scholarly journals Serum Axl predicts histology-based response to induction therapy and long-term renal outcome in lupus nephritis

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212068 ◽  
Author(s):  
Ioannis Parodis ◽  
Huihua Ding ◽  
Agneta Zickert ◽  
Guillaume Cosson ◽  
Madiha Fathima ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Renal Outcome

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 OP0165 LONG-TERM OUTCOME OF A RANDOMIZED CONTROLLED TRIAL COMPARING TACROLIMUS WITH MYCOPHENOLATE MOFETIL AS INDUCTION THERAPY OF SEVERE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 104.1-104
Author(s):  
C. C. Mok ◽  
L. Y. Ho ◽  
C. H. To ◽  
K. Y. S. Ying
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Roc Analysis ◽  
Controlled Trial ◽  
Renal Flare ◽  
Stage 4 ◽  
Ckd Stage ◽  
Renal Prognosis ◽  
The Mean

Background:Objectives:To report the 10-year outcome of a cohort of patients with lupus nephritis (LN) treated with combined glucocorticoids with either mycophenolate mofetil (MMF) or tacrolimus (TAC) as induction in a randomized controlled trial (RCT).Methods:150 patients with active lupus nephritis were randomized to receive either MMF (2-3g/day) (N=76) or TAC (0.1-0.06mg/kg/day) (N=74) in combination with high-dose prednisolone (0.6mg/kg/day for 6-8 weeks and tapered) as induction therapy between 2005 and 2012. Complete renal (CR) or good partial renal responders were switched to azathioprine (AZA) (2mg/kg/day) for maintenance. We hereby report the 10-year outcomes of the patients in terms of renal flares (proteinuric/nephritic), renal function decline (drop in eGFR by ≥30% from baseline), development of chronic kidney disease (CKD) stage 4/5 (eGFR<30ml/min) and mortality. Factors affecting renal prognosis were studied by Cox regression analysis. Renal parameters (urine P/Cr ratio [uPCr], eGFR) at different time points from 6 to 24 months were studied for their predictive value of a poor renal prognosis by ROC analysis.Results:150 patients (92% women) with active LN were studied (ISN/RPS class III±V 36%; IVG/S±V 46%; pure V 19%). The mean age was 35.5±12.8 years and SLE duration was 50.2±62 months. The mean histological activity and chronicity score was 8.2±3.4 and 2.6±1.6, respectively. At baseline, 59(39%) patients were hypertensive, 62(41%) had active urinary casts, 112(75%) had microscopic hematuria and 67% patients had eGFR<90ml/min. As reported previously, the rate of complete renal response (CR) was 59% in the MMF and 62% in the TAC group (p=0.71). Maintenance therapy with AZA was given to 79% patients. After a follow-up of 118.2±42 months, proteinuric and nephritic renal flares occurred in 34% and 37% of patients treated initially with MMF and 53% and 30% in those treated with TAC, respectively. There was a total of 77 renal flares in 43 (57%) patients treated with MMF (0.11/patient-year) and 92 renal flares in 46 (62%) of patients treated with TAC (0.12/patient-year; p=0.44). The cumulative risk of having a renal flare of patients treated with MMF/AZA was 28% at 3 years, 42% at 5 years and 58% at 10 years, whereas the corresponding figures for patients treated with TAC/AZA was 32% at 3 years, 53% in 5 years and 66% in 10 years (p=0.43). For those who achieved CR after induction therapy, the mean time to first renal flare was 70.4±47.1 months in the MMF group and 65.2 ±50 months in the TAC group (p=0.61). The cumulative incidence of a composite outcome of decline of eGFR by ≥30%, development of CKD stage 4/5 or death at 5 and 10 years was 24% and 33%, respectively, in patients treated with MMF, and 17% and 33%, respectively, in those treated with TAC (p=0.90). Factors significantly associated with this outcome were first time lupus nephritis (HR 0.26[0.11-0.59]; p=0.001), uPCR at 6 months (HR 1.33[1.02-1.76]; p=0.04) and eGFR at 6 months (HR 0.98[0.97-0.997]; p=0.02). Exploratory ROC analysis demonstrated that an eGFR cut-off of 80ml/min (AUC 0.70; sensitivity 0.64, specificity 0.66) and uPCR cut-off of 0.75 (AUC 0.73; sensitivity 0.69, specificity 0.74) at month 18 best predicted CKD stage 4/5 or decline of eGFR by ≥30%.Conclusion:Long-term data of our RCT showed that TAC remained non-inferior to MMF as induction therapy of LN in terms of renal flares, renal function decline and mortality. Relapsed renal disease, lower eGFR and more proteinuria post-induction therapy were associated with a poorer outcome. An uPCR ≤0.75 and eGFR of >80ml/min at 18 months best predicted a better outcome at 10 years, and should be considered as a target for induction/consolidation therapy.Acknowledgments:NILDisclosure of Interests:None declared

scholarly journals Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

2015 ◽  
Vol 75 (3) ◽  
pp. 526-531 ◽  
Author(s):  
Farah Tamirou ◽  
David D'Cruz ◽  
Shirish Sangle ◽  
Philippe Remy ◽  
Carlos Vasconcelos ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Positive Predictive Value ◽  
Maintenance Therapy ◽  
Early Response ◽  
Renal Outcome ◽  
Proliferative Lupus Nephritis ◽  
Long Term Follow Up

ObjectiveTo report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.MethodsIn 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.ResultsDeath (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.ConclusionsThe long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.Trial registration numberNCT00204022.

scholarly journals A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

2015 ◽  
Vol 2 (1) ◽  
pp. e000123-e000123 ◽  
Author(s):  
F. Tamirou ◽  
B. R. Lauwerys ◽  
M. Dall'Era ◽  
M. Mackay ◽  
B. Rovin ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Outcome

scholarly journals Predictors of Long-Term Renal Outcome in Lupus Nephritis Trials: Lessons Learned from the Euro-Lupus Nephritis Cohort

2015 ◽  
Vol 67 (5) ◽  
pp. 1305-1313 ◽  
Author(s):  
Maria Dall'Era ◽  
Miriam G. Cisternas ◽  
Dawn E. Smilek ◽  
Laura Straub ◽  
Frédéric A. Houssiau ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lessons Learned ◽  
Renal Outcome

scholarly journals Long-term mortality and renal outcome in a cohort of 100 patients with Lupus Nephritis

2010 ◽  
Vol 62 (6) ◽  
pp. 873-880 ◽  
Author(s):  
Mikkel Faurschou ◽  
Lene Dreyer ◽  
Anne-Lise Kamper ◽  
Henrik Starklint ◽  
Søren Jacobsen
Keyword(s):  
Lupus Nephritis ◽  
Renal Outcome ◽  
Long Term Mortality

scholarly journals Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case–control study

2022 ◽  
Vol 62 (1) ◽  
Author(s):  
Fernanda Nogueira Holanda Ferreira Braga ◽  
Marta Maria das Chagas Medeiros ◽  
Antonio Brazil Viana Junior ◽  
Matheus Eugênio de Sousa Lima ◽  
Levi Coelho Maia Barros ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Serum Creatinine ◽  
Roc Curve ◽  
End Stage Renal Disease ◽  
Renal Outcome ◽  
Renal Outcomes ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Lupus nephritis (LN) is a major source of morbidity and mortality in patients with systemic lupus erythematosus (SLE), with 10–25% of patients progressing to end-stage renal disease (ESRD). Objective This study aims to elucidate the predictive capabilities of 24-h proteinuria (24PTU) and serum creatinine (sCr) after 12 months of treatment with respect to long-term renal outcomes in LN in a single-center cohort of LN patients. Methods A retrospective analysis was performed on 214 patients diagnosed with LN followed in our center. Values of 24PTU and sCr were assessed at baseline and after 3, 6 and 12 months, and after 5 years and/or the last evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months or longer. End-stage renal disease (ESRD) was defined as the need for permanent dialysis. Receiver operating characteristics curves (ROC) were used to test the best cut-off value of 24PTU and sCr at 12 months who predict bad long-term renal outcomes.  Results The mean follow-up period was 11.2 ± 7.2 years. The best cut-off values for 24PTU and sCr as predictor of CKD were, respectively, 0.9 g/24 h and 0.9 mg/dL. ROC curve for 24PTU had a slightly lower performance than ROC curve for sCr as predictor for CKD (PTU AUC = 0.68; sCr AUC = 0.70), but sensitivity and specificity were better for 24PTU (24PTU: sensitivity = 63.5%, specificity = 71.2%; sCr: sensitivity = 54.8%, specificity = 75.3%). When the outcome was ESRD the best cut-off points were 0.9 g/24hs and 1.3 mg/dL for 24PTU and sCr, respectively, and the curve performance was better for 24PTU (PTU AUC = 0.72; sCr AUC = 0.61). Conclusions In this ethnically diverse population with LN followed for a long time (> 10 years), levels of 24PTU > 0.9/day at 12 months was a good predictor of bad long-term renal outcome. The serum creatinine > 0.9 mg/dL and > 1.3 mg/dL at 12 months were also good predictors of CKD and ESRD, respectively. Patients with 24PTU < 0.9 g/day and sCr < 1.3 mg/dL at 12 months are not likely to develop ESRD because of the high negative predictive values (NPV) (93.2% and 82%). 24PTU and sCr are relevant as components for a treat-to-target strategy for LN treatment, since their high NPV corroborates their importance as good predictors of long-term renal outcome.

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