Phosphate feeding and calcification
Increasing evidence has proven that arterial calcification is one of the major predictors of morbidity and mortality in chronic kidney disease. Its precipitate is calcium phosphate salt; with this in mind, El-Abbadi et al. tested the effect of dietary phosphate feeding on the development of medial calcification. When uremia was induced in calcification-prone DBA/2 mice, the authors found that extensive arterial medial calcification developed only if the uremic mice were placed on a high-phosphate diet. Moderately uremic mice on the high-phosphate diet developed calcification and had significantly increased serum levels of fibroblast growth factor 23 (FGF-23) and osteopontin, despite the fact that their serum phosphate levels were not notably high. Remarkably, calcification developed in the absence of significant atherosclerosis. Hence, it appears that phosphate loading in uremia plays a significant role in calcification. It is also likely that FGF-23 and osteopontin may be involved in this process, at a minimum by being markers of the injury and possibly by playing a role in the induction of calcification. See page 1297.
VEGF and lupus nephritis
Vascular endothelial growth factor (VEGF) is an important peptide that plays a central role in many vascular and nonvascular processes, including preservation of renal function. In this issue, Avihingsanon et al. present the prognosis of 35 patients with lupus nephropathy. When the authors measured their intrarenal VEGF expression and renal histopathology, they found that the patients with class III or IV lupus nephritis (ISN/RPS categorization) had lower levels of intrarenal VEGF in comparison with kidney biopsies taken from ten donor kidneys sampled at the time of allograft reperfusion. A negative correlation was found between the reduced VEGF mRNA and glomerular endocapillary proliferation, crescent formation, and a high histological activity index. The level of intrarenal VEGF mRNA accurately predicted the deterioration of renal function within 12 months. Larger studies are required to determine whether intrarenal VEGF is an excellent biomarker of deterioration of renal function in lupus nephritis. Nevertheless, these findings raise the interesting question of what causes decreased expression of intrarenal VEGF in patients destined for disease progression; seeking the answer will form an exciting new project. See page 1340.
HIF and AKI
The central player in the pathway of gene activation is hypoxia-inducible factor-1
(HIF-1). HIF-1 was identified when mutations in this pathway led to kidney tumors of the von Hippel–Lindau type. In addition, this transcription factor mediates a vast array of responses to hypoxia, including inducing the transcription of normal physiological mediators such as VEGF, angiopoietin, and erythropoietin, and a number of factors involved in acute kidney injury (AKI). In a new study, Kolyada et al. examined the outcomes of patients with AKI and related them to a non-synonymous polymorphism in the coding region of the HIF-1 gene, a change known to enhance transactivation. They found that the patients with the T alleles had higher incidences of shock and organ failure, including dialysis and death. Higher plasma angiopoietin-2 levels were seen in some of the TT-allele patients, which were associated with in-hospital organ failure or death. These studies suggest a role for HIF-1 in the etiology of AKI complications. See page 1322.
