundation’s (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) publication identified the stages of kidney disease as defined by the glomerular filtration rate (GFR).5 After 10 years of study and analysis, NKF revised CKD staging to better reflect patient needs and recent research findings (Figure 1).6 Proteinuria, in the form of albumin, was found to be the most predictive factor in CKD progression. CKD stage 3 was split into stages 3a and 3b because a single category was too large to be useful for medication dosing, research, and treatment. All hypertension medication class recommendations in this article use the new CKD stages. However, when the international experts of the Kidney Disease Improving Global Outcomes (KDIGO) work group published new guidelines for hypertension management in patients with CKD, the group noted that few hypertension studies reported outcomes by CKD stage.7 So although we will refer to stages of CKD, the data for choosing medications as identified by CKD stage are limited. That said, many references still refer to the choice of a particular medication by CKD stage, such as move to a loop diuretic by stage 4.8 Management of hypertension in patients with CKD depends largely on patient comorbidities. Albuminuria, especially in a patient with diabetes, poses an especially high risk.7 Diabetes is a major risk factor and can increase the risk of CVD by two to three times for every level of CKD. The risk of CVD must be treated as a multiplicative risk factor in CKD. www.JAAPA.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
37
REVIEW ARTICLE
Key points CKD and hypertension are intrinsically linked; 90% of patients with stages 4 or 5 CKD have hypertension. BP goals for patients with CKD depend on whether the patient has diabetes and/or albuminuria. Diuretics, ACE inhibitors, and ARBs are first-line medications for hypertension in patients with CKD. BP control using an RAAS agent is the most effective method to reduce BP and progression to kidney failure in patients with CKD.
With all the published data and meta-analyses unable to define the ideal BP in patients with CKD, most practitioners will aim for a BP between 130-140/80-90 mm Hg. Data are being collected in the Systolic Blood Pressure Intervention Trial (SPRINT), which has enrolled more than 9,000 patients with CKD. Patients are randomly assigned a systolic BP goal of either 120 or 140 mm Hg.16 SPRINT’s strengths are its multiyear design and large, diverse cohort. Although the choice of BP medication is important, the most important factor is the actual lowering of the BP. Kidneys are sensitive organs and increased pressure can cause irreversible damage. Patients should take the BP medication that is the most effective for their condition. Most practitioners have written a prescription and found out later that the patient never filled it due to cost or stopped taking the medication because of adverse reactions. Small differences among BP medications are less important than the interaction between the practitioner and the patient to explain the need for improved hypertension control.
BP goals are based on the presence or absence of diabetes and/or albuminuria (urine albumin excretion greater than 30 mg in 24 hours via spot urine) (Table 1). Lowering BP below a systolic pressure of 130 mm Hg may not slow CKD progression and may actually increase the incidence of serious adverse reactions.9-12 The most recent study shows that goals below 130/80 mm Hg may in fact ACE INHIBITORS AND ARBS lead to an increase in mortality in patients with CKD All classes of BP medications have a role in hypertension stages 4 and 5.13 However, that study was done in older management in patients with CKD. Diuretics and reninwhite men followed by the Los Angeles Veterans Admin- angiotensin-aldosterone-system (RAAS) blockers are the istration, and may not be pertinent to other patient most common initial medications. For patients with albupopulations. Evidence about BP goals is conflicting, and minuria, RAAS blockade is vital. Angiotensin-converting KDIGO erred on the side of safety with its recommenda- enzyme (ACE) inhibitors produce a vasodilator effect in the efferent arterioles. Every large RAAS study has shown tions (Table 1).4 A recent meta-analysis of trials of hypertension man- that the blockade of the RAAS system slows CKD progression in patients with proteinuria.7,17,18 However, due to agement involved 9,287 patients with CKD and included 14 all races, sexes, and ages, including children. Although teratogenicity, RAAS blockers are contraindicated in pregthe study authors found a decrease in CKD progression nancy and should be used cautiously in women who are with tighter BP goals, they found no effect on cardiovas- capable of conception.5 cular events or death. The results from the individual RAAS inhibition affects the changes in sodium and the trials used for the meta-analysis were inconsistent but kidneys. Healthy kidneys are extremely sensitive to sodium albuminuria was found to be a strong predictor of progression. This complicated determining whether hypertension management slowed CKD progression. The authors postulate that the proteinuric kidney, known to have high glomerular pressure, may be more sensitive to a lower BP. By the time the patient has progressed to stage 4 or 5 (GFR less than 30 mL/min/1.73m2), 90% of patients have hypertension.4 Recent recommendations from the International Society of Hypertension in Blacks aim for a BP of 135/85 mm Hg; for patients with end organ damage (including CKD), the goal BP is 130/80 mm Hg.15 However, no hard evidence supports this goal. FIGURE 1. CKD stages per KDIGO 38
www.JAAPA.com
Volume 27 • Number 9 • September 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Managing hypertension in patients with chronic kidney disease TABLE 1.
BP goals as defined by KDIGO
Diabetes
Albuminuria
Goal BP (mm Hg)
No
No
140/90
No
Yes
130/90
Yes
No
140/90
Yes
Yes
130/90
and will correct for sodium intake. However, as the kidneys fail in patients whose CKD is progressing, they become more sodium-sensitive and the RAAS system is inappropriately stimulated.4 Blockade of the RAAS system with either an ACE inhibitor or an angiotensin receptor blocker (ARB) can help shift the sensitivity of the arteriole and decrease reabsorption of sodium and water.8 A recent study in the Netherlands showed that adding dietary sodium restriction to RAAS control was more effective than dual medication blockade in patients with CKD.19 Remember, these patients, especially those who are black and/or older, are exquisitely sensitive to sodium. Up to 30% of all patients with CKD also have a genetic component that increases their sodium sensitivity.4 Lifestyle modifications can be an extremely effective treatment in these patients. A 20% to 30% increase in serum creatinine is acceptable with initiation of RAAS blockade.20 Many practitioners will recheck both serum creatinine and potassium within 4 weeks after initiation and/or dose changes and again at 2 months. Removing RAAS blockade when the patient reaches CKD stage 4 or 5 is controversial.21 Given the 20% to 30% increase in serum creatinine with RAAS as a patient progresses to kidney failure, the remaining amount of kidney function, no matter how small, may be important. Also, older patients are more susceptible to hyperkalemia and dehydration. Although prospective studies have never shown that holding an ACE inhibitor or ARB in a select patient population is productive, some nephrologists will decide to stop these medications in a very select population regardless of the dearth of data.22 Table 2 contains specific dosing and guidelines for CKD stage for RAAS blockade medications and the various classes of antihypertensives. Fosinopril is unusual among the RAAS blockade agents because it is very proteinbound, so renal dosing is not needed.23 Both fosinopril and candesartan have been shown in studies to trend toward reducing cardiovascular outcomes in patients with CKD but neither study reached statistical significance.23,24 Irbesartan has been shown to slow progression of CKD in a post hoc analysis of the Irbesartan Diabetic Nephropathy Trial.25 As to the debate whether an ACE inhibitor or an ARB is better for CKD management, KDIGO states that no head-to-head studies demonstrate either class is superior.7 When ACE inhibitors were introduced in 1977, the trials JAAPA Journal of the American Academy of Physician Assistants
were conducted in patients with type 2 diabetes. By the time ARBs were introduced in 1995, RAAS inhibition was considered standard of care for type 2 diabetes and the trial focus was shifted to patients with type 1 diabetes and CKD. Because of these design differences, comparing ACE inhibitors with ARBs is impossible. However, meta-analysis of trials using combination therapy of an ACE inhibitor and an ARB did not reveal a delay in CKD progression. The analysis demonstrated that combining an ACE inhibitor and an ARB caused more adverse reactions, including hyperkalemia, hypotension, and renal failure.26,27 Combining ACE inhibitors and ARBs is not recommended. DIURETIC DOSING Diuretics are the mainstay of hypertension management and should be prescribed to all patients with CKD. Volume expansion and sodium sensitivity are dominant components of hypertension in patients with CKD.4 A recent report concluded that furosemide actually decreased albuminuria in patients with heart failure.28 Diuretics are even useful in older adults.29 The recent Systolic Hypertension in the Elderly program showed that diuretics will decrease cardiac endpoints in older adults. The major question is then not whether to use a diuretic but when to move from a thiazidebased diuretic to a loop diuretic as CKD progresses. Thiazide diuretics are especially useful when the patient’s BP is more than 20 points above goal and the GFR is greater than 60 mL/min/1.73m2.8,30 This class of diuretics inhibits the sodium/chloride cotransport system in the distal tubules. Thiazide diuretics decrease edema, ameliorate the effects of other antihypertensives (especially ACE inhibitors and ARBs), and minimize hyperkalemia. As the GFR falls below 30 mL/min/1.73m2, thiazide diuretics are unable to reach the distal tubules and a loop diuretic may be more beneficial in managing hypertension and edema.7 Loop diuretics inhibit the sodium/potassium/chloride cotransport systems in the ascending loop of Henle.31 Loop diuretics include furosemide, bumetanide, and torsemide, and are effective at all stages of CKD. Bumetanide and torsemide have better absorption (furosemide absorption can be as low as 10%) but they are dosed differently than furosemide.31 As renal failure progresses, higher doses of furosemide are required and twice-daily dosing is usually warranted. Loop diuretics, like thiazide diuretics, reduce the risk of hyperkalemia that might occur due to reduced renal function and the concomitant use of ACE inhibitors or ARBs. Potassium-sparing diuretics include aldosterone antagonists, triamterene, and amiloride. Triamterene and amiloride are less effective in fluid removal when compared with thiazide and loop diuretics, and are contraindicated in patients with CKD because of the risk of hyperkalemia. Spironolactone, an aldosterone antagonist, reduces albuminuria when used adjunctively with ACE inhibitors or ARBs. Because ARBs, ACE inhibitors, and spironolactone www.JAAPA.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
39
REVIEW ARTICLE TABLE 2.
Hypertension medications
Medication class and typical dosing range in patients without CKD
Renal dosing, precautions, and adverse reactions
Alpha-adrenergic agonists Clonidine Oral: 0.1-0.3 mg every 12 hours Transdermal patch: 0.1-0.6 mg applied weekly Methyldopa 500-2,000 mg daily in two to four divided doses
• Adverse reactions: vasodilation; drowsiness, especially in older adults; bradycardia • Reduced adverse reactions with transdermal patch • Renally excreted—patients with CKD may respond to lower doses or experience more toxicity. • GFR >50 mL/min: dose every 8 hours • GFR 10-50 mL/min: dose every 8 to 12 hours • GFR
