Multitarget Therapy for Induction Treatment of Lupus Nephritis

Background:Although, most lupus nephritis patients present with chronic glomerulonephritis or nephrotic syndrome, some patients develop rapidly progressive glomerulonephritis (RPGN), which is a clinical syndrome characterized by rapid loss of renal function over a short period of time (days to months). Multitarget therapy using tacrolimus and mycophenolate mofetil (MMF) has been reported to be effective as induction therapy of Class III to Class V lupus nephritis1. However, its efficacy on lupus nephritis presented with RPGN has not been well reported.Objectives:We aimed to examine the efficacy of multitarget therapy on lupus nephritis presented with RPGN.Methods:We retrospectively analyzed patients with biopsy-proven lupus nephritis, who clinically showed RPGN, and were treated by multitarget therapy with tacrolimus and MMF in our department. Data were expressed as mean±SD.Results:Five lupus nephritis patients (3 female) with RPGN were treated by multitarget therapy as induction therapy. Mean age was 36.6±13.5 years old. Renal biopsy at treatment revealed Class IV(A) in 2, Class IV(A+C) in 1 and Class IV(A)+V in 2. The percentage of glomerular crescents was 23.1±25.4%. eGFR and proteinuria at the initiation of treatment were 46.8±11.5 mL/min/1.73m2and 7.7±3.4 g/gCr, respectively. Patients were initially treated with methylprednisolone pulse therapy followed by 0.8-1.0 mg/kg of prednisolone (PSL), 2-3 mg/day of tacrolimus and 1000 mg/day of MMF. At 6 months, eGFR and proteinuria improved to 72.9±11.3 mL/min/1.73m2and 0.19±0.13 g/gCr, respectively. At 12 months, eGFR and proteinuria further improved to 76.8±7.8 mL/min/1.73m2and 0.10±0.07 g/gCr, respectively and the dose of PSL was reduced to 6.6±1.5 mg/day. Three patients became positive for cytomegalovirus antigenemia and were successfully treated with antiviral therapy.Conclusion:Multitarget therapy is effective in lupus nephritis even in patients presented with RPGN.References:[1]Liu Z, Zhang H, Liu Z,et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial.Ann Int Med2015; 162: 18-26.Disclosure of Interests:Yoichi Imai: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc. b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.

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Multitarget Therapy for Induction Treatment of Lupus Nephritis

Annals of Internal Medicine ◽

10.7326/p15-9000 ◽

2015 ◽

Vol 162 (1) ◽

pp. I-24

Keyword(s):

Lupus Nephritis ◽

Induction Treatment ◽

Multitarget Therapy

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European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211898 ◽

2017 ◽

Vol 76 (12) ◽

pp. 1965-1973 ◽

Cited By ~ 31

Author(s):

Noortje Groot ◽

Nienke de Graeff ◽

Stephen D Marks ◽

Paul Brogan ◽

Tadej Avcin ◽

...

Keyword(s):

Lupus Nephritis ◽

Maintenance Treatment ◽

Low Dose ◽

Diagnosis And Treatment ◽

Nominal Group ◽

Induction Treatment ◽

Expert Committee ◽

Evidence Based ◽

Childhood Onset ◽

Dose Prednisone

Lupus nephritis (LN) occurs in 50%–60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to generate diagnostic and management regimens for children and adolescents with rheumatic diseases including cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of childhood LN. Recommendations were developed using the European League Against Rheumatism standard operating procedures. A European-wide expert committee including paediatric nephrology representation formulated recommendations using a nominal group technique. Six recommendations regarding diagnosis and 20 recommendations covering treatment choices and goals were accepted, including each class of LN, described in the International Society of Nephrology/Renal Pathology Society 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a disease-modifying antirheumatic drug after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. The SHARE recommendations for diagnosis and treatment of LN have been generated to support uniform and high-quality care for all children with SLE.

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318 Autophagy-related protein p62 expression is associated with clinicopathologic features and prednisone plus ctx induction treatment efficacy in lupus nephritis

10.1136/lupus-2017-000215.318 ◽

2017 ◽

Author(s):

S Sun ◽

J Chen ◽

Q Yan ◽

C Bao ◽

Q Fu

Keyword(s):

Lupus Nephritis ◽

Treatment Efficacy ◽

Induction Treatment ◽

Clinicopathologic Features ◽

Related Protein

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Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE

Pediatric Rheumatology ◽

10.1186/s12969-021-00627-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Mileka Gilbert ◽

Beatrice Goilav ◽

Joyce J. Hsu ◽

Paul J. Nietert ◽

Esra Meidan ◽

...

Keyword(s):

Lupus Nephritis ◽

Induction Therapy ◽

Pediatric Nephrology ◽

Response To Treatment ◽

Individual Treatment ◽

Induction Treatment ◽

Childhood Onset ◽

Renal Flare ◽

Treatment Plans

Abstract Background Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare. Methods Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination. Results Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05). Conclusions Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

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Multitarget Therapy for Maintenance Treatment of Lupus Nephritis

Journal of the American Society of Nephrology ◽

10.1681/asn.2017030263 ◽

2017 ◽

Vol 28 (12) ◽

pp. 3671-3678 ◽

Cited By ~ 43

Author(s):

Haitao Zhang ◽

Zhengzhao Liu ◽

Minlin Zhou ◽

Zhangsuo Liu ◽

Jianghua Chen ◽

...

Keyword(s):

Lupus Nephritis ◽

Maintenance Treatment ◽

Multitarget Therapy

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Comparing the Efficacy and Safety of Induction Therapies for the Treatment of Patients with Proliferative Lupus Nephritis in South Africa

International Journal of Nephrology ◽

10.1155/2020/2412396 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Phelisa Sogayise ◽

Udeme Ekrikpo ◽

Ayanda Gcelu ◽

Bianca Davidson ◽

Nicola Wearne ◽

...

Keyword(s):

South Africa ◽

Lupus Nephritis ◽

Induction Therapy ◽

Randomized Study ◽

Induction Treatment ◽

Limited Data ◽

Proliferative Lupus Nephritis ◽

Significant Difference ◽

Kidney Replacement Therapy

Background. Lupus nephritis (LN) can be complicated with requirement for kidney replacement therapy and death. Efficacy of induction therapies using mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVCYC) has been reported from studies, but there is limited data in Africans comparing both treatments in patients with proliferative LN. Methods. This was a retrospective study of patients with biopsy-proven proliferative LN diagnosed and treated with either MMF or IVCYC in a single centre in Cape Town, South Africa, over a 5-year period. The primary outcome was attaining complete remission after completion of induction therapy. Results. Of the 84 patients included, mean age was 29.6 ± 10.4 years and there was a female preponderance (88.1%). At baseline, there were significant differences in estimated glomerular filtration rate (eGFR) and presence of glomerular crescents between both groups ( p ≤ 0.05 ). After completion of induction therapy, there was no significant difference in remission status (76.0% versus 87.5%; p = 0.33 ) or relapse status (8.1% versus 10.3%; p = 0.22 ) for the IVCYC and MMF groups, respectively. Mortality rate for the IVCYC group was 5.5 per 10,000 person-days of follow-up compared to 1.5 per 10,000 person-days of follow-up for the MMF group ( p = 0.11 ), and there was no significant difference in infection-related adverse events between both groups. Estimated GFR at baseline was the only predictor of death (OR: 1.0 [0.9–1.0]; p = 0.001 ). Conclusion. This study shows similar outcomes following induction treatment with MMF or IVCYC in patients with biopsy-proven proliferative LN in South Africa. However, a prospective and randomized study is needed to adequately assess these outcomes.

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