eMedicine Specialties > Nephrology > Glomerular Diseases

Glomerulonephritis, Crescentic: Follow-up

Author: Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine; Consulting Physician, Timmins and District Hospital, Ontario, Canada
Contributor Information and Disclosures

Updated: Sep 25, 2008

Follow-up

Further Inpatient Care

• 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.^4,1
• 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.¹
• 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.³ Further study of CAMPATH-1H as an induction agent is warranted.

Further Outpatient Care

• 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 (eg, Randomized trial of prolonged REmission-MAINtenance therapy in systemic vasculitis [REMAIN]).
• 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

Inpatient & Outpatient Medications

• 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.

Transfer

• Patients may need to be transferred to another center for the following:
  • Plasmapheresis
  • Dialysis
  • Ventilatory support

Deterrence/Prevention

• 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.

Complications

• Renal failure
• Pulmonary edema
• Pulmonary hemorrhage
• Respiratory failure

Prognosis

• 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.⁵
• 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 if fibrocellular or acellular)
  • Initial serum creatinine level of more than 500 µmol/L or GFR of less than 5 mL/min at presentation
  • Oliguria
  • Presence of anti-GBM antibody
  • Age older than 60 years
  • Coexistence of HLA-DR2 and HLA-B7

Patient Education

• 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.

Miscellaneous

Medicolegal Pitfalls

• A high index of clinical awareness is important in order to make an early diagnosis in patients presenting with ill-defined fever, weight loss, anorexia, arthralgias, hemoptysis, middle ear effusions, deafness, nasal septal perforation, and saddle nose deformity.
• Consider eradication of S aureus in anterior nares of patients with Wegener granulomatosis for sustained remission.
• Be careful with immunosuppressive therapy (both cytotoxic agents and high-dose corticosteroids) in patients who may have active infection.
• Ensuring that the patient has no active infection is important before starting immunosuppressive therapy in order to prevent significant morbidity and mortality associated with treatment of this disease.
• Intravenous immunoglobulin may be useful to control disease activity when the patient has associated active infection and the need to hold immunosuppressive agents.
• The adverse effects and toxicities of long-term corticosteroid and immunosuppressive therapy must be discussed with the patient.
• With long-term steroid use, monitoring the patient for the development of diabetes, peptic ulcer disease, and osteoporosis is important, as is prescribing cytoprotective agents (to prevent peptic ulceration) and preventive therapy for steroid-induced osteoporosis.
• In patients who are in the reproductive age group, discuss and document the effect on fertility of cytotoxic therapy. Patients should be counseled for sperm or egg preservation, or consideration should be given to leuprolide therapy to inhibit gametogenesis during treatment with cyclophosphamide therapy.
• To prevent risk of hemorrhagic cystitis, patients on oral cyclophosphamide should be encouraged to drink plenty of fluids so that the metabolites of cyclophosphamide do not concentrate in the bladder.
• The possibility of late malignancy associated with cytotoxic therapy should be discussed and documented in the patient's chart.
• Failure to diagnose or empirically treat pending diagnosis, with a resulting rise of serum creatinine to unsalvageable levels (>6 mg/dL or 500 µmol/L), is a potential medicolegal pitfall.

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