Optimum therapeutic approaches for lupus nephritis: what therapy and for whom?

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.     

Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.     

Mycophenolate mofetil in lupus nephritis

There is an increasing body of literature suggesting the efficacy and tolerability of mycophenolate mofetil (MMF) for the treatment of lupus nephritis. The rationale for its use is based upon its successful profile as an immunosuppressive agent for prevention of allograft rejection, as well as studies in murine models of lupus which have reported improved renal function and animal survival compared to placebo. This report reviews the data regarding MMF therapy in murine lupus models, and describes the initial anecdotal experience with MMF in human lupus, especially in patients with glomerulonephritis who were unresponsive to corticosteroids and cyclophosphamide, or who had unacceptable toxicity on this standard of care regimen. The results of several nonblinded, controlled clinical trials are also described, in which MMF was compared to intravenous or oral cyclophosphamide in patients with lupus nephritis. MMF was found to be well tolerated, with most studies showing fewer infections than that associated with cyclophosphamide. Efficacy of MMF was at least equivalent to cyclophosphamide, and therefore appears to provide an alternative as a standard of care for induction and maintenance treatment of lupus nephritis.     

Lupus nephritis: treatment with mycophenolate mofetil

OBJECTIVE: To evaluate the safety and efficacy of mycophenolate mofetil (MMF) treatment in patients with lupus nephritis. METHODS: Eighteen patients with biopsy-proven lupus nephritis (17 females, one male; mean age 31.6 yr; mean lupus duration 92 months; mean duration of nephritis 57 months; nine with focal proliferative glomerulonephritis, three with diffuse proliferative glomerulonephritis, six with membranous nephropathy) were included. With five exceptions, all patients had been treated previously with cyclophosphamide and were selected because of either toxicity or inadequate clinical response to treatment. MMF was given at 2 g daily in combination with steroids for up to 31 months (mean 15.3 months). The side-effects of MMF were recorded and efficacy was assessed as the renal function profile. RESULTS: Complete remission was observed in 10/18 patients and another 4/18 went into partial remission. Both creatinine clearance and proteinuria were significantly improved during MMF treatment in patients with the proliferative forms of nephritis. MMF demonstrated a steroid-sparing effect in the whole population. Treatment failure was recorded in 4/18 patients, all with membranous nephropathy. Two patients developed gastrointestinal complaints and infectious meningitis occurred in one patient. CONCLUSION: MMF appears to be an efficacious and safe treatment in patients with proliferative forms of lupus nephritis who do not respond to or cannot tolerate conventional treatment. The efficacy of MMF in lupus membranous nephropathy remains unclear.     

Three Decades of Progress in Treating Childhood-Onset Lupus Nephritis

Summary

Background and objectives

Childhood-onset lupus nephritis (LN) carries a worse renal prognosis compared with adults. Controlled treatment trials in children are lacking. We compared renal and patient survival in a cohort of pediatric patients followed over 3 decades.

Design, settings, participants, & measurements

A retrospective analysis was conducted on 138 patients with childhood-onset systemic lupus erythematosus from 1980 to 2010. The core cohort included 95 with severe LN: 28 progressed to end-stage renal disease (ESRD group) whereas 67 did not (no-ESRD group). Patients were stratified into four “eras” according to the introduction of the primary immuno-suppressive drug: era 1: triple oral therapy with corticosteroids (CS), cyclophosphamide (CYC), and azathioprine (AZA); era 2: intravenous CYC; era 3: mycophenolate mofetil (MMF) ± CYC; era 4: rituximab (RTX) ± CYC ± MMF.

Results

Mean age at diagnosis was 12.3 ± 2.9 years with median follow-up of 5 years. Poor renal function (estimated GFR < 60 ml/min per 1.73 m²) and nephrotic proteinuria at diagnosis imparted a poor prognosis. Increasing proteinuria correlated with progression of kidney disease. The addition of MMF in era 3 improved 5-year renal survival from 52% to 91% and overall patient survival from 83% to 97%. African-American ethnicity was associated with significant risk for progression to ESRD whereas Hispanic ethnicity conferred an advantage. Infection and cardiovascular disease were the primary causes of patient demise.

Conclusions

Renal and patient survival in childhood-onset LN has improved during the past 3 decades with progressive treatment regimens. Future trials in children are very much warranted.     

The safety and efficacy of MMF in lupus nephritis: a pilot study.

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.     

How to manage patients with lupus nephritis

The clinical and renal biopsy predictors of assistance in determining therapy are reviewed. While pulse cyclophosphamide remains the most effective treatment for proliferative nephritis, there is increasing interest in other agents, such as azathioprine, particularly to maintain remission. While lupus membranous nephropathy has attracted limited study, preliminary work suggests a role for cyclophosphamide. Newer therapies, including cyclosporine A, mycophenolate mofetil, immunoadsorption, intravenous immune globulin, LJP-394, high-dose immunoablation and nucleoside analogues require further study but offer hope for those failing conventional treatments.     

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus

OBJECTIVE: To report the first clinical experience with mycophenolate mofetil (MMF, CellCept) in: children with lupus nephritis. METHODS: Eleven children with various forms of lupus nephritis were treated with oral MMF at a mean dose of 22 mg/kg/day (range 17-42) for a mean of 9.8 months (range 3-17). All children received concomitant prednisone and 7/11 were taking concomitant hydroxychloroquine. Indications for MMF included treatment refractory nephritis despite high dose oral or IV prednisone, azathioprine, and/or cyclophosphamide. Treatment outcome was monitored through assessment of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, renal function, and serologic markers such as complement and anti dsDNA antibodies. RESULTS: While renal function normalized in 4/4 patients with membranous glomerulonephritis, little effect was observed in children with proliferative glomerulonephritis. Ten children experienced a marked reduction in SLEDAI score. Anti-dsDNA antibody and serum complement levels improved or remained stable in 80% of the children. Concomitant prednisone was decreased in 6/11 patients (55%) without deterioration of renal function. Adverse events, observed in 8 patients (73%), were not dose dependent, and included infections, leukopenia, nausea, pruritus, headache, and fatigue. CONCLUSION: MMF may represent a valuable alternative to traditional cytotoxic agents for children with class V lupus nephritis, but was less effective in attenuating disease progression in class IV glomerulonephritis. MMF had a steroid sparing effect and appeared to be effective in controlling serologic disease activity in pediatric onset SLE. Adverse events such as infections may limit its use and remain a concern.     

The effects of cyclophosphamide and mycophenolate on end-stage renal disease and death of lupus nephritis

Debate continues about the optimal treatment modality of lupus nephritis (LN). We compared the efficacy and safety of intravenous cyclophosphamide (CYC) and mycophenolate mofetil (MMF) for LN treatment in Korea. After searching for systemic lupus erythematosus (SLE) patients diagnosed between 1998 and 2007 with the diagnostic code of ICD10, we selected the 71 patients who were treated with CYC or MMF without any other immunosuppressant except systemic steroid. Composite outcome was defined as progression to end-stage renal disease (ESRD) and/or all-cause mortality. The initial manifestations of the CYC group were more severe than those of the MMF group. The mean daily MMF dose was 980 ± 100 mg for 21.67 ± 18.25 months. The mean monthly dose per CYC pulse therapy was 850 ± 30 mg for 17.04 ± 13.15 months. The incidence of composite outcome was 5/20 (25%) in the MMF group and 4/51 (7.8%) in the CYC group. The relative risk (RR) for composite outcome in the CYC group was 0.249 (95% CI for RR: 0.067-0.934, p?=?0.039) compared with the MMF group with Cox's hazard proportional analysis. In Kaplan-Meier analysis, the probability of composite outcome was lower in the CYC group than in the MMF group (Log rank test p-value?=?0.026). The results of this retrospective study suggest that intravenous CYC therapy may be more efficacious in averting ESRD and death than MMF. These results need to be confirmed in a larger randomized controlled trial.     

Immunosuppressive treatment for pure membranous lupus nephropathy in a Hispanic population

Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n?=?18), intravenous cyclophosphamide (IVC) (n?=?16), or azathioprine (AZA) (n?=?26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19–16.4, p?=?0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08–5.64, p?=?0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010–1.14, p?=?0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.     

Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.     

Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide‐resistant proliferative lupus nephritis

Objective

Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B cell–dependent diseases, including systemic lupus erythematosus (SLE). The purpose of this study was to investigate the histopathologic and clinical effects of combination treatment with rituximab and cyclophosphamide (CYC) in patients with CYC‐resistant proliferative lupus nephritis.

Methods

Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Renal biopsies were performed before treatment and during followup. SLE activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group index. In 6 of the 7 patients, immunostaining of lymphocyte subpopulations in the renal tissue was performed before treatment and during followup.

Results

At 6 months of followup, significant clinical improvement was noted, with a reduction in SLEDAI scores (from a mean of 15 to 3), anti–double‐stranded DNA antibody levels (from a mean of 174 IU/ml to 56 IU/ml), and anti‐C1q antibody levels (from a mean of 35 units/ml to 22 units/ml). On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted (from 6 to 3). A reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium was noted in 50% of the patients on repeat biopsy.

Conclusion

At 6 months of followup, all patients had responded both clinically and histopathologically to combination therapy. For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option.

     

Low dose cyclosporine A in the treatment of resistant proliferative lupus nephritis

Objective: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis.

Methods: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti–double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs.

Results: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7?±?24.9 and 35.2?±?19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period.

Conclusions: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.     

Lupusnephritis

During the course of systemic lupus erythematosus (SLE) 30?C90% of patients develop a renal manifestation which has proven to be decisive for morbidity and mortality. Histologically six different classes have been described leading to different treatment strategies. In mesangial proliferative lupus nephritis (class II) extrarenal manifestations determine the immunosuppressive treatment. However, in class III and IV (focal or diffuse proliferative manifestation) cyclophosphamide or possibly mycophenolate mofetil (MMF) as an alternative is necessary. In membranous lupus nephritis (class V) dual renin-angiotensin aldosterone (RAAS) blockade is most important. With class I (minimal mesangial lupus nephritis) and class VI (sclerosis) no immunosuppressive therapy is needed. New treatment options concentrate on B-cell depletion, inhibition of cytokines and co-stimulatory molecules. Recently, for the first time in SLE, a monoclonal antibody (belimumab) against B lymphocyte-stimulating factor (Blys) has been approved for treatment in combination with standard therapy.     

Lupusnephritis

During the course of systemic lupus erythematosus (SLE) 30?C90% of patients develop a renal manifestation which has proven to be decisive for morbidity and mortality. Histologically six different classes have been described leading to different treatment strategies. In mesangial proliferative lupus nephritis (class II) extrarenal manifestations determine the immunosuppressive treatment. However, in class III and IV (focal or diffuse proliferative manifestation) cyclophosphamide or possibly mycophenolate mofetil (MMF) as an alternative is necessary. In membranous lupus nephritis (class V) dual renin-angiotensin aldosterone (RAAS) blockade is most important. With class I (minimal mesangial lupus nephritis) and class VI (sclerosis) no immunosuppressive therapy is needed. New treatment options concentrate on B-cell depletion, inhibition of cytokines and co-stimulatory molecules. Recently, for the first time in SLE, a monoclonal antibody (belimumab) against B lymphocyte-stimulating factor (Blys) has been approved for treatment in combination with standard therapy.     

Management of lupus nephritis—current perspectives

Systemic lupus is a complex disease that poses a lot of management challenges. The introduction of the International Society of Nephrology (ISN)/RPS classification, which has attempted to bring about a more standardized approach to reporting of renal biopsy, plays an important role in the management and prognostication in patients with lupus nephritis (LN). The standard of care for severe proliferative LN had been with pulse cyclophosphamide. There is emerging evidence for use of mycophenolate mofetil (MMF) as an alternative therapy for both induction and maintenance therapy, especially in milder forms of disease. Many biological response modifiers are in the pipeline. Rituximab is the most studied one in the setting of refractory LN with conflicting evidence. Azathioprine remains a cheaper alternative to the more powerful, expensive therapies and has a role in maintenance immuno-suppression. The optimal management of membranous lupus remains controversial till date.     

Tratamiento de inducción en la nefritis lúpica tipo IV

The ideal therapy for lupus nephritis (LN) should reduce mortality. Although cyclophosphamide (CYC) has been used in the clinical setting for 30 years, the ability of this drug to achieve this goal is not supported by robust evidence.The first National Institutes for Health (NIH) trial in 1986 led to a shift from oral to intravenous (IV) CYC. The three NIH trials together then led to the dogma that high-dose IV CYC is the only cytotoxic agent superior to steroids alone in LN and to its general acceptance as the standard of care. Since then, high-dose IV CYC has been shown to have no impact on survival and to have a large number of adverse effects.The Euro-Lupus Nephritis Trial found that low-dose IV CYC could be used as an alternative to high-dose regimens and was associated with fewer secondary effects. Other studies have shown that other agents such as mycophenolate mofetil (MMF) have similar or even greater efficacy and a better safety profile.IV CYC is the only drug for which long-term data on LN is available. As evidence of other therapies such as MMF accumulates, however, IV CYC might no longer be considered the standard treatment for LN.     

Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis

OBJECTIVE: Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B cell-dependent diseases, including systemic lupus erythematosus (SLE). The purpose of this study was to investigate the histopathologic and clinical effects of combination treatment with rituximab and cyclophosphamide (CYC) in patients with CYC-resistant proliferative lupus nephritis. METHODS: Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Renal biopsies were performed before treatment and during followup. SLE activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group index. In 6 of the 7 patients, immunostaining of lymphocyte subpopulations in the renal tissue was performed before treatment and during followup. RESULTS: At 6 months of followup, significant clinical improvement was noted, with a reduction in SLEDAI scores (from a mean of 15 to 3), anti-double-stranded DNA antibody levels (from a mean of 174 IU/ml to 56 IU/ml), and anti-C1q antibody levels (from a mean of 35 units/ml to 22 units/ml). On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted (from 6 to 3). A reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium was noted in 50% of the patients on repeat biopsy. CONCLUSION: At 6 months of followup, all patients had responded both clinically and histopathologically to combination therapy. For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option.     

Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide

Objective

There is a need to identify clinical characteristics and/or biomarkers that can predict treatment outcome in lupus nephritis. To this end, we utilized data from the Aspreva Lupus Management Study to identify possible baseline and early predictors of renal response to mycophenolate mofetil (MMF) or intravenous (IV) cyclophosphamide (CYC).

Methods

Patients with class III–V lupus nephritis were randomized to MMF or IV CYC. We assessed predictors of renal response, including baseline demographic, clinical, laboratory, and histologic characteristics, as well as early clinical and laboratory data, obtained within the first 2 months of therapy. Odds ratios (ORs) and 95% confidence intervals for renal response were calculated for each putative predictor.

Results

Normalization of C3, C4, or both by week 8 was strongly predictive of renal response at week 24 (ORs 2.5, 2.6, and 2.9, respectively; P < 0.05). Reduction in proteinuria by ≥25% by week 8 was predictive of renal response at week 24 (OR 3.2, P < 0.05). Reduction in anti–double‐stranded DNA (anti‐dsDNA) by week 8 was not predictive of renal response. Only 3 baseline characteristics (C4 level, time since diagnosis of lupus nephritis, and estimated glomerular filtration rate [GFR]) were predictive of renal response; the remaining characteristics (age, age at lupus nephritis onset, time since diagnosis of systemic lupus erythematosus, sex, histopathologic class, anti‐dsDNA antibody level, C3 level, level of proteinuria, and use of angiotensin‐converting enzyme inhibitors, statins, or hydroxychloroquine) were not.

Conclusion

This study demonstrates that baseline C4 level, time since diagnosis of lupus nephritis, baseline estimated GFR, early normalization of complement, and reduction in proteinuria independently predict renal response to therapy at 6 months.