Crescentic Glomerulonephritis Follow-up
- Author: Malvinder S Parmar, MB, MS; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Further Outpatient Care
See the list below:
- After induction of remission with oral cyclophosphamide and steroids, conversion to oral azathioprine (2 mg/kg/d) at 3 months appears to be safe and effective compared to continuation of cyclophosphamide for 1 year (if clinical signs of activity are minimal and preferably ANCA is negative) (CYCAZAREM). The duration of maintenance therapy with azathioprine to prevent further relapses is unknown but should be at least for 2 years. Studies of longer periods of azathioprine maintenance (2 y vs 4 y) are in progress.
- Monitor BUN, electrolyte, and serum creatinine levels in all patients.
- Drug-responsive relapses may occur as late as 2-4 years after remission.
- RPGN may recur after renal transplantation. At present, after initiating dialysis, a waiting period of 3-6 months is recommended before considering renal transplantation.
- No convincing evidence suggests that a bilateral nephrectomy performed before a renal transplantation reduces the risk of recurrent disease in patients with renal allografts.
- For patients who have achieved remission, evaluation at 2-month intervals is usually sufficient. The following testing is recommended:
- Urinalysis with special emphasis on the presence of cellular casts: BUN, electrolyte, and serum creatinine levels should be evaluated in all patients.
- C-reactive protein or ESR (whichever correlates better with disease activity in a given patient)
- ANCA (in ANCA-positive patients at 6- to 9-mo intervals): An increasing ANCA titer is often evidence of an impending relapse. A 4-fold or higher rise in ANCA titer may herald a relapse and require preemptive intervention.
- Anti-GBM titers in patients with anti-GBM
Further Inpatient Care
See the list below:
- Intensive plasma exchange: Plasmapheresis (2-4 L of plasma qd or 3 times/wk), combined with glucocorticoids and cytotoxic agents, is beneficial in anti–GBM-mediated disease, provided therapy is initiated before renal failure has progressed to require dialysis support. Plasma exchange is also valuable as an adjunctive measure in patients with positive ANCA results who present with life-threatening pulmonary hemorrhage (ie, MEthylprednisolone versus Plasma EXchange [MEPEX]) or advanced renal failure.[13, 1]
- Plasma exchange increased the rate of renal recovery in ANCA-associated systemic vasculitis that presented with renal failure when compared with intravenous methylprednisolone; however, patient survival and adverse event rates were similar in both groups.
- In the absence of any response within 3-5 weeks, acceptance of a diagnosis of end-stage renal disease is preferable to death secondary to iatrogenic causes.
- High-dose intravenous immunoglobulin has been reported to be successful in suppressing the activity of pauci-immune ANCA-positive vasculitis. The mechanism is not clear, but pooled normal immunoglobulin contains antibodies that neutralize ANCA and suppress complement activation through a nonspecific effect of the immunoglobulin heavy chains.
- Intravenous immunoglobulin may have a role in the temporary management of severe pauci-immune vasculitis when severe infection is present in patients in whom it is desirable to withhold cytotoxic agents and high-dose corticosteroids until the infection is controlled.
- In difficult to treat cases of ANCA-associated vasculitis, humanized monoclonal anti-CD52 antibodies (alemtuzumab, CAMPATH-1H) that selectively deplete lymphocytes may be considered. In a recent study by Walsh et al, CAMPATH-1H induced remission in such a group of patients, but relapse and adverse events were common. Further study of CAMPATH-1H as an induction agent is warranted.
Inpatient & Outpatient Medications
See the list below:
- Administer oral cyclophosphamide for 4-6 months, followed by azathioprine or methotrexate until the patient is in remission for 6 months to 1 year.
- Administer prednisone as a low-dose alternative for 6-9 months.
- Administer trimethoprim-sulfamethoxazole 160/800 mg bid (for Wegener granulomatosis) if renal function normal. Decrease the dose as guided by renal function. A lower dosage as PCP prophylaxis may be considered.
See the list below:
- Patients may need to be transferred to another center for the following:
- Ventilatory support
See the list below:
- Because patients with pauci-immune vasculitis typically have a prodrome lasting for weeks to months—during which time they experience 1 or more vague symptoms (eg, intermittent fever, weight loss, anorexia, arthralgias, shortness of breath, hemoptysis, middle ear effusions, conjunctivitis, episcleritis, nasal septal perforation, saddle nose deformity)—a high index of clinical awareness, early diagnosis, and treatment may prevent significant morbidity and mortality associated with this condition.
See the list below:
- Renal failure
- Pulmonary edema
- Pulmonary hemorrhage
- Respiratory failure
See the list below:
- In general, the prognosis is poor and aggressive therapy is warranted. The chance of renal recovery exceeds the chance of dying in most cases. Intravenous methylprednisolone as an adjunctive therapy plus less than 18% normal glomeruli and severe tubular atrophy increased the chance of therapy-related death over the chance of dialysis independence. Plasma exchange treatment plus severe tubular atrophy and less than 2% normal glomeruli increased the chance of therapy-related death over that of dialysis independence.
- Fifty percent of patients require maintenance dialysis within 6 months of disease onset.
- Spontaneous remission is uncommon, except among patients with infection as the basis for formation of antigen-antibody complexes, in whom removal of the antigen can take place.
- Poor prognostic factors are as follows:
- Large crescents in more than 80% of glomeruli (especially circumferential fibrocellular or fibrous/acellular crescents)
- Initial serum creatinine level of more than 500 µmol/L or GFR of less than 5 mL/min at presentation
- Presence of anti-GBM antibody
- Age older than 60 years
- Coexistence of HLA-DR2 and HLA-B7
See the list below:
- Patients receiving immunosuppressive therapy should be educated about early signs of infection and advised to see their physician or health care worker at the early signs of infection in order to monitor WBC count.
- Patients on a high dose of prednisone should be monitored for the development of diabetes and peptic ulcer disease and receive therapy to prevent steroid-induced osteoporosis.
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. 2007 Jul. 18(7):2180-8. [Medline].
Gupta R, Singh L, Sharma A, Bagga A, Agarwal SK, Dinda AK. Crescentic glomerulonephritis: a clinical and histomorphological analysis of 46 cases. Indian J Pathol Microbiol. 2011 Jul-Sep. 54(3):497-500. [Medline].
Bollée G, Flamant M, Schordan S, Fligny C, Rumpel E, Milon M, et al. Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis. Nat Med. 2011 Sep 25. 17(10):1242-50. [Medline]. [Full Text].
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. Jul 2010. 363(3):221-32. [Medline].
Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. Aug 2013. 369(5):417-27. [Medline].
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. Jul 2010. 363(3):211-20. [Medline].
De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. Aug 2005. 52(8):2461-9. [Medline].
Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. Jan 2005. 352(4):351-61. [Medline].
Walsh M, Casian A, Flossmann O, Westman K, Höglund P, Pusey C, et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. Aug 2013. 84(2):397-402. [Medline].
Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. Mar 2013. 14:73. [Medline].
Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. Dec 2010. 304(21):2381-8. [Medline].
Roubaud-Baudron C, Pagnoux C, Méaux-Ruault N, Grasland A, Zoulim A, LE Guen J, et al. Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. J Rheumatol. Jan 2012. 39(1):125-30. [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. 1995 Jul. 101 Suppl 1:29-34. [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. 2008 Sep. 67(9):1322-7. [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. 2007 Jul. 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. 2000 Sep. 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. 2005 Jun. 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. 2004 Aug. 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. 1992 Sep. 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. 2005 Jan 27. 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. 1997 Feb. 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. 2006 Jul. 65(7):841-4. [Medline].
Garcia-Canton C, Toledo A, Palomar R, et al. Goodpasture's syndrome treated with mycophenolate mofetil. Nephrol Dial Transplant. 2000 Jun. 15(6):920-2. [Medline].
Goek ON, Stone JH. Randomized controlled trials in vasculitis associated with anti-neutrophil cytoplasmic antibodies. Curr Opin Rheumatol. 2005 May. 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. 2003 Nov. 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. 2003 Jul 3. 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). 1985 Jul. 64(4):219-27. [Medline].
Jordan SC. Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin. J Clin Immunol. 1995 Nov. 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. 2005 Apr. 19(2):307-20. [Medline].
Masala A, Faedda R, Alagna S, et al. Use of testosterone to prevent cyclophosphamide-induced azoospermia. Ann Intern Med. 1997 Feb 15. 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. 1999 Sep. 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. 1989 Mar-Apr. 10(2):143-6. [Medline].
Stilmant MM, Bolton WK, Sturgill BC, et al. Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. 1979 Feb. 15(2):184-95. [Medline].
Thompson CH, Kalowski S. Anti-glomerular basement membrane nephritis due to hydralazine. Nephron. 1991. 58(2):238-9. [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. 2007 Sep. 72(6):676-82. [Medline].
Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaître O, Cohen P, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. Nov 2014. 371(19):1771-80. [Medline].