Several of these genes (e.g. claudin-1) have also been implicated in the pathogenesis of epithelial–mesenchymal transition of tubular epithelial cells. Adriamycin also has effects that are not specific to the kidney and that are currently used therapeutically in the treatment of many types of cancers. Acute cellular changes include alterations FK228 supplier in DNA structure (intercalation, cross-linking or binding), inhibition of

topoisomerase 11, free radical generation causing DNA damage and lipid peroxidation, direct cell membrane effects, necrosis, apoptosis and promotion of senescence-like growth arrest. Delayed effects include reactive oxygen species generation causing mitochondrial DNA damage.5 Adriamycin also causes tubulotoxicity independent of its effects on glomeruli via

tubular cell chemokine release (CCL2 & CCL5) and oxidant injury via reactive oxygen species and/or Fas/FasL interactions. These and other organ effects (myelotoxicity,64 hepatotoxicity65 and cardiomyopathy66) may potentially contribute to Adriamycin-induced nephropathy. The most important factor in successful use of this model is the dose of Adriamycin. As there are variations in batch potency and species sensitivity, dose-finding studies are usually required to ascertain the exact dose required to induce the pathological changes required to test the investigator’s hypotheses. As little as 0.5 mg/kg difference in dose can mean the difference between success and failure, particularly in mice.

The intravenous route of Adenosine administration is preferable. Adriamycin nephropathy is a well-established DNA Damage inhibitor rodent model, which is analogous to human focal segmental glomerulosclerosis, characterized by reductions in glomerular filtration rate, proteinuria, glomerulosclerosis associated with changes in the glomerular filtration barrier, and tubulointerstitial fibrosis. The most common method of administration is intravenous via tail vein injection as it is most reproducible in inducing renal injury. Difficulties in using the model may arise due to a number of issues including batch variation and genetic variation in the rodent used. Notwithstanding these shortcomings, this model has facilitated the study of the pathophysiology and possible therapeutics of chronic proteinuric renal disease. The authors acknowledge the National Health and Medical Research Council of Australia for their support. “
“Mean corpuscular volume (MCV) is a measure of size of red blood cells. Recently a few studies showed an association of macrocytosis with all-cause mortality. We aimed to assess the relationship of MCV with cardiovascular (CV) morbidity and mortality in patients with chronic kidney disease (CKD), and the effect of MCV on endothelial function. This is an observational cohort study with a prospectively maintained cohort of patients with stage 1–5 CKD.