Chronic Glomerulonephritis 

Updated: Feb 01, 2017
Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FASN 

Overview

Practice Essentials

Nearly all forms of acute glomerulonephritis have a tendency to progress to chronic glomerulonephritis. The condition is characterized by irreversible and progressive glomerular and tubulointerstitial fibrosis, ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy, the net results are chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular disease. Chronic glomerulonephritis is the third leading cause of CKD, and accounting for about 10% of all patients on dialysis.

The exact cause of CKD in patients with chronic glomerulonephritis may never be known in some patients. Therefore, it has generally been accepted that the diagnosis of CKD can be made without knowledge of the specific cause.[1]

The National Kidney Foundation (NKF) defines CKD on the basis of either of the following:

  • Evidence of kidney damage based on abnormal urinalysis results (eg, proteinuria or hematuria) or structural abnormalities observed on ultrasound images

  • A GFR of less than 60 mL/min for 3 or more months

In accordance with this definition, the NKF developed guidelines that classify the progression of renal disease into five stages, from kidney disease with a preserved GFR to end-stage kidney failure. This classification includes treatment strategies for each progressive level, as follows:

  • Stage 1 – This stage is characterized by kidney damage with a normal GFR (≥ 90 mL/min); the action plan consists of diagnosis and treatment, treatment of comorbid conditions, slowing of the progressing of kidney disease, and reduction of cardiovascular disease risks

  • Stage 2 – This stage is characterized by kidney damage with a mild decrease in the GFR (60-90 mL/min); the action plan is estimation of the progression of kidney disease

  • Stage 3 – This stage is characterized by a moderately decreased GFR (to 30-59 mL/min); the action plan consists of evaluation and treatment of complications

  • Stage 4 – This stage is characterized by a severe decrease in the GFR (to 15-29 mL/min); the action plan is preparation for renal replacement therapy

  • Stage 5 – This stage is characterized by kidney failure; the action plan is kidney replacement if the patient is uremic

At the later stages of glomerular injury, the kidney are small and contracted and biopsy results cannot help distinguish the primary disease. Histology and clues to the etiology are often derived from other systemic diseases (if present). Considerable cause-specific variability is observed in the rate at which acute glomerulonephritis progresses to chronic glomerulonephritis.

The prognosis depends on the type of chronic glomerulonephritis (see Etiology). ESRD and death are common outcomes unless renal replacement therapy is instituted.

Pathophysiology

Reduction in nephron mass from the initial injury reduces the GFR. This reduction leads to hypertrophy and hyperfiltration of the remaining nephrons and to the initiation of intraglomerular hypertension. These changes occur in order to increase the GFR of the remaining nephrons, thus minimizing the functional consequences of nephron loss. The changes, however, are ultimately detrimental because they lead to glomerulosclerosis and further nephron loss.

In early renal disease (stages 1-3), a substantial decline in the GFR may lead to only slight increases in serum creatinine levels. Azotemia (ie, a rise in blood urea nitrogen [BUN] and serum creatinine levels) is apparent when the GFR decreases to less than 60-70 mL/min. In addition to a rise in BUN and creatinine levels, the substantial reduction in the GFR results in the following:

  • Decreased production of erythropoietin, thus resulting in anemia

  • Decreased production of vitamin D, resulting in hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, and renal osteodystrophy

  • Reduction in acid, potassium, salt, and water excretion, resulting in acidosis, hyperkalemia, hypertension, and edema

  • Platelet dysfunction, leading to increased bleeding tendencies

Accumulation of toxic waste products (uremic toxins) affects virtually all organ systems. Azotemia occurring with the signs and symptoms listed above is known as uremia. Uremia occurs at a GFR of approximately 10 mL/min. Some of these toxins (eg, BUN, creatinine, phenols, and guanidines) have been identified, but none has been found to be responsible for all the symptoms.

Etiology

The progression from acute glomerulonephritis to chronic glomerulonephritis is variable, depending to a considerable extent on the cause of the condition. Whereas complete recovery of renal function is the rule for patients with poststreptococcal glomerulonephritis, several other glomerulonephritides, such as immunoglobulin A (IgA) nephropathy, often have a relatively benign course, and many do not progress to ESRD. Progression patterns may be summarized as follows:

  • Rapidly progressive glomerulonephritis or crescentic glomerulonephritis – About 90% of patients progress to ESRD within weeks or months.

  • Focal segmental glomerulosclerosis – About 80% of patients progress to ESRD in 10 years; patients with the collapsing variant (malignant focal segmental glomerulosclerosis) have a more rapid progression; this form may be idiopathic or related to HIV infection

  • Membranous nephropathy – About 20-30% of patients with membranous nephropathy progress to chronic renal failure (CRF) and ESRD in 10 years

  • Membranoproliferative glomerulonephritis – About 40% of patients with membranoproliferative glomerulonephritis progress to CRF and ESRD in 10 years[2]

  • IgA nephropathy – About 10% of patients with IgA nephropathy progress to CRF and ESRD in 10 years[3, 4]

  • Poststreptococcal glomerulonephritis – About 1-2% of patients with poststreptococcal glomerulonephritis progress to CRF and ESRD; older children who present with crescentic glomerulonephritis are at greatest risk

  • Lupus nephritis – Overall, about 20% of patients with lupus nephritis progress to CRF and ESRD in 10 years; however, patients with certain histologic variants (eg, class IV) may have a more rapid decline.[5] The presence of antineutrophil cytoplasmic antibody (ANCA) is also  an independent risk factor for poor renal outcomes.[6]

Epidemiology

In the United States, chronic glomerulonephritis is the third leading cause of ESRD and accounts for 10% of patients on dialysis.

In Japan and some Asian countries, chronic glomerulonephritis has accounted for as many as 40% of patients on dialysis; however, subsequent data suggest that in Japan, for instance, the rate of chronic glomerulonephritis in patients on dialysis is 28%.[7, 8] The cause of this declining rate is not known. Concurrent with the decline in chronic glomerulonephritis in these countries is an increase in diabetic nephropathy in up to 40% of patients on dialysis.

Patient Education

Dietary education is paramount in managing patients with CKD. The typical dietary restriction is to 2 g of sodium, 2 g of potassium, and 40-60 g of protein a day. Additional restrictions may apply for diabetes, hyperlipidemia, and fluid overload.

Patients should be educated regarding the types of ESRD therapy. The specific choices of ESRD therapy include hemodialysis, peritoneal dialysis, and renal transplantation. For further information, see Mayo Clinic - Kidney Transplant Information.

Patients opting for hemodialysis should be educated on home hemodialysis (in which patients are trained to do their dialysis at home) and center hemodialysis (in which patients come to a center 3 times a week for 3.5- to 4-hour dialysis sessions). They should also be educated on the types of vascular access. Arteriovenous fistulae should be created when the GFR falls below 25 mL/min or the serum creatinine level is greater than 4 mg/dL to allow maturation of the access before the initiation of dialysis.

In the United States and most developed countries, patients on dialysis can travel. In fact, there are even dialysis cruises. However, patients should inform their social workers to make the necessary arrangements beforehand to ensure that the destination has the right resources to continue dialysis.

Sexual dysfunction and loss of libido are common in patients with kidney disease, especially men. Patients should be instructed to seek medical therapy if they experience these symptoms.

Renal failure and hypertension worsen during pregnancy in patients with CKD, particularly when the serum creatinine level exceeds 2 mg/dL, and this leads to decreased fetal viability and increased maternal morbidity in pregnant women with CKD. Therefore, women with CKD should consult their doctors before becoming pregnant.[9, 10]

 

Presentation

History

The history should begin by focusing on cause-specific symptoms to determine the source of the chronic kidney disease (CKD) if this is unknown. Recognition of such symptoms facilitates the planning of further workup and management of the disease (if systemic).

The next step is to look for symptoms related to uremia to determine if renal replacement therapy is needed. The following symptoms suggest uremia:

  • Weakness and fatigue

  • Loss of energy, appetite, and weight

  • Pruritus

  • Early morning nausea and vomiting

  • Change in taste sensation

  • Reversal in sleep pattern (ie, sleepiness in daytime and wakefulness at night)

  • Peripheral neuropathy

  • Seizures

  • Tremors

The presence of edema and hypertension suggests volume retention. Dyspnea or chest pain that varies with position suggests fluid overload and pericarditis, respectively. Leg cramps may suggest hypocalcemia or other electrolyte abnormalities. Weakness, lethargy, and fatigue may be due to anemia.

Physical Examination

Cause-specific physical examination findings are discussed elsewhere, in articles describing the specific causes (see Etiology). Uremia-specific physical findings include the following:

  • Hypertension

  • Jugular venous distention (if severe volume overload is present)

  • Pulmonary rales (if pulmonary edema is present)

  • Pericardial friction rub in pericarditis

  • Tenderness in the epigastric region or blood in the stool (possible indicators of uremic gastritis or enteropathy)

  • Decreased sensation and asterixis (indicators of advanced uremia)

Complications

The presence of the following complications generally indicates a need for urgent dialysis:

  • Metabolic acidosis

  • Pulmonary edema

  • Pericarditis

  • Uremic encephalopathy

  • Uremic gastrointestinal bleeding

  • Uremic neuropathy

  • Severe anemia and hypocalcemia

  • Hyperkalemia

 

DDx

 

Workup

Laboratory Studies

Urinalysis

The presence of dysmorphic red blood cells (RBCs), albumin, or RBC casts suggests glomerulonephritis as the cause of renal failure. Waxy or broad casts are observed in all forms of chronic kidney disease (CKD), including chronic glomerulonephritis. Low urine specific gravity indicates loss of tubular concentrating ability, an early finding in persons with CKD. See Urinalysis.

Urinary protein excretion

Urinary protein excretion can be estimated by calculating the protein-to-creatinine ratio on a spot morning urine sample. The ratio of urinary protein concentration (in mg/dL) to urinary creatinine (in mg/dL) reflects 24-hour protein excretion in grams. For instance, if the spot urine protein value is 300 mg/dL and the creatinine value is 150 mg/dL, the protein-to-creatinine ratio is 2. Thus, in this example, the 24-hour urine protein excretion is 2 g.[11]

The estimated creatinine clearance rate is used to assess and monitor the glomerular filtration rate (GFR). The 2 formulas available for calculation of the GFR are the Cockcroft-Gault formula, which estimates creatinine clearance, and the Modification of Diet in Renal Disease (MDRD) Study formula, which is used to calculate the GFR directly.

The Cockcroft-Gault formula is simple to use but overestimates the GFR by 10-15% because creatinine is both filtered and secreted. The MDRD formula is much more complex but can be determined with a smartphone and tablet application available from the National Kidney Foundation or can be calculated online through the Hypertension, Dialysis, and Clinical Nephrology Web site.

The estimated creatinine clearance rate is also used to monitor response to therapy and to initiate an early transition to renal replacement therapy (eg, dialysis access placement and transplantation evaluation). The degree of proteinuria, especially albuminuria, helps predict the renal prognosis in patients with chronic glomerulonephritis. Patients with proteinuria exceeding 1 g/day have an increased risk of progression to end-stage renal failure.

Complete blood count

Anemia is a significant finding in patients with some decline in the GFR. Physicians must be aware that anemia can occur even in patients with serum creatinine levels lower than 2 mg/dL. Even severe anemia can occur at low serum creatinine levels. Anemia is the result of marked impairment of erythropoietin production.

Serum chemistry

Serum creatinine and urea nitrogen levels are elevated. Impaired excretion of potassium, free water, and acid results in hyperkalemia, hyponatremia, and low serum bicarbonate levels, respectively. Impaired vitamin D-3 production results in hypocalcemia, hyperphosphatemia, and high levels of parathyroid hormone. Low serum albumin levels may be present if uremia interferes with nutrition or if the patient is nephrotic.

Levels of fibroblast growth factor 21 (FGF21) have been found to be significantly elevated in patients with CKD[12] and the high levels of FGF21 may explain the excess overall and cardiovascular mortality in patients with CKD. These adverse effects of elevated FGF21 are not clearly understood but research is under way to elucidate its biologic effects.

Other Studies

Renal ultrasonography

Obtain a renal ultrasonogram to determine renal size, to assess for the presence of both kidneys, and to exclude structural lesions that may be responsible for azotemia. Small kidneys often indicate an irreversible process.

Kidney biopsy

If the kidney is small, kidney biopsy is usually unnecessary; no specific pattern of disease can be discerned at this point. A kidney biopsy may be considered in the minority of patients who exhibit an acute exacerbation of their chronic disease. This may be particularly pertinent to patients with preserved kidney size and in those with lupus nephritis.

In early stages, the glomeruli may still show some histologic evidence of the primary disease. In advanced stages, the glomeruli are hyalinized and obsolescent. The tubules are disrupted and atrophic, and marked interstitial fibrosis and arterial and arteriolar sclerosis occur.

 

Treatment

Approach Considerations

Patients with chronic kidney disease (CKD) who are admitted to the hospital should receive careful monitoring of weight, intake, output, and renal function so that acute kidney injury (AKI) can be diagnosed and treated early if it occurs,. All potentially nephrotoxic agents must be adjusted for the degree of CKD. Furthermore, agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, and intravenous (IV) contrast media must be avoided unless the benefits clearly outweigh the risks; they are strongly associated with AKI.

Progression from CKD to end-stage renal disease (ESRD) can be slowed by a variety of measures, including aggressive control of diabetes, hypertension, and proteinuria. Dietary protein restriction, phosphate restriction, and hyperlipidemia control may have significant impact on retarding disease progression. In obese patients, weight reduction and bariatric surgery may have beneficial effects on CKD.[13]

Specific therapies for some glomerular diseases (eg, lupus) should be implemented in appropriate settings. Aggressively manage anemia and renal osteodystrophy (eg, hyperphosphatemia, hypocalcemia, or hyperparathyroidism) before initiating renal replacement therapy. Also, aggressively manage comorbid conditions, such as heart disease and diabetes.

Nephrotic patients (urinary protein excretion >3.5 g/day) may have hyperlipidemia. As a part of cardiovascular health care, the lipid profile should be checked, and lipid-lowering therapy should be started for patients with hyperlipidemia.

Steroid therapy may induce or exacerbate diabetes, hypertension, weight gain, fat redistribution in the trunk (buffalo hump) and face (moon facies), cosmetic problems (eg, hirsutism and acne), and osteoporosis.

Monitor fasting blood glucose levels and blood pressure. Obtain baseline bone densitometry values. Repeat bone densitometry for bone pain. Oral calcium supplements (1 g/day) and vitamin D (400-800 IU/day) are recommended for prophylaxis against osteoporosis.

Pharmacologic Therapy

Blood pressure management

The target blood pressure for patients with proteinuria in excess of 1 g/day is less than 125/75 mm Hg; for patients with proteinuria of less than 1 g/day, the target pressure is less than 130/80 mm Hg.

Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used and are usually the first choice for treatment of hypertension in patients with chronic kidney disease (CKD). ACEIs are renoprotective agents that have additional benefits beyond lowering pressure. They effectively reduce proteinuria, in part by reducing the efferent arteriolar vascular tone, thereby decreasing intraglomerular hypertension.

In particular, ACEIs have been shown to be superior to conventional therapy in slowing the decline of the glomerular filtration rate (GFR) in patients with diabetic and nondiabetic proteinuric nephropathies. Therefore, ACEIs should be considered for treatment of even normotensive patients with significant proteinuria.[14]

The role of angiotensin II receptor blockers (ARBs) in renal protection is increasingly being established, and these medications have been found to retard the progression of CKD in patients with diabetic or nondiabetic nephropathy, much as ACEIs do.[15]

A combination of ACEI therapy and ARB therapy has been shown to achieve better pressure control and preservation of renal function than either therapy alone could. Therefore, in patients without hyperkalemia or an acute rise in serum creatinine levels after the use of either therapy, combination therapy should be attempted.[16]

However, in patients with vascular disease or diabetes, combination ACEI and ARB therapy has been associated with increased adverse effects, including hyperkalemia, worsening renal function, and mortality. As such, combination ACEI and ARB therapy should not be used to treat hypertension in these groups of patients with CKD.[17]

Diuretics are often required because of decreased free-water clearance, and high doses may be required to control edema and hypertension when the GFR falls below 25 mL/min. Diuretics are also useful in counteracting the hyperkalemic potential of ACEIs and ARBs. However, they should be used with caution when given together with ACEIs or ARBs because the decline in intraglomerular pressure induced by ACEIs or ARBs may be exacerbated by the volume depletion induced by diuretics, potentially precipitating ARF.

Beta blockers, calcium channel blockers,[18] central alpha2 agonists (eg, clonidine), alpha1 antagonists, and direct vasodilators (eg, minoxidil and nitrates) may be used to achieve the target pressure.

Fibrosis inhibition

Because progressive fibrosis is the hallmark of chronic glomerulonephritis, some investigators have focused on finding inhibitors of fibrosis in an attempt to slow progression. Of the many compounds that have been considered, pirfenidone, an inhibitor of transforming growth factor beta and hence of collagen synthesis, has emerged as the best candidate.

Cho et al, in an open-label study involving 21 patients with idiopathic and postadaptive focal segmental glomerulosclerosis, found that pirfenidone yielded a median 25% improvement in the rate of decline of the estimated GFR; the drug did not affect proteinuria or blood pressure.[19] Among the adverse events attributed to therapy were dyspepsia, sedation, and photosensitive dermatitis. It is hoped that pirfenidone therapy will prove an effective means of slowing progressive fibrosis; however, more studies are needed.

Role of antioxidants (bardoxolone)

Cells have the ability to produce antioxidants, anti-inflammatory and detoxifying enzymes that are useful for cell viability, but this pathway is constantly being inhibited by an enzyme called KEAP. Inhibition of KEAP may therefore improve the antioxidant activity of cells and promote cell viability. Bardoxolone, an oleanolic acid derivative, blocks Keap and has been postulated as a potential mechanism to retard progression of CKD. In one study, patients receiving bardoxolone had significant increases in the mean (± standard deviation) estimated GFR, as compared with placebo, at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone may have promise for the treatment of CKD, however a phase 3 randomized clinical trial failed to achieve the primary end point and was associated with side effects and so the study was stopped.[20] It is not likely that Bardoxolone will be used for renoprotection any time soon.

Role of sodium bicarbonate

Sodium bicarbonate has been shown to reduce tubulointerstitial injury and endothelin production with substantial benefits in slowing progressive kidney damage. In one study on patients with advanced kidney failure, the administration of sodium bicarbonate preserved GFR decline.[20] Even in patients with relatively preserved GFR in stage 2 CKD, the administration of sodium bicarbonate was shown to preserve kidney function over 5 years.[21] A study in patients with stage 4 CKD found that 1 year of consuming a diet that included fruits and vegetables dosed to reduce dietary acid by half had effects comparable to those of daily oral sodium bicarbonate at 1.0 mEq/kg per day.[22]

Role of direct renin inhibitors

Preliminary studies using aliskiren,[23] a direct renin inhibitor, show reductions in proteinuria over 6 months, but larger studies did not show benefit.

Management of other problems

Renal osteodystrophy can be managed early by replacing vitamin D and by administering phosphate binders. Seek and treat nonuremic causes of anemia, such as iron deficiency, before instituting therapy with erythropoietin.

Treat hyperlipidemia (if present) to reduce overall cardiovascular comorbidity, even though evidence for lipid lowering in renal protection is lacking.

Renal Replacement Therapy

Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, and renal transplantation).

Arrange permanent vascular access when the GFR falls below 20-25 mL/min, when the serum creatinine level exceeds 4 mg/dL, or when the rate of increase in the serum creatinine level indicates the need for dialysis within 1 year. Arteriovenous fistulas are preferred to arteriovenous grafts because of their long-term high-patency rates and should be placed whenever possible. Place peritoneal dialysis catheters 2-3 weeks before anticipated dialysis therapy.

Preemptive transplantation before the initiation of dialysis results in better survival than transplantation after the initiation of dialysis. Therefore, preemptive transplantation should be explored from live donors. Patients without live donors can be placed on the deceased donor wait list when the GFR falls below 20 mL/min to accrue time. Patients who opt for no treatment when it is indicated should be informed of imminent renal failure in a shorter time.

Expose patients to educational programs for early rehabilitation from dialysis or transplantation.

Consultations

Patients with any evidence of kidney disease should be referred to a kidney specialist (ie, a nephrologist). Early referral of patients with CRF (serum creatinine, 1.5-2 mg/dL) to a nephrologist is important for managing complications and organizing the transition to renal replacement therapy. Some evidence indicates that early referral of CRF patients to a nephrologist improves the short-term outcome. The nephrologist will usually determine the frequency of visits on the basis of the degree of CKD.

When dialysis is imminent, a surgical consultation should be sought for creation of an arteriovenous fistula or graft to allow insertion of a peritoneal dialysis catheter. Consultation with a transplant surgeon is appropriate for evaluation for kidney transplantation.

Diet and Activity

Protein-restricted diets (0.4-0.6 g/kg/day) are controversial but may be beneficial in slowing the decline in the GFR and reducing hyperphosphatemia (serum phosphate > 5.5 mg/dL) in patients with serum creatinine levels higher than 4 mg/dL. Monitor these patients for signs of malnutrition, which may contraindicate protein restriction. Educate patients about how potassium-rich diets help control hyperkalemia. Many dietary restrictions are no longer necessary with the initiation of renal replacement therapy.

Encourage patients to increase their activity level as tolerated. Increased activity may aid in blood pressure control.

In obese patients with mild to moderate CKD, weight loss may help reverse renal dysfunction, manifesting as reduction in proteinuria and albuminuria.[24, 13]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Medications used to treat chronic glomerulonephritis include angiotensin-converting enzyme (ACE) inhibitors (ACEIs), diuretics, calcium channel blockers, beta-adrenergic blockers, and alpha-adrenergic agonists.

ACE Inhibitors

Class Summary

ACEIs are renoprotective agents. They decrease intraglomerular pressure and, consequently, glomerular protein filtration by decreasing efferent arteriolar constriction.

Enalapril (Vasotec)

Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, thus decreasing aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Captopril

Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. It is rapidly absorbed, but bioavailability is significantly reduced with food intake. Captopril achieves a peak concentration in 1 hour and has a short half-life. It is cleared by the kidney; impaired renal function requires reduction of the dosage. The drug is absorbed well orally.

It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction. Give captopril at least 1 hour before meals. If it is added to water, use it within 15 minutes. The dose can be low initially, then titrated upward as needed and as tolerated by the patient.

Lisinopril (Prinivil, Zestril)

Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Benazepril (Lotensin)

Benazepril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Fosinopril

Fosinopril is a competitive ACE inhibitor. It prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Quinapril (Accupril)

Quinapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Diuretics, Loop

Class Summary

Diuretics are used to treat edema and hypertension. 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.

Diuretics, Thiazide

Class Summary

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.

Calcium Channel Blockers

Class Summary

Calcium channel blockers are used to treat hypertension, angina, and atrial fibrillation.

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. It benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. It can be used during pregnancy if clinically indicated.

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. By interrupting re-entry at the AV node, it can restore normal sinus rhythm (NSR) in patients with paroxysmal supraventricular tachycardias.

Diltiazem (Cardizem, Dilacor XR, Diltzac, Matzim LA)

During depolarization, diltiazem inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.

Beta-Blockers, Beta-1 Selective

Class Summary

Beta-adrenergic blockers compete with beta-adrenergic agonists for available beta-receptor sites. These agents inhibit mainly beta1 receptors (located mainly in cardiac muscle).

Metoprolol (Lopressor, Toprol XL)

Metoprolol is a selective beta1-adrenergic blocker that decreases the automaticity of contractions. During intravenous (IV) administration, carefully monitor blood pressure, heart rate, and electrocardiographic readings.

Bisoprolol (Zebeta)

Bisoprolol is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.

Esmolol (Brevibloc)

Esmolol is an ultra–short-acting beta2-blocker. It is particularly useful in patients with labile arterial pressure, especially if surgery is planned, because it can be discontinued abruptly if necessary. It may be useful as a means to test beta-blocker safety and tolerance in patients with a history of obstructive pulmonary disease who are at possible risk of bronchospasm from beta-blockade. The elimination half-life of esmolol is 9 minutes.

Atenolol (Tenormin)

Atenolol selectively blocks beta-1 receptors with little or no effect on beta-2 receptors.

Beta-Blockers, Nonselective

Class Summary

Nonselective beta-blockers inhibit both beta1 receptors (located mainly in cardiac muscle) and beta2 receptors located in the bronchial and vascular musculature. These agents slow the sinus rate and decrease AV nodal conduction. Carefully monitor blood pressure.

Propranolol (Inderal LA, InnoPran XL)

Propranolol is a class II antiarrhythmic nonselective beta-adrenergic receptor blocker. It has membrane-stabilizing activity and decreases the automaticity of contractions.

Sotalol (Betapace, Sorine)

This class III antiarrhythmic agent blocks K+ channels, prolongs action potential duration (APD), and lengthens the QT interval. It is a non–cardiac selective beta-adrenergic blocker. Sotalol is shown to be effective in the maintenance of sinus rhythm, even in patients with underlying structural heart disease.

Labetalol (Trandate)

Labetalol blocks alpha-, beta1-, and beta2-adrenergic receptor sites, decreasing blood pressure.

Penbutolol

Pindolol has mild intrinsic sympathomimetic activity and negative chronotropic and inotropic effects.

Penbutolol (Levatol)

Penbutolol has mild intrinsic sympathomimetic activity and negative chronotropic and inotropic effects.

Alpha-Blockers, Antihypertensives

Class Summary

Alpha1 antagonists may be used to achieve the target pressure. Peripheral alpha-antagonists inhibit postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decreasing total peripheral resistance and blood pressure. These drugs often cause marked hypotension after the first dose. High doses are likely to cause postural hypotension. Of the peripheral alpha-antagonists, doxazosin and terazosin are selective for alpha1 -receptors. Prazosin is nonselective and inhibits both alpha1- and alpha2-receptors.

Doxazosin (Cardura, Cardura XL)

Doxazosin, a quinazoline compound, is a selective alpha1-adrenergic antagonist. It inhibits postsynaptic alpha-adrenergic receptors, causing vasodilation of veins and arterioles and decreases total peripheral resistance and blood pressure.

Prazosin (Minipress)

Prazosin treats prostatic hypertrophy. It improves urine flow rates through relaxation of smooth muscle, accomplished by blocking alpha1-adrenoceptors in the bladder neck and prostate. When increasing the dose, administer the first dose of each increment at bedtime to reduce syncopal episodes. Although doses higher than 20 mg/day usually do not increase efficacy, some patients may benefit from doses as high as 40 mg/day.

Terazosin

Terazosin decreases arterial tone by allowing peripheral postsynaptic blockade. It has minimal alpha2 effect.

Vasodilators

Class Summary

These drugs act directly on the smooth muscle in the peripheral vasculature to cause vasodilation. Tachycardia and fluid retention are common adverse effects. Prolonged use of minoxidil can cause hypertrichosis. Hydralazine can cause a lupuslike syndrome in certain populations of slow acetylators. Examples of direct vasodilators are minoxidil and hydralazine. Vasodilators may be used to achieve the target pressure.

Minoxidil

Minoxidil relaxes arteriolar smooth muscle, causing vasodilation, which, in turn, may reduce blood pressure.

Hydralazine

Hydralazine decreases systemic resistance through direct vasodilation of arterioles. It is used to treat hypertensive emergencies. The use of a vasodilator reduces systemic vascular resistance, which, in turn, may allow forward flow, improving cardiac output.

Nitroprusside sodium (Nitropress)

Nitroprusside sodium produces vasodilation and increases inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing the heart rate.

Nitroglycerin (Nitro-Bid, Nitrostat, Nitro-Dur, Nitrolingual, NitroMist)

Nitroglycerin is primarily a venodilator that decreases both preload and afterload.

Alpha2 Agonists, Central-Acting

Class Summary

Alpha-adrenergic agonists are used in combination with other agents for management of hypertension.

Clonidine (Catapres, Duraclon, Nexiclon XR)

Clonidine stimulates presynaptic (central) alpha2-adrenergic receptors, thereby reducing norepinephrine release and peripheral vasoconstriction.