eMedicine Specialties > Nephrology > Glomerular Diseases
Glomerulonephritis, Crescentic: Treatment & Medication
Updated: Sep 25, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Early and aggressive treatment is warranted to preserve renal function. Principles of general therapy are listed in Medication.
For specific therapies, see the following related articles:
- RPGN type I: See Goodpasture Syndrome.
- RPGN type II: See Lupus Nephritis.
- RPGN type III: See Glomerulonephritis, Rapidly Progressive.
Consultations
A nephrologist should be involved early in the disease course.
Diet
- Renal diet: Provide a low-salt, low-protein (0.8 g/kg/d) diet, if renal dysfunction is present. Restrict potassium if the patient has hyperkalemia. Avoid malnutrition.
Activity
No specific limitations are necessary other than limiting activity after renal biopsy.
Medication
Principles of therapy include supportive and specific therapies. Supportive therapy involves control of infection, control of volume status (providing dialysis if required), and smoking cessation. Specific therapy is directed toward providing immunosuppressive therapy (eg, glucocorticoids, cyclophosphamide, azathioprine, mycophenolate [MMF]), plasma exchange (in patients presenting with life-threatening pulmonary hemorrhage or advanced renal failure, ie, creatinine level of >500 µmol/L1 ), and anticoagulant agents.
Recently, monoclonal antibodies (eg, infliximab, rituximab),2 alemtuzumab,3 pentoxifylline (reduces TNF), mizoribine (a purine synthesis inhibitor), and antithymocyte globulin have been used with encouraging results in a small number of patients, but controlled trials are needed.
At present, the mainstay of therapy remains cyclophosphamide and steroids for induction of remission.
Glucocorticoids
Pulses of intravenous methylprednisolone (5-20 mg/kg) followed by high-dose oral prednisone (2 mg/kg) daily or on alternate days for 2-3 months have shown improved 1-year renal survival rates of 40-70%.
Methylprednisolone (Solu-Medrol)
Potent anti-inflammatory steroid with greater anti-inflammatory potency and fewer tendencies to induce retention of salt and water than prednisolone.
Adult
0.5-1 g (5-20 mg/kg) IV bolus qd for 3 d, followed by prednisone 2 mg/kg PO daily or on alternate days for 2-3 mo
Pediatric
30 mg/kg IV qd for 3 d, followed by prednisone 2 mg/kg PO qd
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
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
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; may result in partial loss of hypertension control
Prednisone (Deltasone, Orasone, Sterapred)
Decreases inflammation through multiple mechanisms. Reduced to its pharmacologically active form prednisolone. When used on a long-term basis, alternate-day therapy may elicit fewer adverse effects than daily therapy.
Adult
2 mg/kg PO qd for 2-3 mo; then, taper dose
Pediatric
Administer as in adults
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Immunosuppressive agents (cytotoxics)
Addition of cytotoxic agents to corticosteroids has yielded varying success in treating patients with crescentic glomerulonephritis. Although pulse cyclophosphamide is often preferred in lupus nephritis, oral cyclophosphamide appears to have an advantage in Wegener granulomatosis.
Oral versus intravenous: Recently completed, prospectively randomized Cyclophosphamide daily oral versus PulSed (CYCLOPS) trial has shown very little difference in time to remission and time to relapse between daily oral or intermittent intravenous cyclophosphamide for induction therapy.
Cyclophosphamide 3 mg/kg/d for 12 weeks is a common recommendation, but the duration of therapy may be longer (4-6 mo) in patients with pauci-immune glomerulonephritis. This therapy should be followed by the administration of azathioprine (1.5-2 mg/kg/d) or methotrexate (5-20 mg qwk as a single dose) until the patient is in remission for at least 6-12 months. The duration of azathioprine therapy to prevent further relapses is unknown, but it should be at least for 2 years.
Continuing cyclophosphamide for longer than 6 months is not necessary, as recently shown by Cyclophosphamide versus Azathioprine during Remission (CYCAZAREM) trial, where the time to relapse was identical whether the patient was given cyclophosphamide for less than 6 months or more than 6 months.
Recent evidence suggests that mycophenolate mofetil (CellCept) 0.75-1 g bid may also be effective in patients with pauci-immune vasculitis.
Cyclophosphamide (Cytoxan)
Activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none–type reaction.
Adult
3 mg/kg PO qd for 12 wk
Pediatric
2 mg/kg/d PO qd
Allopurinol may increase risk of bleeding or infection and may enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide, while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity, severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; young adults in reproductive age group should be advised about the risk of infertility, and appropriate steps should be taken to avoid this problem (either considering use of a sperm bank or use of leuprolide to suppress gonadotrophic function during the treatment course); malignancy of urinary bladder or lymphatic system may occur
Azathioprine (Imuran)
Mechanism by which azathioprine affects autoimmune diseases is unknown. Slow acting, and its effects may persist after discontinuation.
Adult
1.5-2 mg/kg PO qd until remission for 6-12 mo
Pediatric
2-2.5 mg/kg PO qd
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur
Antibiotics
Therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.
Trimethoprim-sulfamethoxazole (Septra, Septra DS)
Long-term treatment with TMP (160 mg) and SMX (800 mg) bid has been reported in a prospective, controlled, double-blind trial to sustain remission of Wegener granulomatosis. The mechanism of this effect is not clear. Eradication of Staphylococcus aureus in the anterior nares of patients with Wegener granulomatosis has recently been reported to sustain remission of Wegener granulomatosis. TMP-SMX is also helpful as Pneumocystis carinii pneumonia (PCP) prophylaxis in patients who are on corticosteroids and other immunosuppressive agents.
Adult
TMP 160 mg/SMX 800 mg PO q12h; adjust dose per renal function:
CrCl >25 mL/min: No change
CrCl 15-25 mL/min: Reduce dose by 50%
CrCl <15 mL/min: Not recommended
Pediatric
<2 months: Do not administer
>2 months: 5-10 mg/kg/d PO tid/qid, based on TMP
May increase PT when used with warfarin (perform coagulation tests, and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
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
Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with chronic alcoholism, the elderly, patients receiving anticonvulsant therapy, or patients with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMX; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation
More on Glomerulonephritis, Crescentic |
| Overview: Glomerulonephritis, Crescentic |
| Differential Diagnoses & Workup: Glomerulonephritis, Crescentic |
 Treatment & Medication: Glomerulonephritis, Crescentic |
| Follow-up: Glomerulonephritis, Crescentic |
| Multimedia: Glomerulonephritis, Crescentic |
| References |
| « Previous Page | Next Page » |
References
[Best Evidence] Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. Jul 2007;18(7):2180-8. [Medline].
Walsh M, Jayne D. Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int. Sep 2007;72(6):676-82. [Medline].
Walsh M, Chaudhry A, Jayne D. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis. Sep 2008;67(9):1322-7. [Medline].
European therapeutic trials in ANCA-associated systemic vasculitis: disease scoring, consensus regimens and proposed clinical trials. European Community Study Group on Clinical Trials in Systemic Vasculitis ECSYSVASTRIAL. Clin Exp Immunol. Jul 1995;101 Suppl 1:29-34. [Medline].
de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, et al. Chances of renal recovery for dialysis-dependent ANCA-associated glomerulonephritis. J Am Soc Nephrol. Jul 2007;18(7):2189-97. [Medline].
Aoki S, Kotooka N, Yokoyama M, et al. Recurrence of rapidly progressive glomerulonephritis probably associated with two different kinds of drugs. Clin Nephrol. Sep 2000;54(3):249-51. [Medline].
Bachmeyer C, Cadranel JF, Demontis R. Rituximab is an alternative in a case of contra-indication of cyclophosphamide in Wegener's granulomatosis. Nephrol Dial Transplant. Jun 2005;20(6):1274. [Medline].
Bombassei GJ, Kaplan AA. The association between hydrocarbon exposure and anti-glomerular basement membrane antibody-mediated disease (Goodpasture's syndrome). Am J Ind Med. 1992;21(2):141-53. [Medline].
Booth AD, Pusey CD, Jayne DR. Renal vasculitis--an update in 2004. Nephrol Dial Transplant. Aug 2004;19(8):1964-8. [Medline].
Cole E, Cattran D, Magil A, et al. A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. Am J Kidney Dis. Sep 1992;20(3):261-9. [Medline].
Couser WG. Idiopathic rapidly progressive glomerulonephritis. Am J Nephrol. 1982;2(2):57-69. [Medline].
Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. Jan 27 2005;352(4):351-61. [Medline].
European Vasculitis Study Group. Clinical trial protocol: REMAIN. Randomised trial or prolonged remission-maintenance therapy in systemic vasculitis. June 2003.
Falk RJ, Jennette JC. ANCA small-vessel vasculitis. J Am Soc Nephrol. Feb 1997;8(2):314-22. [Medline].
Flossmann O, Jones RB, Jayne DR, et al. Should rituximab be used to treat antineutrophil cytoplasmic antibody associated vasculitis?. Ann Rheum Dis. Jul 2006;65(7):841-4. [Medline].
Garcia-Canton C, Toledo A, Palomar R, et al. Goodpasture's syndrome treated with mycophenolate mofetil. Nephrol Dial Transplant. Jun 2000;15(6):920-2. [Medline].
Goek ON, Stone JH. Randomized controlled trials in vasculitis associated with anti-neutrophil cytoplasmic antibodies. Curr Opin Rheumatol. May 2005;17(3):257-64. [Medline].
Jarraya F, Abid M, Jlidi R, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with benzylthiouracil therapy: report of the first case. Nephrol Dial Transplant. Nov 2003;18(11):2421-3. [Medline].
Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. Jul 3 2003;349(1):36-44. [Medline].
Jayne DRW, Gaskin G, (EUVAS). Randomized trial of cyclophosphamide versus azathioprine during remission in ANCA-associated vasculitis (CYCAZAREM). J Am Soc Nephrol. 1999;10:105A.
Johnson JP, Moore J Jr, Austin HA 3rd, et al. Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors. Medicine (Baltimore). Jul 1985;64(4):219-27. [Medline].
Jordan SC. Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin. J Clin Immunol. Nov 1995;15(6 Suppl):76S-85S. [Medline].
Kallenbach M, Duan H, Ring T. Rituximab induced remission in a patient with Wegener's granulomatosis. Nephron Clin Pract. 2005;99(3):c92-6. [Medline].
Langford CA. How can relapses be detected and prevented in primary systemic small-vessel vasculitides?. Best Pract Res Clin Rheumatol. Apr 2005;19(2):307-20. [Medline].
Masala A, Faedda R, Alagna S, et al. Use of testosterone to prevent cyclophosphamide-induced azoospermia. Ann Intern Med. Feb 15 1997;126(4):292-5. [Medline].
Murray AN, Cassidy MJ, Templecamp C. Rapidly progressive glomerulonephritis associated with rifampicin therapy for pulmonary tuberculosis. Nephron. 1987;46(4):373-6. [Medline].
Nowack R, Gobel U, Klooker P, et al. Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol. Sep 1999;10(9):1965-71. [Medline].
Ogata H, Kubo M, Tamaki K, et al. Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis. Nephron. 1998;78(3):319-22. [Medline].
Pagniez D, Fortin F, Delvallez L, et al. [Favorable course under cotrimoxazole of excavated pneumopathy complicating rapidly progressive glomerulonephritis: Wegener's granulomatosis?]. Rev Med Interne. Mar-Apr 1989;10(2):143-6. [Medline].
Stilmant MM, Bolton WK, Sturgill BC, et al. Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. Feb 1979;15(2):184-95. [Medline].
Thompson CH, Kalowski S. Anti-glomerular basement membrane nephritis due to hydralazine. Nephron. 1991;58(2):238-9. [Medline].
Further Reading
Keywords
crescentic glomerulonephritis, idiopathic crescentic glomerulonephritis, idiopathic rapidly progressive glomerulonephritis, RPGN, GN, renal failure, kidney failure, acute nephritic syndrome, anti–glomerular basement membrane disease, anti-GBM disease, glomerulopathy, glomerular filtration rate, GFR, antineutrophil cytoplasmic antibody, ANCA, azotemia, oliguria, Goodpasture syndrome, Wegener granulomatosis, systemic lupus erythematosus, SLE, poststreptococcal glomerulonephritis, PSGN, membranoproliferative glomerulonephritis, MPGN
