Colin Tang

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 substi...

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 cyclophosphamide 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 >/=24 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.

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.

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Background Severe acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection. Methods We conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy. Results Among these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS. Conclusion Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.

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.

Pilot study of pegylated interferon‐alpha 2a in dialysis patients with chronic hepatitis C virus infection

Aim:  Pegylated interferon (PEG‐IFN) combined with ribavirin is recommended for the treatment of chronic hepatitis C virus (HCV) infection in patients without renal failure. The optimal treatment of hepatitis C in dialysis patients remains to be established. A high incidence of adverse effects has been observed with conventional interferon and PEG‐IFN alpha‐2b in dialysis patients.

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

Prospective Study on Lamivudine‐Resistant Hepatitis B in Renal Allograft Recipients

4168.3 ± 1176.5 per patient, compared with

A Combination of Biocompatible Peritoneal Dialysis Solutions and Residual Renal Function, Peritoneal Transport, and Inflammation Markers: A Randomized Clinical Trial

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