RESUMO
INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of coronary angiography (CA). The aim of this randomized, parallel group, single blind, sham-controlled trial was to assess the safety and efficacy of the remote ischemic preconditioning on the prevention of CI-AKI. METHODS: Patients of 18-80 years of age with CKD 3 and 4, who were admitted for elective coronary angiography in a tertiary care hospital in eastern India were randomized in a 1:1 ratio to standard care with ischemic preconditioning (n = 45; intermittent arm ischemia through 4 cycles of 5-min inflation and 5-min deflation of a blood pressure cuff) or with standard care and sham ischemic preconditioning (n = 42). Overall, both study groups were at moderate risk of developing CI-AKI according to the Mehran risk score. The primary endpoint was the incidence of CI-AKI, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 h after contrast medium exposure. RESULTS: CI-AKI occurred in 8 patients (19.04%) in the control group and 2 (4.4%) in the remote ischemic preconditioning group (odds ratio, 0.198, 95% confidence interval, 0.087 to 0.452; P = 0.04). No major adverse events were related to remote ischemic preconditioning. CONCLUSIONS: This study indicates that remote ischemic preconditioning is a simple and well-tolerated procedure, which reduces the incidence of CI-AKI in CKD 3 and 4 patients undergoing coronary angiography.
RESUMO
INTRODUCTION: There is a higher prevalence of non-dipping pattern in hypertensive chronic kidney disease (CKD) patients. Nocturnal hypertension has been shown to predict cardiovascular mortality and morbidity and is often superior to daytime blood pressure. We studied the effect of shifting or adding antihypertensive to night time on blood pressure profile of CKD III-IV patients. METHODS: In this single-center, prospective, randomized controlled trial, eligible participants were adults from eastern India aged 18-65 years with CKD stages 3 and 4, with a non-dipping pattern on ambulatory blood pressure monitor (ABPM). The intervention group received all the antihypertensives in the night time whereas the standard care group continued to take the medication in the morning. Both groups were followed up for 1 year. The primary outcome was the number of patients changed from non-dippers to dippers in the standard care group and intervention group. Secondary outcomes included a change in estimated glomerular filtration rate (eGFR) and change in the cardiac structure. RESULTS: 39 patients in the intervention group and 36 patients in the standard care group were analyzed. 10 patients (26%) reverted to dipping pattern in the intervention group as compared to none in the standard care group. Mean changes in eGFR were -2.55 and -0.18 mL/min/1.73 m2 in the standard care and intervention group at the end of the study, respectively. Between-group difference in eGFR was significant at 1 year (5.22 [95% CI, 4.3-6.1] ml/min/1.73 m2); (P = 0.03). The cardiac structure showed no significant changes in either group. CONCLUSIONS: Bedtime administration of antihypertensives reverted non-dippers to dippers and slowed the decline in eGFR in CKD stages 3 and 4 compared to morning administration of antihypertensives.
RESUMO
The transcription factor p63 (Trp63) plays a key role in homeostasis and regeneration of the skin. The p63 gene is transcribed from dual promoters, generating TAp63 isoforms with growth suppressive functions and dominant-negative ΔNp63 isoforms with opposing properties. p63 also encodes multiple carboxy (C)-terminal variants. Although mutations of C-terminal variants have been linked to the pathogenesis of p63-associated ectodermal disorders, the physiological role of the p63 C-terminus is poorly understood. We report here that deletion of the p63 C-terminus in mice leads to ectodermal malformation and hypoplasia, accompanied by a reduced proliferative capacity of epidermal progenitor cells. Notably, unlike the p63-null condition, we find that p63 C-terminus deficiency promotes expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) (Cdkn1a), a factor associated with reduced proliferative capacity of both hematopoietic and neuronal stem cells. These data suggest that the p63 C-terminus plays a key role in the cell cycle progression required to maintain the proliferative potential of stem cells of many different lineages. Mechanistically, we show that loss of Cα, the predominant C-terminal p63 variant in epithelia, promotes the transcriptional activity of TAp63 and also impairs the dominant-negative activity of ΔNp63, thereby controlling p21(Waf1/Cip1) expression. We propose that the p63 C-terminus links cell cycle control and the proliferative potential of epidermal progenitor cells via mechanisms that equilibrate TAp63 and ΔNp63 isoform function.
