Many nephrologists, myself included, are eager to find alternatives to cyclophosphamide in the management of lupus nephritis. As many of these patients are young men and women of child-bearing age, the effects of cyclophosphamide on fertility, along with bone marrow and other adverse effects make alternative medications more attractive. Several studies have suggested that mycophenolate mofetil (MMF) may be superior and less toxic than cyclophosphamide in the management of lupus nephritis. In the May issue of the Journal of the American Society of Nephrology, investigators report the result of a study comparing IV cyclophsphamide with oral MMF. While a reprint is not yet available for review, preliminary reports suggest that MMF is slightly more effective and less toxic in this trial. In a 24-week open-label induction study of 370 patients with class III-V lupus, there were no differences in the primary end-point (a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine) or the secondary end-point (complete renal remission, systemic disease activity and damage, and safety). As well, there were no differences in the rate of adverse events between the 2 groups. For the studied patients, IV cyclophosphamide and oral MMF share similar efficacy and harm. This study adds to the growing evidence base showing no difference between these 2 treatment strategies.
UKidney Nephrology News and Insights
Professor Jonathan Sprent and Dr Kylie Webster from Sydney's Garvan Institute of Medical Research, in collaboration with colleagues, Dr Shane Grey and Stacey Walters reported a major breakthrough in the area of transplantation tolerance in this month's issue of the Journal of Experimental Medicine. This fascinating report describes a method of inducing tolerance of islet cell grafts transplanted into mice. The technique involves combining an antibody with IL2 in a complex that upregulated T-regulatory cells, suppressing T-Killer cells that lead to acute rejection. No immunosuppression was required by the animals and 80% enjoyed tolerance of the graft. While these results are preliminary and in an animal model, it does offer a glimpse at a potential strategy that might obviate or significantly reduce the need for toxic medications in human transplant recipients of all kinds.
Estimates of glomerular filtration rate (GFR) have been the mainstay of kidney functional assessment for some time and have been the most widely relied upon test to predict progression to end-stage renal disease (ESRD). Urinary microalbuminuria (MAU) has more recently been added to the assessment of chronic kidney disease. In this month's issue of the Journal of the American Society of Nephrology, researches confirm that the use of these two tests in conjunction improves the accuracy of predicting which patients will go on to develop ESRD. According to their analysis, if one uses eGFR and MAU together, the number of patients referred to a nephrologist that ultimately develop ESRD would fall from 38.4 to 11.4. This dramatic reduction implies that these 2 tests when used in conjunction greatly increases the diagnostic and prognostic accuracy of primary care physicians assessing for chronic kidney disease.
For a presentation on this topic, please see these links on UKidney:
After disappointing findings in the 4D Study, a subsequent trial reported in a recent issue of the New England Journal of Medicine once again demonstrated disappointing results with statin therapy in patients with end-stage renal failure. In the AURORA study, 2776 patients aged 50-80 were randomized to 10 mg of Crestor or placebo. Despite an average of 43% reduction in LDL, there was no change in the primary end-point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke after 3.8 years of follow-up.
This study is an unfortunate reminder of the difficulty creating measurable impact on hard clinical end-points in patients with end-stage renal failure.