Desmond Yh Yap

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.

Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome

Aim:  This pilot study compared mycophenolate mofetil (MMF) and tacrolimus (Tac) in the treatment of severe membranous lupus nephritis (MLN).

Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments

Background. Antiviral treatment has improved the short-term outcome of kidney transplant recipients with chronic hepatitis B infection, but its long-term impact, especially in patients who have developed drug resistance, remains uncertain. Methods. Sixty-three hepatitis B surface antigen positive (HBsAg+) and 63 HBsAg− patients who have undergone kidney transplantation from 1985 to 2008 were retrospectively reviewed and their clinical outcomes were compared. Results. With lamivudine as initial treatment, 62% of patients developed drug resistance after 4 years. Lamivudine resistance was associated with a higher incidence of chronic hepatitis but had no significant impact on liver stiffness score or patient survival during follow-up. Salvage treatment with adefovir or entecavir was well tolerated, and resulted in a three-log decrease in hepatitis B deoxynucleic acid after 6 months and normalization of alanine aminotransferase in 75% of patients. The survival rate of HBsAg+ patients transplanted in the recent era of antiviral treatment was 81% at 10 years. Treatment of hepatitis B with nucleoside/nucleotide analogues resulted in significantly improved patient survival (83% vs. 34% at 20 years, P=0.006). Although antiviral treatment was associated with reduced mortality because of liver complications (P=0.036), liver-related deaths still accounted for 40% of mortalities in HBsAg+ patients in the era of antiviral therapies and 22.2% of all deaths that occurred in patients who had received antiviral treatment. Conclusion. Treatment of HBsAg+ renal transplant recipients with nucleoside/nucleotide analogues confers long-term survival benefit, and that rescue therapy with adefovir or entecavir is effective and well tolerated in patients who had developed resistance to lamivudine.

Overview of lupus nephritis management guidelines and perspective from Asia

Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short‐term treatment response rate and long‐term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis – the Steering Group for the Asian Lupus Nephritis Network (ALNN) – met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought.

Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus nephritis

OBJECTIVE We investigated the long-term outcome of patients with proliferative LN treated with CSs and MMF. METHODS This was a single-centre retrospective study on patients with biopsy-proven class III/IV ± V LN treated with prednisolone and MMF continuously as both early and maintenance immunosuppression. RESULTS Sixty-five patients were included, and followed for 91.9 (47.7) months. All received prednisolone and MMF as induction immunosuppression. In 31 patients, maintenance immunosuppression comprised prednisolone and MMF only (MMF-MMF group). MMF was replaced with AZA in 23 patients (MMF-AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF-CNI) at sometime during follow-up. Ten-year patient and renal survival rates were 91% and 86%, respectively, and were similar in the three groups. MMF-MMF group showed better relapse-free survival than MMF-AZA and MMF-CNI patients (76% vs 56% vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF-MMF vs MMF-AZA or MMF-CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI, P = 0.490). Patients treated with MMF for >24 months had better relapse-free survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs 28% at 10 years; P < 0.001). Renal function at 10 years was better in the MMF-MMF group. Anaemia was associated with MMF treatment. Other adverse events were comparable and relatively minor with MMF, AZA or CNI as maintenance. CONCLUSION Long-term treatment with CSs and MMF from induction to maintenance phase is associated with relatively favourable long-term outcome in Chinese LN patients. Discontinuation of MMF before 24 months may increase the risk of flares.

Cost Comparison Between Mycophenolate Mofetil and Cyclophosphamide-Azathioprine in the Treatment of Lupus Nephritis

Objective. To compare the healthcare expenditure associated with mycophenolate mofetil (MMF)-based immunosuppression in contrast to conventional therapy in patients with lupus nephritis. Methods. Our retrospective single-center study compared the major healthcare costs during the first 24 months of treatment incurred by immunosuppressive medications, hospitalization, and complications in patients with severe lupus nephritis who had been treated with prednisolone and either MMF or sequential cyclophosphamide induction followed by azathioprine maintenance (CTX-AZA). Results. Forty-four patients were studied (22 in each group). Baseline demographic and clinical measures, and remission rates after treatment, were similar between the 2 groups. Immunosuppressive drug cost was 13.6-fold higher in the MMF group (US

Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study

4168.3 ± 1176.5 per patient, compared with

Long-term data on tacrolimus treatment in lupus nephritis

285.0 ± 70.6 in the CTX-AZA group, mean difference

Pathogenesis of Renal Disease in Systemic Lupus Erythematosus—The Role of Autoantibodies and Lymphocytes Subset Abnormalities

3883.2 ± 251.3; p < 0.001). MMF treatment was associated with a lower incidence of infections (12.0 episodes/1000 patient-months, compared with 32.4 in the CTX-AZA group; p = 0.035). Combined cost of hospitalization and treatment of infections was 82.5% lower in the MMF group (mean difference –2208.7 ± 1700.6; p = 0.120). Overall treatment expenditure on immunosuppressive drugs, hospitalization, and treatment of infections was 1.57-fold higher in the MMF group (mean US

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

4635.9 compared with