Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis

Background: The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known. Methods: In 42 patients with diffuse proliferative lupus nephritis we compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months. Complete remission was defined as a value for urinary protein excretion that was less than 0.3 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration, and values for serum creatinine and creatinine clearance that were no more than 15 percent above the base-line values. Partial remission was defined as a value for urinary protein excretion that was between 0.3 and 2.9 g per 24 hours, with a serum albumin concentration of at least 3.0 g per deciliter. Results: Eighty-one percent of the 21 patients treated with mycophenolate mofetil and prednisolone (group 1) had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone (group 2). The improvements in the degree of protelnuria and the serum albumin and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in group 1 and in 33 percent of those in group 2 (P=0.29). Other adverse effects occurred only in group 2; they included amenorrhea (in 23 percent of the patients), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent and 11 percent, respectively. Conclusions: For the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone. (C) 2000, Massachusetts Medical Society.published_or_final_versio

A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade

Persistent proteinuria in patients with quiescent lupus can result from membranous lupus nephritis and/or glomerular scarring following previous flares. This pilot study examined the effects of tacrolimus over two years in six patients with membranous/inactive lupus nephritis and persistent proteinuria despite angiotensin inhibition/blockade. Tacrolimus treatment reduced proteinuria and increased serum albumin (time effect, P = 0.047 and 0.032 respectively). Compared with baseline levels, proteinuria improved by more than 50% in five patients (83.3%) and hypoalbuminaemia was corrected in four patients. The efficacy was most prominent in four patients with biopsy-proven membranous lupus nephritis, whose protienuria improved by over 80%. One patient developed biopsy-proven chronic nephrotoxicity after 10 months of tacrolimus treatment, despite non-excessive blood levels. These data suggest that tacrolimus is an effective treatment for proteinuria due to membranous lupus nephritis, but should probably be reserved for patients who are refractory to other non-nephrotoxic treatments, in view of the potential risk of subclinical nephrotoxicity. © 2007 SAGE Publications.link_to_subscribed_fulltex

Angiotensin inhibition or blockade for the treatment of patients with quiescent lupus nephritis and persistent proteinuria

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) reduces proteinuria and the rate of renal function deterioration in diabetic nephropathy and other glomerular diseases, but its role in quiescent lupus nephritis has not been established. We conducted a retrospective study to investigate the effects of ACEI/ARB on proteinuria and renal function in patients with persistent proteinuria (> 1 g/day) despite resolution of acute lupus nephritis following immunosuppressive treatment. Fourteen out of 92 patients were included. The duration of treatment with ACEI/ARB was 52.1 ± 35.7 months. The levels of proteinuria, serum albumin, serum creatinine, systolic and diastolic blood pressure were 1.10 to 6.90 g/day, 35.8 ± 3.6 g/L, 102.54 ± 34.48 μmol/L, 137.6 ± 10.9 and 81.9 ± 9.2mmHg at baseline. Proteinuria and serum albumin showed significant sustained improvements after 6 and 24 months of treatment. Comparison of slopes for serial proteinuria, albumin and reciprocal of serum creatinine before and after treatment showed significant improvements in six (43%), eight (57%) and two patients, respectively. At last follow-up proteinuria remained significantly lower (0.36 g/day, P = 0.043) and albumin higher (41.3 ± 2.2 g/L, P = 0.023). Eleven (78.6%) patients had proteinuria improved by >50%, and five had insignificant proteinuria at last follow-up. Systolic blood pressure was significantly reduced from 6 months onwards, but this did not correlate with proteinuria reduction. Diastolic blood pressure, serum creatinine, creatinine clearance, anti-dsDNA, C3 and haemoglobin were not altered. We conclude that ACEI/ARB effectively reduces proteinuria and improves serum albumin in patients with persistent proteinuria despite quiescent lupus nephritis. © 2005 Edward Arnold (Publishers) Ltd.link_to_subscribed_fulltex

Prospective study on lamivudine-resistant hepatitis B in renal allograft recipients

The natural history of lamivudine-resistant hepatitis B virus (HBV) infection in renal transplant recipients (RTx) is unclear, despite its increasing incidence. Twenty-nine HBsAg-positive RTx with rising HBV DNA received lamivudine therapy. The course of lamivudine-resistant HBV infection was studied prospectively. During 68.7 ± 12.5 months of follow-up, 14 (48.3%) patients developed lamivudine resistance, at 10-35 months (mean 16.9 ± 7.0). All showed mutant sequences at codons 552 and 528 of the YMDD motif, while 13 patients demonstrated wild-type sequence at codon 555. Lamivudine resistance was unrelated to patient demographics, HBeAg status/sero-conversion, or genotype. Following resistance, HBV DNA and alanine aminotransferase showed an initial increase followed by spontaneous gradual reduction. The subsequent peak HBV DNA was lower (1.25 ± 1.09 × 109 vs. 6.26 ± 12.23 × 109 copies/mL, p = 0.011), while that of alanine aminotransferase was higher (196 ± 117 vs. 77 ± 47 iμ/I, p = 0.005), compared with pretreatment levels. Post-resistance hepatitic flare occurred in 11 (78.6%) patients. This was transient in four (36.4%), but became chronic in six (54.5%) patients. Decompensation was noted in one patient during this flare, but all survived. We conclude that drug resistance is prevalent in lamivudine-treated RTx. Despite a lower ensuing peak viremia compared with baseline, hepatitic flare is common. While most patients have spontaneous resolution, a minority may develop potentially fatal decompensation during the preceding exacerbation.link_to_subscribed_fulltex

Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis

Mycophenolate mofetil (MMF) and the sequential use of cydophosphamide followed by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated with less drug toxicity. Results from an extended long-term study, with median follow-up of 63 mo, that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented. Thirty-three patients were randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm, both in combination with prednisolone. More than 90% in each group responded favorably (complete or partial remission) to induction treatment. Serum creatinine in both groups remained stable and comparable over time. Creatinine clearance increased significantly in the MMF group, but the between-group difference was insignificant. Improvements in serology and proteinuria were comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up (P = 0.667). Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients (11 and nine patients relapsed, respectively) and between those with MMF treatment for 12 or S24 mo. MMF treatment was associated with fewer infections and infections that required hospitalization (P = 0.013 and 0.014, respectively). Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death (P = 0.062 by survival analysis). It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients. Copyright © 2005 by the American Society of Nephrology.link_to_subscribed_fulltex

Response to adefovir or entecavir in renal allograft recipients with hepatitic flare due to lamivudine-resistant hepatitis B

We studied the effects of adefovir or entecavir in six kidney transplant recipients (mean age 45.7 ± 7.8 yr) who developed hepatitic flare due to lamivudine-resistant hepatitis B virus (HBV) infection, with 18 months of follow-up. All patients had elevated alanine aminotransferase (ALT) levels and HBV DNA >105 copies/mL (median 2.15 × 108 copies/mL) at baseline. Serum creatinine and creatinine clearance levels were 137.8 ± 59.7 μmol/L and 62.6 ± 18.7 mL/min, respectively. Four patients were treated with adefovir and two with entecavir. Median HBV DNA decreased to 1.99 × 105 copies/mL (p = 0.028) after six months, 1.5 × 104 copies/mL (p = 0.043) after 12 months, and 7.35 × 104 copies/mL (p = 0.068) after 18 months of treatment. There was a corresponding improvement in ALT (34.5 ± 19.1 U/L after 18 months, p = 0.029 compared with baseline). The rate of HBV DNA suppression was variable, and three patients took over six months for the viral load to decrease to <105 copies/mL. After 18 months, HBV DNA was <105 copies/mL in four patients and <102 copies/mL in one patient. Treatment was well-tolerated and renal function remained stable. We conclude that both adefovir and entecavir are effective in the treatment of lamivudine-resistant HBV in renal allograft recpients, and the reduction of HBV DNA to <105 copies/mL could be slow. © 2009 John Wiley & Sons A/S.link_to_subscribed_fulltex

Quality of life comparison between corticosteroid-and-mycofenolate mofetil and corticosteroid-and-oral cyclophosphamide in the treatment of severe lupus nephritis

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment. © 2006 Edward Arnold (Publishers) Ltd.link_to_subscribed_fulltex

Survival analysis and causes of mortality in patients with lupus nephritis

BACKGROUND: This study aimed to define the causes and associated risks of death compared with the local general population in Chinese patients with lupus nephritis in the recent era. METHODS: The records of all lupus nephritis patients followed in a single centre during 1968-2008 were reviewed. The causes of death were identified, the survival curves constructed and the standardized mortality ratios (SMRs) of potential risk factors were calculated with reference to the local general population. RESULTS: Two hundred and thirty systemic lupus erythematosus patients with history of renal involvement (predominantly Class III/IV lupus nephritis with or without membranous features) were included. The follow-up was 4076.6 person-years (mean 17.7 +/- 8.9 years). Twenty-four patients (10.4%) died, and 85% of the deaths occurred after 10 years of follow-up. The 5-, 10-, and 20-year survival rates were 98.6, 98.2 and 90.5%, respectively. The leading causes of death were infection (50.0%), cardiovascular disease (20.8%) and malignancy (12.5%). The renal survival rates at 5, 10 and 20 years were 99.5, 98.0 and 89.7%, respectively. The SMR in patients with renal involvement, end-stage renal disease (ESRD), malignancy or cardiovascular disease was 5.9, 26.1, 12.9 and 13.6, respectively. CONCLUSIONS: Lupus nephritis is associated with a 6-fold increase in mortality compared with the general population. Lupus patients who develop ESRD have a 26-fold excess in the risk of death, which is more than twice the risk associated with malignancy or cardiovascular disease in these patients.link_to_OA_fulltex

Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine

The short-term outcome of patients with diffuse proliferative lupus nephritis (DPLN) has improved with advances in immunosuppressive treatment. However, the impact of different immunosuppressive regimens on long-term renal function remains to be defined. This prospective cohort study examined the long-term renal function and disease relapse in adults with biopsy-proven DPLN, significant proteinuria, and hypoalbuminemia, who had been treated with sequential immunosuppression comprising prednisolone and oral cyclophosphamide as induction followed by low-dose prednisolone and azathioprine as maintenance. Sixty-six patients with 68 episodes of DPLN were included, with follow-up of 91.7 ± 36.7 months. 82.4% achieved complete remission and 39.1% relapsed during follow-up. Patients in partial remission were at higher risk of relapse compared with those in complete remission (hazard ratio 6.2, P < 0.001). Serum creatinine remained stable over time (P = 0.931), while creatinine clearance showed a significant increase with time after treatment (P = 0.032). Three (4.4%) patients had doubling of baseline creatinine, but none reached end-stage renal failure or died. Univariate and mixed model analyses showed that the evolution of long-term renal function was significantly influenced by the chronicity score and creatinine clearance at baseline, and by the renal function at one year after treatment. These data demonstrate the efficacy of sequential immunosuppression in preserving renal function in most Chinese subjects with DPLN. The results also indicate that irreversible renal scarring (as reflected by baseline chronicity score), renal reserve (as reflected by renal function at baseline and one year), and an induction regimen that is effective in preserving the nephron mass are critical determinants of long-term renal outcome. © 2005 Edward Arnold (Publishers) Ltd.link_to_subscribed_fulltex