Therapy of lupus nephritis with mycophenolate mofetil

Introduction Mycophenolate mofetil is an immunosupressive agent used in transplantation and subsequently in a variety of autoimmune conditions. It inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on the kidney. The major experience in systemic lupus erythematosus has focused on proliferative lupus nephritis. Materials and methods In our study we treated 8 female patients having proliferative lupus nefritis with combination therapy of prednisone (1mg/kg body weight) and mycophenolate mofetil (2g per day). Complete remission was defined as a value for urinary protein excretion that was less than 0.5g per 24 hours, with normal urinary sediment, a normal serum albumin concentration and improved or stable serum creatinine. Partial remission was defined as a daily proteinuria below 2g in the previosly nephrotic patient or minimum 30% from starting values, with normal urinary sediment, serum albumin of minimum 30g/L and stable serum creatinine. Results Two patients had a complete remission after 7 and 2 months respectively. Five patients had a partial remission after 5.2?4.3 months of therapy. One patient did not react to therapy. There were no side effects during the course of therapy. Discussion Considering the fact that 7/8 patients have had nephrotic range proteinuria and that 50% of patients were refractory on standard induction therapy, the results of this study are a good indicator of value of mycophenolate mofetil in the therapy of proliferative forms of lupus nephritis. Conclusion Mycophenolate mofetil has satisfactory results in the treatment of proliferative forms of lupus nephritis with minimal side effects.

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AB0348 ALBUMIN-TO-GLOBULIN RATIO AS A POTENTIAL PREDICTOR OF RENAL REMISSION IN LUPUS NEPHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4111 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1199.1-1199

Author(s):

T. Knežević ◽

I. Padjen ◽

S. Bulimbašić ◽

M. Ćorić ◽

V. Ivković ◽

...

Keyword(s):

Complete Remission ◽

Lupus Nephritis ◽

Serum Creatinine ◽

Partial Remission ◽

Class Iii ◽

American College Of Rheumatology ◽

Potential Marker ◽

Renal Histology ◽

Albumin To Globulin Ratio ◽

Class Iv

Background:Optimal prognostic predictors in lupus nephritis (LN) are still not clearly defined. Studies have recently shown that albumin-to-globulin ratio (A/G) is not only a good predictor of outcomes in malignancy, infection and renal disease, but is also a potential marker of increased immunoglobulin synthesis and LN activity and might be useful as a predictor of the development of LN in SLE patients. Studies on the role of A/G in predicting outcomes in LN are, however, lacking.Objectives:To assess a potential prognostic value of A/G at renal biopsy in predicting outcomes in LN.Methods:In this retrospective study we analyzed the demographic, histologic, laboratory and clinical characteristics of patients with biopsy-proven LN diagnosed between 2011 and 2020. All patients met the 1997 revised American College of Rheumatology classification criteria for SLE. Complete remission was defined as proteinuria <0.5 g/day and serum creatinine within 10% from baseline, and partial remission as more than 50% reduction in proteinuria to sub-nephrotic levels and serum creatinine within 10% from baseline.Results:We have included 55 patients (80% women) with biopsy-proven LN (age at biopsy 38±13 years). On renal histology, one patient was class I LN, two patients were class II, 7 were class III, 5 were class III+V, 23 were class IV, two were class IV+V, 11 class VI and 4 had other features. Median eGFR and proteinuria at biopsy were 69 (IQR: 44, 100) mL/min/1.73 m2 and 3.5 (2.3, 5.6) g/day, respectively. Baseline mean A/G was 1.12±0.29 and did not differ between LN classes (p=0.91). At one-year follow-up eGFR increased non-significantly (69 vs. 82 mL/min/1.73 m2, p=0.13) and proteinuria decreased (3.5 vs. 0.6 g/day, p<0.001). Eighteen patients achieved complete remission (CR), 16 partial remission and 21 did not achieve remission. None progressed to ESRD and two patients died, both from sepsis. A/G at the time of biopsy did not differ between group which achieved CR/PR vs. no remission (p>0.05; Figure 1) and was not a significant predictor of remission in a multivariate regression model (OR 5.9, 95% CI 0.6, 63.2).Conclusion:While being a potential marker for transition of SLE to LN, A/G was not showed to be a predictor of renal remission in LN.References:[1]Liu XR, et al. Lupus. 2021 Jan 6:961203320981139.[2]Kwon OC, et al. Semin Arthritis Rheum. 2018 Dec;48(3):462-466ckDisclosure of Interests:None declared

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Characteristics of lupus and lupus nephritis at a tertiary care center in Lebanon

Lupus ◽

10.1177/0961203319877459 ◽

2019 ◽

Vol 28 (13) ◽

pp. 1598-1603 ◽

Cited By ~ 1

Author(s):

S H Koubar ◽

J Kort ◽

S Kawtharani ◽

M Chaaya ◽

M Makki ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Kidney Disease ◽

Complete Remission ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Partial Remission ◽

Care Center ◽

Tertiary Care ◽

Tertiary Care Center ◽

Systemic Lupus

Introduction Systemic lupus erythematosus affects 4.8–78.5 people per 100,000 worldwide, 90% of whom are females. Geography and ethnicity have been shown to significantly affect the prevalence and natural history of the disease. Lupus nephritis affects around half of patients with systemic lupus erythematosus. Data about systemic lupus erythematosus and lupus nephritis in the Middle East are still scarce. In this study, we aimed to describe the characteristics of systemic lupus erythematosus and lupus nephritis at a tertiary care center in Lebanon. Methods This is a retrospective chart review of all biopsy-proven lupus nephritis patients admitted to the American University of Beirut medical center between January 2000 and December 2018. Patients above 12 years of age who had any International Society of Nephrology/Renal Pathology Society (ISN/RPS) class of lupus nephritis on their renal biopsy were included in the study. Results The study included 55 patients with lupus nephritis. Upon presentation of systemic lupus erythematosus, the most common clinical feature was arthritis, seen in 83% of patients, followed by anemia (82%) and malar rash (48%). In total 93% had positive ANA, 89% had positive anti-dsDNA and 98% of patients had proteinuria. The most common ISN/RPS class of lupus nephritis in our series was IV (49%). At the time of the biopsy 15% of patients underwent dialysis. At 6 months, 11/27 had complete remission, 6/27 had partial remission and 10/27 had no remission. At 1 year, 8/23 had complete remission, 4/23 had partial remission and 11/23 had no remission. During the study period, 15 out of 35 patients available for analysis had chronic kidney disease (CKD) and six out of 34 patients developed end-stage kidney disease requiring renal replacement therapy. In comparison to other series in the region, our series had more males affected, higher creatinine at the time of biopsy and greater degree of proteinuria. Conclusion Our study provided insight on the demographics, characteristics, and outcomes of lupus nephritis in Lebanon. Interestingly, male gender was present in a quarter of patients. This warrants further investigation and confirmation. We are hoping to expand this experience into a national prospective registry to further characterize this entity in our region.

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Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.131995 ◽

2010 ◽

Vol 69 (12) ◽

pp. 2083-2089 ◽

Cited By ~ 302

Author(s):

Frédéric A Houssiau ◽

David D'Cruz ◽

Shirish Sangle ◽

Philippe Remy ◽

Carlos Vasconcelos ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Serum Creatinine ◽

Statistical Significance ◽

Immunosuppressive Treatment ◽

Randomised Trial ◽

Target Dose ◽

Renal Flare ◽

Intent To Treat

BackgroundLong-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment.MethodsA total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months.ResultsThe baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out.ConclusionsFewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.

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Rituximab treatment for lupus nephritis: A systematic review

Clinical & Investigative Medicine ◽

10.25011/cim.v43i2.33864 ◽

2020 ◽

Vol 43 (2) ◽

pp. E47-54

Author(s):

Zijie Yuan ◽

Qifang Xie ◽

Xiaochuan Wu ◽

Boyu Tan ◽

Xianhua Zhang

Keyword(s):

Systematic Review ◽

Mycophenolate Mofetil ◽

Complete Remission ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Activity Index ◽

Remission Rate ◽

Complete Remission Rate ◽

Significant Difference ◽

Total Remission

Purpose: We used the Cochrane systematic review to analyze the effectiveness and safety of rituximab for lupus nephritis. Methods: Systematic search was performed among Cochrane clinical controlled trials database, MEDLINE, MEDLINE-IN-Process and Other Non-Indexed Citations, EMBASE, EBSCO CINAHL, CNKI, VIP and Wanfang database from the establishment of the database to February 2016. The effectiveness and safety were evaluated in terms of the complete remission rate, total remission rate, urinary protein, Systemic Lupus Erythematosus Disease Activity Index changes and adverse events rate. Data were analyzed by the Review Manager Software version 5.3. Results: Five RCTs that met the inclusion criteria, including a total of 238 patients, were enrolled in our study. The results showed that the complete remission rate in rituximab group was a significantly higher than that of cyclophosphamide group. The difference between the two groups was statistically significant (OR=2.80, 95%CI(1.08,7.26), P=0.03). But there was no significant difference between the two groups in partial and total remission rate. The complete remission rate, partial remission rate and total remission rate in rituximab treatment group was similar compared with mycophenolate mofetil group and rituximab combined with cyclophosphamide group. The adverse reaction rate was also similar among the groups. Conclusion: The study systematically analyzed the effectiveness and safety of rituximab for lupus nephritis, which suggested that the complete remission rate of rituximab in the treatment of lupus nephritis was a significantly higher than that of cyclophosphamide group, while the effectiveness and safety was of no difference compared with cyclophosphamide and mycophenolate mofetil.

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Association Between Hypoalbuminemia, Degree of Proteinuria, and Lupus Nephritis Class: A Single-Center Cross-Sectional Biopsy Study

Nephro-Urology Monthly ◽

10.5812/numonthly.112883 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Ngoc Nguyen Thi ◽

Dien Tran Minh ◽

Huong Nguyen Thu ◽

Phuong Luong Thi ◽

Nam Thai Thien ◽

...

Keyword(s):

Lupus Nephritis ◽

Serum Albumin ◽

Renal Biopsy ◽

Serum Albumin Level ◽

Albumin Level ◽

Viet Nam ◽

Albumin Concentration ◽

Single Center ◽

Cross Sectional ◽

The Mean

Background: The current study intended to determine whether serum albumin level and urine protein/creatinine rate (uPCR) are appropriate predictors of severe lupus nephritis in childhood-onset SLE. Objectives: Following a cross-sectional single-center design, 85 LN children referred to the National Children Hospital, Ha Noi, Viet Nam, from 6/2019 to 6/2020 were recruited. Renal biopsy was performed for all participants. Methods: Following a cross-sectional single-center design, 85 LN children referred to the National Children Hospital, Ha Noi, Viet Nam, from 6/2019 to 6/2020 were recruited. Renal biopsy was performed for all participants. Results: The mean SLEDAI score of all patients was 14.69. The proportion of patients with high and very high SLEDAI was 61.2 and 17.6%, respectively. The mean concentration of serum albumin was 28.55 g/L, and the proportion of decreased albumin concentration was 55.3%. The median uPCR was 446.6 mg/mmol in which 76.5% of values were ≥ 200 mg/mmol. Pathological morphology of LN class from I to VI was observed in 0%, 17.6%, 37.6 %, 37.6%, 7.1%, and 0%, respectively. Serum albumin level and uPCR presented the predictive value for severe and active LN (class IV and V); (AUC: 0.725 P < 0.001 for both). Conclusions: Serum albumin and uPCR were appropriate predictors for severe and active LN in Vietnamese children.

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Mycophenolate Mofetil Therapy in Lupus Nephritis

Journal of the American Society of Nephrology ◽

10.1681/asn.v104833 ◽

1999 ◽

Vol 10 (4) ◽

pp. 833-839

Author(s):

MARY ANNE DOOLEY ◽

FERNANDO G. COSIO ◽

PATRICK H. NACHMAN ◽

MICHAEL E. FALKENHAIN ◽

SUSAN L. HOGAN ◽

...

Keyword(s):

Clinical Trials ◽

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Adverse Events ◽

Serum Creatinine ◽

Lupus Erythematosus ◽

Transplant Rejection ◽

Initial Therapy ◽

Controlled Clinical Trials ◽

The Mean

Abstract. Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26 ± 0.46 μM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53 ± 3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/diarrhea (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.

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The Impact of Baseline Serum Creatinine on Complete Remission Rate and Long-Term Outcome in Patients with Severe Lupus Nephritis

Nephron Extra ◽

10.1159/000448487 ◽

2016 ◽

Vol 6 (2) ◽

pp. 12-21 ◽

Cited By ~ 4

Author(s):

Stephen M. Korbet ◽

William L. Whittier ◽

Edmund J. Lewis ◽

Keyword(s):

Complete Remission ◽

Lupus Nephritis ◽

Serum Creatinine ◽

Remission Rate ◽

Term Outcome ◽

Baseline Serum ◽

Long Term Outcome ◽

Severe Lupus Nephritis ◽

The Impact

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Fortification of blood plasma from cancer patients with human serum albumin decreases the concentration of cisplatin-derived toxic hydrolysis products in vitro

Metallomics ◽

10.1039/c4mt00220b ◽

2014 ◽

Vol 6 (11) ◽

pp. 2034-2041 ◽

Cited By ~ 16

Author(s):

Thomas T. Morris ◽

Yibing Ruan ◽

Victor A. Lewis ◽

Aru Narendran ◽

Jürgen Gailer

Keyword(s):

Side Effects ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Cancer Patients ◽

Albumin Concentration ◽

Serum Albumin Concentration ◽

Hydrolysis Products ◽

Human Serum Albumin Concentration

Boosting the human serum albumin concentration in cancer patients is suggested to be a feasible strategy to possibly reduce the severe toxic side-effects of cisplatin.

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Longterm Followup After Tapering Mycophenolate Mofetil During Maintenance Treatment for Proliferative Lupus Nephritis

The Journal of Rheumatology ◽

10.3899/jrheum.101249 ◽

2011 ◽

Vol 38 (7) ◽

pp. 1304-1308 ◽

Cited By ~ 15

Author(s):

KATERINA LASKARI ◽

ATHANASIOS G. TZIOUFAS ◽

ANNA ANTONIOU ◽

HARALAMPOS M. MOUTSOPOULOS

Keyword(s):

Mycophenolate Mofetil ◽

Complete Remission ◽

Lupus Nephritis ◽

Maintenance Treatment ◽

Remission Maintenance ◽

Proliferative Lupus Nephritis ◽

Increased Risk ◽

Study Population ◽

Risk Of Disease ◽

Relapse Rates

Objective.To determine the timing for safe reduction of mycophenolate mofetil (MMF) dose during remission-maintenance therapy of proliferative lupus nephritis.Methods.The study population consisted of 44 patients evaluated retrospectively; MMF dose was empirically tapered in 18/44 patients until the latest observation.Results.Patients reducing MMF ≤ 18 months after remission/complete remission had a 6.8-fold/6.3-fold higher risk of relapse compared to those taking a stable dose (p = 0.001, p = 0.011, respectively). Reducing MMF later than 18 months was not associated with increased relapse rates.Conclusion.Reducing MMF > 1.5 years after remission/complete remission seems to warrant drug tapering without increased risk of disease flare in proliferative lupus nephritis.

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