Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy (RESCUE)

Peking University

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Glomerulonephritis, IGA; Kidney Diseases; Rapidly Progressive Glomerulonephritis; Acute Renal Insufficiency

Treatments: Procedure: Plasma Exchange (PE); Drug: Methylprednisolone pulse

Study type: Interventional

Funder types: Other

Identifiers

NCT02647255

RESCUE

Details and patient eligibility

About

Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. This study will evaluate the efficacy and safety of plasma exchange as adjunctive therapy for severe crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.

Full description

IgA nephropathy (IgAN) is one of the most common glomerulonephritides and is characterized by a highly variable clinical course and diverse histopathological lesions. Although most affected individuals develop chronic, slowly progressive renal injury, a subgroup of patients (<5% of all IgAN patients) with diffuse crescent formation, which is termed as crescentic IgA nephropathy (CreIgAN) and often leads to rapidly progressive kidney failure. The recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest high-dose steroids and cyclophosphamide therapy for CreIgAN. However, this suggestion is mainly based on several small observational studies, and the 1- and 5-year renal survival rates of patients treated with this regimen were as low as 65% and 28%, respectively, in one large cohort of CreIgAN patients. The efficacy of plasma exchange (PE) in severe CreIgAN is not well evaluated, although several anecdotal reports have indicated benefit of PE in combination with immunosuppressive therapies in IgAN patients. Retrospective cohort study in our unite also supported the benefit of PE as additional therapy for CreIgAN patients. However, randomized controlled trial is needed to evaluate the efficacy and safety of plasma exchange as adjunctive therapy for crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.

Enrollment: 10 patients

Sex: All

Ages: 14 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Biopsy-proven within 3ws
2. Primary IgAN or Henoch-Schönlein Purpura nephritis of crescent >50%(>8 glomeruli)
3. Serum creatinine ≥ 200 μmol/l， rapidly deterioration of renal function

Exclusion criteria

1. <14 or >65 years old
2. With high Scr requiring dialysis for≥ 3w
3. Scr>200μmol/L ≥1 yr before entry
4. Main of old crescent ; Fibrous crescent>50%
5. Anti-glomerular basement membrane (GBM) or antineutrophil cytoplasmic antibody (ANCA) antibody positive
6. Women in gestational and lactational period
7. With diabetes or uncontrollable malignant hypertension or Thrombotic Microangiopathy
8. With Malignancy
9. Chronic active infection including HBV hepatitis C virus (HCV) HIV or active tuberculosis
10. Other autoimmune disease
11. A second clearly defined cause of renal failure
12. Contraindication of plasma exchange treatment or steroid pulse
13. Patients who are unlikely to comply with the study protocol in the view of the treating physician.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

PE and methylprednisolone pulse

Experimental group

Description:

Plasma exchange(PE) and methylprednisolone pulse therapy: plasma exchange \>7 within 3ws, Volume: 60ml/kg/course; Replacement fluid: 5% albumin or fresh frozen plasma and methylprednisolone pulse therapy Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month.

Treatment:

Procedure: Plasma Exchange (PE)

Drug: Methylprednisolone pulse

Methylprednisolone pulse

Active Comparator group

Description:

Methylprednisolone pulse alone: methylprednisolone 7-15mg/kg/d 3 times on consecutive or alternate days Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month.

Treatment:

Drug: Methylprednisolone pulse