Vincenzo Savica

The Effect of Nutrition on Blood Pressure

The incidence and severity of hypertension are affected by nutritional status and intake of many nutrients. Excessive energy intake and obesity are major causes of hypertension. Obesity is associated with increased activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, possibly other mineralcorticoid activity, insulin resistance, salt-sensitive hypertension and excess salt intake, and reduced kidney function. High sodium chloride intake strongly predisposes to hypertension. Increased alcohol consumption may acutely elevate blood pressure. High intakes of potassium, polyunsaturated fatty acids, and protein, along with exercise and possibly vitamin D, may reduce blood pressure. Less-conclusive studies suggest that amino acids, tea, green coffee bean extract, dark chocolate, and foods high in nitrates may reduce blood pressure. Short-term studies indicate that specialized diets may prevent or ameliorate mild hypertension; most notable are the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits, vegetables, and low-fat dairy products, and the DASH low-sodium diet. Long-term compliance to these diets remains a major concern.

Carnitine: an osmolyte that plays a metabolic role.

Carnitine, gamma‐trimethyl‐beta‐hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic ones. It is the sole source of carbon and nitrogen in some bacteria; it serves as osmoprotectant in others. It is a carrier of acyl moieties, and exclusively of long‐chain fatty acids for mitochondrial beta‐oxidation in mammals. The conspicuously similar composition of the intracellular milieu among widely different species in relation to organic osmolyte systems involves the methylamine family to which carnitine belongs. This prompted us to examine the osmolytic properties of carnitine in an attempt to clarify the metabolic functions carnitine has acquired during evolution. An understanding of the metabolic functions of this organic compatible solute impinge on research involving this compound. J. Cell. Biochem. 80:1–10, 2000.

Plasma and Muscle Carnitine Levels in Haemodialysis Patients with Morphological-Ultrastructural Examination of Muscle Samples

The present study investigates 14 patients on intermittent haemodialysis. Pre-dialysis blood and muscle samples taken for determining plasma free- and acetylcarnitine levels. The tissue fragments were used for light and electron microscopy studies. Our results support the findings of other investigators that patients on haemodialysis generally display decreased free- and acetylcarnitine levels both in plasma and skeletal muscle when compared with control values. Muscle carnitine deficiency was apparently more severe in the longer-term haemodialysis patients. Moreover, a significant correlation (p less than 0.05) between plasma and muscle free-carnitine values was found. Morphologically no pathological alterations were observed in the muscle fibres in 13 of the patients. Light and electron microscopic studies of the muscle fibre of the 14th patient showed a typical nemaline myopathy with rod bodies in the cytoplasm. The muscle free-carnitine concentration in this patient was among the lowest of the group.

Salivary Phosphate-Binding Chewing Gum Reduces Hyperphosphatemia in Dialysis Patients

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders, only half of hemodialysis (HD) patients achieve recommended serum phosphate levels. A hyperphosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients. We hypothesized that binding salivary phosphate during periods of fasting in addition to using phosphate binders with meals could improve the treatment of hyperphosphatemia. We assessed the phosphate-binding capacity of the natural polymer chitosan by (31)P nuclear magnetic resonance and established that 10 and 20% (wt/vol) middle viscosity chitosan solutions bind 30 and 50% of the phosphate contained in PBS, respectively. Thirteen HD patients with serum phosphate levels >6.0 mg/dl despite treatment with sevelamer hydrochloride chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 wk at fast in addition to their prescribed phosphate-binding regimen. Salivary phosphate and serum phosphate significantly decreased during the first week of chewing; by the end of 2 wk, salivary phosphate decreased 55% from baseline (73.21 +/- 19.19 to 33.19 +/- 6.53; P < 0.00001), and serum phosphate decreased 31% from baseline (7.60 +/- 0.91 to 5.25 +/- 0.89 mg/dl; P < 0.00001). Salivary phosphate returned to baseline by day 15 after discontinuing the chewing gum, whereas serum phosphate levels took 30 d to return to baseline. Parathyroid hormone and serum calcium concentrations were not affected by the gum. In conclusion, adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in HD patients.

Pain in end-stage renal disease: a frequent and neglected clinical problem

Pain is a major health problem in end-stage renal disease (ESRD) affecting half of the dialysis patients; most of them experience a moderate to severe degree of pain. Nevertheless, the impact of chronic pain and its consequences are often underestimated. Sources of pain related to the uremic environment are renal bone disease (osteitis fibrosa cystica, amyloidosis, osteomalacia), osteoarthritis, calcific uremic arteriolopathy and peripheral neuropathy. Moreover, comorbid conditions such as ischemic peripheral artery disease, diabetic neuropathy, osteopenia/ osteoporosis (due to long-standing hypertension, diabetes, or old age) result in various kinds of pain. Also the primary kidney disease (e.g. autosomal dominant polycystic kidney disease (ADPKD)) as well as performance of hemodialysis or peritoneal dialysis are important causes of pain. Potential consequences of persistent pain are disturbed sleep, weakened memory/attention, altered mood (anxiety and depressive disorder), impotence, poorer physical state, less social activities and consideration of withdrawal from dialysis. Consequently the health-related-quality of life (HRQOL) is diminished, associated with a higher morbidity and mortality. In the therapy of pain the WHO three-step analgesic ladder adapted for ESRD, was shown to be effective in dialysis patients. Of fundamental importance are various forms of non-pharmacological strategies including electrotherapy. Recently the so-called high tone external muscle stimulation (HTEMS) was very effective in the management of neuropathic pain in ESRD patients.

Involvement of Interleukin-18 in Patients on Maintenance Haemodialysis

Maintenance dialysis induces a clinical state of immunodeficiency. The pathway of circulating T cells from haemodialyzed patients is changed and characterized by an increase of Th1 cells. The unbalanced T helper differentiation derives from an altered regulation of interleukin-12 (IL-12), which represents an important inducer of Th1. IL-18 is a pro-inflammatory cytokine expressed by a variety of cell types that is structurally related to the Th1 family and shares biological properties with IL-12 as the promotion of Th1 responses. To explain the involvement of IL-18 in the typical disorders of dialysis, we analyzed IL-18 serum levels in a group of haemodialyzed patients. We enrolled 16 patients on chronic haemodialysis (HD) treatment for end-stage renal failure and 16 healthy volunteers as the control group. IL-18 levels were assessed by immunoenzymatic methods (detection limit was <12.5 pg/ml). HD patients strongly showed higher IL-18 serum levels compared to healthy donors (508.47 ± 314.39 vs. 193.44 ± 56.33 pg/ml, p < 0.005). Moreover, IL-18 levels in HD directly correlated to dialytic age (Rho = 0.544, p = 0.0419) and indirectly to Kt/V (Rho = 0.703, p = 0.0086). Our data represent the first evidence of the relation between IL-18 serum levels and HD. In the light of our results, we think that the unbalanced T helper differentiation may depend, at least in part, on an abnormality in the IL-18 production.

Uraemic autonomic neuropathy

Symptoms of uraemic autonomic neuropathy are often vague and aspecific. A correct diagnosis of autonomic dysfunction is possible by using several simple and non-invasive tests of parasympathetic and sympathetic control of the cardiovascular system. A defective regulation of the heart rate, due mostly to an afferent lesion, is more common than damage of reflex blood pressure control. The former appears isolated in 14 to 34% of uraemics on haemodialysis and combined to the latter in 18 to 26%. Contradictory results are reported about influence of intermittent haemodialysis, continuous ambulatory peritoneal dialysis and kidney transplantation on disturbed autonomic nervous system. Pathogenesis of uraemic autonomic neuropathy remains unknown and some mechanisms are only putative.

Impact of parathyroidectomy on cardiovascular outcomes and survival in chronic hemodialysis patients with secondary hyperparathyroidism. A retrospective study of 50 cases prior to the calcimimetics era

BackgroundIn chronic hemodialysis patients with secondary hyperparathyroidism, pathological modifications of bone and mineral metabolism increase the risk of cardiovascular morbidity and mortality. Parathyroidectomy, reducing the incidence of cardiovascular events, may improve outcomes; however, its effects on long-term survival are still subject of active research.We compared, in hemodialysis patients, the results of parathyroidectomy, in terms of cardiovascular outcomes and mortality, with those present in patients following medical treatment only, prior to the diffusion of calcimimetics.MethodsFrom January 2004 to December 2006, 30 hemodialysis patients, affected by severe and unresponsive secondary hyperparathyroidism, underwent parathyroidectomy - 15 total parathyroidectomy and 15 total parathyroidectomy + subcutaneous autoimplantation. During a 5-year follow-up, patients did not receive a renal transplantation and were evaluated for biochemical modifications and major cardiovascular events - death, cardiovascular accidents, myocardial infarction and peripheral vascular disease. Results were compared with those obtained in a control group of 20 hemodialysis patients, affected by secondary hyperparathyroidism, and refusing surgical treatment, and following medical treatment only.ResultsThe groups were comparable in terms of age, gender, dialysis vintage, and comorbidities. Postoperative cardiovascular events were observed in 18/30 - 54% - surgical patients and in 4/20 - 20%- medical patients, with a mortality rate respectively of 23.3% in the surgical group vs. 15% in the control group. Parathyroidectomy was not associated with a reduced risk of cardiovascular morbidity and survival rate was unaffected by surgical treatment.ConclusionsIn secondary hyperparathyroidism hemodialysis patients affected by severe cardiovascular disease, surgery did not modify cardiovascular morbidity and mortality rates. Therefore, in secondary hyperparathyroidism hemodialysis patients, resistant to medical treatment, only an early indication to calcimimetics, or surgery, in the initial stage of chronic kidney disease - mineral bone disorders, may offer a higher long-term survival. Further studies will be useful to clarify the role of secondary hyperparathyroidism in determining unfavorable cardiovascular outcomes and mortality in hemodialysis population.

Vitamin D receptor gene polymorphism and left ventricular hypertrophy in chronic kidney disease.

FokI and BsmI polymorphisms of vitamin D receptor (VDR) gene are regarded as reliable markers of disturbed vitamin D signaling pathway. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD) patients. Since BsmI polymorphism has been associated with LVH in ESRD patients, we addressed this study in patients with chronic kidney disease (CKD) not yet on dialysis. One hundred and forty five patients with CKD stage 3 were genotyped for FokI and BsmI VDR polymorphisms, in order to assess the relationships between these VDR polymorphisms, some markers of mineral bone disorders, and LVH measured by echocardiography. Patients bearing either the Ff heterozygous or FF homozygous genotype had significantly higher PTH values than those bearing the ff genotype. The relationships between VDR genotypes and LVH revealed a highly significant association of the BsmI Bb heterozygous genotype with LVH. In patients with CKD stage 3 BsmI B allele was independently related to LVH. Since LVH is a frequent finding in dialysis population due to several mechanisms, the presence of the same relationship in patients with CKD strengthens the hypothesis that alterations of vitamin D signaling are implicated in LVH development in patients with renal diseases.

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.