Zaki Morad

Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis

Background:  The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.

Normalized bioimpedance indices are better predictors of outcome in peritoneal dialysis patients.

♦ Background: While phase angle of bioimpedance analysis (BIA) has great survival-predicting value in dialysis populations, it is known to be higher in male than in female subjects. In this study, we aimed to explore the factors influencing the predictive value of phase angle and to identify the appropriate physics terms for normalizing capacitance (C) and resistance (R). ♦ Methods: We formulated body capacitive index (BCI), CBMI (capacitance × height2/weight), body resistive index (BRI), RBMI (resistance × weight/height2), and CH2 (capacitance × height2). We also studied H2/R, R/H, and reactance of a capacitor/height (XC /H). There are 3 components in this study design: (1) establishment of normal values in a control Malaysian population, (2) comparison of these with a CAPD population, and (3) prediction of survival within a CAPD population. We initially performed a BIA study in 206 female and 116 male healthy volunteers, followed by a prospective study in a cohort of 128 CAPD patients [47 with diabetes mellitus (DM), 81 non-DM; 59 males, 69 females] for at least 2 years. All the parameters during enrolment, including BIA, serum albumin, peritoneal equilibrium test, age, and DM status, were analyzed. Outcome measurement was survival. ♦ Results: In healthy volunteers, both genders had the same BCI (2.0 nF kg/m2). On the contrary, female normal subjects had higher BRI than male normal subjects (median 15 642 vs 13242 Ω kg/m2, p < 0.001) due to higher fat percentage (35.4% ± 0.4% vs 28.0% ± 0.6%, p < 0.001), resulting in a lower phase angle (mean 5.82 ± 0.04 vs 6.86 ± 0.07 degrees, p < 0.001). Logistic regression showed that BCI was the best risk indicator in 128 CAPD patients versus 322 normal subjects. In age- and body mass index (BMI)-matched head-to-head comparison, BCI had the highest χ2 value (χ2 = 102.63), followed by CH2 (or H2/XC; χ2 = 81.00), BRI (χ2 = 20.54), and XC/H (χ2 = 20.48), with p value < 0.001 for these parameters. In comparison, phase angle (χ2 = 11.42), R/H (χ2 = 7.19), and H2/R (χ2 = 5.69) had lower χ2 values. 35 (27.3%) patients died during the study period. Univariate analysis adjusted for DM status and serum albumin level demonstrated that non-surviving patients had significantly higher CH2 (245 vs 169 nF m2, p < 0.001) and BCI (4.0 vs 2.9 nF m2/kg, p = 0.005) than patients that survived. CH2 was the best predictor for all-cause mortality in Cox regression analysis, followed by BCI, phase angle, and XC/H. ♦ Conclusion: Measures that normalize, such as BCI and CH2, have higher risk discrimination and survival prediction ability than measures that do not normalize, such as phase angle. Unlike phase angle, measurement of BCI overcomes the gender effect. In this study, the best risk indicator for CAPD patients versus the general population is BCI, reflecting deficit in nutritional concentration, while CH2 reflects total nutritional deficit and thus is the major risk indicator for survival of CAPD patients.

Funding Renal Replacement Therapy in Southeast Asia: Building Public-Private Partnerships in Singapore, Malaysia, Thailand, and Indonesia

The provision of renal replacement therapy (RRT) in developing economies is limited by lack of financial and other resources. There are no national reimbursement policies for RRT in many countries in Asia. The Southeast Asia countries of Singapore, Malaysia, Thailand, and Indonesia have adopted a strategy of encouraging public-private partnerships to increase the RRT rates in their respective countries. The private organizations include both for-profit and philanthropic bodies. The latter raise funds from ordinary citizens, corporations, and faith-based groups, as well as receive subsidies from the government to support RRT for patients in need. The kidney foundations of these countries play a leadership role in this public-private partnership. Many of the private organizations that support RRT are providers of treatment in addition to offering financial assistance to patients, with hemodialysis being the most frequently supported modality. Public-private partnership in funding RRT is sustainable over the long term with proper organization and facilitated by support from the government.

Review article: Use of renal registry data for research, health-care planning and quality improvement: What can we learn from registry data in the Asia–Pacific region?

SUMMARY:  We review renal registry data from the Asia–Pacific region with an emphasis on their uses in health care and in dialysis care in particular. The review aims to demonstrate the information value of registry data. While renal registry provides a useful data resource for epidemiological research, there are severe methodological limitations in its application for analytical or therapeutic research. However, it is the use of renal registry data for public health and health‐care management purposes that registry really comes into its own, and it is primarily for these that governments have invested in national patient and disease registries. We apply data from several renal registries in the Asia–Pacific region to illustrate its wide application for planning dialysis services, for evaluating dialysis practices and health outcomes, with a view to improving the quality of dialysis care. In the course of preparing the review, we have found that the quality and accessibility of renal registry data were highly variable across the region. Given the value of renal registry, every country in the Asia–Pacific region should establish one or should ensure that their current registries are better resourced and developed. Greater data sharing and collaboration among registries in the region could help advance the nephrology to serve our patients better.

A challenge to chronic kidney disease in Asia: The report of the second Asian Forum of Chronic Kidney Disease Initiative

Background:  The Asian Forum of Chronic Kidney Disease Initiative started in 2007 in Hamamatsu, Japan when delegates from 16 countries joined together to facilitate collaboration in studying chronic kidney disease (CKD) in the Asia–Pacific region. Based on the outcome of the first meeting, the second meeting was organized as a consensus conference to frame the most relevant issues, and develop research recommendations and action plan.

Conversion to enteric-coated mycophenolate sodium from mycophenolate mofetil in stable renal transplant patients: results of an Asia-Pacific study.

Mycophenolate mofetil has proven efficacy in the prophylaxis of acute rejection in solid organ transplantation; however, gastrointestinal intolerance can risk this efficacy because of associated dose adjustments and discontinued treatment. Enteric‐coated mycophenolate sodium has demonstrated improved gastrointestinal tolerability, but the data in Asian subjects are scarce.

Observational cohort study to determine the long-term safety and efficacy of GerEPO for the treatment of renal anaemia in patients with chronic kidney disease.

To the Editor, We have previously reported in the Nephrology journal the results of a clinical trial which showed therapeutic equivalence between a biogeneric epoetin, GerEPO and Eprex with respect to haemoglobin (Hb) response among patients on dialysis. The duration of the trial treatment was only 3 months, which was insufficient for safety evaluation. Following demonstration of equivalent efficacy, we have initiated an observational cohort study in late 2005 to evaluate the long-term safety of GerEPO. As of July 2007, 263 patients have been enrolled and observed up to 18 months of the study. The Hb levels of all patients have increased significantly from a mean 9.4 g/dL at baseline to 10.7 g/dL and on a median dose of 8000 IU/week GerEPO (interquartile range 6000–12 000 IU/week). Patients’ mean blood pressure (BP) did not show significant increase from baseline, but they had required increasing use of antihypertensive drugs. At baseline, only 26.3% of patients were on the medication, while at 18 months of the study, the percentage of patients on antihypertensive drugs has increased to 55.6%. There have been 307 adverse events (AE) reported to date. The most commonly reported AE has been headache (incidence, 9.6%), followed by anaemia (6.9%), increase BP/hypertension (6.1%) and dizziness (3.5%). Five patients have had severe hypertension resulting in one being withdrawn from the study, four patients have had arteriovenous fistula thrombosis associated with increased Hb, and there have been 22 reported deaths while during the study. In December 2006, one patient was reported to have pure red cell aplasia, which was subsequently confirmed to be antiEPO antibody positive. The Data and Safety Monitoring Board convened to review the case and all the safety data recommended patients who were on s.c. administration of GerEPO be discontinued from the trial. However, the Clinical Trial Exemption (the regulatory authorization under which GerEPO was used for clinical trial purpose in Malaysia) was eventually suspended by the regulatory authority and the trial was thereby prematurely terminated. A long-standing issue concerning biosimilars is distinguishing between the high quality ones with proven efficacy and safety from the numerous unproven ones. While a randomized therapeutic equivalence trial is the most reliable tool to evaluate efficacy, a longer term study is required to evaluate safety. Such requirements are already enshrined in regulatory guidelines such as those of the European Medicines Agency. By these standards, unfortunately, the safety track record of GerEPO could not bear scrutiny.