Peter Stenvinkel

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally believed that the elevated levels of urea in chronic kidney disease (CKD) patients have negligible toxicity. Both oxidative stress and insulin resistance are commonly observed in patients with end-stage renal disease (ESRD). In this issue of NDT-E you will find a full paper published in J Clin Invest by D’Apolito et al who sought to determine if urea promoted uremic oxidative stress and insulin resistance. Indeed, the authors showed that treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced reactive oxygen species (ROS) production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Of note, the antioxidative SOD/catalase mimetic treatment prevented the development of insulin resistance in normal mice after urea infusion. Thus, this study suggests that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by ESRD.
In another study published in NDT Rosalind et al identified a rare VDR haplotype that is protective against diabetic nephropathy in patients with type-1 diabetes. As always, replication in a large, independent cohort is required to confirm this finding. In another Ms recently published in NDT Lesley et al validated the CKD-EPI equation, based on S-creatinine, age, sex and race and showed it to be more accurate than the MDRD study equation. For those of you that need an update on kidney disease in the fields of diabetology and cardiology, the two excellent reviews by Guntram Schernthaner and Charles A. Herzog are highly recommended. For your benefit both are included as full papers in this issue of NDT-E, which also includes two presentations from the World Congress of Nephrology in Milano 2009. In the first talk Luigi Gnudi, London, UK will discuss the interplay between hyperglycemia and vascular hemodynamics. In the other talk Toshio Miyata from Sendai in Japan will discuss the associations between advanced glycation, hypoxia and oxidative stress.

Enjoy this issue of NDT-E!

Peter Stenvinkel – Editor in Chief NDT-Educational