Rituximab-induced long-term remission of membranous lupus nephritis

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

Download Full-text

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2568 ◽

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

Download Full-text

AB0750 FUNCTIONAL CONDITION OF KIDNEYS IN THE LONG-TERM COURSE OF SLE IN ADOLESCENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3930 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1403.2-1403

Author(s):

L. Bohmat ◽

N. Shevchenko ◽

I. Bessonova

Keyword(s):

Renal Function ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Disease Duration ◽

Renal Involvement ◽

Clinical Manifestations ◽

Clinical Analysis ◽

Average Dose ◽

One Year

Background:Lupus nephritis is the most severe and adverse systemic lupus erythematosus (SLE) syndrome. According to modern recommendations, the clinical manifestations of active nephritis should be taken under medical control in 6 months after the start of the disease’s treatment1.Objectives:The aim of this study was to examine the functional status of the kidneys in children with SLE in the course of the disease for more than one year.Methods:The analysis included case histories of 43 patients with SLE, mostly females (41), aged 7 to 18 years (mean age 14.4 years) with disease duration of 4.75 ± 0.58 years of whom 22 were less than three years, 21 - more than three years. All children received corticosteroid therapy, at the time of the examination the average dose was 13.85 ± 1.86 mg per day in terms of prednisolone. The second component of therapy was azathioprine (average dose 97.61 ± 2.11 mg). All children received hydroxychloroquine (5 mg/kg per day).To determine the functional state of the kidneys a clinical analysis of urine, a study of the scope of specific gravity of urine during the day (Zymnytsky test), the content of creatinine and urea in serum to determine the glomerular filtration rate (GFR), the level of microalbuminuria per day were evaluated.Results:Renal involvement in the developed SLE occurred in 73.08% of patients. Among them, therapy during the first 6 months was considered quite effective in 58.06% of patients. It was found that in children with disease duration from one to three years proteinuria was registered in 68.18%, a decrease in GFR in 4.45% and hyperfiltration in 9.09%. In the group of children with duration of SLE more than three years revealed deeper changes in renal function; there was proteinuria in 90.47%, the frequency of GFR decreased was in 19.04%, a decrease of renal concentration function was in 14.28% of cases.Indicators of renal function in children with SLE depending on the duration of the disease (M ± m)IndicatorDuration of the diseasefrom 1 year to 3 years n = 22over 3 yearsn = 21Creatinine, mmol/l0,080 ± 0,0140,090 ± 0,018Мочевина, mmol/l5,66 ± 1,425,63 ± 1,61GFR, ml/min117,05 ± 19,68100,20 ± 18,98 *Microalbuminuria, mg/day24,41 ± 13,1334,73 ± 24,76Density min1,007 ± 0,0051,006 ± 0,005Density max1,024 ± 0,0051,019 ± 0,005 ***р<0,03;**р<0,01 the probability of differences when comparing between groupsConclusion:Long-term follow-up of children with SLE over one year reveals a prolongation of renal dysfunction, which worsens after three years, and is the basis for the development of irreversible renal impairment.References:[1]European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative /Noortje Groot, Nienke de Graeff, Stephen D Marks et all. //Ann Rheum Dis. 2017 Dec;76(12):1965-1973.Disclosure of Interests:None declared

Download Full-text

E088 Antiphospholipase A2 receptor antibodies, a marker of idiopathic membranous nephropathy, are not present in membranous lupus nephritis

Rheumatology ◽

10.1093/rheumatology/kez110.086 ◽

2019 ◽

Vol 58 (Supplement_3) ◽

Author(s):

Filipa Farinha ◽

Ruth Pepper ◽

David A Isenberg ◽

Anisur Rahman

Keyword(s):

Lupus Nephritis ◽

Membranous Nephropathy ◽

Idiopathic Membranous Nephropathy ◽

Receptor Antibodies ◽

Membranous Lupus Nephritis

Download Full-text

Initial renal histology and early response predict outcomes of Brazilian lupus nephritis patients

Lupus ◽

10.1177/0961203319890681 ◽

2019 ◽

Vol 29 (1) ◽

pp. 83-91

Author(s):

G Vajgel ◽

C B L Oliveira ◽

D M N Costa ◽

M A G M Cavalcante ◽

L M Valente ◽

...

Keyword(s):

Kidney Disease ◽

Lupus Nephritis ◽

Confidence Interval ◽

Odds Ratio ◽

Estimated Glomerular Filtration Rate ◽

Interstitial Fibrosis ◽

End Stage ◽

Class Iv

Objective We analyzed baseline and follow-up characteristics related to poorer renal outcomes in a Brazilian cohort of admixture race patients with lupus nephritis. Methods Overall, 280 outpatients with a diagnosis of systemic lupus erythematosus and previous kidney biopsy of lupus nephritis were recruited from August 2015 to December 2018 and had baseline laboratory and histologic data retrospectively analyzed; patients were then followed-up and data were recorded. The main outcome measure was the estimated glomerular filtration rate at last follow-up. Secondary analyses assessed the impact of initial kidney histology and treatment in long-term kidney survival. Results Median duration of lupus nephritis was 60 months (interquartile range: 27–120); 40 (14.3%) patients presented progressive chronic kidney disease (estimated glomerular filtration rate <30 and ≥10 ml/min/1.73 m2) or end-stage kidney disease at last visit. Adjusted logistic regression analysis showed that class IV lupus nephritis (odds ratio 14.91; 95% confidence interval 1.77–125.99; p = 0.01) and interstitial fibrosis ≥25% at initial biopsy (odds ratio 5.87; 95% confidence interval 1.32–26.16; p = 0.02), lack of complete or partial response at 12 months (odds ratio 16.3; 95% confidence interval 3.74–71.43; p < 0.001), and a second renal flare (odds ratio 4.49; 95% confidence interval 1.10–18.44; p = 0.04) were predictors of progressive chronic kidney disease. In a Kaplan-Meier survival curve we found that class IV lupus nephritis and interstitial fibrosis ≥25% were significantly associated with end-stage kidney disease throughout follow-up (hazard ratio 2.96; 95% confidence interval 1.3–7.0; p = 0.036 and hazard ratio 4.96; 95% confidence interval 1.9–12.9; p < 0.0001, respectively). Conclusion In this large cohort of admixture race patients, class IV lupus nephritis and chronic interstitial damage at initial renal biopsy together with non-response after 1 year of therapy and relapse were associated with worse long-term renal outcomes.

Download Full-text

OP0046 Effect of Rituximab in Patients with Lupus Nephritis during Long-Term Follow-Up

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-eular.5679 ◽

2014 ◽

Vol 73 (Suppl 2) ◽

pp. 78.1-78

Author(s):

M. Tsanyan ◽

S. Soloviev ◽

S. Radenska-Lopovok ◽

E. Aleksandrova ◽

E. Nikolaeva ◽

...

Keyword(s):

Lupus Nephritis ◽

Long Term Follow Up

Download Full-text

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206897 ◽

2015 ◽

Vol 75 (3) ◽

pp. 526-531 ◽

Cited By ~ 68

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.

Download Full-text