Guido Bellinghieri

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.

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.

Parathyroidectomy in Chronic Renal Failure: Short- and Long-Term Results on Parathyroid Function, Blood Pressure and Anemia

To evaluate the long-term results of parathyroidectomy (PTX) on parathyroid function, blood pressure and anemia, data of 45 patients with secondary Hyperparathyroidism in dialysis who had undergone PTX were collected retrospectively from 8 different dialysis units. The patients, 25 M and 20 F, mean age 56 ± 11 years, who were followed up for an average period of 3.3 ± 2.3 years, were divided into four groups according to the surgical procedure: 19 patients had had a subtotal PTX; 10 patients had undergone total PTX with autotransplantation (AT); 10 patients had had total PTX without AT, and 6 patients had undergone partial PTX. Taking a reduction in intact PTH >50% as sign of successful PTX, only 5 patients did not attain this result. Considering values of PTH between 20 and 200 pg/ml at the mid-term observation (1–2 years) as the optimal result, values under 20 pg/ml as an expression of permanent hypoparathyroidism, and those above 200 pg/ml as indicating persistent/recurrent hyperparathyroidism, 65.5% of patients operated with subtotal PTX and total PTX + AT had a therapeutic success, versus 31.2% of patients in the other two groups, due to excess permanent hypoparathyroidism and persistent/recurrent hyperparathyroidism; 20 of 45 patients with preoperative hypertension experienced a statistically and clinically significant decrease in blood pressure levels. An increase in serum hemoglobin was also observed, despite a reduction of administered erythropoietin. In conclusion, the results of PTX obtained from this multicenter study are comparable to those reported by single leading centers. Recommended surgical procedures are subtotal PTX and total PTX with AT. The fall in blood pressure in hypertensive patients is clinically significant, and improvement in anemia is also observed with a reduction in erythropoietin dosage.

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.

Metabolic syndrome after kidney transplantation.

Metabolic syndrome (MS) can be linked to the progression of chronic renal transplant dysfunction (CRTD). Hyperfiltration in transplanted patients is a further risk factor for MS and for the progression of CRTD. Many studies show in kidney-transplanted subjects a prevalence of MS at 60% after 6 years posttransplantation. We studied 182 patients (126 men and 56 women) with functioning renal transplant in Messina and Rovigo Renal Units. In our patients we saw at 6 years postkidney transplant in men a prevalence of MS at 20% (NCEPATPIII criteria) or 30% (Rovigo-Messina more strict criteria), and women at 6 years posttransplantation a prevalence of MS at 25% (NCEPATPIII criteria) or 50% (Rovigo-Messina criteria). In our patients, the period of graft function was over 15 years. This result is due to continued follow-up of metabolic parameters and to moderate protein (0.8-0.9 g/kg/day), low lipid, and low caloric intake. These strategies permit the avoidance of hyperfiltration, the reduction of hyperlipidemia and obesity. Special attention is due to women 50-65 years old. In these patients the prevalence of metabolic syndrome 6 years posttransplant is very high (60%). Postmenopausal syndrome is an additional risk factor for MS, atherosclerosis, and the progression of CRTD.

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.

Emerging drugs for hyperphosphatemia

Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.

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.