Membranous Nephropathy in Systemic Lupus Erythematosus: Long-Term Outcome and Prognostic Factors of 103 Patients

doi:10.1016/j.semarthrit.2011.08.002

Seminars in Arthritis and Rheumatism

Volume 41, Issue 5, April 2012, Pages 642-651

https://doi.org/10.1016/j.semarthrit.2011.08.002 Get rights and content

Objectives

The objective of this study was to evaluate the clinical features, course, outcome, and prognostic indicators in lupus membranous nephritis (LMN) and to compare data of “pure” LMN vs “mixed” forms.

Methods

We retrospectively examined medical records and kidney biopsies of 103 patients with a diagnosis of LMN.

Results

Sixty-seven patients had “pure” LMN and 36 had “mixed” forms. Patients with mixed LMN had more frequent nephrotic syndrome (66.6 vs 44.7%, P = 0.05), low C3 (83.3 vs 62.6%, P = 0.05) and C4 (80.5 vs 52.2%, P = 0.005), anti-DNA positivity (86.0 vs 62.6%, P = 0.03), and a tendency toward a lower creatinine clearance (93 ± 29 vs 112 ± 50 mL/min, P = 0.07). Moreover, mixed membranous nephritis had a higher activity and chronicity index (6.5 ± 2.1 vs 1.4 ± 2.03, P = 0.005 and 2.4 ± 1.7 vs 1.4 ± 1.8, P = 0.0001, respectively). Methylprednisolone pulses and immunosuppressive therapy were more often used in patients with mixed forms (86.1 vs 60.6%, P = 0.016 and 83.3 vs 57.5%, P = 0.008, respectively). After a mean follow-up of 156.5 ± 104.5 months, there was no difference in the 2 subgroups concerning the number of patients achieving remission and patient/renal survival (94.5 vs 94.0% and 85.8 vs 86% at 10 years). At multivariate analysis, serum creatinine at presentation (P = 0.0013), chronicity index (P = 0.007), failure of achieving remission (P = 0.000001), and occurrence of nephritic flares (P = 0.00167) were independent predictors of chronic renal insufficiency.

Conclusions

Despite the differences in clinical and histological presentation, a therapy tailored on the grounds of clinical and histological features may reduce the differences in the outcome of white patients with mixed and pure membranous nephritis.

Section snippets

Methods

One hundred three patients with biopsy-proven LMN were diagnosed and followed in 2 Italian renal units (Ospedale Maggiore, Ospedale San Carlo in Milan) from January 1974 to December 2008. Of them, 67 had pure membranous nephritis (class V) and 36 mixed LMN (18 class V+III, 18 class V+IV). The clinical characteristics at presentation of this cohort are reported in Table 1. Six patients were lost to follow-up within a few months after renal biopsy, all with pure LMN. The mean follow-up of the

Comparison Between Proliferative and Nonproliferative Membranous Lupus Nephritis

We compared the clinical and histological characteristics at presentation and the treatment and the outcome of patients with pure LMN with those of with mixed LMN.

In Table 1, the demographic and clinical characteristics at presentation of the 2 groups are compared. Patients with mixed LMN had a higher frequency of nephrotic syndrome, low C3 and C4, anti-DNA positivity, and a tendency toward a lower creatinine clearance. Moreover, mixed LMN had a higher activity and chronicity index.

Discussion

In this retrospective study, we report on a large cohort of LMN followed for a mean period of 13 years, 1 of the longest follow-ups reported until now to the best of our knowledge. Patients have been divided into pure LMN and mixed LMN with the aim of comparing their clinic presentation, course, and long-term outcome.

To the more severe histological picture of mixed LMN in terms of activity and chronicity index, corresponds a more severe clinical presentation than in patients with pure LMN;

Acknowledgments

We would like to thank Alessia and Andrea Centa and Marina Balderacchi for their secretarial assistance.

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Cited by (44)

Membranous Lupus Nephritis: A Clinical Review
2019, Advances in Chronic Kidney Disease
Citation Excerpt :
In addition, it is also widely believed that the presence of an accompanying proliferative lesion is associated with worse renal outcomes.6,56,87 However, the evidence is not clear as other cohort studies report no differences in patient or renal survival in patients with mixed vs pure MLN after long-term follow-up.57,88 One of the caveats of studying the long-term outcome of patients with MLN is that it is one of the lesions that is prone to class switch, with multiple studies demonstrating a change from an MLN to a proliferative LN or a mixed lesion on repeat biopsy in 25%-100% of patients,89-92 especially in patients with persistent proteinuria and worsening kidney function.90
Membranous lupus nephritis (MLN) (Class V lupus nephritis [LN]) is a distinct form of LN defined by the presence of subepithelial immune complex deposits seen on kidney biopsy. MLN is often associated with the nephrotic syndrome. The histology of MLN closely resembles that of idiopathic (primary) membranous nephropathy (pMN). However, MLN typically has abundant mesangial deposits that are absent in primary membranous nephropathy. The clinical presentation, management, and prognosis of MLN differ from that of the proliferative forms of LN (Class III, IV, or Mixed III/IV + V). Although immunosuppressive therapy is often warranted in MLN, the optimal treatment regimen remains unclear. Here we describe the clinical presentation, histologic features, and natural history of MLN. We also review the role of supportive treatment and discuss when to deploy immunosuppressive management in MLN.
Effect of complete or partial proteinuria recovery on long-term outcomes of lupus nephritis
2018, Seminars in Arthritis and Rheumatism
We aimed to evaluate the effect of complete recovery (CR), partial recovery (PR), and no recovery (NR) of proteinuria at 2 years from the diagnosis of LN on long-term renal and extra-renal outcomes.
Patients with LN and proteinuria attending the Lupus Center from 1970 to 2015 were analyzed. At 2 years from diagnosis of LN, patients were divided into three groups (CR, PR, and NR), and long-term outcomes were studied up to 15 years or last visit available. CR was defined as resolution of proteinuria, PR as a reduction ≥50% in baseline proteinuria, and NR as a reduction <50% compared to baseline. Long-term outcomes examined included renal outcomes [low eGFR, ESRD, and composite renal (low eGFR, ESRD, and dialysis/transplant)], cardiovascular outcomes, damage, and death. Kaplan–Meier plots, time-independent and time-dependent Cox proportional hazards models were applied to examine the effect of CR, PR, or NR on long-term outcomes.
Of 277 patients, 71.8% achieved CR, 18.4% PR, and 9.8% NR at 2 years. CR compared to NR and CR compared to PR were protective against low eGFR and composite renal outcome in time-independent and time-dependent analyses. CR compared to PR protected against damage in the time-independent analysis. Overall, the comparison of CR and PR favored CR for long-term renal outcomes.
CR at 2 years from diagnosis of LN protected against renal outcomes (low eGFR, ESRD/dialysis, and transplant). CR is more favorable compared to PR and clinicians should aim for CR to improve long-term outcomes in LN.
Can we manage lupus nephritis without chronic corticosteroids administration?
2018, Autoimmunity Reviews
The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950′s, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity.
GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage.
In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.
Membranous Lupus Nephritis: The Same, But Different
2016, American Journal of Kidney Diseases
Citation Excerpt :
However, severe hypoalbuminemia is clearly linked to increased thrombotic risk, particularly in primary membranous nephropathy, and patients with serum albumin levels < 2.8 g/dL should be considered for prophylactic anticoagulation, depending on the individual bleeding risk.25,26 Antiphospholipid antibodies are associated with a higher incidence of arterial and/or venous thrombosis in patients with SLE, particularly lupus anticoagulant and IgG β2-glycoprotein 1 antibodies.27,28 The coexistence of antiphospholipid antibodies and hypoalbuminemia is likely to increase the risk for thromboembolic disease and lower the threshold for initiating anticoagulation.
Membranous lupus nephritis (MLN) has a favorable prognosis compared to proliferative lupus nephritis (PLN) or combined MLN/PLN, although a significant proportion of cases will progress to end-stage kidney disease. There is considerable morbidity associated with thrombotic complications and treatment. Nondirected care includes renin-angiotensin-aldosterone system blockade, cardiovascular risk management, and antimalarial agents. There may be a role for corticosteroid monotherapy in some patients, but this requires further investigation. Clinical trials and observational reports have led to different immunosuppression regimens for MLN, although high-grade evidence favoring a particular agent remains elusive. Established medications used in the treatment of PLN, such as mycophenolate, cyclophosphamide, and azathioprine, may also be efficacious in MLN, or at least steroid sparing. The calcineurin inhibitors appear promising as an alternative treatment in MLN, particularly with emerging experimental data supporting their nonimmunologic antiproteinuric effects. There is also emerging evidence for “multitargeted therapy” in combined MLN/PLN, although the long-term efficacy is still unproved.
Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature
2019, Reumatologia Clinica
Citation Excerpt :
Research on MLN frequency, natural history, prognosis and treatment was further limited due to a lack of uniform definition over the past several decades, making it difficult to get consistent information from the published literature about MLN.1 An Italian study15 has reported the outcome in 103 patients with MLN, but a third of them had mixed forms. More recently, Mejía-Vilet et al.13 have reported the results of a cohort of 60 Hispanic and Mexican-mestizo patients with pure MLN suggesting an impact of ethnicity on the response to different immunosuppressants (azathioprine, cyclophosphamide or mycophenolate).
The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN.
We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA.
Mean age was 34.2 ± 12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98 ± 0.78 mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24 h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death.
Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis.
Los conocimientos sobre el curso y el desenlace a largo plazo de la nefritis lúpica membranosa (NLM) pura son todavía escasos. El objetivo de este estudio es evaluar las características clínicas, curso, desenlace e indicadores pronósticos de la NLM y determinar el impacto de la etnicidad y tipo de cobertura sanitaria en el curso y pronóstico de la NLM.
Se realizó una revisión retrospectiva de las historias de 150 pacientes con NLM de España y Estados Unidos.
La edad media fue 34,2 ± 12,5 y el 80% eran mujeres. El 68% de los pacientes tenían síndrome nefrótico al diagnóstico. La creatinina sérica media fue 0,98 ± 0,78 mg/dl. El 6% de los pacientes fallecieron y el 5,3% desarrollaron insuficiencia renal terminal (IRT). El sexo masculino, la hipertensión, la dislipemia, la alta proteinuria basal, la alta creatininemia y un aclaramiento de creatinina reducido predijeron el desarrollo de IRT. La edad, la insuficiencia cardíaca, la arteriopatía periférica, la hemodiálisis y el no haber recibido micofenolato de mofetilo o antimaláricos predijeron el fallecimiento.
La NLM pura suele debutar con síndrome nefrótico, alta proteinuria y creatininemia normal. Su pronóstico es favourable en términos de mantenimiento de la función renal aunque la proteinuria habitualmente persiste durante el seguimiento. La enfermedad cardiovascular basal y no tener cobertura sanitaria se relacionan con mal pronóstico.
The clinicopathological features and renal prognostic factors in pure membranous lupus nephritis—a large series cohort study from China
2024, Lupus

View all citing articles on Scopus

: Present address of Beniamina Gallelli, MD, Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Sant'Anna, Como, Italy.

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Systemic lupus erythematosusMembranous Nephropathy in Systemic Lupus Erythematosus: Long-Term Outcome and Prognostic Factors of 103 Patients

Objectives

Methods

Results

Conclusions

Section snippets

Methods

Comparison Between Proliferative and Nonproliferative Membranous Lupus Nephritis

Discussion

Acknowledgments

Semin Arthritis Rheum

Am J Kidney Dis

Am J Kidney Dis

Am J Med

Am J Med

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Kidney Int

Prognostic determinants in lupus nephritis: a long-term clinicopathologic study

Lupus

Renal involvement in systemic lupus erythematosusA study of 180 patients from a single center

Medicine

Lupus membranous nephropathy: long-term outcome

Clin Nephrol

Factors affecting outcome and prognosis in membranous lupus nephropathy

Nephrol Dial Transplant

Lupus nephritis: clinical and pathological correlation

Q J Med

Systemic lupus erythematosus with membranous lupus nephropathy in Malaysian patients

Q J Med

Long-term outcome in systemic lupus erythematosus membranous glomerulonephritisLupus Nephritis Collaborative Study Group

J Am Soc Nephrol

Systemic lupus erythematosus
Membranous Nephropathy in Systemic Lupus Erythematosus: Long-Term Outcome and Prognostic Factors of 103 Patients