Nephrology Referral and Outcomes in Critically Ill Acute Kidney Injury Patients

Background

Delayed nephrology consultation (NC) seems to be associated with worse prognosis in critically ill acute kidney injury (AKI) patients.

Design, Setting, Participants, & Measurements

The aims of this study were to analyze factors related with timing of NC and its relation with AKI patients'' outcome in intensive care units of a tertiary hospital. AKI was defined as an increase ≥50% in baseline serum creatinine (SCr). Early NC and delayed NC were defined as NC performed before and two days after AKI diagnosis day. Multivariable logistic regression and propensity scores (PS) were used to adjust for confounding and selection biases. Hospital mortality and dialysis dependence on hospital discharge were the primary outcomes.

Results

A total of 366 AKI patients were analyzed and NCs were carried out in 53.6% of the patients. Hospital mortality was 67.8% and dialysis required in 31.4% patients (115/366). Delayed NCs (34%) occurred two days after AKI diagnosis day. This group presented higher mortality (OR: 4.04/CI: 1.60–10.17) and increased dialysis dependence (OR: 3.00/CI: 1.43–6.29) on hospital discharge. Four variables were retained in the PS model for delayed NC: diuresis (1000 ml/24 h - OR: 1.92/CI: 1.27–2.90), SCr (OR: 0.49/CI: 0.32–0.75), surgical AKI (OR: 3.67/CI: 1.65–8.15), and mechanical ventilation (OR: 2.82/CI: 1.06–7.44). After correction by PS, delayed NC was still associated with higher mortality (OR: 3.39/CI: 1.24–9.29) and increased dialysis dependence (OR: 3.25/CI: 1.41–7.51). Delayed NC was associated with increased mortality either in dialyzed patients (OR: 1.54/CI: 1.35–1.78) or non-dialyzed patients (OR: 2.89/CI: 1.00–8.35).

Conclusion

Delayed NC was associated with higher mortality and increased dialysis dependence rates in critically ill AKI patients at hospital discharge. Further studies are necessary to ascertain whether this effect is due to delayed nephrology intervention or residual confounding factors.     

Phase transitions in phospholipid vesicles Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol

We have studied the solid to liquid-crystalline phase transition of sonicated vesicles of dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine. The transition was studied by both fluorescence polarization of perylene embedded in the vesicles, and by the efflux rate of trapped ²²Na⁺.Fluorescence polarization generally decreases with temperature, showing an inflection in the region 32–42°C with a mid-point of approximately 37.5 °C. On the other hand, the perylene fluorescence intensity increases abruptly in this region. To explain this result, we have proposed that, for $\text{T < T}{}_{\mathrm{<mtext>c</mtext>}}$ where $\text{T}{}_{\mathrm{<mtext>c</mtext>}}$ is the transition temperature, perylene is excluded from the hydrocarbon interior of the membranes, whereas, $\text{T < T}{}_{\mathrm{<mtext>c</mtext>}}$ this probe may be accommodated in the membrane interior to a large extent.The self-diffusion rates of ²²Na⁺ through dipalmitoylphosphatidylglycerol vesicles exhibit a complex dependence on temperature. There is an initial large increase in diffusion rates (approximately 100-fold) between 30 and 38 °C, followed by a decrease (approximately 4-fold) between 38 and 48 °C. A monotonic increase is then observed at temperatures higher than 48 °C. The local maximum of ²²Na⁺ self-diffusion rates at approximately 38 °C coincides with the mid-point of phase transition as detected by changes in fluorescence polarization of perylene with the same vesicles. Vesicles composed of dipalmitoylphosphatidylcholine show the same general behavior in terms of ²²Na⁺ self-diffusion rates at different temperatures, except that the local maximum occurs at approximately 42 °C.The temperature dependence of the permeability and the appearance of a local maximum at the phase transition region could be explained in terms of a domain structure within the plane of the membranes. This explanation is based on the possibility that boundary regions between liquid and solid domains would exhibit relatively high permeability to ²²Na⁺.Mixed vesicles composed of equimolar amounts of dipalmitoyl phospholipids and cholesterol show no abrupt changes in the temperature dependence of either perylene fluorescence polarization or ²²Na⁺ diffusion rate measurements. This is taken to indicate the absence of agross phase transition in the presence of cholesterol.     

TRPM8 Channel Activation Induced by Monoterpenoid Rotundifolone Underlies Mesenteric Artery Relaxation

In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca²⁺ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca²⁺. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.     

Interactions of La with phosphatidylserine vesicles binding, phase transition, leakage and fusion

The interaction of La³⁺ with phosphatidylserine vesicles is elucidated by binding studies, differential scanning calorimetry, X-ray diffraction, freeze fracture electron microscopy, and release of vesicle contents. La³⁺ effectively competes with Ca²⁺ for phosphatidylserine binding sites. The saturation level is close to a La/lipid ratio of 1:3. A concentration of 0.1 mM of La³⁺ is sufficient to induce fusion between sonicated vesicles.     

Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies

Background

Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo.

Methodology/Principal Findings

In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats.

Conclusions/Significance

Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.     

Antigen-Specific T-cell factors in the immune response to poly(Tyr,Glu)-poly(Pro)-poly(Lys)

The production by T cells of an antigen-specific factor capable of replacing the T-cell function in specific antibody formation was used as a tool for studying the cellular aspects of the genetic control of immune responses. The ability of different T-cell populations to produce a cooperative signal and the ability of B-cell populations to react to this signal were studied in different mouse strains. The antigen used was the synthetic polypeptide poly(LTyr,LGlu)-poly-(LPro) —poly(lXys), (T,G)-Pro -L, the response to which was found not to beH-2-linked. It was found that the SWR strain of mice, a low responder to (T,G)-Pro -L, is not capable of producing a T-cell factor specific to this antigen, but its B cells react normally to an active factor produced in a high responder strain. In the DBA/1 strain, also a low responder to (T,G)-Pro -L, the bone marrow cells are not able to cooperate with an active T-cell factor to produce anti-(T,G)-Pro —L-specific antibodies, while their T cells do produce a (T,G)-Pro -L-specific factor. The SWR (low responder) B cells can be triggered by DBA/1 (low responder) T cells factor specific to (T,G)-Pro —L to produce an antibody response to this immunogen. These results suggest that the immune response to (T,G)-Pro -L is controlled by two genes which are expressed in different lymphocyte populations.     

Facile synthesis of 2-hydroxyacetophenone from racemic styrene oxide catalyzed by engineered enzymes

Biotechnology Letters - We describe a system that allows for biocatalyzed in vivo synthesis of α-hydroxy ketones from racemic epoxide starting material by in vivo co-expression of native and...     

Photo-oxygenation of glycosylfurans. Rearrangement of C-glycosyl into O-glycosyl derivatives

Photo-oxygenation of 3-ethoxycarbonyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran and 3-hydroxymethyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran yields the corresponding endo-peroxides which rearrange at room temperature into the O-glycosyl derivatives ethyl 2,3-O-isopropylidene-β-d-erythrofuranosyl 2-acetylfumarate and 2,3-O-isopropylidene-β-d-erythrofuranosyl 3-acetyl-3-hydroxymethylacrylate, respectively. The endo-peroxides can be reduced without rearrangement, yielding C-glycosyl derivatives. Alcoholysis of the O-glycosyl derivatives yields 2,3-O-isopropylidene-d-erythrose, dialkyl 2-acetyl-3-alkoxysuccinates, 4-ethoxycarbonyl-5-methoxy-5-methyl-2-oxo-2,5-dihydrofuran and 4-hydroxymethyl-5-methoxy-5-methyl-2-oxo-2,5-dihydrofuran.     

The influence of sympathomimetic and sympatholytic agents on the salivary flow rate and concentration of Ca, P and protein in the parotid gland of the goat

1. The role of the sympathetic autonomic division on the parotid gland of normal and thyroparathyroidectomized (t.x.p.t.x.) goats was studied. 2. The salivary flow rate and concentration of Ca, P and protein was tested during the intravenous infusions of sympathomimetic and sympatholytic agents. 3. The intravenous infusion of isoprenaline modified the salivary flow rate and the concentration of total protein. 4. None of the tested drugs modified significantly the concentration of Ca and P in the parotid saliva. 5. The results obtained in normal and t.x.p.t.x animals were similar; it seems that PTH is not involved in the observed changes.     

Interactions of La3+ with phosphatidylserine vesicles binding,phase transition,leakage and fusion

The interaction of La³⁺ with phosphatidylserine vesicles is elucidated by binding studies, differential scanning calorimetry, X-ray diffraction, freeze fracture electron microscopy, and release of vesicle contents. La³⁺ effectively competes with Ca²⁺ for phosphatidylserine binding sites. The saturation level is close to a La/lipid ratio of 1:3. A concentration of 0.1 mM of La³⁺ is sufficient to induce fusion between sonicated vesicles.