Copeptin and insulin resistance: effect modification by age and 11 ß-HSD2 activity in a population-based study.

PURPOSE: Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11ß-hydroxysteroid-dehydrogenase-type 2 (11ß-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11ß-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. METHODS: This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11ß-HSD2 activity were presented as appropriate. RESULTS: Plasma copeptin was higher in men [median 5.2, IQR (3.7-7.8) pmol/L] than in women [median 3.0, IQR (2.2-4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11ß-HSD2 activity was high [ß (95% CI) = 0.32 (0.17-0.46), P < 0.001] or if age was high [ß (95% CI) = 0.34 (0.20-0.48), P < 0.001], but not if either 11ß-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10-3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74-1.69), P = 0.605), after full adjustment. CONCLUSIONS: Our data suggest that age and apparent 11ß-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.

Seasonality of sodium and potassium consumption in Switzerland. Data from three cross-sectional, population-based studies.

BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.

[Renal aspects of sodium glucose cotransporter 2 inhibitors]. / Les inhibiteurs du cotransporteur SGLT2 comme nouveau traitement du diabète: aspects rénaux.

It has been known for centuries that the kidneys play a role in glucose homeostasis, yet the underlying tubular mechanisms have only been recently identified by studying patients with familial glucosuria. These insights have lead to the commercialization of a novel class of oral antidiabetic agents named gliflozines. Gliflozines induce renal glucosuria by blocking the Na-glucose cotransporter SGLT2, localized in the proximal tubule, and allow a reduction of 0.5 to 1% of glycated hemoglobin. They also diminish proximal sodium reabsorption, and reduce the glomerular hyperfiltration that is often seen in the early stages of diabetes. Preliminary data suggest that they may decrease blood pressure and have renoprotective effects. This article provides an overview of the role of kidneys in glucose homeostasis and the renal effects of SGLT2-inhibitors.

[What to expect from dialysis in the future?]. / Que peut-on attendre de la dialyse dans le futur?

The number of people with end stage kidney failure is increasing worldwide, mainly due to aging of the population. Hence the need for renal replacement therapy is continually expanding. Kidney transplantation, haemodialysis and peritoneal dialysis are currently the gold standard of renal replacement therapy. These three techniques have all their specific advantages and shortcomings. Facing the high complication rate of actual techniques, an increasingly migrant population and the growing desire to respect the environment, alternatives are needed. New techniques that might improve some of these points are in development and will be reviewed in this article.

[Dialysis and ecology: can we do better in the future?]. / Dialyse et écologie: est-il possible de faire mieux à l'avenir?

Development of dialysis has saved the lives of many patients. However, haemodialysis and peritoneal dialysis are very demanding in resources such as water and electricity, and generate a large amount of waste. In this article, we will review the environmental aspects of dialysis. Different solutions will be discussed, such as recycling of water discharged during reverse osmosis, the integration of solar energy, recycling of waste plastics, and the use of other techniques such as sorbent dialysis. In a world where natural resources are precious and where global warming is a major problem, it is important that not only dialysis, but all branches of medicine become more attentive to ecology.

[Sleep disorders in patients with chronic renal insufficiency]. / Troubles du sommeil chez des patients présentant une insuffisance rénale chronique.

Sleep disorders, especially insomnia, daytime sleepiness, sleep apnea syndrome and restless legs syndrome are very frequently encountered in patients with chronic renal failure whether or not they undergo renal replacement therapy. The causes of sleep disorders are multifactorial and not only linked to the renal disease itself, but also to its treatment and its associated psychosocial factors. This article discusses the prevalence and physiopathology of the most frequently encountered sleep disorders in chronic renal failure patients, and highlights the actually available therapeutic options.

[Renal sympathetic denervation: perspective of a promising treatment for hypertension]. / Denervation rénale endovascu- laire par radiofréquence: perspective d'un traitement prometteur de l'hypertension artérielle.

The crucial role of the sympathetic nervous system activity in the initiation and maintenance of hypertension was already in mind in the 1920s when surgical options were proposed to severely hypertensive patients. Despite constant evolution of pharmacological treatments, one estimates that 15-30% of hypertensive patients are still not well controlled and present resistant hypertension. The development of a new endovascular catheter used for selective sympathetic renal denervation by radiofrequency offers new perspectives of treatment. Encouraged by the recent results of the first clinical trials in a targeted population, this procedure could be used in some more indications in the future. However, long term morbidity and mortality of this technique are still not known.

[Do endothelin receptors antagonists have a place in the treatment of arterial hypertension?]. / Les antagonistes des récep- teurs de l'endothéline ont-ils une place dans le traitement de l'hyper- tension artérielle?

The discovery in 1988 of endothelin, the most potent human endogenous vasoconstrictor, has opened the race to the discovery of a new weapon against arterial hypertension. The development of the endothelin receptors antagonists (ERAs) and the demonstration of their efficacy in preclinical models initially raised a wave of enthusiasm, which was however tempered due to their unfavorable side effect profile. In this article we will review the phases of the development ERAs, and their current and future place as therapeutic tool against arterial hypertension.

[New radiological techniques to investigate patients suffering from chronic kidney disease]. / Nouvelles techniques radiologiques pour les patients insuffisants rénaux.

Radiological investigations using gadolinium or intravenous iodinated contrast products are used cautiously in patients suffering from chronic kidney disease because of their risk of acute kidney injury and systemic nephrogenic fibrosis. In this article, we review several radiological alternatives that can be useful to obtain renal anatomical and/or functional information in this patient population. The basic principles, indications, and advantages and limitations of Doppler ultrasound with measurement of the resistance index, contrast-enhanced ultrasound, and a technique called BOLD-MRI (blood-oxygenation level dependent-MRI) are discussed.

[Managing hypertension: the uncertainty of definitions and targets]. / Traiter l'hypertension artérielle: l'incertitude des definitions et des cibles.

In clinical practice, physicians are confronted with a multitude of definitions and treatment goals for arterial hypertension, depending of the diagnostic method used (e.g. office, home and ambulatory blood pressure measurement) and the underlying disease. The historical background and evidence of these different blood pressure thresholds are discussed in this article, as well as some recent treatment guidelines. Besides, the debate of the "J curve", namely the possible risks associated with an excessive blood pressure reduction, is discussed.

[Nutrition and hypertension: more than table salt]. / Alimentation et hypertension artérielle: au-delà du sel de table.

The role of dietary sodium intake in the development, and its impact on the treatment, of hypertension are well recognized. However, many other nutritional compounds have been shown, or are believed, to influence blood pressure. Some compounds, such as caffeine and fructose, may raise arterial blood pressure, whereas others might lower arterial blood pressure, for example garlic, dark chocolate, fibers and potassium. In this article, we review several alimentary compounds and their (hypothesized) mechanisms of action, as well as the available evidence supporting a role of these compounds in the "non pharmacological" treatment and prevention of hypertension.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

[Hypertension genetics: what have we learned so far?]. / Génétique et hypertension artérielle: qu'avons nous-appris?

Hypertension is a common, modifiable and heritable cardiovascular risk factor. Some rare monogenic forms of hypertension have been described, but the majority of patients suffer from "essential" hypertension, for whom the underlying pathophysiological mechanism is not clear. Essential hypertension is a complex trait, involving multiple genes and environmental factors. Recently, progress in the identification of common genetic variants associated with blood pressure and hypertension has been made thanks to large-scale international collaborative projects involving geneticists, epidemiologists, statisticians and clinicians. In this article, we review some basic genetic concepts and the main research methods used to study the genetics of hypertension, as well as selected recent findings in this field.

[Hypertension in solid organ transplants]. / L'hypertension chez les transplantés d'organes.

Hypertension is highly prevalent in transplantation and affects all type of organs. With the introduction of calcineurin inhibitors as immunosuppressive drugs, acute allograft rejection episodes have been significantly reduced and hence patient and allograft survival rates have dramatically improved. However, cardiovascular complications have become an important cause of morbidity and mortality. Treating cardiovascular risk factors such as diabetes, dyslipidemia and hypertension seems obvious, however in this population, there is little evidence for specific blood pressure targets, or for the best strategy to achieve blood pressure control. The aim of this article is to review the epidemiology and physiopathology of hypertension in transplant recipients as well as its clinical management.

[Plasmapheresis, a safe treatment when applied to the correct indication and with awareness of the complications]. / Plasmaferese: veilig bij een goede indicatiestelling en kennis van de complicaties.

Plasmapheresis is an extracorporeal technique used to remove pathogenic macromolecules from the circulation, particularly autoantibodies. This is illustrated in 2 female patients. The first patient, aged 61 years, was treated successfully with non-selective plasmapheresis for acute humoral rejection shortly after receiving a renal allograft. In the second patient, aged 82 years, plasmapheresis for refractory myasthenia gravis had to be stopped because of bradycardia and hypotension during the procedure. She was treated successfully with immunoglobulins. Plasmapheresis is used to treat neurological, renal, haematological and systemic disorders. In nonselective plasmapheresis, the plasma is replaced with saline and albumin or donor plasma. In selective plasmapheresis a highly selective filter is used to remove a specific, pathogenic macromolecule. Adverse effects of the treatment include disturbances of the acid-base equilibrium or the coagulation, and allergic reactions. Most of these complications, however, can nowadays be avoided.

[Plasmapheresis: technique, complications and indications]. / La plasmaphérèse: technique, complications et indications.

Plasmapheresis is an extracorporeal technique used to remove pathogenic macromolecules from the plasma. Plasmapheresis is used to treat neurological, renal, hematological as well as systemic diseases, which explains why many different specialties in medicine can be involved. Plasmapheresis has evolved in forty years into a frequently used, relatively safe procedure. Nowadays a large spectrum of different techniques exists, each with its own possible complications. In this article we will give an overview of these different techniques, their complications and indications, in order to familiarize the reader with this fascinating treatment.

Combination of a normal D-dimer concentration and a non-high pretest clinical probability score is a safe strategy to exclude deep venous thrombosis.

BACKGROUND: Serial ultrasonography is reliable for the diagnosis of deep venous thrombosis in symptomatic patients, but the low prevalence of thrombosis in this group renders the approach costly and inconvenient to patients. We studied the clinical validity of the combination of a pretest clinical probability score and a D-dimer test in the initial evaluation of patients suspected of deep venous thrombosis. METHODS AND RESULTS: Patients with a normal D-dimer concentration (<500 fibrin equivalent units [FEU] microg/L) and a non-high probability score (<3) had no further testing. Patients with a normal D-dimer concentration and a high probability score (> or =3) underwent one ultrasonogram. Serial ultrasonography was performed in patients with an abnormal D-dimer concentration. Patients were followed for 3 months. A total of 812 patients were evaluable for efficacy. Only 1 of 176 patients (0.6%; 95% CI, 0.02% to 3.1%) with a normal D-dimer concentration and a non-high probability score developed thrombosis during follow-up. A normal D-dimer concentration and a high probability score were found in 39 patients; 3 of them (7.7%; 95% CI, 1.6% to 20.9%) had thrombosis at presentation, and one (2.8%; 95% CI, 0.07% to 14. 5%) developed pulmonary embolism during follow-up. In 306 of 597 patients (51.3%) with an abnormal D-dimer concentration, thrombosis was detected by serial ultrasonography. Six patients (2.1%; 95% CI, 0.8% to 4. 4%) developed thrombosis during follow-up. No deaths due to thromboembolism occurred during follow-up. The total need for ultrasonography was reduced by 29%. CONCLUSION: The combination of a non-high pretest clinical probability score and a normal D-dimer concentration is a safe strategy to rule out deep venous thrombosis and to withhold anticoagulation.

[Thyrotoxic crisis in a patient with Graves' disease]. / Thyreotoxische storm bij een patiënt met de ziekte van Graves.

A 33-year-old man presented with diarrhoea, dyspnoea, palpitations, fever and shock. One year and a half before admission, Graves'-hyperthyroidism had been diagnosed, for which he was treated with thiamazole and levothyroxine as block-replacement therapy. A diagnosis of thyrotoxic crisis, precipitated by lack of compliance with antithyroid drug therapy and possibly an underlying infection, was made. Euthyroidism was achieved with propylthiouracil, potassium iodide, corticosteroids and propranolol. However, the propylthiouracil had to be stopped due to agranulocytosis, after which hyperthyroidism recurred. An emergency thyroidectomy was then performed; the patient recovered completely. Thyrotoxic crisis is a rare, potentially life-threatening disease in patients with underlying un(der)treated hyperthyroidism. It is characterised by fever, tachycardia, and neurological and gastrointestinal symptoms.

[Methemoglobinemia due to ingestion of isobutyl nitrite ('poppers')]. / Methemoglobinemie door drinken van isobutylnitriet ('poppers').

Two male students, aged 20 and 21 years, developed central cyanosis shortly after drinking 5 ml of 'poppers' (isobutyl nitrite). They presented with methaemoglobinaemia and were hospitalised. After treatment with oxygen and intravenous fluids they could be discharged in good health the following day. Poppers are alkyl nitrites with vasdilative and oxidizing properties. They are used as party drugs (i.e. inhaled) because of their short-lived euphoric effect. Overdose can result in methaemoglobinaemia: the presence of oxidized haemoglobin which is unable to transport oxygen. Depending on the serum level of methaemoglobin this may result in central cyanosis, unconsciousness, coma and even death. Patients with high methaemoglobin levels should be treated with i.v. methylene blue.

[Retroperitoneal bleeding caused by renal angiomyolipoma]. / Retroperitoneale bloeding uit een renaal angiomyolipoma.

An 81-year-old woman presented with left-flank pain, anaemia and a fast irregular pulse while using oral anticoagulation. Diagnostic investigation revealed retroperitoneal bleeding caused by a medium-sized renal angiomyolipoma. Angiomyolipoma was also found in the contralateral kidney. No tuberous sclerosis was ascertained. Bleeding stopped after discontinuation of anticoagulant therapy. Renal angiomyolipoma is an uncommon benign tumour which is frequently associated with tuberous sclerosis. Spontaneous retroperitoneal bleeding is a potentially life-threatening complication. This type of tumour is usually found incidentally on radiological examination.