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Biomedical subjects

Guido Bellinghieri

Publications and source records attributed to Guido Bellinghieri.

At least 19 recordsLinked to original sources
PubMed2007

Phosphate salivary secretion in hemodialysis patients: implications for the treatment of hyperphosphatemia.

BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000-1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. METHODS: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon's test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. RESULTS: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.

Female↗
PubMed2006

Vascular erectile dysfunction in chronic renal failure.

The prevalence of erectile dysfunction (ED) has increased dramatically worldwide in parallel with the aging of the population. In 1995, ED was estimated to be present in more than 150 million men. Considering population aging in Western countries, estimates predict that more than 300 million men will be affected by ED by the year 2025. ED is a common and often distressing side effect of renal failure. It is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialysis treatment. Uremic men of different ages report a high variety of sexual problems including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenetic mechanisms include physiologic, psychologic, and organic causes. Since the release of sildenafil citrate, the relationship between ED and the presence of cardiovascular disease (CVD) has been evaluated in several studies. Many of the risk factors for ED are the same as those for cardiac disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be considered a symptom of vascular endothelial damage. Therefore, it can be expected that impotence will appear along with CVD, and the presence of ED suggests the existence of CVD. An accurate evaluation of the sexual histories of all men who present to internists, cardiologists, and also nephrologists for early detection of ED may allow for early diagnosis and management of CVD.

Humans↗
PubMed2006

Newer aspects of carnitine metabolism in uremia.

New knowledge on the physiologic role of L-carnitine and on the rationale of its use in patients on maintenance hemodialysis is provided. In particular, carnitine normalizes plasma and muscle carnitine levels and modifies both enzymatic pattern of muscle and morphology of single fibers, improving exercise tolerance. In addition, carnitine reduces erythropoietin requirements, the number of hypotensive episodes, improves ejection fraction, and decreases hospitalization.

Carnitine↗
PubMed2006

L-arginine: a new opportunity in the management of clinical derangements in dialysis patients.

L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism. Rats receiving arginine-supplemented parenteral nutrition showed an increased ability to synthesize acute phase proteins when challenged with sepsis. Finally, L-arginine exerts antihypertensive and antiproliferative effects on vascular smooth muscles. It has been shown to reduce systemic blood pressure in some forms of experimental hypertension. Endothelial dysfunction and reduced nitric oxide bioactivity are associated with increased incidence of cardiovascular diseases. A beneficial effect of acute and chronic L-arginine supplementation on endothelial derived nitric oxide production and endothelial function has been shown. In end-stage renal disease patients, the rate of de novo arginine synthesis seemed to be preserved. Our preliminary data on a group of dialysis patients showed that predialysis arginine levels were stable in a normal range during the dialysis session and that hypertensive patients had lower arginine-citrulline ratio than normotensive patients.

Adult↗
PubMed2006

Nutritional status in hemodialysis patients: options for on-line convective treatment.

Although hemodialysis (HD) has improved the life expectancy of patients with end-stage renal disease (ESRD), uremic patients continue to experience high morbidity and mortality. Two of the most important risk factors for morbidity and mortality are protein-energy malnutrition (PEM) and inflammation. The causes for PEM in ESRD are numerous. The use of materials for dialysis, especially of the dialyzer membrane, is reported as one of the recognized causes for chronic inflammation in hemodialysis. We performed a 6-month prospective study examining the influence of on-line predilution hemodiafiltration on the inflammatory and nutritional status in a population of male hemodialysis patients using ultrapure dialysis fluid and polyamide dialyzers. We evaluated serum C-reactive protein, albumin, and transferrin and some nutritional parameters such as body mass index (BMI), phase angle (phi), fatty mass (FM), and free fatty mass (FFM) using bioelectrical impedance (BIA). Results showed significant amelioration of BMI and the re-equilibrium of the acute phase protein after on-line predilution hemodiafiltration. These results support the hypothesis that on-line predilution hemodiafiltration, as convective extracorporeal treatment, may be used to treat malnourished hemodialysis patients and to prevent malnutrition in the ESRD patient at risk for malnutrition.

Aged↗
PubMed2006

Prevalence of SENV-H and SENV-D virus: epidemiological study in blood donors and dialysis patients.

INTRODUCTION: Recently, the identification of the SEN virus as a possible etiological agent of parental transmission hepatitis led to the study of the prevalence of such pathogen agents, particularly SENV-H, in our population. This paper compares the rate prevalence in high-risk subjects, such as dialysis patients, and low-risk subjects, such as blood donors. MATERIAL AND METHODS: The study was carried out on SEN virus DNA extracted from serum of dialysis patients and blood donors, and the presence of viral genomes was performed by the nested PCR method. RESULTS: The results showed a higher prevalence in male blood donors, supporting the hypothesis of an epidemiological role for sexual and also parental transmission, as is clearly demonstrated by the high prevalence in dialysis patients. The result reduced the importance of the possible etiological role of the SEN virus due to the high percentage of positivity in healthy population, and it induces one to consider poorly significant the pathogenicity of such viral agents. CONCLUSION: For this instance, the authors, in agreement with the phylogenically related TT virus, described SEN viruses as absolutely not pathogens and considered them as "simple guests."

Adolescent↗
PubMed2005

Italian audit on therapy of hypertension in chronic kidney disease: the TABLE-CKD study.

A large body of evidence supports the validity of decreasing blood pressure to target levels in patients with essential hypertension to prevent cardiovascular disease. This issue becomes even more critical in chronic kidney disease because of the remarkably greater risk for cardiovascular fatal and nonfatal events. Indeed, renal patients should maintain blood pressure levels less than those suggested for the general population. Paradoxically, management of hypertension in this high-risk patient population is far from optimal and certainly worse with respect to essential hypertension. The Target Blood Pressure Levels in Chronic Kidney Disease (TABLE-CKD) study, performed in Italian patients with mild to advanced chronic kidney disease regularly followed-up by nephrologists, has shown that the prevalence of patients at target blood pressure is less than 20%. The assessment of antihypertensive strategy in these patients, however, suggests that there is room for improvement; in particular, a more aggressive treatment of volume expansion may ameliorate hypertension control in this population characterized by a high salt sensitivity of blood pressure.

Age Distribution↗
PubMed2005

Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients.

Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients.

Acute-Phase Proteins↗
PubMed2005

L-carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients.

Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis (MHD) or chronic peritoneal dialysis patients. We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status. MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg (n = 48) or placebo (n = 65) thrice weekly at the end of each hemodialysis treatment for 6 months. The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin, blood hemoglobin, and body mass index. Conversely, in the placebo-treated group, a significant decrease was reported for serum albumin, serum transferrin, and body mass index, whereas the other considered measures did not change significantly. These preliminary findings suggest that in MHD patients, L-carnitine therapy may suppress inflammation, particularly among those patients with C-reactive protein > or =3 mg/dL, and may improve protein-energy nutritional status.

Aged↗
PubMed2005

Pharmacological treatment of acute and chronic hyperuricemia in kidney diseased patients.

Several trials argued the possibility that hyperuricemia may have a direct effect on cardiovascular and renal disease. It has been shown that an elevated serum uric acid concentration is a predictor of cardiovascular events such as myocardial infarction. It also predicts the development of hypertension and in hypertensive patients, hyperuricemia is associated with increased cardiovascular morbidity and mortality. Hyperuricemia is a complication often seen in patients with chronic and acute renal disease. The relationship between serum uric acid level and the appearance or progression of renal dysfunction has been debated in the last years. During chemotherapy for hematological malignancies or more rarely for solid tumors, acute renal failure, secondary to a sudden marked increase in uric acid, is not such a rare complication. The therapeutic intervention includes hyper hydration, urinary alkalinization, and the use of uric acid decreasing agents such as allopurinol and rasburicase, a recent recombinant-urate oxidase. In our personal experience, patients with acute renal failure due to hyperuricemia, showed a better renal prognosis with rasburicase than allopurinol. Chronic hyperuricemia is also associated with chronic tubulo-interstitial disease with glomerular sclerosis, and renal dysfunction. Experimental trials showed that uric acid can affect kidneys through different mechanisms at glomerular, tubulo-interstitial and vascular level. Although allopurinol is often the drug of choice, caution must be used to avoid serious side effects. New therapeutic options, for treating hyperuricemia are needed in patients with renal dysfunction for slowing the progression to end stage kidney disease.

Acute Disease↗
PubMed2004

Ultrastructural changes of corpora cavernosa in men with erectile dysfunction and chronic renal failure.

Erectile dysfunction (ED) is a common and often distressing side effect of renal failure. Uremic men of different ages report a high variety of sexual problems, including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenic mechanisms include physiologic, psychologic, and organic causes. To determine the contribution of morphologic factors to impotence we studied the ultrastructure of the corpora cavernosa in 20 patients with end-stage renal disease who were treated with chronic dialysis and compared the findings with 6 individuals with no clinical history of impotence. Our results indicated that in male uremic patients with sexual disturbances there were major changes in smooth muscle cells. This was characterized by reduction of dense bodies in the cytoplasm, thick basement membranes, and increased interstitial collagen fibers with resultant reduction of cell-to-cell contact. In addition, there was thickening and lamination of basement membranes of endothelial cells and increased accumulation of collagen between nerve fibers. These alterations were more evident in patients with longer time on dialysis and were independent of type of primary renal disease. We hypothesize that ED in dialysis patients is not related to the primary disease but to the uremic state.

Adult↗
PubMed2004

Carnitine system in uremic patients: molecular and clinical aspects.

Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease.

Carnitine↗
PubMed2003

Physical exercise increases urinary excretion of lipoxin A4 and related compounds.

Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA(4) (iLXA(4)) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA(4) excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA(4) urinary excretion in nine healthy volunteers (0.061 +/- 0.023 vs. 0.113 +/- 0.057 ng/mg creatinine; P = 0.028). iLXA(4) levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation (r = 0.988) was denoted between iLXA(4) ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA(4)-related nature. These findings show for the first time that an increase in excretion of LXA(4)-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.

Adult↗
PubMed2003

Carnitine and hemodialysis.

Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in the beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading in some patients to carnitine depletion with a relative increase of esterified forms. The authors found a decrease in plasma-triglyceride and increase of high-density lipoprotein cholesterol (HDL-Chol) in dialysis patients during carnitine treatment. Many studies have shown that L-carnitine supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells. In addition, carnitine supplementation may improve protein metabolism and insulin resistance. Recently, carnitine supplementation has been approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Regular carnitine supplementation in hemodialysis patients can improve their lipid metabolism, protein nutrition, antioxidant status, and anemia requiring large doses of erythropoietin, It also may reduce the incidence of intradialytic muscle cramps, hypotension, asthenia, muscle weakness, and cardiomyopathy.

Carnitine↗
PubMed2003

History of L-carnitine: implications for renal disease.

L-carnitine (LC) plays an essential metabolic role that consists in transferring the long chain fatty acids (LCFAs) through the mitochondrial barrier, thus allowing their energy-yielding oxidation. Other functions of LC are protection of membrane structures, stabilizing a physiologic coenzyme-A (CoA)-sulfate hydrate/acetyl-CoA ratio, and reduction of lactate production. On the other hand, numerous observations have stressed the carnitine ability of influencing, in several ways, the control mechanisms of the vital cell cycle. Much evidence suggests that apoptosis activated by palmitate or stearate addition to cultured cells is correlated with de novo ceramide synthesis. Investigations in vitro strongly support that LC is able to inhibit the death planned, most likely by preventing sphingomyelin breakdown and consequent ceramide synthesis; this effect seems to be specific for acidic sphingomyelinase. The reduction of ceramide generation and the increase in the serum levels of insulin-like growth factor (IGF)-1, could represent 2 important mechanisms underlying the observed antiapoptotic effects of acetyl-LC. Primary carnitine deficiency is an uncommon inherited disorder, related to functional anomalies in a specific organic cation/carnitine transporter (hOCTN2). These conditions have been classified as either systemic or myopathic. Secondary forms also are recognized. These are present in patients with renal tubular disorders, in which excretion of carnitine may be excessive, and in patients on hemodialysis. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading, in some patients, to carnitine depletion with a relative increase in esterified forms. Many studies have shown that LC supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells.

Animals↗
PubMed2003

Effects of manidipine and nifedipine on blood pressure and renal function in patients with chronic renal failure: a multicenter randomized controlled trial.

Several studies suggest the distinctive advantages of ACE-inhibitors and calcium-channel blockers in protecting the residual renal function in hypertensive patients. Pre-clinical and clinical studies have shown rare adverse events in the treatment with manidipine, which is commonly used as antihypertensive drug. We therefore decided to compare the effects of manidipine and nifedipine, on blood pressure, and renal function. One hundred and one hypertensive patients with chronic renal failure were randomly assigned to receive either manidipine 20 mg daily or nifedipine 60 mg daily, respectively. Patients were assessed every two weeks during the active treatment period with the final follow-up after three months. The primary endpoint was the achievement of DBP < or = 90 mmHg or a 10 mmHg DBP reduction from the baseline values, whilst the secondary endpoints was the improvement of the renal function assessed through the creatinine clearance, creatinine blood levels, protein and sodium urine excretion. Significant reduction in SBP (p < 0.001) and DBP (p < 0.001), compared to the baseline values, was reached in both treatments. Creatinine blood levels (p < 0.05) and creatinine clearance (p < 0.01) significantly increased in the manidipine group. Protenuria did not significantly change in the manidipine group but increased in the nifedipine group (p < 0.05). The number of patients with severe adverse reactions differed significantly (p < 0.01) between the groups with the highest frequency for nifedipine (14.5%) compared to manidipine (8.5%). The withdrawal rate was not significantly different between the groups. Manidipine is equally safe and effective as nifedipine and it may have more activity on renal function and less severe side effects compared to nifedipine.

Adult↗
PubMedDate not supplied

Nutritional therapy in chronic kidney disease.

In patients with chronic kidney disease (CKD), specialized nutritional therapy may help reduce the risk of electrolyte imbalances, vitamin deficiencies, and protein energy malnutrition. Protein-restricted diets may slow the progression of renal disease and decrease the risk of morbidity and mortality in patients with CKD. In this review, we discuss some of the major nutritional concerns in individuals with CKD and offer practical recommendations for dietary therapy.

Adolescent↗