Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: Long‐term followup of a cohort of 145 patients participating in randomized controlled studies

Objective

Immunosuppressive agents have become the standard of therapy for proliferative lupus nephritis, but some patients may relapse after discontinuing treatment. We reviewed the cases of renal flares in a cohort of patients who participated in 2 randomized controlled clinical trials at the National Institutes of Health and explored the prevalence, outcome, and predictive factors of renal flares.

Methods

Data were obtained on 145 patients treated with pulse cyclophosphamide, pulse methylprednisolone, or the combination of both. Patients had not received immunosuppressive therapy for at least 6 months and had experienced complete or partial response according to defined criteria. Renal flares were classified as either proteinuric or nephritic based on changes in urinary protein and sediment. Most patients who experienced a flare received additional immunosuppressive therapy.

Results

Seventy‐three patients had a complete response, and 19 had partial response/stabilization. Forty‐one of these patients (45%) experienced renal flares (nephritic in 33, proteinuric in 8) after a mean followup of 117 months; 31 of them received additional immunosuppressive therapy. The median time to renal flare was 36 months in the complete responders and 18 months in the partial responders. Eleven of the 41 patients (27%) progressed to end‐stage renal disease (ESRD); 9 had nephritic flares (all severe except for 1) and 2 had proteinuric flares (1 in each responder group). Compared with patients who had a complete response, those with a partial response were more likely to experience a flare, to have a severe nephritic flare, or to progress to ESRD. Low C4 at the time of response and African American ethnicity were significant independent risk factors for renal flare, by multivariate Cox proportional hazards analysis.

Conclusion

Nephritic flares are common in patients with proliferative lupus nephritis, even in those with a complete response to therapy, but they do not necessarily result in loss of renal function if treated with additional immunosuppressive agents. Renal flares are an important feature of the natural history of lupus nephritis and provide an opportunity for additional preventive strategies, as well as measures of efficacy in future therapeutic trials.

     

Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis

OBJECTIVE: To study the incidence, predictors, and outcome of renal flares after successful cyclophosphamide (CYC) treatment for diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE). METHODS: Between 1988 and 2001, patients with biopsy-proven SLE DPGN who were treated initially with prednisone and CYC were studied. Those who responded to CYC were followed up for the occurrence of renal flares. The cumulative risk, predictors, and outcome of renal flares were evaluated. RESULTS: We studied 189 patients (167 women; and 22 men) with SLE DPGN. All were initially treated with prednisone and CYC (49% orally; 51% by intravenous pulse). At the last dose of CYC, 103 patients (55%) and 52 patients (28%) had achieved complete and partial renal responses, respectively. Azathioprine (AZA) was given as maintenance therapy in 117 patients (75%). After a mean followup of 96.5 months, 59 patients (38%) experienced renal flares (42% nephritic; 58% proteinuric). The median time to relapse was 32 months. The cumulative risk of renal flare was 28% at 36 months and 44% at 60 months. Independent predictors of nephritic flares were persistently low C3 levels after CYC treatment and absence of AZA maintenance therapy. At the last clinic visit, 16 patients (10.3%) had developed doubling of the serum creatinine level (cumulative risk of creatinine doubling 7.4% at 5 years after renal biopsy and 14.3% at 10 years). Ten patients (6.5%) developed end-stage renal disease (ESRD). Renal survival rates at 5 and 10 years were 94.9% and 87.5%, respectively. Increasing histologic chronicity scores, failure to achieve complete response, persistent hypertension after CYC treatment, and nephritic renal flares were unfavorable factors for doubling of the serum creatinine level and for ESRD by univariate analysis. The occurrence of nephritic flares was the only predictor of creatinine doubling by Cox regression analysis. CONCLUSION: In patients with SLE DPGN, renal flares are common despite initial responses to CYC. Nephritic renal flares are associated with a decline in renal function. Maintenance therapy with AZA reduces, but does not completely prevent, renal flares. More effective maintenance treatment for SLE DPGN after an initial response to CYC should be evaluated.     

Lupus nephritis flares

The clinical course of lupus nephritis varies remarkably among SLE patients, even between those with the same histological type. Current immunosuppressive agents induce remission in the majority of the patients with proliferative lupus nephritis, but a substantial proportion of them - ranging in different studies from 27% to 66% - will flare. Flares represent a significant problem because of the potential for cumulative damage that may lead to deterioration of renal function as well as toxicity due to the additional immunosuppression. Maintenance therapy with azathioprine, mycophenolate mofetil or quarterly pulses of cyclophosphamide is usually recommended. Renal flares can be characterized as nephritic or nephrotic and can be mild or severe. The majority of the patients that flare restore renal function, if diagnosed early and treated promptly. However, current immunosuppressive agents have limitations concerning efficacy and toxicity profiles. Unresolved management issues include the value of repeat renal biopsy and issues related to optimal strategy/regimen to prevent flares. Renal flares are an important feature of the natural history of lupus nephritis and provide an opportunity for additional preventive strategies, as well as measures of efficacy in future therapeutic trials.     

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.     

Longterm followup of childhood lupus nephritis

OBJECTIVE: To determine the longterm outcome in children with onset of lupus nephritis before 18 years of age. METHODS: Sixty-seven patients with onset of lupus nephritis prior to age 18 were identified. The mean followup time was 11 years (range 5-19). The mean age at diagnosis was 13.2 years (range 4-17). The male:female ratio was 1:3.8. Renal biopsies were classified using the WHO classification. Fifteen patients had Class II, 8 patients Class III, 32 patients Class IV, and 11 patients Class V and one patient refused biopsy. The cohort consists of the 66 patients who had a renal biopsy. Five patients received cyclophosphamide (CYC) and 17 received azathioprine (AZA) as part of the initial treatment of Class IV nephritis. Eight additional patients received CYC because of a flare of disease while receiving AZA, and 8 other patients received AZA because of a flare of disease while taking prednisone therapy. RESULTS: Four patients died; 6 developed endstage renal disease (ESRD); all but one of the patients who died and/or had ESRD had WHO Class IV [diffuse proliferative glomerulonephritis (DPGN)]; only 2 Caucasians developed ESRD, although 16 out of 36 Caucasians had DPGN; serum creatinine at followup was normal in 84% of the survivors; presently 70% of the patients take less than 7.5 mg prednisone/day and 62% do not take cytotoxic drugs. No patient is currently treated with CYC. All 8 patients with Class III nephritis were taking medication at last followup. CONCLUSION: The longterm outcome in this group of children with lupus nephritis, in whom AZA was the most commonly used immunosuppressive agent, was excellent, with 94% patient survival at a mean followup of 11 years. Our results suggest that non-Caucasian patients with pediatric onset lupus nephritis may be at increased risk for renal failure compared to Caucasians.     

Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus

OBJECTIVE: To retrospectively evaluate longterm clinical and immunological effects of anti-CD20 treatment in patients with systemic lupus erythematosus (SLE) with active nephritis or autoantibody-mediated cytopenias refractory to conventional immunosuppressive treatment. METHODS: Anti-CD20 treatment (rituximab) was added to the ongoing immunosuppressive treatment in 31 SLE patients with active nephritis (n = 17), thrombocytopenia (n = 10), and hemolytic anemia (n = 4) refractory to conventional therapy. Disease activity was evaluated by the SLE Disease Activity Index. The median followup time after anti-CD20 treatment was 22 months (range 1-61 mo). RESULTS: Complete B cell depletion was obtained in all patients. In 11 of the 17 lupus nephritis patients complete or partial responses were achieved after 6-12 months. Eight of these patients increased their glomerular filtration rate (GFR) by > 25%. The responders were characterized by having shorter nephritis duration, a baseline GFR > 30 ml/min, and detectable circulating CD19+ B lymphocytes before B cell depletion. Anti-CD20 treatment was highly effective in patients with autoimmune thrombocytopenia, inducing a significant increase of platelet counts after 1 month (p < 0.01). Five of 10 patients achieved complete normalization of their platelet counts within 6 months. The anti-CD20 treatment was followed by a significant reduction of autoantibodies against dsDNA and platelets, in nephritic and in thrombocytopenic patients, respectively. CONCLUSION: Addition of anti-CD20 treatment to conventional immunosuppressive therapy may be a beneficial strategy in refractory lupus nephritis and autoimmune cytopenias, possibly by reducing the levels of pathogenic autoantibodies.     

Long-term followup of patients treated with total lymphoid irradiation for lupus nephritis

OBJECTIVE: To describe the long-term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis. METHODS: Twenty-one patients with biopsy-proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high-dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil). RESULTS: The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end-stage renal disease (ESRD). The probability of long-term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients. CONCLUSION: Overall, patients with lupus nephritis treated with TLI do not appear to have better 10-year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.     

Efficacy of rituximab combined with cyclophosphamide in a patient with systemic lupus erythematosus and peritoneal vasculitis refractory to conventional inmunosupressive therapy

Peritoneal vasculitis is a rare and severe clinical manifestation of systemic lupus erythematosus. We report a patient who presented with ascites due to peritoneal vasculitis and cutaneous, articular, hematological and renal inflammatory activity. Treatment with glucocorticoids and immunosuppressive drugs was ineffective. In view of the resistance to different therapies, 4 weekly infusions of 375mg/m2 of rituximab (RTX) were started, in association with cyclophosphamide pulses during the first and the third weeks. With this treatment strategy, the patient reached a complete response which was achieved in later flares of inflammatory activity (the second and third flares were multisystemic and with ascites again, and the fourth flare with nephritis).     

Mesangial lupus nephritis in Chinese is associated with a high rate of transformation to higher grade nephritis

Mesangial lupus nephritis was thought to be a mild form of lupus nephritis. However, case reports suggest that this type of nephritis could be associated with a high rate of transformation to more serious classes. We retrospectively reviewed the clinical features, clinical response at one year following treatment, as well as the long-term outcome of patients with mesangial lupus nephritis identified on their first renal biopsy. The possible clinical parameters that may predict poor outcome were examined. Nineteen patients with a median duration of follow-up of 9.6 (2.5-11.4) years were identified. At one year after biopsy, eight patients achieved complete remission, two patients achieved partial remission and nine patients had no response. Of the 10 responders, four relapsed after a median duration of 53 (42-97) months. Nine out of 10 patients (six nonresponders and four responders who relapsed) who underwent a second biopsy showed transformation to a higher grade nephritis. The long-term outcome remained favourable in nine patients. Responders and patients who were given angiotensin-converting enzyme inhibitors were associated with favourable long-term outcome. Our data highlight that renal biopsy should be repeated early in Chinese patients with mesangial nephritis who failed to respond to treatment in order to identify those who may require intense immunosuppressive therapy.     

Management of hepatitis B reactivation in patients with lupus nephritis

Hepatitis B is endemic in many Asian countries and immunosuppression may precipitate hepatitic flare. There is little data on the treatment of hepatitis B in patients with systemic lupus erythematosus. We monitored serial transaminase and HBV DNA levels in our HBsAg-positive patients with a history of lupus nephritis and instituted anti-viral treatment in patients who showed virological reactivation. This retrospective pilot study reports the data with this pre-emptive management strategy. Amongst 228 patients with lupus nephritis, eight (3.51%) were HBsAg-positive and five had received Lamivudine treatment for hepatitis B. In two patients the virological flares were preceded by lupus flares that necessitated an increase in immunosuppressive treatment. Median HBV DNA level was 1.9 × 10⁷ copies/mL (range 1.2 × 10⁴–1.0 × 10⁹ copies/mL) at baseline, and it decreased by 2–5 logs after treatment. Four patients had abnormal transaminase levels at baseline, with mean alanine aminotransferase at 125.0 ± 67.4 U/L, and all achieved normalisation after 3–24 months (median 13 months) of treatment. Discontinuation of Lamivudine treatment was attempted in three patients after 9–15 months. In one patient treatment was recommenced because of virological flare. For the remaining two patients in whom treatment was not interrupted, one showed sustained viral suppression and one developed drug resistance. All antiviral treatments were well-tolerated. These results indicate the importance of serial monitoring of HBV DNA and transaminase levels, and prompt anti-viral therapy, in the management of HBsAg-positive lupus patients. Also, it may be feasible to discontinue treatment in stable patients to avoid the selection of drug-resistant variants.     

Disease activity in systemic lupus erythematosus patients with end-stage renal disease: systematic review of the literature

It is not unusual that patients with systemic lupus erythematosus (SLE) progress to terminal renal failure and subsequently require renal replacement therapy. Previous studies have shown that clinical and/or serological remission in patients with SLE is common in those who develop end-stage renal disease (ESRD). On the other hand, the persistence of lupus activity among patients undergoing long-term dialysis is not rare, either. The aim of this study is to define, by means of a systematic review, the course of SLE activity in patients who developed ESRD. Data were obtained through searches for articles in the MEDLINE (1966 to 2011), SCielo, and LILACS databases, using the following keywords: "chronic renal failure", "systemic lupus erythematosus", "end-stage renal disease", "lupus activity", "disease activity", "lupus flare", "hemodialysis", and "renal replacement therapy" and their corresponding translations in Portuguese. Twenty-four articles were found which evaluated the degree of lupus activity in patients with ESRD. Fifteen of these studies spoke of a substantial reduction of clinical and/or serological activity after the development of ESRD, while nine articles found that the amount of clinical and/or serological activity was similar to that of the phase prior to terminal renal failure, or it occurred in at least 50% of the patients studied. Although the majority of studies showed that lupus flares tend to decrease in frequency in patients who develop ESRD, in this scenario, one should be prepared to correctly diagnose a recurrence of the disease, as well as to perform appropriate therapy.     

Treatment response and progression to end stage renal disease in adolescents and young adults with lupus nephritis: A follow up study in an Egyptian cohort

BackgroundLupus nephritis (LN) badly affects the outcome in adolescents and young adults with systemic lupus erythematosus (SLE). Many have renal disease at onset and the significance of remission and relapse in adolescents and young adults is poorly evaluated.Aim of workTo outline the clinical and laboratory characteristics of treatment resistance, renal relapse and progression to end-stage renal disease (ESRD) in adolescents and young adults with LN.Patients and methodsEighty-five biopsy-proven LN patients were examined; SLE disease activity and renal damage were evaluated at baseline and followed up at 6 and 12 months. Laboratory and immunology profiles were assessed. Patients were evaluated for predictors of treatment response, renal flares, and renal survival.ResultsThe patients mean age was 15.12 ± 4.53 years. Female/male ratio was 10.5:1. 12.9% had treatment resistance, 87.1% achieved remission: complete (CR 31.8%) and partial (PR 55.2%) within 1st year. 27 (31.8%) developed a relapse within the 1st year (9 after CR and 18 after PR). Nephrotic range proteinuria persisted in 24 (28.2%) patients (13 PR and the 11 non-responders). Baseline hypertension (p = 0.034), persistent nephrotic range proteinuria (<0.001) and PR (p < 0.001) were predictive for renal flares. Treatment resistance (p = 0.021), disease relapse (p < 0.001), persistent nephrotic range proteinuria (p < 0.001) were predictors of ESRD, especially in males (p = 0.035). Autoimmune profile and histopathology class showed insignificant differences among groups.ConclusionPrevention and aggressive management of hypertension, proteinuria and renal flares is expected to prevent progression to ESRD in lupus nephritis in adolescent and young adult SLE patients.     

Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine

OBJECTIVE: To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model. RESULTS: We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function. CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.     

Analysis of lupus activity in end-stage renal disease treated by hemodialysis

OBJECTIVE: The activity of systemic lupus erythematosus (SLE) has been reported to decrease in patients who have developed end-stage renal disease (ESRD). However, extrarenal symptoms attributable to the disease activity are noted, especially during the first year of dialysis. We studied the clinical course and evaluate the disease activity of SLE in patients with ESRD on hemodialysis for more than 6 months. SUBJECT AND METHODS: Fourteen patients with SLE who had been initiated on maintenance dialysis at our center between 1982 and 1999 were examined retrospectively. Their clinical details, organ system manifestations, serologic profiles and immunosuppressive treatment regimens were reviewed. Patients with and without postdialysis flaras of SLE were compared statistically. RESULTS: Five patients exhibited 6 SLE flares under treatment with corticosteroids. Two flares occurred within the first year of the initiation of dialysis, and in 1 patient, aggravation of the disease activity was noted 98 months after the initiation of dialysis. Polyarthritis was noted in 5 cases and fever in 4 cases. The serum complement levels decreased in all 6 cases with relapse of SLE activity. Compared with the other 9 patients who did not exhibit SLE relapse, no significant differences were found in 5 patients who did with respect to the demographic and serologic features at the initiation of dialysis. CONCLUSION: We conclude that the disease activity does not always burn out in patients of SLE who show progression to ESRD. SLE flares can sometimes occur even after one year of the initiation of dialysis. SLE patients on dialysis should be carefully followed up by clinical and serological monitoring, and treated by appropriate immunosuppressive therapy.     

Clinical prognostic factors in lupus nephritis. The importance of hypertension and smoking.

BACKGROUND--Many previous studies of the influence of sociodemographic and clinical factors on the development of renal failure in patients with lupus nephritis have been based on selected subgroups of patients and have yielded conflicting results. We sought to determine the prognostic importance of patient demographic characteristics (age, gender, race, and socioeconomic status), smoking status, and hypertension in the development of end-stage renal disease (ESRD) among patients with lupus nephritis. METHODS--This retrospective cohort study followed an inception cohort of 160 adults with lupus nephritis. The outcome measure was the development of ESRD, defined as the institution of maintenance dialysis or measurement of a creatinine clearance of 10 mL/min or less. Life-table analysis was used to determine differences between patient subgroups in the time to development of ESRD. RESULTS--End-stage renal disease developed in 41 (26%) of 160 patients followed up for a median of 6.4 years. Hypertension and smoking status at the onset of nephritis were strongly associated with differences in the time to development of ESRD. The median time to ESRD among patients with moderate to severe hypertension (diastolic blood pressure, greater than or equal to 105 mm Hg) was 7 months, among patients with mild hypertension (diastolic blood pressure, 90 to 104 mm Hg) it was 146 months, and among normotensive patients it was greater than 273 months. The median time to ESRD among smokers was 145 months and among nonsmokers it was greater than 273 months. These effects persisted in multivariable analyses adjusting for differences among patients in age, gender, socioeconomic status, renal histology, and immunosuppressive treatment. The independent effects of hypertension and smoking resulted in shorter times to renal failure among patients who were both hypertensive and smoking, compared with nonsmoking hypertensive patients. The development of ESRD did not differ among patient demographic subgroups. CONCLUSION--Patient demographic characteristics had no detectable impact on the rate of progression to ESRD in this cohort. Hypertension and smoking appear to be important, potentially modifiable, factors influencing the prognosis of patients with lupus nephritis.     

Long‐term followup of patients treated with total lymphoid irradiation for lupus nephritis

Objective

To describe the long‐term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis.

Methods

Twenty‐one patients with biopsy‐proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high‐dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil).

Results

The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end‐stage renal disease (ESRD). The probability of long‐term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients.

Conclusion

Overall, patients with lupus nephritis treated with TLI do not appear to have better 10‐year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.

     

Urinary MCP-1 as diagnostic and prognostic marker in patients with lupus nephritis flare

Aim of the study: This study aimed to assess correlation of urinary monocytic chemoattractant protein-1 (UMCP-1) with severity of lupus nephritis and its role as predictor of outcome. Method: Twenty patients with lupus nephritis flare were included in the study. Ten patients in each group of stable systemic lupus erythematosus and non-renal flare were taken as controls. Biopsy was done to define lupus nephritis stage. UMCP-1 levels were measured in all patients at the time of entry and at four and eight weeks of follow-up. Results: Mild, moderate and severe lupus nephritis flare was noted in one, five and 15 patients, respectively. UMCP-1 levels were high in patients with severe lupus nephritis flare (2.74?±?0.95?ng/mg creatinine) as compared to patients with moderate (1.43?±?0.46?ng/mg creatinine) and mild lupus nephritis flare (0.76?±?0.57?ng/mg creatinine) (P?=?0.0093). Baseline mean UMCP-1 levels in lupus nephritis flare, non-renal flare and stable SLE patients were 2.32?±?1.06, 0.171?±?0.03 and 0.213?±?0.026?ng/mg creatinine, respectively. The difference among the three groups was very significant (P?相似文献   

Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria

Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, ≥50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2±3.3 months of MMF therapy, at a mean daily dose of 2.3±0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47±1.26 vs. 1.33±0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2±0.4 vs. 3.7±0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7±20.0 to 18.6±14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2±3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments.Dr. Bonfá’s work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, grant 304756/2003-2.     

Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for diffuse proliferative glomerulonephritis

The incidence of renal flares and the long-term outcome in a group of 33 systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (CYC) are evaluated. Fifteen patients (45%) experienced a flare of renal disease at some time after the discontinuation of the immunosuppressive (IS) therapy; among these half (24%) were 'early' flares occurring shortly after the discontinuation of therapy, and the other half (21%) were 'late' flares occurring more than 2 y after the discontinuation of the treatment. Nine patients (27%) showed a poor renal outcome at the end of follow-up. On multiple regression analysis, a younger age and a high activity index (AI) on renal histology were found to be correlated with the occurrence of renal flares. Our results suggest that the combination of pulse steroids with a short course of pulse CYC (six to nine pulses) is effective in both controlling disease activity and in preventing the occurrence of renal flares in DPGN. However, short term IS therapy might not be sufficient to maintain disease control in younger patients with active lesions on renal histology. Such patients might be candidates to receive more prolonged IS treatment.     

Current management of lupus nephritis: popular misconceptions

The management of lupus nephritis is typified by popular misconceptions: that there is a 'standard of care', that treatment has well-defined aims and that the optimum length of treatment is established. In reality, however, uncertainties still exist and the evidence base remains weak. Until recently, initial therapy for class IV lupus nephritis typically involved intravenous cyclophosphamide, yet although cyclophosphamide is superior to azathioprine in improving renal function, it is not superior in terms of mortality. In fact, recent studies show mycophenolate mofetil to be superior to cyclophosphamide in terms of response rate and safety profile and at least as effective as other immunosuppressants. The role of steroids is unclear. Clearly, no standard of care exists in lupus nephritis. The Euro-Lupus Nephritis Trial found that treatment response at six months, in terms of reduced serum creatinine and proteinuria, was the best predictor of long-term renal outcome. Proteinuria, however, can take a long time to reach baseline levels, and normalization of urine is not the same as loss of histological disease activity. Response to treatment thus is not the same as disease remission. Although treatment should aim to reduce the risk of end-stage renal disease and death, control of proteinuria and prevention of flares are also important. Patients who have nephritic flares are almost seven times as likely to progress to end-stage renal disease compared with those who do not. Regimens involving maintenance phases have been developed, but uncertainty remains about the risk of flares and how they can be predicted. The optimum duration of treatment has yet to be determined.