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Authors: BRAGANCA, Ana Carolina DeCANALE, DanieleGONCALVES, Janaina GarciaBRANDAO, Thais Prevital BastosSHIMIZU, Maria Heloisa MassolaVOLPINI, Rildo AparecidoSEGURO, Antonio CarlosANDRADE, Lucia
Citation: NEPHROLOGY DIALYSIS TRANSPLANTATION, v.27, suppl.2, p.336-337, 2012
Abstract: Introduction and Aims: Renal ischemia/reperfusion injury (IRI), a common cause of acute kidney injury (AKI), activates pathways of cell proliferation and cell death. AKI induces normally quiescent renal cells to enter the cell cycle and triggers the induction of cell cycle inhibitors, including the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1), which is protective against AKI. In mice lacking the p21 gene, AKI is more severe and the resulting renal cell death is more widespread. The potent immunomodulatory and antiproliferative properties of 25-hydroxyvitamin D [25 (OH)D] suggest that it plays a role in the pathophysiology of renal and cardiovascular disease. By altering the levels of several key cell cycle regulators and arresting cells in G0/G1, 25(OH)D can control renal inflammation. It is known that p21, which also arrests cells in G1, is a genomic target of 25(OH)D in many cell types. Prior vitamin D deficiency (VDD) is a major predictor of mortality in critically ill patients. Here, we evaluated the effect of VDD in IRI-induced AKI, hypothesizing that VDD decreases p21 expression and would thus be harmful in AKI. Methods: Wistar rats were fed 25(OH)D-depleted or normal diets for 30 days. On day 28, some rats were induced to IRI by 45-min clamping of both renal arteries. We studied four groups: C (control, n = 7); VDD (n = 5); IRI (n = 7); and VDD+IRI (n = 8). At 48 h after IRI, we measured inulin clearance (CIn); proteinuria; serum levels of 25(OH)D, Ca, and P; urinary volume and osmolality; and fractional excretion of phosphate (FEP). Immunoblotting for p21 and aquaporin 2 (AQP2) was performed in kidney tissue. Data are expressed as mean ± SEM. Results: VDD, IRI and VDD+IRI rats showed higher urine output, higher water intake and lower urinary osmolality. Renal function was impaired in IRI rats. AKI was more severe in VDD+IRI rats, as evidenced by proteinuria and lower CIn. p21 expression was higher in IRI rats than in control rats (134 ± 13.7 vs. 100 ± 1.0%; P < 0.05); in IRI rats than in VDD+IRI and VDD rats (134 ± 13.7 vs. 85.5 ± 1.9 and 64.4 ± 1.7%; P < 0.01); and in control rats than in VDD rats (100 ± 1.0 vs. 64.4 ± 1.7%; P < 0.05). In VDD rats, markedly increased urine output and decreased urinary osmolality were accompanied by decreased AQP2 expression (26.2 ± 0.6; P < 0.001 vs. controls), which was also lower in VDD+IRI rats than in IRI rats (25.2 ± 0.8 vs. 49 ± 1.0; P < 0.001). Conclusions: In otherwise healthy individuals with VDD, renal expression of p21 is downregulated more than usual. This appears to prevent the natural triggering of p21 upregulation in AKI, thereby increasing its severity. VDD might also cause tubular dysfunction (urinary concentrating defect). Further studies are needed in order to determine whether the correction of VDD provides clinical benefits in AKI.
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Comunicações em Eventos - FM/MCM
Departamento de Clínica Médica - FM/MCM

Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - HC/InCor
Instituto do Coração - HC/InCor

Comunicações em Eventos - LIM/12
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais

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