Does calcium disodium EDTA slow CKD progression?

G iven the increasing incidence and prevalence of chronic kidney disease (CKD), approaches to slow disease progression are essential. For more than a decade, Ja-Liang Lin and colleagues have published randomized placebo-controlled clinical trials reporting that treatment with calcium disodium EDTA slows CKD progression. Lead chelation has been implicated as the mechanism, and benefits in diabetic and nondiabetic patients with CKD with mean blood lead levels as low as 2.6 g/dL have been reported (Table 1). Similar study designs have been used across publications. Initially, patients are observed to compare CKD progression prior to chelation. Then, patients whose chelatable lead levels are within certain ranges (generally 60-600 g excreted in a 72-hour urine collection after intravenous administration of 1 g of calcium disodium EDTA and thus lower than the level commonly considered for chelation in lead poisoning) are randomly assigned. The treatment group receives weekly calcium disodium EDTA until lead levels decrease to a defined target. The control group receives placebo infusions. In the follow-up period, chelation is repeated for defined indications, such as increased serum creatinine level or chelatable lead levels higher than specified cutoffs. The results of their latest trial, which is focused on patients with type 2 diabetes with nephropathy, are reported in this issue of the American Journal of Kidney Diseases and are consistent with earlier trials in observing a benefit of calcium disodium EDTA in slowing CKD progression. The present study builds on a 2006 study of patients with diabetes by including a larger sample size and doubling the follow-up time. The chelation data reported by these authors to date are summarized in Table 1. Strengths of this body of research include prospective study design with longitudinal statistical analyses, randomization, assessment of bioavailable lead dose, and controlling for multiple risk factors for CKD progression. However, a number of limitations also have been raised. First, the results are at best single blinded. The researchers are not blinded and the treatment protocol, which includes additional calcium disodium EDTA infusions as needed based on lead levels during follow-up, may differ from the placebo protocol; therefore, patients may be able to discern their treatment group. Second, the generalizability of these findings to other populations is commonly questioned, in particular, whether lead exposure in Taiwanese patients is higher compared with