eMedicine Specialties > Nephrology > Glomerular Diseases
Glomerulonephritis, Chronic: Treatment & Medication
Updated: Oct 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Progression from CKD to 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. Specific therapies for some glomerular diseases (eg, lupus) should be implemented in appropriate settings. Aggressively manage anemia and renal osteodystrophy (eg, hyperphosphatemia, hypocalcemia, hyperparathyroidism) before renal replacement therapy. Also, aggressively manage comorbid conditions, such as heart disease and diabetes.
- The target pressure for patients with proteinuria greater than 1 g/d is less than 125/75 mm Hg; for patients with proteinuria less than 1 g/d, 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 CRF. ACEIs are renoprotective agents that have additional benefits beyond lowering pressure. ACEIs effectively reduce proteinuria, in part by reducing the efferent arteriolar vascular tone, thereby decreasing intraglomerular hypertension. Particularly, ACEIs have been shown to be superior to conventional therapy in slowing the decline of the GFR in patients with diabetic and nondiabetic proteinuric nephropathies. Therefore, consider ACEIs for treatment of even normotensive patients with significant proteinuria.3
- 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 in a manner similar to that of ACEIs.
- Combination therapy with ACEIs and ARBs has been shown to confer superior pressure control and preservation of renal function than either therapy alone. Therefore, in patients without hyperkalemia or an acute rise in serum creatinine levels following the use of either therapy, combination therapy should be attempted.
- 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 to less than 25 mL/min. Diuretics are also useful in counteracting the hyperkalemic potential of ACEIs and ARBs. However, diuretics 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 volume depletion induced by diuretics, potentially precipitating acute renal failure.
- Beta-blockers, calcium channel blockers, central alpha-2 agonists (eg, clonidine), alpha-1 antagonists, and direct vasodilators (eg, minoxidil, nitrates) may be used to achieve the target pressure.
- Because progressive fibrosis is the hallmark of chronic glomerulonephritis, some investigators have focused their work on finding inhibitors of fibrosis in an attempt to slow progression. Of many compounds, pirfenidone, an inhibitor of transforming growth factor beta, and hence of collagen synthesis, has emerged as the candidate compound. Cho et al performed an open label study on 21 patients with idiopathic and postadaptive focal segmental glomerulosclerosis.4 They found a median 25% improvement in the rate of decline of the estimated GFR (P <0.01). Pirfenidone did not effect proteinuria or blood pressure. Among the adverse events attributed to therapy were dyspepsia, sedation, and photosensitive dermatitis. Pirfenidone offers hope in slowing progressive fibrosis; however more studies are needed.
- 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.
- Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, renal transplantation). Arrange permanent vascular access when the GFR decreases to less than 20-25 mL/min, when the serum creatinine level is greater than 4 mg/dL, or if the rate of rise 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 prior to anticipated dialysis therapy.
- Treat hyperlipidemia (if present) to reduce overall cardiovascular comorbidity, even though evidence for renal protection is lacking.
- Expose patients to educational programs for early rehabilitation from dialysis or transplantation.
Surgical Care
Create access for dialysis when the GFR decreases to less than 25 mL/min.
Consultations
- Nephrologists: Early referral of patients with CRF to a nephrologist is important for the management of complications and the organization of the transition to renal replacement therapy (eg, hemodialysis, peritoneal dialysis, renal transplantation). Some evidence indicates that early referral of a patient with CRF (serum creatinine, 1.5-2 mg/dL) to a nephrologist improves the short-term outcome.
- Surgeons: When dialysis is imminent, seek consultation for creation of an arteriovenous fistula or graft for the insertion of a peritoneal dialysis catheter.
- Transplantation surgeons: Seek consultations for evaluation for kidney transplantation.
Diet
- Protein-restricted diets (0.4-0.6 g/kg/d) are controversial but may be beneficial in slowing the decline in the GFR and in reducing hyperphosphatemia (serum phosphate, >5.5 mg/dL) in patients with serum creatinine levels of greater than 4 mg/dL. Monitor these patients for signs of malnutrition, which may contraindicate protein restriction.
- Educate patients about how diets rich in potassium help control hyperkalemia.
- Many dietary restrictions are no longer necessary with the initiation of renal replacement therapy.
Activity
- Encourage patients to increase their activity level as tolerated. Increased activity may aid in blood pressure control.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Angiotensin-converting enzyme inhibitors
For renoprotection. Decrease intraglomerular pressure and, consequently, glomerular protein filtration, by decreasing efferent arteriolar constriction.3
Enalapril (Vasotec)
Competitive inhibitor of ACE. Reduces angiotensin II levels, thus decreases aldosterone secretion. Decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.
Adult
2.5-10 mg PO qd; not to exceed 40 mg qd
Pediatric
Not established
NSAIDs may reduce hypotensive effects; may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects may be enhanced when administered concurrently with diuretics
Documented hypersensitivity; hyperkalemia; AV block; hypotension; sick sinus syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal impairment, valvular stenosis, or severe congestive heart failure; causes increase in serum potassium levels, which require careful monitoring
Diuretics
Treat edema and hypertension. Increase urine excretion by inhibiting sodium and chloride transporters.
Furosemide (Lasix)
DOC as a diuretic. Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Adult
1-2 mg/kg PO/IV qd/bid; not to exceed 600 mg/d
0.1-0.4 mg/kg/h continuous IV infusion
Pediatric
1-2 mg/kg PO/IV qd/bid; not to exceed 6 mg/kg/dose
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration with aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently
Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter
Metolazone (Mykrox, Zaroxolyn)
Treats edema in congestive heart failure. Increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. May be more effective in impaired renal function.
Adult
5-20 mg PO qd
Pediatric
Not established
Thiazides may decrease effect of anticoagulants, sulfonylureas, and gout treatments; anticholinergics and amphotericin B may increase toxicity of thiazides; effects of thiazides may decrease when used concurrently with bile acid sequestrants, NSAIDs, or methenamine; when administered concurrently, thiazides increase toxicity of anesthetics, diazoxide, digitoxin, lithium, loop diuretics, antineoplastics, allopurinol, calcium salts, vitamin D, and nondepolarizing muscle relaxants
Documented hypersensitivity; hepatic coma or anuria
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hepatic or renal disease, diabetes mellitus, gout, or lupus erythematosus
Calcium channel blockers
Treat hypertension, angina, and atrial fibrillation.5
Amlodipine (Norvasc)
Blocks slow calcium channels, causing relaxation of vascular smooth muscles.
Adult
2.5-10 mg PO qd
Pediatric
Not established
May increase effects of benazepril, beta-blockers, and cyclosporine
Documented hypersensitivity; hypotension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause hypotension, severe left ventricular dysfunction, or sick sinus syndrome; caution in hepatic and renal dysfunction
Nifedipine (Procardia)
Relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. SL administration generally safe, despite theoretical concerns.
Adult
Short-acting: 10 mg PO tid
Long-acting: 30 mg PO qd; not to exceed 120-180 mg qd
Pediatric
Not established
Caution with coadministration of any agent that can lower blood pressure, including beta-blockers and opioids; H2 blockers (cimetidine) may increase toxicity
Documented hypersensitivity; hypotension; sick sinus syndrome; AV blocks; aortic stenosis; acute MI; cardiogenic shock
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Short-acting forms not recommended for hypertensive emergencies because sudden fall in blood pressure may cause cerebral and cardiac ischemia; may cause lower extremity edema; allergic hepatitis is rare
Beta-adrenergic blockers
Compete with beta-adrenergic agonists for available beta-receptor sites. Propranolol, nadolol, timolol, penbutolol, carteolol, sotalol, and pindolol inhibit both beta-1 receptors (located mainly in cardiac muscle) and beta-2 receptors (located mainly in bronchial and vascular musculature), thus inhibiting chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.
Metoprolol (Lopressor)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult
50 mg PO bid, qwk to desired effect; not to exceed 450 mg/d
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in second and third trimesters, beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Alpha-adrenergic agonists
Used in combination with other agents for management of hypertension.
Clonidine (Catapres)
Stimulates presynaptic (central) alpha-2 agonist, thereby reducing norepinephrine release and peripheral vasoconstriction.
Adult
0.1-0.2 mg PO bid/tid; not to exceed 2.4 mg qd
Pediatric
Not established
TCAs inhibit hypotensive effects; coadministration with beta-blockers may potentiate bradycardia; TCAs may enhance hypertensive response associated with abrupt clonidine withdrawal; hypotensive effects are enhanced by narcotic analgesics
Documented hypersensitivity; breastfeeding; abrupt discontinuation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cerebrovascular disease, coronary insufficiency, sinus node dysfunction, and renal impairment
More on Glomerulonephritis, Chronic |
| Overview: Glomerulonephritis, Chronic |
| Differential Diagnoses & Workup: Glomerulonephritis, Chronic |
 Treatment & Medication: Glomerulonephritis, Chronic |
| Follow-up: Glomerulonephritis, Chronic |
| References |
| Further Reading |
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References
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Further Reading
Clinical guidelines:
ACR Appropriateness Criteria® renal failure. American College of Radiology - Medical Specialty Society. 1995 (revised 2008). 10 pages. NGC:007019
Clinical trials:
Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
Etanercept for the Treatment of Lupus Nephritis
Retinoids for Minimal Change Disease and Focal Segmental Glomerulosclerosis
Keywords
glomerulonephritis, chronic glomerulonephritis, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, poststreptococcal glomerulonephritis, glomerulonephritis treatment, crescentic glomerulonephritis, glomerulosclerosis, rapidly progressive glomerulonephritis, RPGN, focal segmental glomerulosclerosis, FSGS, glomerular fibrosis, tubulointerstitial fibrosis, lupus nephritis, azotemia, uremia
