scholarly journals SAT0185 PREDICTORS OF POOR RENAL OUTCOME IN PATIENTS WITH PROLIFERATIVE LUPUS NEPHRITIS: A 36-MONTHS COHORT STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1034.2-1034
Author(s):  
M. Luis ◽  
A. R. Prata ◽  
H. Assunção ◽  
J. A. P. Da Silva ◽  
L. Inês
Keyword(s):  
Diabetes Mellitus ◽  
Cohort Study ◽  
Lupus Nephritis ◽  
Induction Therapy ◽  
Antihypertensive Drugs ◽  
Univariate Analysis ◽  
Unmet Need ◽  
Renal Outcome ◽  
Induction Treatment ◽  
Renal Response

Background:The EULAR/ERA-EDTA recommendations for lupus nephritis (LN) state that renal response should be achieved within 12 months following induction therapy. However, there is an unmet need for early predictors of renal outcome in order to adjust the immunosuppression regimen and optimize the renal outcome.Objectives:To identify predictors of poor renal outcome at baseline, 3 months and 6 months after starting induction therapy.Methods:Retrospective cohort study over 36 months including patients with Systemic lupus erythematosus (SLE) fulfilling the ACR’97 and/or the SLICC’12 classification criteria and with biopsy-proven proliferative LN (class III/IV), enrolled in the CHUC Lupus Cohort from 1999 to 2018. Poor renal outcome was defined as longer time to complete renal response (CRR), characterized by proteinuria <0.5g/day and normal renal function, according to EULAR/ERA-EDTA criteria. Clinical-analytical characteristics at baseline, 3 months and 6 months after starting induction treatment were compared using survival analysis for time-to-CRR. Variables with p<0.25 on univariate analysis using Log-Rank tests were further evaluated as predictors applying multivariate Cox proportional hazards regression models (Backward Stepwise method, Wald-based) with estimation of hazard ratios (HR) and 95% confidence intervals (95%CI).Results:56 patients were included (76.8% female, age at LN diagnosis 30.0 ± 13.2 years). Over the follow-up, 51 patients (91.1%) achieved CRR, within a median time of 6.0 months. In multivariate analysis, predictors of poor renal outcome were proteinuria >2g/day at baseline (HR 1.98; 95%CI 1.04-3.77; p=0.037) and induction therapy with pulse cyclophosphamide (CYC), as compared to mycophenolate mofetil (MMF) (HR=2.05; 95%CI 1.07-3.94; p=0.030) (Figure 1). Diabetes mellitus (HR=6.0; 95%CI 1.24-29.07; p=0.026) and negative anti-RNP antibody (HR 3.17; 95%CI 1.27-7.93; p=0.013) at baseline predicted poor renal outcome at 3 months. At this timepoint, level of proteinuria and clearance rate were not predictive of renal response. At 6 months, no predictors of LN outcome were found for those patients that did not achieve CRR up to this timepoint. Use of glucocorticoid pulses and/or antihypertensive drugs did not predict LN outcome.Figure 1.Conclusion:In this SLE cohort, most patients with proliferative LN achieved CRR. Proteinuria above 2 g/day at baseline and diabetes mellitus were predictors of poor renal outcome, while positive anti-RNP was protective. Induction treatment with CYC was associated with poorer outcome as compared with MMF. Given the retrospective non-randomized nature of this study, caution is needed when drawing conclusions regarding both treatments efficacy.Disclosure of Interests:Mariana Luis: None declared, Ana Rita Prata: None declared, Helena Assunção: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Luís Inês: None declared

SAT0184 MAINTENANCE THERAPY WITH AZATHIOPRINE ASSOCIATED WITH HIGHER RISK OF FLARE IN PROLIFERATIVE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1033-1034
Author(s):  
M. Luis ◽  
A. R. Prata ◽  
H. Assunção ◽  
J. A. P. Da Silva ◽  
L. Inês
Keyword(s):  
Renal Function ◽  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
Arterial Hypertension ◽  
Antihypertensive Drugs ◽  
Angiotensin Receptor Blockers ◽  
Univariate Analysis ◽  
Unmet Need ◽  
Induction Treatment ◽  
Frequent Event

Background:Goals of lupus nephritis (LN) maintenance treatment include prevention of LN flares and long-term preservation of renal function, while minimizing drug iatrogenicity. There is an unmet need for identifying predictors of LN flare in order to guide optimization of maintenance immunosuppression.Objectives:To identify predictors of LN flare after attainment of complete renal response (CRR) in patients with proliferative LN.Methods:Retrospective cohort study over 36 months including patients with SLE fulfilling the ACR’97 and/or the SLICC’12 classification criteria, enrolled in the CHUC Lupus Cohort between 1999 and 2018, with a biopsy-proven proliferative LN (class III/IV) and who attained CRR (proteinuria <0.5g/day and normal renal function, according to EULAR/ERA-EDTA definition) following induction treatment. Only proteinuric flares were considered and defined as doubling of proteinuria to >1g/day. Clinical-analytic characteristics at baseline (time of first CRR attainment after induction) were compared using survival analysis for time-to-flare. Variables with p<0.10 on univariate analysis with Log-Rank tests were further evaluated as predictors with multivariate Cox proportional hazards regression models (Backward Stepwise method, Wald-based), with estimation of hazard ratios (HR) with 95% confidence intervals (95%CI).Results:A total of 50 patients in CRR were included in the analysis (78.4% female, age at baseline 30.0 ± 12.5 years-old). Over the follow-up period, 10 patients (20.0%) experienced a proteinuric flare, within a mean time of 29.1 months (95%CI 26.89-31.37). In univariate analysis, age <30years (p=0.020), arterial hypertension (p=0.020) and presence of anti-RNP antibody (p=0.002) at baseline were associated with higher risk of LN proteinuric flares. In multivariate analysis, age <30 years (HR 26.56; 95%CI 1.93-365.08; p=0.014), arterial hypertension (HR 8.30; 95%CI 1.21-56.92; p=0.031), use of antihypertensive antiproteinuric drugs (angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers) (HR 11.18; 95%CI 1.24-100.66; p=0.031) and maintenance therapy with azathioprine (HR 6.23; 95%CI 1.51-25.66; p=0.011) (Figure 1) were predictors of LN proteinuric flares.Figure 1.Conclusion:In patients with proliferative LN, proteinuric flares are a frequent event after induction treatment leads to CRR. Younger age, arterial hypertension, use of antihypertensive drugs and use of azathioprine as maintenance therapy were risk factors for LN proteinuric flare in this cohort.Disclosure of Interests:Mariana Luis: None declared, Ana Rita Prata: None declared, Helena Assunção: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Luís Inês: None declared

Early predictors of renal outcome in patients with proliferative lupus nephritis: a 36-month cohort study

Rheumatology ◽  
2021 ◽  
Author(s):  
Mariana S F Luís ◽  
Irene E M Bultink ◽  
José A P da Silva ◽  
Alexandre E Voskuyl ◽  
Luís S Inês
Keyword(s):  
Cohort Study ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Renal Outcome ◽  
Induction Treatment ◽  
Class Iii ◽  
Early Predictors ◽  
Renal Flare ◽  
Proliferative Lupus Nephritis

Abstract Objectives To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative LN. Methods This was a retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centres. CRR and renal flare were defined as proteinuria &lt;0.5 g/day with normal renal function and proteinuria &gt;1 g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with P &lt; 0.10 on univariate analysis with log-rank tests were further tested with multivariate Cox proportional hazards regression models. Results We included 104 patients [81.7% female, mean (s.d.) age at baseline 32.0 (13.3) years]. Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria &lt;2 g/day at baseline [hazard ratio (HR) = 1.80, 95% CI 1.16, 2.79, P &lt; 0.01] and 3 months (HR = 2.32, 95% CI 1.24, 4.32, P &lt; 0.01) after starting induction therapy were independent predictors of CRR. Renal flares occurred in 18.4% of patients reaching CRR, after a mean time of 16.5 (8.6) months. Age up to 25 years at time of LN diagnosis (HR = 5.41, 95% CI 1.72, 16.97, P &lt; 0.01) and positive anti-RNP (HR = 3.52, 95% CI 1.21, 10.20, P = 0.02) were independent predictors of renal flares. Conclusion In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.

Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1358-1362 ◽  
Author(s):  
D Jesus ◽  
M Rodrigues ◽  
J A P da Silva ◽  
L Inês
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Induction Therapy ◽  
Cyclosporine A ◽  
Induction Treatment ◽  
Class Iii ◽  
Class V ◽  
Renal Response ◽  
Prednisolone Dose ◽  
The Mean

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2–3 g and CsA was dosed up to 2.6–3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.

Lupus Nephritis: Induction Therapy

Lupus ◽  
2005 ◽  
Vol 14 (3_suppl) ◽  
pp. 27-32 ◽  
Author(s):  
TM Chan
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Adverse Effects ◽  
Induction Therapy ◽  
Chinese Patients ◽  
Renal Outcome ◽  
Induction Treatment ◽  
Renal Survival ◽  
Proliferative Lupus Nephritis

Effective induction therapy is of pivotal importance in minimizing renal parenchymal damage by the active immune-mediated inflammatory processes in severe proliferative lupus nephritis. Preservation of nephron mass is prerequisite to long-term renal survival. Data from US-based studies have shown improved efficacy with induction treatment comprising corticosteroid and cyclophosphamide, compared with corticosteroid treatment alone. Data from European studies have shown similar efficacy with a modified treatment regimen, in which smaller doses of cyclophosphamide were given at weekly or fortnightly intervals over a shortened treatment duration, and the treatment related adverse effects appeared less frequent with the reduced-dose regimen. We have also reported that sequential immunosuppression with prednisolone and oral cyclophosphamide as induction followed by azathioprine maintenance was associated with a high incidence of remission and relatively favourable long-term renal outcome in Chinese patients. However, cyclophosphamide treatment is associated with considerable adverse effects, which could be potentially fatal. Mycophenolate mofetil selectively inhibits lymphocyte proliferation, and thus targets an instrumental step in the pathogenesis of systemic lupus erythematosus. There is accumulating evidence that the combined use of mycophenolate mofetil and corticosteroid presents an effective treatment for severe proliferative lupus nephritis in different ethnic groups, and is associated with much fewer adverse effects compared with cyclophosphamide-based regimens. Recent data from our group also demonstrate the long-term efficacy of mycophenolate mofetil in preserving renal survival, when used continuously as both induction and maintenance therapy.

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

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.

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

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.

Complete renal response at 12 months after induction therapy is associated with renal relapse-free rate in lupus nephritis: a single-center, retrospective cohort study

Lupus ◽  
2019 ◽  
Vol 28 (4) ◽  
pp. 501-509 ◽  
Author(s):  
K Ichinose ◽  
M Kitamura ◽  
S Sato ◽  
M Eguchi ◽  
M Okamoto ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Induction Therapy ◽  
Predictive Factors ◽  
Lupus Erythematosus ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Renal Response

Background Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). Methods We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993–2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. Results Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5–154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44–0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06–0.74, p = 0.00098) levels. Conclusions Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

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