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Due to the rarity and rapid progressive course of the disease, patients were less likely to participate in randomization.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PE and methylprednisolone pulse | Experimental | 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. |
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| Methylprednisolone pulse | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Plasma Exchange (PE) | Procedure | PE treatment>7 within 3weeks; Volume exchanged: 60ml/kg/course; Replacement fluid: 5% Albumin or fresh frozen plasma; PE was performed by dialysis machine (IQ-21, Asahi Japan) and plasma separator (OP- 08W, Asahi Japan) |
| Measure | Description | Time Frame |
|---|---|---|
| End-stage renal disease or death | End-stage renal disease: defined as a need for maintenance dialysis > 6 months; or need kidney transplantation , and death; during follow-up. | 12 months after final subject is enrolled |
| Measure | Description | Time Frame |
|---|---|---|
| Renal remission | Renal remission: defined as the independent of dialysis, or serum creatinine under 200μmol/l within 6 months, and lasts without a first relapse until at least 12 months after randomization | 12 months after final subject is enrolled |
| Proteinuria remission |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of serious adverse events | Serious adverse events are defined as: Clinically apparent gastrointestinal haemorrhage requiring hospitalization or prolonging the time of hospitalization. Serious infections requiring hospitalization or prolonging the time of hospitalization. Severe allergic reaction requiring hospitalization or prolonging the time of hospitalization. Chronic viral infection, including HIV hepatitis B virus(HBV) and HCV Other adverse events |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hong Zhang, MD, PHD | Renal Division, Department of Medicine, Peking University First Hospital;Peking University Institute of Nephrology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Renal Division, Department of Medicine, Peking University First Hospital | Beijing | Beijing Municipality | 100034 | China | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21949093 | Background | Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011 Oct;22(10):1795-803. doi: 10.1681/ASN.2011050464. Epub 2011 Sep 23. | |
| 24029421 | Background | Lv J, Yang Y, Zhang H, Chen W, Pan X, Guo Z, Wang C, Li S, Zhang J, Zhang J, Liu L, Shi S, Wang S, Chen M, Cui Z, Chen N, Yu X, Zhao M, Wang H. Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study. J Am Soc Nephrol. 2013 Dec;24(12):2118-25. doi: 10.1681/ASN.2012101017. Epub 2013 Sep 12. |
| Label | URL |
|---|---|
| KDIGO Clinical Practice Guideline for Glomerulonephritis (GN) | View source |
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| ID | Term |
|---|---|
| D005922 | Glomerulonephritis, IGA |
| D007674 | Kidney Diseases |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D010951 | Plasma Exchange |
| D010956 | Plasmapheresis |
| ID | Term |
|---|---|
| D001803 | Blood Transfusion |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D001781 | Blood Component Removal |
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|
| Methylprednisolone pulse | Drug | methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod |
|
|
Proteinuria remission: defined as proteinuria < 0.5g/d for ≥3months |
| At the 12th month and 36th month after randomization |
| From 12 months after first subject enrolled to 12 months after final subject is enrolled |
| Renal division, Peking University First Hospital |
| Beijing |
| Beijing Municipality |
| 100034 |
| China |
| 3955907 | Background | Abe T, Kida H, Yoshimura M, Yokoyama H, Koshino Y, Tomosugi N, Hattori N. Participation of extracapillary lesions (ECL) in progression of IgA nephropathy. Clin Nephrol. 1986 Jan;25(1):37-41. |
| 12381947 | Background | Tang Z, Wu Y, Wang QW, Yu YS, Hu WX, Yao XD, Chen HP, Liu ZH, Li LS. Idiopathic IgA nephropathy with diffuse crescent formation. Am J Nephrol. 2002 Sep-Dec;22(5-6):480-6. doi: 10.1159/000065281. |
| 12808169 | Background | Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant. 2003 Jul;18(7):1321-9. doi: 10.1093/ndt/gfg081. |
| 19342865 | Background | Pankhurst T, Lepenies J, Nightingale P, Howie AJ, Adu D, Harper L. Vasculitic IgA nephropathy: prognosis and outcome. Nephron Clin Pract. 2009;112(1):c16-24. doi: 10.1159/000210570. Epub 2009 Apr 3. |
| 17582159 | Background | Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD; European Vasculitis Study Group. 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. doi: 10.1681/ASN.2007010090. Epub 2007 Jun 20. |
| 2345159 | Background | Nicholls K, Becker G, Walker R, Wright C, Kincaid-Smith P. Plasma exchange in progressive IgA nephropathy. J Clin Apher. 1990;5(3):128-32. doi: 10.1002/jca.2920050303. |
| 3300287 | Background | Lai KN, Lai FM, Leung AC, Ho CP, Vallance-Owen J. Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature. Am J Kidney Dis. 1987 Jul;10(1):66-70. doi: 10.1016/s0272-6386(87)80014-8. |
| 17285293 | Background | Fujinaga S, Ohtomo Y, Umino D, Mochizuki H, Murakami H, Shimizu T, Yamashiro Y, Kaneko K. Plasma exchange combined with immunosuppressive treatment in a child with rapidly progressive IgA nephropathy. Pediatr Nephrol. 2007 Jun;22(6):899-902. doi: 10.1007/s00467-006-0428-4. Epub 2007 Feb 7. |
| 3966468 | Background | Nicholls K, Walker RG, Dowling JP, Kincaid-Smith P. "Malignant" IgA nephropathy. Am J Kidney Dis. 1985 Jan;5(1):42-6. doi: 10.1016/s0272-6386(85)80134-7. |
| 8643167 | Background | Roccatello D, Ferro M, Coppo R, Giraudo G, Quattrocchio G, Piccoli G. Report on intensive treatment of extracapillary glomerulonephritis with focus on crescentic IgA nephropathy. Nephrol Dial Transplant. 1995 Nov;10(11):2054-9. |
| 23868759 | Background | Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, Szczepiorkowski ZM, Williams ME, Wu Y, Shaz BH. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013 Jul;28(3):145-284. doi: 10.1002/jca.21276. |
| 38299639 | Derived | Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D051437 | Renal Insufficiency |
| D016060 |
| Sorption Detoxification |
| D005112 | Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |