Development of a practical prediction score for chronic kidney disease after cardiac surgery.

BACKGROUND: Chronic kidney disease (CKD) is a frequent and serious complication of cardiac surgery. This study was designed to establish a scoring system, calculated in the immediate postoperative period, to assess the risk of CKD at 1 yr in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We conducted a cohort study including patients with preoperative estimated glomerular filtration rate above 60 ml min-1 (1.73 m)-2 who underwent cardiac surgery with cardiopulmonary bypass. We identified risk factors for de novo CKD at 1 yr using logistic regression. We derived a risk score for CKD, and externally validated this score in a second cohort. RESULTS: The incidence of CKD was 18% and 23% in the derivation and validation cohorts, respectively. We developed a scoring system that included (i) the occurrence of postoperative acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria, (ii) age older than 65 yr, (iii) preoperative glomerular filtration rate <80 ml min-1 (1.73 m)-2, (iv) aortic cross-clamping time longer than 50 min, and (v) the type of surgery (aortic or cardiac transplantation). This score predicted CKD with good accuracy (area under the receiver operating characteristic curve: 0.81; 95% confidence interval: 0.77-0.86 in the derivation cohort), and with fair accuracy in the validation cohort (area under the receiver operating characteristic curve: 0.78; 95% confidence interval: 0.72-0.83). CONCLUSIONS: We provide an easy-to-calculate scoring system to identify patients at high risk of developing CKD after cardiac surgery with cardiopulmonary bypass. This system might help clinicians to target more accurately patients requiring monitoring of renal function after cardiac surgery, and to design appropriate interventional trials aimed at preventing CKD or mitigating its consequences.

Seizure-related opening of the blood-brain barrier produced by the anticholinesterase compound, soman: new ultrastructural observations.

Previous macroscopic and light microscopic observations established that the organophosphate soman, an irreversible inhibitor of cholinesterases, produces seizure-related opening of the blood-brain barrier (BBB) to proteins. In Wistar rats, this BBB alteration was found to be reversible. This alteration was greatest during the first hour of seizures, and was topographically limited to sensitive areas such as the thalamus. In contrast, the hippocampus remained free of any vascular leakage. The present study is an attempt to elucidate, in rat thalamus, the subcellular mechanisms involved in soman-induced BBB alteration. A combination of three ultrastructural approaches was used: examination of ultra-thin sections, freeze-fracture, and post-embedding protein A-gold immunocytochemistry of the endogenous, normally exclusively blood-borne, albumin. Our findings show that soman-induced seizure activity produced no discernible structural change in the endothelial tight junctions, whereas it unambiguously increased the number of endothelial vesicles. Finally, immunolabelled albumin clearly crossed the endothelium, but was not systematically found inside the endothelial vesicles. Altogether, the present ultrastructural study confirms that soman can alter the integrity of the BBB, and demonstrates that the blood-to-brain passage of proteins does not mainly derive from the opening of tight junctions. Although transcytosis is clearly increased through the cerebral endothelium, there is little evidence that blood-borne proteins penetrate the brain in this way. The actual mechanisms of transport thus remain to be clarified.

Antiproliferative effects of SR31747A in animal cell lines are mediated by inhibition of cholesterol biosynthesis at the sterol isomerase step.

SR31747A is a new sigma ligand exhibiting immunosuppressive properties and antiproliferative activity on lymphocyte cells. Only two subtypes of sigma receptor, namely the sigma1 receptor and emopamil-binding protein, have been characterised molecularly. Only the sigma1 receptor has been shown to bind (Z)N-cyclohexyl-N-ethyl-3-(3-chloro4-cyclohexylphenyl)pro pen-2-ylamine hydrochloride (SR31747A) with high affinity. It was demonstrated that the SR31747A effect on the inhibition of T-cell proliferation was consistent with a sigma1 receptor-mediated event. In this report, binding experiments and sterol isomerase assays, using recombinant yeast strains, indicate that the recently cloned emopamil-binding protein is a new SR31747A-binding protein whose activity is inhibited by SR31747A. Sterol analyses reveal the accumulation of a delta8-cholesterol isomer at the expense of cholesterol in SR31747A-treated cells, suggesting that cholesterol biosynthesis is inhibited by SR31747A at the delta8-delta7 sterol isomerase step in animal cells. This observation is consistent with a sterol isomerase role of the emopamil-binding protein in the cholesterol biosynthetic pathway in animal cells. In contrast, there is no evidence for such a role of the sigma1 receptor, in spite of the structural similarity shared by this protein and yeast sterol isomerase. We have found that SR31747A also exerts anti-proliferative effects at nanomolar concentrations on various established cell lines. The antiproliferative activity of SR31747A is reversed by cholesterol. Sterol-isomerase overproduction enhances resistance of CHO cells. This last observation strongly suggests that sterol isomerase is implicated in the antiproliferative effect of the drug in established cell lines.