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Proteinuria Medication

  • Author: Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Dec 10, 2015
 

Medication Summary

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockres (ARBs) reduce intraglomerular pressure by inhibiting angiotensin II ̶ mediated efferent arteriolar vasoconstriction.[25] These drugs also have a proteinuria-reducing effect, which is independent of their antihypertensive effect.

In addition, ACE inhibitors have renoprotective properties, which may be partially due to the other hemodynamic and nonhemodynamic effects of these drugs. ACE inhibitors reduce the breakdown of bradykinin (an efferent arteriolar vasodilator), restore the size and charge selectivity to the glomerular cell wall (GCW), and reduce the production of cytokines, such as transforming growth factor – beta (TGF-beta), that promote glomerulosclerosis and fibrosis.

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ACE Inhibitors

Class Summary

ACE inhibitors reduce intraglomerular pressure and may restore size and charge integrity to the GCW. They also reduce level of profibrotic cytokines. ACE inhibitors reduce proteinuria and also reduce rate of deterioration of renal function in patients with diabetic and nondiabetic renal disease associated with proteinuria.

Lisinopril (Zestril, Prinivil)

 

Lisinopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. The target blood pressure is less than 125/75 mm Hg in patients with proteinuria of greater than 1 g/day.

Patients who develop a cough, angioedema, bronchospasm, or other hypersensitivity reactions after starting ACE inhibitors should receive an angiotensin receptor blocker.

Ramipril (Altace)

 

Ramipril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Captopril

 

Captopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Enalapril (Vasotec)

 

Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, decreasing aldosterone secretion.

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Angiotensin II Receptor Antagonists (ARBs)

Class Summary

Angiotensin II receptor blockers reduce blood pressure and proteinuria, protecting renal function and delaying the onset of end-stage renal disease.

Candesartan (Atacand)

 

Candesartan blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors do. In addition, candesartan does not affect the response to bradykinin and is less likely to be associated with cough and angioedema. This drug can be used in patients who are unable to tolerate ACE inhibitors.

Eprosartan (Teveten)

 

Eprosartan is a nonpeptide angiotensin II receptor antagonist that blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors do. In addition, eprosartan does not affect the response to bradykinin and is less likely to be associated with cough and angioedema. This drug can be used in patients who are unable to tolerate ACE inhibitors.

Irbesartan (Avapro)

 

Irbesartan blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II at the tissue receptor site. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors do. In addition, it does not affect the response to bradykinin and is less likely to be associated with cough and angioedema.

Losartan (Cozaar)

 

Losartan blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors do. In addition, Losartan does not affect the response to bradykinin and is less likely to be associated with cough and angioedema. It can be used in patients who are unable to tolerate ACE inhibitors.

Olmesartan (Benicar)

 

Olmesartan blocks the vasoconstrictive effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptors in vascular smooth muscle. Its action is independent of the pathways for angiotensin II synthesis.

Valsartan (Diovan)

 

Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from AT1 receptors and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

Valsartan may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors do. In addition, it does not affect the response to bradykinin and is less likely to be associated with cough and angioedema. Valsartan can be used in patients who are unable to tolerate ACE inhibitors.

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Diuretics, Loop

Class Summary

Patients with fluid overload should be treated with diuretics. Use a combination of diuretics acting at different sites of the nephron (eg, loop diuretic ± thiazide ± spironolactone). They increase urine excretion by inhibiting sodium and chloride transporters.

Furosemide (Lasix)

 

Furosemide is the diuretic of choice. It increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule.

Bumetanide (Bumex)

 

Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle. These effects increase the urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs after administration, renal vascular resistance decreases, and renal blood flow is enhanced. In terms of effect, 1 mg of bumetanide is equivalent to approximately 40 mg of furosemide.

Ethacrynic acid (Edecrin)

 

Ethacrynic acid increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. This agent is used only in refractory cases. Continuous IV infusion is preferable in many cases. It is indicated for temporary treatment of edema associated with heart failure when greater diuretic potential is needed.

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Diuretics, Thiazide

Class Summary

Patients with fluid overload should be treated with diuretics. Use a combination of diuretics acting at different sites of the nephron (eg, loop diuretic ± thiazide ± spironolactone). Diuretics are used to treat edema and hypertension. They increase urine excretion by inhibiting sodium and chloride transporters.

Metolazone (Zaroxolyn)

 

Metolazone treats edema in congestive heart failure. It increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. It may be more effective in cases of impaired renal function.

Hydrochlorothiazide (Microzide)

 

Hydrochlorothiazide inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions.

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Aldosterone Antagonists, Selective

Class Summary

Patients with fluid overload should be treated with diuretics. Use a combination of diuretics acting at different sites of the nephron (eg, loop diuretic ± thiazide ± spironolactone). Aldosterone antagonists are used to lower the blood pressure and normalize serum potassium.

Spironolactone (Aldactone)

 

Spironolactone is the agent most commonly used to treat hyperaldosteronism because it directly antagonizes aldosterone effects at the distal tubule.

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Calcium Channel Antagonists

Class Summary

These agents may help to reduce proteinuria.

Diltiazem (Cardizem, Dilacor, Tiazac, Dilacor, Cartia XT)

 

During depolarization, diltiazem inhibits the influx of extracellular calcium across myocardial and vascular smooth muscle cell membranes. (Serum calcium levels remain unchanged.) The resultant decrease in intracellular calcium inhibits the contractile processes of myocardial smooth muscle cells, resulting in dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.

Diltiazem decreases conduction velocity in the atrioventricular node. In addition, it increases the refractory period by blocking calcium influx. This, in turn, stops the reentrant phenomenon.

The drug decreases myocardial oxygen demand by reducing peripheral vascular resistance, reducing the heart rate by slowing conduction through the sinoatrial and atrioventricular nodes and reducing left ventricular inotropy.

Diltiazem slows atrioventricular nodal conduction time and prolongs the atrioventricular nodal refractory period, which may convert supraventricular tachycardia or slow the rate in atrial fibrillation. It also has vasodilator activity but may be less potent than other agents. Total peripheral resistance, systemic blood pressure, and afterload are decreased.

Amlodipine (Norvasc)

 

Amlodipine blocks slow calcium channels, causing relaxation of vascular smooth muscles.

Nifedipine (Procardia)

 

Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Sublingual administration is generally safe, theoretical concerns notwithstanding.

Felodipine

 

Felodipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Calcium channel blockers potentiate ACE inhibitor effects. Renal protection is not proven, but these agents reduce morbidity and mortality rates in congestive heart failure. Calcium channel blockers are indicated in patients with diastolic dysfunction. They are effective as monotherapy in black patients and elderly patients.

Isradipine (DynaCirc)

 

Isradipine is a dihydropyridine calcium-channel blocker. It inhibits calcium from entering select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization. This causes relaxation of coronary vascular smooth muscle, which results in coronary vasodilation. Vasodilation reduces systemic resistance and blood pressure, with a small increase in resting heart rate. Isradipine also has negative inotropic effects.

Verapamil (Calan, Isoptin, Verelan)

 

During depolarization, verapamil inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. It can diminish premature ventricular contractions (PVCs) associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia.

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Contributor Information and Disclosures
Author

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF Clinical Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Research Director, Internal Medicine Training Program, Advocate Christ Medical Center; Consulting Staff, Associates in Nephrology, SC

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF is a member of the following medical societies: American Heart Association, American Medical Association, American Society of Hypertension, American Society of Nephrology, Chicago Medical Society, Illinois State Medical Society, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Otsuka, Mallinckrodt, ZS Pharma<br/>Author for: UpToDate, ACP Smart Medicine.

Coauthor(s)

Tejas Desai, MD Staff Nephrologist, WG (Bill) Hefner VA Medical Center

Tejas Desai, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Pankaj Jawa, MD Assistant Professor of Medicine, Division of Nephrology and Hypertension, The Brody School of Medicine at East Carolina University

Pankaj Jawa, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Transplantation, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

George R Aronoff, MD Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

Kevin McLaughlin, MBChB, PhD, MSc Associate Professor, Assistant Dean, Department of Medicine, University of Calgary Faculty of Medicine, Calgary Health Region

Kevin McLaughlin, MBChB, PhD, MSc is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation, and College of Physicians and Surgeons of Alberta

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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