Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis.

BACKGROUND & AIMS: Protein-Energy Wasting (PEW) is the depletion of protein/energy stores observed in the most advanced stages of Chronic Kidney Disease (CKD). PEW is highly prevalent among patients on chronic dialysis, and is associated with adverse clinical outcomes, high morbidity/mortality rates and increased healthcare costs. This narrative review was aimed at exploring the pathophysiology of PEW in end-stage renal disease (ESRD) on hemodialysis. The main aspects of nutritional status evaluation, intervention and monitoring in this clinical setting were described, as well as the current approaches for the prevention and treatment of ESRD-related PEW. METHODS: An exhaustive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, nutritional intervention and outcome of PEW in ESRD on hemodialysis. RESULTS AND CONCLUSION: The pathogenesis of PEW is multifactorial. Loss of appetite, reduced intake of nutrients and altered lean body mass anabolism/catabolism play a key role. Nutritional approach to PEW should be based on a careful and periodic assessment of nutritional status and on timely dietary counseling. When protein and energy intakes are reduced, nutritional supplementation by means of specific oral formulations administered during the hemodialysis session may be the first-step intervention, and represents a valid nutritional approach to PEW prevention and treatment since it is easy, effective and safe. Omega-3 fatty acids and fibers, now included in commercially available preparations for renal patients, could lend relevant added value to macronutrient supplementation. When oral supplementation fails, intradialytic parenteral nutrition can be implemented in selected patients.

Hyper/hypoglycemia and acute kidney injury in critically ill patients.

BACKGROUND & AIMS: Abnormalities of blood glucose (BG) concentration (hyper- and hypoglycemia), now referred to with the cumulative term of dysglycemia, are frequently observed in critically ill patients, and significantly affect their clinical outcome. Acute kidney injury (AKI) may further complicate glycemic control in the same clinical setting. This narrative review was aimed at describing the pathogenesis of hyper- and hypoglycemia in the intensive care unit (ICU), with special regard to patients with AKI. Moreover, the complex relationship between AKI, glycemic control, hypoglycemic risk, and outcomes was analyzed. METHODS: An extensive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, treatment and outcome of hypo- and hyperglycemia in critically ill patients with AKI. RESULTS AND CONCLUSION: Patients with AKI are at increased risk of both hyper-and hypoglycemia. The available evidence does not support a protective effect on the kidney by glycemic control protocols employing Intensive Insulin Treatment (IIT), i.e. those aimed at maintaining normal BG concentrations (80-110 mg/dl). Recent guidelines taking into account the high risk for hypoglycemia associated with IIT protocols in critically ill patients, now suggest higher BG concentration targets (<180 mg/dl or 140-180 mg/dl) than those previously recommended (80-110 mg/dl). Notwithstanding the limited evidence available, it seems reasonable to extend these indications also to ICU patients with AKI.

[Disglycemia in patients with acute kidney injury in the ICU]. / Alterazioni glicemiche nel danno renale acuto in terapia intensiva.

Derangements of glucose metabolism are common among critically ill patients. Critical illness- associated hyperglycemia (CIAH) is characterized by raised blood glucose levels in association with an acute event that is reversible after resolution of the underlying disease. CIAH has many causes, such as changes in counter-regulatory hormone status, release of sepsis mediators, insulin resistance, drugs and nutritional factors. It is associated with increased mortality risk. This association appears to be strongly influenced by diabetes mellitus as a comorbidity, suggesting the need for an accurate individualization of glycemic targets according to baseline glycemic status. Hypoglycemia is also very common in this clinical context and it has a negative prognostic impact. Many studies based on intensive insulin treatment protocols targeting normal blood glucose values have in fact documented both an increased incidence of hypoglycemia and an increased mortality risk. Finally, glycemic control in the ICU is made even more complex in the presence of acute kidney injury. On one hand, there is in fact a reduction of both the renal clearance of insulin and of gluconeogenesis by the kidney. On the other hand, the frequent need for renal replacement therapy (dialysis / hemofiltration) may result in an energy intake excess, under the form of citrate, lactate and glucose in the dialysate/reinfusion fluids. With regard to the possible renal protective effects afforded by intensive glycemic control protocols, the presently available evidence does not support a reduction in the incidence of AKI and/or the need for RRT with this approach, when compared with standard glucose control. Thus, the most recent guidelines now suggest higher blood glucose targets (<180 mg/dl or 140-180 mg/dl) than in the past (80-110 mg/dl). Albeit with limited evidence, it seems reasonable to extend these indications also to patients with AKI in the intensive care unit. Further studies are needed in order to better ascertain the effects of dysglycemia on the outcome of patients with AKI.

[Nutritional support in acute kidney injury]. / Supporto nutrizionale nel danno renale acuto.

Optimal nutritional requirements and nutrient intake composition for patients with acute kidney injury is still a partially unresolved issue. Targeting nutritional support to the actual protein and energy needs improves the clinical outcome of critically ill patients. So far, very few data are currently available on this topic in acute kidney injury. In this specific clinical condition, the risk for under- 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, since 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.

Conceptual basis and methodology of the SOPHIA study.

To clarify the role of gene polymorphisms on the effect of losartan and losartan plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac, vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48 weeks treatment, an Italian collaborative study - The Study of the Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be given and doubled to 100 mg at week +4 if blood pressure is more than 140/90 mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week +16 will be added if blood pressure is more than 140/90 mmHg. Cardiac mass (echocardiography), carotid intima-media thickness, 24 h ambulatory blood pressure, homeostatic model assessment (HOMA) index, microalbuminuria, plasma renin activity and aldosterone, endogenous lithium clearance, brain natriuretic peptide and losartan metabolites will be evaluated. Genes of the renin-angiotensin-aldosterone system, salt sensitivity, the beta-adrenergic system and losartan metabolism will be studied (Illumina custom arrays). A whole-genome scan will also be performed in half of the study cohort (1M array, Illumina 500 GX beadstation).

Human parvovirus B19 infection mimicking systemic lupus erythematosus in an adult patient.

We report a case of widespread immune activation with moderate cytopenia during acute infection with human parvovirus B19 in an adult female patient, in whom five criteria for the diagnosis of systemic lupus erythematosus were present at disease onset. Our case is unusual due to the presence of a cutaneous rash mimicking leukocytoclastic vasculitis at presentation, moderate leukopenia with thrombocytopenia and the presence of a broad array of autoantibodies. Diagnosis was established on the grounds of serological tests confirming recent infection with human parvovirus B19; spontaneous regression of clinical and laboratory abnormalities was observed within 16 weeks, ruling out classic systemic lupus erythematosus. We conclude by proposing that human parvovirus B19 infection should be included in the differential diagnosis of lupus-like syndromes in adult patients.

-344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension.

Most patients with low renin essential hypertension are not qualitatively different from patients with idiopathic hyperaldosteronism, as in both conditions aldosterone secretion is not appropriately reduced. The aim of the study was to investigate allele and genotype frequencies of the -344C/T polymorphism, located in the promoter region of the aldosterone synthase gene, in 83 patients with idiopathic low renin hypertension characterized by an increased aldosterone to renin ratio, including both patients with low renin essential hypertension (n=53) and subjects with idiopathic hyperaldosteronism (n=30), compared with 78 patients with normal to high renin essential hypertension and 126 normotensive control subjects. The relationship of -344C/T genotypes to basal and postcaptopril plasma aldosterone/plasma renin activity ratio was also examined in the entire hypertensive population. An increased frequency of the T allele and a relative excess of TT homozygosity over CC homozygosity were found in patients with idiopathic low renin hypertension in comparison with both normal to high renin hypertensives and normotensive controls. A higher post-captopril aldosterone to renin ratio was found in the hypertensives with TT genotype than in those with CC genotype, and TT+TC genotypes were associated with a smaller decrease in the aldosterone-to-renin ratio elicited by captopril administration. The present study suggests that the -344C/T polymorphism, or a functional variant in linkage disequilibrium with it, may play a role in the abnormal regulation of aldosterone secretion in idiopathic low renin hypertension.

Heart rate variability in patients with Sjögren's syndrome.

Heart rate variability (HRV) gives information about sympathetic parasympathetic autonomic balance. Our purpose was to determine whether HRV is abnormal in patients with Sjögren's syndrome. In 16 patients with Sjögren's syndrome and 30 matched controls, a short time analysis of HRV was performed for both the frequency and the time domain. In the time domain, patients tended to display a slower heart rate, greater R-R variability and higher standard deviation of the mean (SDNN) than did healthy subjects, but the differences were not statistically significant. In the frequency domain the spectral measures of HRV showed a slight reduction of LF and an increase of HF; as a result, the ratio between high and low frequencies, representative of sympathovagal modulation, was significantly reduced. Our data suggest an increase in the parasympathetic control of heart rate in patients with Sjögren's syndrome. This predominance in vagal tone could exert a protective and antiarrhythmic role in patients with primary Sjögren's syndrome, and may be relevant with reference to the lower incidence of sudden death in this disorder compared to other major autoimmune diseases.

Liquorice-induced sodium retention. Merely an acquired condition of apparent mineralocorticoid excess? A case report.

Excessive ingestion of liquorice may result in sodium retention, hypertension, hypokalemia, and suppression of renin and aldosterone. Similarities between liquorice-induced effects and congenital apparent mineralocorticoid excess have recently been emphasized, as in both conditions, reduced activity of the enzyme 11 beta-hydroxysteroid dehydrogenase type 2 allows cortisol to act as a potent mineralocorticoid. We report a case of generalized edema without any increase in blood pressure, with biochemical and hormonal features of apparent mineralocorticoid excess, in a young woman who had been ingesting substantial amounts of liquorice for several years. Liquorice-induced wide-spread edema without hypertension in our patient, as well as in a few other cases previously reported, and the more common occurrence of edema associated with hypertension challenge the current explanation of liquorice syndrome as a purely acquired apparent mineralocorticoid excess. Indeed, in both congenital apparent and true mineralocorticoid excess, edema is typically absent, as a result of the sodium escape phenomenon. As pressure-natriuresis may be an essential mechanism accounting for the sodium escape phenomenon, some component of liquorice could partially or completely oppose the circulatory response that converts liquorice-induced sodium retention into blood pressure elevation. In patients with unexplained generalized edema and hypokalemia without hypertension, liquorice ingestion should be carefully investigated and the renin-aldosterone system should be assayed.

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.

Acute effects of intravenous sodium chloride load on calcium metabolism and on parathyroid function in patients with primary aldosteronism compared with subjects with essential hypertension.

To elucidate the mechanisms involved in increased parathyroid function in primary aldosteronism (PA), we evaluated the effects of an intravenous NaCl load on Ca metabolism and plasma level of intact parathyroid hormone (PTH) in patients with PA compared with that in patients with essential hypertension (EH). Sixteen PA patients and 16 EH patients who were well matched for age, gender, body mass index, renal function, and systolic (SBP) and diastolic blood pressure (DBP) were examined. In each subject, after 6 days of a controlled intake of Na, K, and Ca, isotonic saline was infused at a rate of 500 mL/h for 4 h. At baseline, in spite of similar BP values and urinary Na excretion (U[Na]V), urinary excretion of Ca (U[Ca]V) and PTH were higher in the PA group than in the EH group. In both groups, the NaCl load caused a decrease of serum ionized Ca (Ca2+) and an increase in PTH, U(Na)V, and U(Ca)V. However, these changes were significantly greater in the PA group. The increased baseline U(Ca)V in PA could be due to reduced reabsorption of sodium in aldosterone insensitive tubular sites, as a result of the "escape phenomenon." The increased U(Ca)V may explain the higher basal PTH in PA patients, which is needed for maintaining a normal Ca2+. The greater changes in the Ca2+/PTH profile elicited by the saline load in PA patients are apparently due to a higher calciuretic response following a more exaggerated natriuresis in PA.

Use of Fourier shape descriptors to improve the reproducibility of echographic measurements of arterial intima-media thickness.

BACKGROUND: A major source of error in the longitudinal assessment of the intima-media thickness (IMT) is the difficulty in retrieving the same echographic view of the vessel. OBJECTIVE: To present a method for increasing the reproducibility of IMT measurements by ultrasound in large arteries. METHOD: The Fourier descriptor is a well-known means of describing an object's shape. By means of the discrete Fourier transform (DFT), the shape was represented in a frequency domain; the computational advantages of the DFT then permitted a measure of unlikeness between different shapes (the 'distance' measure; DM) to be defined and used as a criterion for reproducing the contour. When the sonographer compared successive images of a complex vascular segment, like the carotid bifurcation, the identity of the echographic cut was deduced from the identity of the vessel's contour. The best match of the baseline image was the view that minimized the contour DM. RESULTS: Preliminary studies in the carotid artery bifurcations of eight subjects showed that the DM responds to systematic variations in the ultrasound interrogation angle and reveals minimal changes in transducer position. Duplicate scans of 12 subjects were performed by three sonographers with different strategies for acquisition of the same images: a low DM was associated with a low difference in pairs of IMT measurements. Data were classified into two groups (normal or borderline vessels with a pooled mean IMT of 0.62 mm and overtly thickened segments with a pooled mean IMT of 1.31 mm). When minimization of the DM was the criterion for the acquisition of replicate scans, the mean absolute difference of paired data for the mean IMT of the distal common carotid artery was 0.03 +/- 0.02 mm for the first group and 0.06 +/- 0.03 mm for the second group. This is a significant reduction in comparison with non-quantitative alternative criteria for image reproduction. For the maximum IMT of the same segments the mean absolute differences were 0.07 +/- 0.03 and 0.13 +/- 0.06 mm in the first and second groups, respectively. CONCLUSION: This method can be applied to the serial assessment of single atherosclerotic segments. The computational time is negligible. By reducing the scatter in sequential IMT data, longitudinal investigations (e.g. of the results of antihypertensive therapy) with shorter durations and smaller sample groups may be rendered feasible.

Effects of reduced preload on diastolic filling in essential hypertensive patients with increased left ventricular mass.

Doppler-derived indices of diastolic filling are widely used in the routine evaluation of essential hypertensives. However, these indices are affected by loading conditions and systolic performance. This study aimed at monitoring the transmitral flow pattern and indices of left ventricular systolic function during acute nonpharmacological isolated reduction of preload in essential hypertensives with left ventricular hypertrophy. Nine essential hypertensive patients with left ventricular hypertrophy and nine age- and sex-matched normotensive controls underwent echocardiographic and Doppler evaluation of both systolic function and diastolic filling indices at baseline and during lower body suction at -40 mm Hg. Lower body suction caused a similar decrease in end-diastolic volume index, stroke volume index, and midwall fractional shortening in the normotensives and hypertensives. Circumferential end-systolic stress was unaffected in both groups. Acceleration time of early diastolic filling and isovolumic relaxation time increased in the normotensives but not in the hypertensives. Deceleration time of early diastolic filling increased in both groups. The ratio of peak velocities during early filling and at atrial contraction decreased in the normotensives, whereas it was unchanged in the hypertensives; this was due to the fact that early filling velocity decreased in both groups, whereas peak velocity at atrial contraction decreased only in the hypertensives. We conclude that Doppler-derived diastolic filling indices are not affected by a reduction of preload in essential hypertensives with left ventricular hypertrophy.

Myocardial ultrasonic tissue characterization in patients with different types of left ventricular hypertrophy: a videodensitometric approach.

Although analysis of the radio frequency signal is the most accurate approach to myocardial tissue characterization, clinical diffusion has been limited because of the complex technology required. Much easier to perform, videodensitometric analysis could represent a valuable alternative. Previous works carried out on radio frequency data have shown that the absolute value of ultrasonic back scatter increases while its diastole-to-systole variation decreases in the hypertrophied myocardium. This study was aimed at clarifying whether alterations in characterization indexes of ultrasonic tissue can be detected by means of a videodensitometric approach, whether a specific type of left ventricular (LV) hypertrophy can be identified with this method, and finally what possible relationships exist between parameters of contractile function and tissue characterization indexes. Myocardial echo intensity (MEI), its cyclic variation (CV), and the dynamic relationship between myocardial signal and wall thickness variations during the cardiac cycle were assessed in 20 healthy subjects, 11 patients with essential hypertension and LV hypertrophy, 15 patients with hypertrophic cardiomyopathy, and 4 patients with primary amyloidosis. The CV was lower in the interventricular septum of patients with cardiac hypertrophy as a group, compared with that of control subjects (13.0% +/- 5.6% versus 18.8% +/- 5.5%, p < 0.001), but it was similar among patients with different types of hypertrophy. In control subjects, a significant inverse correlation was found between the progressive decrease of the myocardial signal and the parallel increase in wall thickness during systole; this correlation was lost in 60% of patients with hypertrophic cardiomyopathy and 50% of those with amyloidosis, but only in 9% of patients with essential hypertension (chi square analysis 12.68, p < 0.01). The CV was associated with systolic wall thickening (r = 0.53, p = 0.0001) and fractional shortening (r = 0.44, p = 0.0014). MEI and its CV per se cannot distinguish among different types of LV hypertrophy; however, the loss of an inverse relationship between the myocardial signal and wall thickness may suggest abnormal myocardial conditions in individual patients with the same disease or comparable wall thickness.

Renal effects of nifedipine and captopril in patients with essential hypertension and reduced renal reserve.

In this study we investigated the short-term effects of calcium channel blockers and angiotensin-converting enzyme inhibitors on renal hemodynamics and the urinary excretion of proteins with different relative mass in subjects with mild to moderate essential hypertension and apparently normal glomerular filtration rate but reduced renal functional reserve. Sixteen subjects underwent the following four treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral nifedipine (20 mg), and (4) high-protein meal plus oral captopril (50 mg). Two urine samples were obtained after meals. Blood samples were drawn at the midpoint of each 120-minute urine collection period. Urine and serum were tested for total protein, immunoglobulin G, albumin, alpha 1-microglobulin, retinol binding protein, and beta 2-microglobulin. Glomerular filtration rate and renal plasma flow were assessed by iothalamate and p-aminohippuric clearance, respectively. Compared with the high-protein meal alone, nifedipine elicited a clear-cut increase in the urinary excretion of total protein (+60%, P < .01), immunoglobulin G (+58%, P < .01), albumin (+25%, P < .05), retinol binding protein (+47%, P < .05), and beta 2-microglobulin (+52%, P < .05); captopril decreased the urinary excretion rate of immunoglobulin G (-26%, P < .05), albumin (-22%, P < .05), and beta 2-microglobulin (-34%, P < .05). The ratio between the clearances of immunoglobulin G and albumin was higher after nifedipine (+21%, P < .01) and unchanged after captopril (-9%, P = NS) compared with the high-protein meal alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of biguanide-induced lactic acidosis: reproposal of the "physiological" approach and review of the literature.

We report a case of severe biguanide-induced lactic acidosis which did not respond to symptomatic alkali treatment via either intravenous bicarbonate infusion or bicarbonate-dialysis. We thus initiated a therapeutic strategy based on insulin and thiamine only in order to reactivate the pyruvate oxidative pathway, in which both drugs play important roles as cofactors. This original "physiological" approach proved effective, and further alkali administration was unnecessary. Our results prompted a review of the literature on the treatment of biguanide-induced lactic acidosis, a situation in which the absence of precise therapeutic rules can undoubtedly affect both the evolution and the prognosis of the syndrome.