Nutritional aspects of Acute Renal Failure

The patient with acute renal failure is a very ill patient suffering from high urea levels causing poor appetite, nausea and vomiting. These patients are usually treated with a low sodium, low protein and, if the potassium in the blood is high, with a low potassium diet (1). This paper discusses whether or not this is the correct treatment. The symptoms of high urea levels in the blood together with increased needs for energy and protein makes it very hard to prevent the patient becoming malnourished. Often energy‐enriched drinks are necessary to achieve recommendations and it is prudent to let the patient eat and drink what they desire. By calculating the energy and protein needs and comparing these with the intake and the state of illness and by following the patient's body weight over time we can obtain information about the state of nourishment. When we alter the food that's offered we achieve better intake and reduce the risk of malnourishment.     

Prehospital Echocardiography During Resuscitation Impacts Treatment in a Physician-Staffed Helicopter Emergency Medical Service: an Observational Study

Background: Patients in cardiac arrest must receive algorithm-based management such as basic life support and advanced (cardiac) life support. International guidelines dictate diagnosing and treating any factor that may have caused the arrest or may be complicating the resuscitation. Ultrasound may be of potential value in this process and can be used in a prehospital setting. The objective is to evaluate the use of prehospital ultrasound during traumatic and non-traumatic CPR and determine its impact on prehospital treatment decisions in a Dutch helicopter emergency medical service (HEMS). Methods: We conducted an observational study in cardiac arrest patients, of any cause, in whom the Nijmegen HEMS performed CPR with concurrent echocardiography. The participating physicians had to adhere to Advanced Life Support protocols as per standard operating procedure. Simultaneous with the interruptions of chest compressions to allow for heart rhythm analysis, ultrasound-trained HEMS physicians performed echocardiography according to study protocol. The HEMS nurse and physician recorded patient data and data on impacted (supported or altered) patient treatment decisions. Results: From February 2014 through November 2016, we included 56 patients who underwent 102 ultrasound examinations. Sixty-two (61%) ultrasound examinations impacted 78 treatment decisions in 49 patients (88%). The impacted treatment was related to termination of CPR in 32 (57%), fluid management (14%), drugs selection and doses (14%), and choice of destination hospital (5%). Causes of cardiac arrest included trauma (48%), cardiac (21%), medical (14%), asphyxia (9%), and other (7%). Conclusion: Prehospital echocardiography has an impact on patient treatment and may be a useful tool to support decision-making during CPR in a Dutch HEMS.     

Prevalence,Awareness, and Management of CKD and Cardiovascular Risk Factors in Publicly Funded Health Care

Background and objectives

It is uncertain how many patients with CKD and cardiovascular risk factors in publicly funded universal health care systems are aware of their disease and how to achieve their treatment targets.

Design, setting, participants, & measurements

The CARTaGENE study evaluated BP, lipid, and diabetes profiles as well as corresponding treatments in 20,004 random individuals between 40 and 69 years of age. Participants had free access to health care and were recruited from four regions within the province of Quebec, Canada in 2009 and 2010.

Results

CKD (Chronic Kidney Disease Epidemiology Collaboration equation; <60 ml/min per 1.73 m²) was present in 4.0% of the respondents, and hypertension, diabetes, and hypercholesterolemia were reported by 25%, 7.4%, and 28% of participants, respectively. Self-awareness was low: 8% for CKD, 73% for diabetes, and 45% for hypercholesterolemia. Overall, 31% of patients with hypertension did not meet BP goals, and many received fewer antihypertensive drugs than appropriately controlled individuals; 41% of patients with diabetes failed to meet treatment targets. Among those patients with a moderate or high Framingham risk score, 53% of patients had LDL levels above the recommended levels, and many patients were not receiving a statin. Physician checkups were not associated with greater awareness but did increase the achievement of targets.

Conclusion

In this population with access to publicly funded health care, CKD and cardiovascular risk factors are common, and self-awareness of these conditions is low. Recommended targets were frequently not achieved, and treatments were less intensive in those patients who failed to reach goals. New strategies to enhance public awareness and reach guideline targets should be developed.     

Pyrido[2,1-f]purine-2,4-dione derivatives as a novel class of highly potent human A(3) adenosine receptor antagonists

1H,3H-Pyrido[2,1-f]purine-2,4-diones, which can be described as fused xanthine structures, have been synthesized by a novel synthetic procedure, and their affinities for the human adenosine A(1), A(2A), and A(3) receptors have been evaluated in radioligand binding studies. The synthetic procedure employed was developed in our laboratory and involved a two-step one-pot reaction that consists of the treatment of 6-aminouracil derivatives with N-bromosuccinimide to generate a 5,5-dibromo-6-imino intermediate that reacts "in situ" with pyridine, 4-methoxypyridine, 4-tert-butylpyridine, or 4-phenylpyridine to afford the corresponding 1H,3H-pyrido[2,1-f]purine-2,4-diones (2-5). Functionalization at the N(3) position in compounds 2-5 was performed by reaction with DBU and different alkyl, alkenyl, alkynyl, or benzyl halides. Binding studies at human adenosine A(1), A(2A), and A(3) receptors revealed significant antagonist effects in the low nanomolar range, in particular against the A(3) receptor. Thus, the 1-benzyl-3-propyl-1H,3H-pyrido[2,1-f]purine-2,4-dione derivative 6, which can be considered a lead compound in this series, exhibited a K(i) value of 4.0 +/- 0.3 nM against the hA(3) receptor. Because xanthine derivatives have traditionally been considered poor A(3) antagonists, the described pyrido[2,1-f]purine-2,4-dione derivatives represent a new family of adenosine receptor antagonists which deserves further exploration.     

The validity of screening based on spot morning urine samples to detect subjects with microalbuminuria in the general population

BACKGROUND: No study has yet investigated the validity of prescreening by albumin measurements in a spot morning urine sample to identify in the general population subjects with microalbuminuria. We therefore tested the diagnostic performance of urinary albumin concentration (UAC) and albumin-creatinine ratio (ACR), measured in a spot morning urine sample, in predicting a urinary albumin excretion (UAE) > or =30 mg in subsequent 24-hour urines (microalbuminuria). METHODS: Subjects (2527) participating in the PREVEND study, a representative sample from the general population, collected a spot morning urine sample and, on average, 77 days later, two 24-hour urine collections. RESULTS: The ROC curve of UAC in predicting microalbuminuria has an area-under-the-curve of 0.92 with a discriminator value of 11.2 mg/L. Using this cut-off value for UAC, sensitivity in predicting microalbuminuria is 85.0%, and specificity 85.0%. For ACR these values are, respectively: area-under-the-curve 0.93, discriminator value 9.9 mg/g, sensitivity 87.6%, and specificity 87.5%. Sensitivity for UAC in predicting microalbuminuria does not differ significantly from the sensitivity for ACR, whereas the difference between the specificities of UAC and ACR reaches statistical significance, but is numerically very small. In various subgroups characterized by differences in urinary creatinine excretion, the area-under-the-ROC curve, sensitivity, as well as specificity, do not increase relevantly compared to the results in the overall study population. This holds true for ACR as well as UAC. CONCLUSION: The diagnostic performance of measuring UAC in a spot morning urine sample in predicting microalbuminuria in subsequent 24-hour urine collections is satisfactory, and, moreover, comparable to that of measuring ACR. In order to keep the burden and costs involved in population screening for microalbuminuria as low as possible, we therefore propose prescreening by measuring UAC in a spot morning urine sample. Those subjects with a UAC above a certain predefined level (e.g., 11 mg/L) should be asked to collect timed urine samples.     

Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension

In the past decade, pulse pressure has emerged as a strong predictor of cardiovascular morbidity and mortality. During aging, elevation of pulse pressure is a consequence of stiffening of the arterial wall. The relationship between pulse pressure and the renal aging process was studied in a cohort of 212 patients with never-treated isolated systolic hypertension. Glomerular filtration rate and effective renal plasma flow were measured using constant infusion of technetium 99m (99mTc)-DTPA and 131I-ortho-iodohippurate, respectively, and timed urine collections. The relationship between pulse pressure and renal function was studied using a linear regression model in the total population and in 40 to 49, 50 to 59, and 60 years and older age categories. In the whole population, there was an inverse relationship between pulse pressure and glomerular filtration rate; however, this relation did not persist after adjustment for age. In fact, the inverse relationship between pulse pressure and glomerular filtration rate was only present in patients 60 years of age or older. This relationship in elderly patients remained after adjustment for age, gender, MAP, and cardiovascular risk factors (P=0.006). It is suggested that pulse pressure, a marker of arterial stiffening, may have a detrimental influence on the age-related decline in glomerular filtration rate, after 60 years of age in patients with never-treated isolated systolic hypertension.     

2,4,6-trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists

Adenosine receptor antagonists usually possess a bi- or tricyclic heteroaromatic structure at their core with varying substitution patterns to achieve selectivity and/or greater affinity. Taking into account molecular modeling results from a series of potent adenosine A1 receptor antagonists, a pharmacophore was derived from which we show that a monocyclic core can be equally effective. To achieve a compound that may act at the CNS we propose imposing a restriction related to its polar surface area (PSA). In consequence, we have synthesized two novel series of pyrimidines, possessing good potency at the adenosine A1 receptor and desirable PSA values. In particular, compound 30 (LUF 5735) displays excellent A1 affinity (Ki = 4 nM) and selectivity (< or =50% displacement of 1 muM concentrations of the radioligand at the other three adenosine receptors) and has a PSA value of 53 A2.     

N6-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA), a very selective agonist with high affinity for the human adenosine A1 receptor

Four subtypes of adenosine receptors are currently known, that is, A(1), A(2A), A(2B), and A(3) receptors. Interestingly, quite substantial species differences exist especially between human and rat A(3) receptors. As a result, ligands such as CCPA, which are very selective for the rat A(1) receptor versus the human A(3) receptor, are substantially less selective when the human A(1) and A(3) receptors are compared. New 2-substituted and 2,N(6)-disubstituted adenosines were synthesized, and their affinities for the human adenosine A(1), A(2A), A(2B), and A(3) receptors were determined. Although large substituents on the C2-position are generally thought to yield adenosine A(2A) receptor selective ligands, the reported series of 2-triazeno-substituted adenosines had a very high affinity for the A(1) receptor. For example, 2-(3-phenylaminocarbonyltriazene-1-yl)adenosine had an affinity of 6.1 +/- 1.3 nM for the human adenosine A(1) receptor. Introduction of a diphenethyl substituent at the N(6)-position of this compound resulted in a high-affinity agonist, 3.1 +/- 0.9 nM, for the human adenosine A(1) receptor with 316- and 45-fold selectivity versus the human A(2A) and human A(3) receptors, respectively. The most selective, high-affinity human adenosine A(1) receptor agonist was the disubstituted compound N(6)-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA). TCPA had an affinity of 2.8 +/- 0.8 nM for the human adenosine A(1) receptor and was 75-fold and 214-fold selective versus the human A(2A) and human A(3) receptors, respectively. In addition, TCPA was a full agonist and inhibited the forskolin-induced cAMP production of CHO cells stably transfected with the human adenosine A(1) receptor with an IC(50) of 1.5 +/- 0.5 nM.     

Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women

Cardiovascular morbidity and mortality is not equally distributed among genders, men being more affected than women. It is not clear whether this is only related to a higher prevalence of the cardiovascular risk factors or to a similar prevalence of the risk factors as in women but a greater vascular susceptibility to these risk factors in men. This was tested by studying the association between various cardiovascular risk factors and urinary albumin excretion (UAE) in a large cohort of male and female subjects. While the prevalence of smoking and hypercholesterolemia was comparable between the genders, obesity was more common in women, and diabetes and hypertension were more frequent in men. The prevalence of microalbuminuria was about twofold higher in men. Interestingly, for a given level of any risk factor, UAE was higher in men than in women. On multivariate analysis with UAE as the dependent variable, an interaction with gender was found for the risk factors age, body mass index, and plasma glucose. Thus, for a higher age, body mass index, and glucose, the UAE is significantly increased in men when compared with women. It is concluded that gender differences exist in the association between cardiovascular risk factors and UAE. This is consistent with a larger vascular susceptibility to these risk factors in men as compared with women.