Extra-renal Flares Research Articles

When is the right time to change therapy? An observational study of the time to response to immunosuppressive drugs in systemic lupus erythematosus

ObjectivesTo analyse the response to immunosuppressants (IS) in extrarenal flares of SLE to determine the most appropriate timing during follow-up for a change in therapeutic strategy.MethodsObservational cohort study including a...

Kidney histopathology in predicting flares following drug withdrawal in proliferative lupus nephritis in clinical remission.

Residual renal histopathological activity at clinical remission in Proliferative Lupus Nephritis (PLN) can predict renal flare upon immunosuppression withdrawal. Data on the role of histological renal remission in predicting extra-renal flares is lacking. We assessed renal histopathology prior to drug withdrawal and the occurrence of renal and extra-renal flares over 52weeks after drug withdrawal in PLN patients in long-term clinical remission. This is a subgroup analysis of a non-inferiority, open-label randomized (1:1) controlled trial. Patients with biopsy-proven Class III/IV LN in the past (biopsy 1), on immunosuppressants (IS) ≥ 3years, in clinical remission for ≥ 1year, on stable prednisolone dose (≤ 7.5mg/day) plus a maintenance IS and hydroxychloroquine (HCQ) were subjected to a repeat renal biopsy (biopsy 2). Individuals with biopsy 2 having activity index (AI) < 4/24 were randomised to either prednisolone or IS withdrawal. Primary end-point was the proportion experiencing a flare [SELENA-SLEDAI flare index (SFI)] at week 52. Twenty-eight eligible patients underwent biopsy 2 and randomized to prednisolone (n = 15) and IS (n = 13) withdrawal. At biopsy 1, 12 (43%) had class III, 15 (53.5%) had class IV, and 1 (3.5%) had class III + V. At biopsy 2, PLN persisted in 4 (14.2%) while 18 (64.2%) were in histological remission (AI = 0) with 6(21.4%) in class II. Following drug withdrawal, 9/28 (32%) had flares especially musculoskeletal (55.5%), mucocutaneous (44.4%), and renal (33.3%). Among the four persistent PLN patients, one of the two (50%) with AI = 1 had extra-renal flare while both the two with AI = 2 (100%) had renal and extra-renal flares. In those with histological remission (biopsy 2), 6/18 (66.6%) experienced extra-renal flare of whom one also had renal flare. Upon drug withdrawal, renal histopathology findings with any activity index can predict renal flare while histological remission is not enough to predict extra-renal flare, thus making it an unsuitable marker for deep SLE remission.

#3191 RISK OF CKD IN LUPUS NEPHRITIS: CORRELATION WITH DURATION OF REMISSION AND DEVELOPMENT OF RENAL AND EXTRARENAL FLARES

Abstract Background and Aims Achievement of remission and prevention of SLE flares are important therapy targets in patients with SLE in order to avoid the development of systemic chronic damage. In patients with lupus nephritis, the correlation between the duration of remission, the occurrence of SLE flares and the development of CKD is unclear. The aims of this study are to investigate a) the risk of CKD in patients with lupus nephritis b) the correlation between the risk of CKD and the development of renal and extrarenal SLE flares c) the correlation between the risk of CKD and the achievement and duration of remission d) the probability and predictors of renal and extrarenal remission. Method This is a retrospective multicentric study of prospectively collected data. Patients were included if they were &amp;gt;18 years old, they had a histological diagnosis of lupus nephritis and they had at least 5 years of follow up after the diagnosis. CKD was defined as eGFR &amp;lt;60 ml/min/1.73m2 without active urinary sediment for at least 3 months. Remission was defined as normal renal function (serum creatinine &amp;lt;1.0 mg/dl, eGFR &amp;gt;60 ml/min/1.73m2), proteinuria &amp;lt;0.5 g/24h and cSLEDAI = 0 for at least 1 year. The probability of developing flares and achieving remission was estimated using Cox regression analysis. Results CKD developed in 57 patients out of the 303 included in the study (18.8%) during a median follow-up of 14.8 years. During the observation 257 patients achieved remission in a median time of 1.4 (0.7-3.6) years, while 46 patients never achieved it. 115 patients maintained remission until the end of follow-up (9.5 (5.8-14.5) years), while 142 developed a flare after a median time of 3.6 (2.3-5.9) years from the beginning of remission. Altogether, in these 142 patients, 174 SLE flares developed during a median follow-up of 17.8 (13.3-24.2) years: 132 renal flares (20 with serum creatinine increase, 112 with proteinuria) and 42 extra-renal flares. CKD developed in 11 patients with creatinine flares (55%), 19 patients with proteinuric flares (16.9%) and 1 patient with extra-renal flares (2.4%) (p&amp;lt;0.0001). The longer was the duration of remission, the lower the probability that remission was interrupted (Figure 1A) by the development of a SLE flare: the risk of flare reduced from 10% when the remission lasted less than 5 years, to 5% if the remission lasted 5-10 years and to 2% if the remission lasted more than 10 years (Figure 1B). CKD developed in 26 out of the 46 patients who never achieved remission (56%), in 31 patients among those who achieved remission but developed SLE flares (21.8%) and in none among those who maintained remission until the end of the observation (p&amp;lt;0.0001). We found that 3 years of persistent remission significantly reduced the risk of CKD development (Figure 2). At multivariate Cox regression analysis, age &amp;gt;40 years (OR: 1.017; 95% CI: 1.005-1.028; p = 0.004), therapy with hydroxychloroquine (OR: 1.384; 95% CI: 1.109-1.661; p = 0.021) and absence of arterial hypertension (OR: 0.699; 95% CI: 0.425-0.975; p = 0.011) were independent predictors of remission. Conclusion in patients with lupus nephritis, the risk of CKD is significantly higher if renal-extrarenal remission is not achieved or if it is interrupted by SLE flares. In particular, the risk of CKD is very high in patients who develop renal flares with creatinine increase. A longer duration of remission is related to a lower risk of SLE flares and of CKD: in particular, 3 years of remission protect from the development of CKD. Age older than 40 years, therapy with hydroxychloroquine and absence of arterial hypertension are associated with the achievement of remission.

Which extra-renal flare is 'difficult to treat' in systemic lupus erythematosus? A one-year longitudinal study comparing traditional and machine learning approaches.

To describe phenotypes and outcomes of extra-renal flares in SLE, to identify clusters of extra-renal flares based on baseline features, and to develop a machine learning (ML) tool capable of predicting 'difficult to treat' (D2T) flares. Extra-renal flares that occurred in our cohort over the last five years with at least one year of follow-up were included. Baseline clinical variables were described and flares assigned to clusters. Attainment of remission and low disease activity state (LLDAS) at 12 months were compared. Flares were then considered 'D2T' in case of non-attainment of LLDAS at 6 and 12 months. Baseline features were used to train a ML model able to predict future D2T-flares, at admission. Traditional approaches were then compared with informatic techniques. Among 420 SLE patients of the cohort, 114 flares occurred between 2015 and 2021; 79 extra-renal flares, predominantly mucocutaneous (24.1%) and musculoskeletal (45.6%), were considered. After 12 months, 79.4% and 49.4% were in LLDAS and in remission, respectively, while 17 flares were classified as D2T (21.5%); D2T flares received a higher cumulative and daily dose of glucocorticoids. Among the clusters, cluster 'D' (mild-moderate flares with mucocutaneous manifestations in patients with history of skin involvement) was associated with the lowest rate of remission. Among clinical data, not being on LLDAS at 3 months was the unique independent predictor of D2T flares. Our clusterization well separates extra-renal flares according to their baseline features and may propose a new identification standard. D2T flares, especially refractory skin manifestations, are frequent in SLE and represent an unmet need in the management of the disease as they are associated with higher glucocorticoid (GC) dosage and risk of damage accrual. Our ML model could help in the early identification of D2T flares, flagging them to elevate the attention threshold at admission.

Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up

ObjectivesPrevious studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of...

Mycophenolate mofetil or tacrolimus compared with azathioprine in long-term maintenance treatment for active lupus nephritis.

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.

SAT0163 IMMUNOSUPPRESSANT WITHDRAWAL AFTER REMISSION ACHIEVEMENT IN LUPUS NEPHRITIS: EFFECT ON FLARE OCCURRENCE

Background:Whether and when immunosuppressive therapy may be safely withdrawn in patients with lupus nephritis (LN) is still poorly defined. Indeed, there is no clear agreement about the optimal duration of maintenance treatment.Objectives:We aimed at assessing the rate and predictors of flare after IS withdrawal in patients with LN in remission.Methods:Patients with systemic lupus erythematosus (SLE) (ACR criteria) and biopsy-proven LN diagnosed between 1990 and 2019, ever treated with IS and currently in follow-up were considered. IS discontinuation was defined as the complete withdrawal of any immunosuppressive drug in patients in remission. Remission was defined as normal serum creatinine, proteinuria &lt;0.5 g/24h, inactive urine sediment, and no extra-renal SLE activity (clinical SLE Disease Activity Index [c-SLEDAI]-2K=0) on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone ≤5 mg/day. Flares were defined according to SLEDAI Flare Index; renal flare was defined as an increase of proteinuria &gt;0.5 g/24h requiring an increase in corticosteroid therapy or the reintroduction of IS. Predictors of a subsequent flare were analyzed by multivariate logistic regression analysis.Results:Out of 456 SLE patients regularly followed-up, 206 (45.1%) had LN and were considered in our study. Eighty-three patients (40.3%) discontinued IS after remission achievement (Table 1). After stopping therapy, patients were followed for a mean±SD of 99±77 months (range 12-378). Nineteen patients (22.8%) developed a flare after IS discontinuation, after a mean±SD follow-up of 78±68 months (range 7-312), and were re-treated; among them, 6 patients (7.2%) experienced a renal and 13 (15.6%) an extra-renal flare. Compared to patients who flared, patients in persistent IS-free remission had longer remission before IS withdrawal (51.2±31.5 vs. 29.3±16.5 months, p&lt;0.001), and continued antimalarials after IS discontinuation (p=0.005). No differences in flare occurrence according to the type of IS discontinued were found. At multivariate analysis, therapy with antimalarials was the strongest protective factor against disease flare (OR 0.06, 95% CI 0.11-0.41, p=0.004) (Table 2). At last follow-up, mean±SD SLEDAI-2K was 3.1±2.8 and 1.5±1.6 in patients who experienced or not a flare after IS discontinuation, respectively (p=0.058), Indeed, 10/19 patients (52.5%) who developed a flare re-achieved remission.Table 1.Characteristics of 83 patients with LN in remission who discontinued immunosuppressive therapy, overall and according to flare occurrenceTotal patients (83)Patients with flare (19)Patients without flare (64)P valueFemale, N(%)72 (88.7)16 (84.2)56 (87.5)nsAge at 2019, years43±1139±11.545±10.40.049SLE duration at 2019, years18±916.7±9.018.6±8.6nsSLE duration at IS discontinuation, years9.7±7.67.1±6.110.5±7.8nsTime to achieve remission, months27±3722.1±35.628.5±37.6nsRemission duration at IS discontinuation, months46±3029 ±16.551±31.5&lt;0.001IS therapy duration, years6.7±4.35.2±3.87.1±4.20.061Anti dsDNA, N(%)65 (78.3)18 (95)47 (73)0.059HCQ after IS discontinuation, N(%)67 (80.7)12 (63.1)55 (85.9)0.005IS, immunosuppressant; HCQ, hydroxychloroquineTable 2.Multivariate logistic regression: predictors of flare occurrenceDependent variable: flare occurrenceOR95% CIp valueNumber of ISs, ever3.2641.030-10.3420.044HCQ therapy after IS discontinuation0.0960.014-0.6520.017Remission duration at IS discontinuation0.9540.912-0.9970.037Cyclophosphamide, ever0.0650.008-0.5480.012IS, immunosuppressant; HCQ, hydroxychloroquineConclusion:Based on our experience, withdrawal of IS is feasible in selected patients with LN, i.e. patients who achieved stable remission and received maintenance therapy with antimalarials. Patients who experience new flares can re-achieve remission with an appropriate treatment.Disclosure of Interests: :Margherita Zen Speakers bureau: BMS, Ely Lilly, Janssen, GSK, Mariele Gatto Speakers bureau: GSK, Francesco Benvenuti: None declared, Francesca Saccon: None declared, Maddalena Larosa: None declared, Luca Iaccarino Speakers bureau: GSK, Pfizer, Janssen, Novartis, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS

Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8years follow up.

The ideal long-term maintenance therapy of Lupus Nephritis (LN) is still a matter of debate. The present study was aimed at comparing the efficacy/safety profile of cyclosporine (CsA), mycophenolate mofetil (MMF) and azathioprine (AZA) in long-term maintenance therapy of LN. We performed a retrospective study of patients with biopsy-proven active LN. After induction therapy, all patients received maintenance therapy with CsA, MMF or AZA based on medical decision. Primary endpoint was complete renal remission (CRR) after 8years (defined as proteinuria < 0.5g/24h, eGFR > 60ml/min/1.73mq); secondary endpoints were: CRR after 1year, renal and extrarenal flares, progression of chronic kidney disease (CKD stage 3 or above) and side-effects. Out of 106 patients, 34 received CsA, 36 MMF and 36 AZA. Clinical and histological characteristics at start of induction therapy were comparable among groups. At start of maintenance therapy, CsA patients had significantly higher proteinuria (P = 0.004) or nephrotic syndrome (P = 0.024) and significantly lower CRR (23.5% vs 55.5% on MMF and 41.7% on AZA, P = 0.024). At one year, CRR was similar in the three groups (79.4% on CsA, 63.8% on MMF, 58.3% on AZA, P = 0.2). At 8years, the primary endpoint was achieved by 79.4% of CsA vs 83.3% of MMF and 77.8% of AZA patients (P = 0.83); 24h proteinuria, serum creatinine, eGFR were similar. CKD stage 3 or above developed in 8.8% of CsA, in 8.3% of MMF and in 8.3% of AZA patients (P = 0.92). Flares-free survival curves and incidence of side-effects were not different. This is the first study comparing CsA, MMF and AZA on long-term LN maintenance therapy. All treatments had similar efficacy in achieving and maintaining CRR, despite more severe baseline clinical features in patients treated with CsA.

Choroidal thickness in lupus nephritis.

This study aimed to compare choroidal thickness between patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) in complete renal remission to that of patients with SLE without LN. This was a retrospective case-control study of 23 SLE patients meeting either the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria and followed at Washington University School of Medicine Rheumatology or Nephrology, and Ophthalmology outpatient clinics. The diagnosis of LN was based on renal pathology, and complete renal remission was defined as proteinuria <500 mg/daily and serum creatinine at baseline. Extra-renal flare status was determined using modified Fortin criteria. Choroidal thickness was measured using spectral-domain optical coherence tomography and read by blinded reviewers. In SLE patients without extra-renal flare, choroidal thickness of LN patients was 281 ± 78 µm compared to 288 ± 70 µm in non-LN SLE patients (p = 0.766) at the fovea. Choroidal thickness was not different in patients with LN in remission compared to non-LN SLE patients in remission. Additional studies are needed to examine choroidal thickness in patients with SLE with active LN.

Role of syndecan-1 (CD138) in Egyptian systemic lupus erythematosus patients with lupus nephritis: Relation to disease activity

BackgroundSyndecan-1, a transmemebrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is readily shed and released under certain pathologic conditions and remains biologically active to plasma cells behaviour. Aim of the workTo assess the level of syndecan-1 in relation to lupus nephritis (LN) and systemic lupus erythematosus (SLE) activity. Patients and methodsThe study included 60 SLE patients subgrouped according to the presence of LN and activity. SLE disease activity index (SLEDAI) was assessed. Serum syndecan-1 level was measured. ResultsThe patients mean age was 25.9 ± 8.6 years, they were 54 females and 6 males with a disease duration of 3.8 ± 3.4 years. There was a significant difference in the level of syndecan-1 between healthy control (46.3 ± 12.2 ng/ml) and SLE patients whether they were with active LN (150.2 ± 31.1 ng/ml) (p < 0.001), extrarenal flare (86.9 ± 16.7 ng/ml) (p < 0.001) or inactive (79.1 ± 19.8 ng/ml) (p < 0.003). Syndecan-1 was significantly higher in patients with active LN compared to those with extrarenal flare and inactive disease (p < 0.001 and p < 0.001 respectively). Serum syndecan-1 level was significantly higher in patients with arthralgia, arthritis, pleurisy and pericarditis) (all p < 0.001). There was a significant correlation between syndecan-1 level and 24 h urinary proteins (r = 0.8, p < 0.0001), and inversely with the complement (C3: r = −0.54, p < 0.0001 and C4: r = −0.48, p < 0.0001). There was a significant correlation between syndecan-1 and SLEDAI (r = 0.68, p < 0.001). ConclusionSerum syndecan-1 is significantly high in active LN patients and can be a useful tool for diagnosis of active nephritis. It correlates with disease activity, consumed complement and proteinuria. It was significantly related to the presence of musculoskeletal manifestations and serositis.

Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab.

B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.

Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis.

LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN. Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment. ClinicalTrials.gov, http://clinicaltrials.gov , NCT00920114.

THU0260 Low Risk of Renal Flares and of Negative Outcomes in Women with Lupus Nephritis Conceiving after Switching Mycophenolate Mofetil to Azathioprine

BackgroundA growing number of women with Lupus nephritis (LN) wish to fulfil their desire for having a child. A common concern is the optimal choice of immunosuppressive treatment during the...

Diagnosis and treatment of lupus nephritis flares—an update

Relapses or flares of systemic lupus erythematosus (SLE) are frequent and observed in 27-66% of patients. SLE flares are defined as an increase in disease activity, in general, requiring alternative treatment or intensification of therapy. A renal flare is indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of active disease. The morbidity associated with renal flares is derived from both the kidney damage due to lupus nephritis and treatment-related toxic effects. Current induction treatment protocols achieve remission in the majority of patients with lupus nephritis; however, few studies focus on treatment interventions for renal flares in these patients. The available data, however, suggest that remission can be induced again in a substantial percentage of patients experiencing a lupus nephritis flare. Lupus nephritis flares are independently associated with an increased risk of deterioration in renal function; prevention of renal flares might, therefore, also decrease long-term morbidity and mortality. Appropriate immunosuppressive maintenance therapy might lead to a decrease in the occurrence of renal and extrarenal flares in patients with SLE, and monitoring for the early detection and treatment of renal flares could improve their outcomes.

Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine

The aim of this study is to report the long-term outcome of pure membranous lupus nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of patients with SLE who had biopsy-confirmed pure MLN was treated initially with prednisone (0.8-1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were followed for the following outcomes: remission rate at 12 months, renal flares, extra-renal flares and renal function deterioration. The cumulative risks of renal flares and renal function decline were studied by Kaplan-Meier analysis. Thirty-eight patients were studied (31 women; age 35.0 +/- 9.2 years; mean SLE duration 48.5 +/- 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients were nephrotic and four (11%) were hypertensive at presentation. All patients were treated with prednisolone (0.85 +/- 0.24 mg/kg/day) and AZA (1.72 +/- 0.43 mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8 (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a follow-up of 12 +/- 5.8 years, 19 episodes of renal flares (15 proteinuric and 4 nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at 5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an augmented dosage of prednisolone, +/- another immunosuppressive agent, resulted in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At last visit, three (8%) patients had doubling of serum creatinine, whereas six (16%) patients had decline of creatinine clearance by >/=30% (none developed end stage renal failure). Seven episodes of thromboembolic complications occurred in five (13%) patients and 11 episodes of infective complications (five major, six minor) were reported in seven (18%) patients. In the absence of co-existing proliferative lesions, MLN runs a relatively benign course with low risk of renal function deterioration. Treatment with high-dose prednisolone and AZA is effective, inexpensive and well-tolerated. Prolonged observation shows that one of three patients develop renal flares, which are often proteinuric and responsive to reinduction therapy.

Does mycophenolate mofetil prevent extra-renal flares in systemic lupus erythematosus? Results from an observational study of patients in a single practice treated for up to 5 years

In this study, the clinical course and change in extra-renal manifestations of patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts of 75 consecutively identified patients on MMF from a single practice were reviewed for demographics, dates of SLE diagnosis, initiation, indication or discontinuation of MMF and other medications. British Isles Lupus Assessment Group (BILAG) organ system data were identified for 3 months prior to MMF and then for the subsequent 5 years. BILAG scores for each organ system and an overall score were calculated for intervals of 6 months. The mean age of 75 subjects was 35.8 years with SLE mean disease duration of 99.2 months. Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%), mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was 3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in composite BILAG scores for 49.3% (37/75) of patients in the first year of treatment and in 20% (15/75) of patients who were still on MMF at >or=5 years. Most flares occurred at second and third year of treatment. The general and renal systems have the most improvement and clinical remissions; the musculoskeletal, mucocutaneous and haematological systems have the most recurrences. Approximately, 50% and 20% of patients taking MMF showed improvement in overall lupus disease activity at both 1 and 5 years, respectively. When evaluating organ system subsets separately, MMF improved disease activity in the first year, but had little effect in preventing new organ-specific flares, with most flares taking place in second and third year of treatment.

Mycophenolate Mofetil for Remission Induction in Severe Lupus Nephritis

Background: Mycophenolate mofetil (MMF) is a potential alternative immunosuppressive to cyclophosphamide or azathioprine for the treatment of lupus nephritis. It has a superior toxicity profile to cyclophosphamide and is more effective than azathioprine when used in combination with cyclosporin for renal transplantation. Methods: This open label study assessed the safety and efficacy of an induction regimen of MMF and prednisolone in 24 patients, with active WHO Class III, IV or V lupus nephritis, without previous exposure to cyclophosphamide or MMF. Patients received MMF 2 g/day and a tapering dose of oral prednisolone and were followed for 12 months. Renal response was defined using the validated BILAG (British Isles Lupus Assessment Group) Index. Results: 20 patients achieved complete renal remission, 2 partial renal remission and 2 had renal disease refractory to MMF. Five patients were withdrawn, 2 for progressive renal disease, 2 for extra-renal flares and 1 following a severe infection. No patient was withdrawn for drug intolerance. There were 18 adverse events of which 10 were infections. Clinical improvement was mirrored by normalisation of complement levels and marked falls in circulating anti-double-stranded DNA antibodies. Follow-up for a mean period of 35 months documented only one episode of renal relapse which subsequently remitted with re-introduction of MMF. One patient died after 18 months’ follow-up with uterine malignancy. Conclusions: MMF with prednisolone was effective for remission induction in severe lupus nephritis and was well tolerated.

Pregnancy in lupus nephritis

Background: Fetal and maternal outcomes of 70 pregnancies in 48 women with lupus nephritis were retrospectively analyzed. Methods: In 13 women, lupus nephritis developed during pregnancy (group A). In 38 patients with known lupus nephritis (including 3 patients in group A who had another pregnancy), 57 pregnancies occurred. In 6 patients, a therapeutic abortion was performed. The remaining 51 pregnancies were considered pregnancies in lupus nephritis (group B). Results: Fetal loss was 36% (38%, group A; 35%, group B); it decreased from 46% in the 1970s to 30% in the last decade. Among 41 live births, there were 13 preterm deliveries and 28 full-term deliveries. At multivariate analysis, proteinuria (P = 0.025), arterial hypertension (P = 0.05), and antiphospholipid antibodies (P = 0.01) were independent predictors of fetal loss. In group A, 3 patients developed acute renal failure, irreversible in 1 patient (7.7%); all other patients recovered after steroid and immunosuppressive therapy. In group B, 12 renal flares and 1 extrarenal flare developed during pregnancy or the postpartum period. Two patients progressed to irreversible renal failure (3.9%), and 1 of the 2 patients died. All other patients recovered. The incidence of renal flares before or during pregnancy was not different (P = 0.51). Renal quiescence at the onset of pregnancy was the only predictor of favorable maternal outcome. Conclusion: Proteinuria, hypertension, and positivity of antiphospholipid antibodies are independent predictors of adverse fetal outcome. Quiescence of renal disease is the only predictor of favorable maternal outcome. © 2002 by the National Kidney Foundation, Inc.

Recurrent Essential Mixed Cryoglobulinemia in Renal Allografts

This report describes two patients in whom essential IgG-IgM mixed cryoglobulinemia (EMC) glomerulonephritis led to end-stage renal disease. Both patients underwent primary hemodialysis, and during the period of uremia clinical and biological manifestations of the disease fully resolved. Transplantation was performed, and in both cases cryoglobulinemia quickly recurred (30 days and 6 months after transplantation, respectively) with clinical renal and extrarenal flare, and reappearance of the biological markers of the disease (decrease in C3 and C4 components of serum complement, detection of rheumatoid activity and of cryoglobulinemia in the serum). The literature on EMC glomerulonephritis leading to end-stage renal disease is reviewed. Factors that may have contributed to extinguishing the disease and to further recurrence following transplantation-consequences of uremic state, alloimmunization and intercurrent infectious disease-are discussed.