Giuseppe Regolisti

Severe Hypomagnesemia During Long-term Treatment With a Proton Pump Inhibitor

Severe hypomagnesemia is a serious clinical ondition that can be complicated by lifehreatening arrhythmias (ventricular tachycardia, entricular fibrillation, and torsades de pointes) nd neurologic manifestations (neuromuscular yperexcitability, frank ataxia, confusion, deirium, and seizures). Moreover, hypokalemia nd hypocalcemia frequently are documented as ccompanying electrolyte disorders. Hypomagesemia is relatively common in hospitalized atients, particularly in intensive care units. eading causes of the acquired disorder are malbsorption, uncontrolled diabetes, chemotherapy, cute pancreatitis, drugs, and refeeding. Very few cases of severe hypomagnesemia elated to long-term use of proton pump inhibiors (PPIs) have been published to date, and he likely pathogenetic mechanisms are not fully lucidated. We report a case of severe symptomatic hypoagnesemia in a patient treated with PPIs for any years because of Barrett esophagus. The ifferential diagnosis and potential pathogenetic echanisms are discussed within a more general onceptual framework of the pathophysiology tate of serum magnesium homeostasis.

Alterations of intestinal barrier and microbiota in chronic kidney disease

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury

IntroductionThe study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.MethodsDemographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.ResultsWe included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.ConclusionsMild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.

The Relationship Between Blood Pressure and Pain

The relationship between pain and hypertension is potentially of great pathophysiological and clinical interest, but is poorly understood. The perception of acute pain initially plays an adaptive role, which results in the prevention of tissue damage. The consequence of ascending nociception is the recruitment of segmental spinal reflexes through the physiological neuronal connections. In proportion to the magnitude and duration of the stimulus, these spinal reflexes cause the activation of the sympathetic nervous system, which increases peripheral resistances, heart rate, and stroke volume. The response also involves the neuroendocrine system, and, in particular, the hypothalamic‐pituitary‐adrenal axis, in addition to further activation of the sympathetic system by adrenal glands. However, in proportion to an elevation in resting blood pressure, there is a contemporary and progressive reduction in sensitivity to acute pain, which could result in a tendency to restore arousal levels in the presence of painful stimuli. The pathophysiological pattern is significantly different in the setting of chronic pain, in which the adaptive relationship between blood pressure and pain sensitivity is substantially reversed. The connection between acute or chronic pain and cardiovascular changes is supported observationally, but some of this indirect evidence is confirmed by experimental models and human studies. The pain regulatory process and functional interaction between cardiovascular and pain regulatory systems are briefly reviewed. Various data obtained are described, together with their potential clinical implications.

Elevation of Angiotensin-II Type-1-Receptor Autoantibodies Titer in Primary Aldosteronism as a Result of Aldosterone-Producing Adenoma

The mechanisms of excess aldosterone secretion in primary aldosteronism (PA) remain poorly understood, although a role for circulating factors has been hypothesized for decades. Agonistic autoantibodies against type-1 angiotensin-II receptor (AT1AA) are detectable in malignant hypertension and preeclampsia and might play a role in PA. Moreover, if they were elevated in aldosterone-producing adenoma (APA) and not in idiopathic hyperaldosteronism (IHA), they might be useful for discriminating between these conditions. To test these hypotheses, we measured the titer of AT1AA in serum of 46 patients with PA (26 with APA, 20 with IHA), 62 with primary hypertension (PH), 13 preeclamptic women, and 45 healthy normotensive blood donors.We found that the AT1AA titer was higher (P<0.05) in both PA and PH patients (2.65±1.55 and 1.86±0.63, respectively) than in normotensive subjects (1.00±0.20). In APA, it was 2-fold higher than in IHA patients (3.43±1.20 versus 1.64±1.39, respectively, P<0.001), despite similar blood pressure values. Of note, it allowed effective discrimination of APA from either PH or IHA, as shown by Receiver Operator Characteristics curve analysis. Moreover, after captopril challenge, plasma aldosterone concentration fell more in AT1AA-positive than in AT1AA-negative PA patients (–32.4% [21.1–42.9] versus 0.0% [0.0–22.6], P=0.015), suggesting an agonistic role for these autoantibodies. Thus, a higher serum AT1AA titer in patients with APA than in IHA and PH patients can be useful in differentiating APA patients from either PH or IHA, and thus in selecting PA patients to be submitted to adrenal vein sampling.

Nutritional assessment and delivery in renal replacement therapy patients.

The present review is aimed at illustrating and discussing literature data and recent guidelines concerning artificial nutrition in patients with acute kidney injury (AKI) on renal replacement therapy (RRT). Protein‐energy wasting often complicates the clinical course of AKI in critically ill patients, increasing their morbidity and mortality risk. The most severe forms of the syndrome – those observed in ICU patients – are characterized by hypercatabolism with relevant lean body mass loss. In this clinical condition, artificial nutrition (enteral and/or parenteral nutrition) is considered an integral part of the complex therapeutic approach. Even though many issues concerning nutrition in AKI are common to other critically ill patients, the presence of AKI with the ensuing impairment of the kidney homeostatic function introduces specific problems and can make more difficult to give the patient an adequate nutrient provision. Thus, peculiarities of the syndrome – and of RRT itself – must be taken into account in nutritional planning for these patients. Recent guidelines have suggested that the enteral route should be the preferred one, even though parenteral nutrition is often required to target nutritional needs (25–30u2003kcal/kg body weight/day, and 1.5u2003+u20030.2u2003g/kg/day to compensate for amino acid losses during RRT). Special attention should be paid to the impact of different forms of RRT on the possible loss of both macro‐ and micronutrients and vitamins, as well as to the risk of metabolic complications. Finally, close integration between nutritional support and RRT is required, aiming at carefully tailoring both therapies on patient’s changing needs.

Increased plasma levels of platelet-derived growth factor (PDGF-BB + PDGF-AB) in patients with never-treated mild essential hypertension

Platelet-derived growth factor (PDGF) could play a role in both vascular hypertrophy and atherosclerotic disease associated with hypertension. To assess whether plasma PDGF level is increased in mild essential hypertension, we measured plasma PDGF concentration in 25 never-treated patients with uncomplicated mild essential hypertension and in 22 normotensive healthy subjects. To evaluate the contribution of platelets to plasma PDGF in the two groups, we also measured plasma beta-thromboglobulin (BTG). Measurement of PDGF was carried out through an enzyme-linked immunoadsorbent assay, which detects two PDGF dimers, namely PDGF-BB and PDGF-AB. Both plasma PDGF and BTG were higher in the hypertensive than in the normotensive subjects. The ratio of PDGF to BTG was similar in the two groups. Plasma PDGF was weakly correlated with plasma BTG in the normotensive subjects, whereas this relationship was lost in the hypertensive patients. Our results suggest that the increase in plasma PDGF (PDGF-AB + PDGF-BB) in never-treated essential hypertension is mainly due to platelet activation. The increased circulating level of PDGF could play a role in the vascular structural changes associated with hypertension.

Serum adipokine zinc α2-glycoprotein and lipolysis in cachectic and noncachectic heart failure patients: relationship with neurohormonal and inflammatory biomarkers

Chronic heart failure is often complicated by the development of cachexia with the loss of fat mass. Zinc α2-glycoprotein (ZAG) is a serum adipokine with lipolytic effects in cancer cachexia. We evaluated in patients with advanced heart failure with (CxHF) or without cachexia (nCxHF) the relationship of ZAG with circulating free fatty acid (FFA), as an index of lipolysis, and with other neurohormonal and inflammatory biomarkers. Two groups, nCxHF (n = 46) and CxHF (n = 18), the latter having a documented, involuntary, edema-free loss of body weight of at least 7.5% in the previous 6 months, underwent plasma determination of FFA, ZAG, norepinephrine (NE), tumor necrosis factor-α, and natriuretic peptide levels (atrial natriuretic, B-type natriuretic peptide). The patients were compared with age-matched healthy controls (CTR) (n = 21). Zinc α2-glycoprotein, atrial natriuretic peptide, B-type natriuretic peptide, and tumor necrosis factor-α circulating levels were similarly greater in CxHF and nCxHF than in CTR. Free fatty acid and NE were higher in CxHF than in nCxHF. A positive correlation between FFA and NE was found in both CxHF (r = 0.73, P < .01) and nCxHF (r = 0.48, P < .01) but only in CxHF between ZAG and FFA (r = 0.54, P = .02) and between ZAG and NE (r = 0.70, P < .01). No correlations between natriuretic peptides and ZAG were found. Serum ZAG levels are increased in advanced heart failure patients compared with CTR, without differences between CxHF and nCxHF. Only in CxHF, ZAG levels are directly correlated to circulating levels of FFA and NE, suggesting a close interaction of ZAG with sympathetic-mediated lipolysis.

Specialized nutritional support interventions in critically ill patients on renal replacement therapy

Purpose of reviewOptimal nutritional requirements and nutrient intake composition for patients with acute kidney injury remain a partially unresolved issue. Targeting nutritional support to the actual protein and energy needs improves the clinical outcome of critically ill patients, yet very few data are currently available on this topic in acute kidney injury. In this specific clinical condition the risk for underfeeding and overfeeding may be increased by factors interfering on nutrient need estimation, such as rapidly changing body weight due to fluid balance variations, nutrient losses and hidden calorie sources from renal replacement therapy. Moreover, as acute kidney injury is now considered a kidney-centered inflammatory syndrome, the renoprotective role of specific pharmaconutrients with anti-inflammatory properties remains to be fully defined. This review is aimed at discussing recently published results concerning quantitative and qualitative aspects of the nutritional approach to acute kidney injury in critically ill patients. Recent findingsNutrient needs in patients with acute kidney injury can be difficult to estimate, and should be directly measured, especially in the ICU setting. In fact, recent findings suggest that hidden calorie sources not routinely taken into account – for example, calories from anticoagulants and replacement solutions for renal replacement therapy – could be quantitatively relevant in these patients. Moreover, recent experimental data indicate a possible role for some pharmaconutrients with anti-inflammatory effects (glutamine, and omega-3 fatty acids), in both the prevention of renal function worsening, and in the fostering of renal function recovery after an episode of acute kidney injury. SummaryAcute kidney injury includes a highly heterogeneous group of patients with widely varying nutrient needs and intakes. Nutritional requirements, in their quantitative and qualitative aspects, should be frequently assessed, individualized, and carefully integrated with renal replacement therapy, in order to avoid both underfeeding and overfeeding, as well as to exploit possible positive pharmacologic effects of specific nutrients.

Eplerenone Use in Primary Aldosteronism During Pregnancy

To the Editor:nnPrimary hyperaldosteronism has rarely been reported in pregnancy (≈30 cases have been described since 1962) and is most often caused by an adrenal adenoma.1–2 Aggressive management is strongly recommended, because the risk of complications in both the mother and the fetus is high.3 Difficulties arise because of limited therapeutic options attributed to fetal toxicity.nnThe following is a case report of primary aldosteronism during pregnancy, treated with eplerenone, an antagonist of mineralocorticoid receptors.nnIn April 2009, a 34-year–old African woman, gravida 1 para 1, at 21 weeks gestation with a male fetus, was referred to our obstetrics and gynecology department for palpitations, uncontrolled hypertension, and severe hypokalemia. Before pregnancy, normokalemia was reported, and blood pressure (BP) was controlled with nifedipine GITS-20 mg/d. At the time of admission, her BP was 155/110 mm Hg and pulse rate was 76 beats per minute. Her physical examination was normal. A fetal ultrasound showed normal growth for gestational age. A 12-lead ECG showed a sinus rhythm (82 beats per minute), supraventricular and ventricular premature beats, and a long QTc (524 ms; normal value <400 ms). A 24-hour ECG showed frequent ventricular premature beats (18 174 in 24 hours) …