Results: Palmitate-BSA, not control-BSA, significantly suppressed EPO transcription in HepG2 and murine kidney in association with increased intracellular lipid droplets, especially under hypoxic conditions. The suppressive effect of palmitate in hypoxia-induced EPO transcription was associated with activation of ER stress signal (ATF4 and XBP-1 activation). Importantly, we identified a novel ATF4 binding site (TGACCTCT) nearby hypoxic
response element (HRE) at 3′-enhancer region of EPO gene. ATF4 overexpression Gemcitabine cell line diminished this enhancer activity, and thereby suppressed EPO transcription without any effect to another HIF target genes, GLUT1 and VEGF. CoCl2-induced plasma EPO level was also reduced in palmitate-BSA-injected mice. Conclusion: Long-chain saturated fatty acid, such as palmitate, suppresses EPO production inversely with activation of ER stress signals. Importantly, hypoxia enhances the effect of palmitate via an increase in intracellular lipid accumulation and ATF4/XBP-1 activation. Underlining the crosstalk of “Lipid nephrotoxicity” and EPO-producing cells, dyslipidemia may contribute to
progression of renal anemia JNK inhibitors in patients with chronic kidney disease. “
“One of the factors that may affect survival and function of kidney graft is its functional mass. In a prospective study, we investigated the impact of the ratio between donor kidney weight in grams and recipient bodyweight in kilograms (DKW/RBW) on creatinine clearance, inulin clearance, and proteinuria: 154 kidneys from deceased donors were weighed and the mean kidney weight was 227 ± 59 g, the bodyweight of the recipients was 64 ± 19 kg. This study showed significant lower values of modification of diet in renal disease (MDRD) in patients with
DKW/RBW ratio 2.5 g/kg and between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg as well as in patients with DKW/RBW ratio <3 g/kg and between 3 and 4 g/kg compared with those with DKW/RBW ratio >4 g/kg; moreover a random coefficient model showed a different time evolution in creatinine clearance values in patients with DKW/RBW ≤ 3 g/kg when compared with patients with DKW/RBW ratio >4 g/kg. There were significant lower values of inulin clearance in patients with DKW/RBW ratio between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg at 12 post-transplant months and a significantly greater occurrence and earlier for appearance of proteinuria in the recipients with DKW/RBW ratio <2.5 g/kg. DKW/RBW ratio did not influence DGF incidence and graft survival. Donor and recipient gender, number of acute rejection episodes and donor age also significantly influenced MDRD values. Measurements of graft weight as well as donor kidney and recipient body matching should be recommended as influencing renal function. "
“Aim: In the absence of a national renal biopsy registry, there is a paucity of information on the pattern of renal disease observed in native renal biopsies in adults in Pakistan.
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