Cardiovascular risk factors in severe chronic renal failure: the role of dietary treatment.

BACKGROUND: Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF). METHODS: Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid. RESULTS: Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p < 0.005) with a reduction of LDL cholesterol (p < 0.01) and an increase of apoA1/apoB ratio (p < 0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p < 0.05) with lower TBARS concentrations (p < 0.01) and a significant reduction of total homocysteine (p < 0.002), Lp(a) (p < 0.002) and CRP levels (p < 0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p < 0.001) and OxLDL (p < 0.006) were associated to a risk of CRP > 0.3 mg/dl. CONCLUSIONS: These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Lp(a) levels: effects of progressive chronic renal failure and dietary manipulation.

Patients with chronic renal failure (CRF) have an increased risk of cardiovascular disease (CVD). Elevated lipoprotein(a) (LP(a)) levels have been shown to be an important risk factor for CVD. This study examined Lp(a) changes during the progression of renal disease in patients following different dietary regimens. Fifty-seven patients with CRF of different etiology and degree (mean age 58 +/- 10 yrs) were divided into four groups according to their serum creatinine (sCr) levels. The first group had sCr 1.5-3; the second 3-6; the third > 6, all on a conventional low-protein diet (CLPD), and the fourth had sCr > 6 on a supplemented vegetarian diet (SVD). Lp(a), apoproteins AI, B, E, CII, CIII, CII/CIII, Apo A/Apo B ratios and the lipid pattern (total cholesterol (TC) and its fractions LDL, HDL, HDL3 and triglycerides) were investigated. Patients with diabetes, proteinuria > 1.5 g/24 h, hepatic disease or taking contraceptives or lipid lowering drugs were excluded. Results were compared with a reference group (N = 12) with sCcr < 1. Lp(a) concentrations increased with the progression of renal failure, and a significant correlation was observed with sCr. Despite the elevated sCr levels, patients on the SVD had an almost normal Lp(a) concentration. Only 15% of the reference group had Lp(a) levels > 30 mg/dl, compared to 33%, 50% and 78% of the 1st, 2nd and 3rd groups and 38% of the 4th group. No relationship was found between Lp(a), lipids or apoproteins. Our results indicate that renal function influences Lp(a) levels and suggest a SVD helps to lower them. This might be ascribed to some antioxidant factors in the SVD.

Lipids and apolipoproteins change during the progression of chronic renal failure.

Uremic hyperlipidemia was recently suggested to contribute to progression of chronic renal failure (CRF). To investigate the relationship between lipoprotein abnormalities and decline of renal function, plasma lipids with apoproteins A1, B, E, CII, CIII, CII/CIII and E/CIII ratios, parathyroid hormone (PTH), insulin and glucose levels were examined in 72 patients with different degrees of CRF and compared to 28 patients of a reference group. A significant decrease of CII/CIII ratio was already evident below a Ccr of 60 ml/min, while increased apo-CIII and triglycerides (TG) with reduced HDL-cholesterol (HDL-C) levels occurred below a Ccr of 30 ml/min. Both TG and apo-CIII showed a positive correlation with creatinine levels. On the contrary, apo-CII/apo-CIII and HDL-C inversely correlated with the progression of renal failure. PTH and insulin showed a positive correlation with TG, the former being also inversely related to apo-CII/apo-CIII ratio. Our results point to early apolipoprotein changes in the course of CRF. Elevated apo-CIII and reduced apo-CII/apo-CIII ratio may be considered the most typical features of uremic hyperlipidemia and likely account for the impaired TG removal and the hypertriglyceridemia (HTG). Secondary hyperparathyroidism may contribute to reduce peripheral lipolytic activity and cause HTG. A contributory role of hyperlipidemia in the progression of renal disease is also supported.

Comparative activities of pefloxacin and ciprofloxacin in the treatment of chronic respiratory tract infections.

To determine the efficacy in vivo of pefloxacin and ciprofloxacin in the treatment of acute infectious bronchopneumopathies, 90 patients, suffering from acute exacerbation of chronic bronchitis and with no known allergies to quinolones, were admitted to the study. Patients were randomly divided into three groups of 30; the first group was dosed with pefloxacin 800 mg i.v. every 24 hours; the second group with pefloxacin 800 mg per os every 24 hours and the third with 500 mg per os of ciprofloxacin every 12 hours. Blood and bronchial secretion samples were simultaneously collected 2, 4, 8, 12, 14 and 24 hours after the first daily dose of antibiotic. Serum and bronchial secretion concentrations of pefloxacin and ciprofloxacin were determined by using a microbiological agar disk diffusion assay, employing Escherichia coli Kp 712 as test organism. Eradication of responsible microorganisms (Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis) were achieved in 98% of patients around 72 hours post treatment. Generally, both antibiotics expressed similar bactericidal properties when orally administered, while intravenous administration of pefloxacin displays a more rapid antibacterial action in comparison with the oral administration schedules. Maximal concentrations of both drugs in bronchial secretion were recorded at the same time after treatment (4 hours), with concentrations of about 2.5 micrograms/ml. Pefloxacin, having a longer half-life, was found 24 hours post-treatment with plasma concentrations of 1.5 micrograms/ml following a single oral dose of 800 mg. Ciprofloxacin, having a shorter half-life, showed a peak of about 1 microgram/ml, 12 hours after administration (500 mg/12 hours/os).

Biofiltration in elderly uremic patients.

We treated five elderly patients with conventional hemodialysis (CH) or biofiltration (BF) to establish whether their dialytic tolerance was better. For three patients treatment time was reduced from twelve to nine hours a week; for the other two, treatment time remained unchanged (10.5-12 h/week) because of their high interdialytic weight gain. At the beginning and end of the study, clinical status, biochemical data, nutritional status and acid-base balance (ABB) were checked. Plasma levels of small molecules, potassium and phosphate were unchanged for all patients. All had a lower number of episodes or less severe hypotension and good control of ABB. No patients had metabolic alkalosis or worsened nutritional status. For all patients BF was an efficacious choice compared to CH, giving them good health.

Are lipid abnormalities reliable cardiovascular risk factors in dialysis patients?

Patients on chronic hemodialysis often present both hyperlipidemia and a high incidence of cardiovascular disease (CVD). Uremic hyperlipidemia has usually been regarded as one of the most important cardiovascular risk factors (CVRF) in these patients. In order to study whether the "uremia-induced" lipid abnormalities are actually associated with evidence of uremic CVD, and consequently may be considered reliable CVRF, 123 patients on chronic dialysis were reviewed for the presence of CVD and, at the same time, examined for their lipoprotein pattern and other clinical and biochemical variables. Lipids and lipoproteins did not prove helpful in our study in identifying patients with CVD. Despite the fact that they had been on dialysis for a shorter time, CVD patients were significantly older and had higher blood pressure than patients without CVD. Our data suggest that the uremia-induced lipid abnormalities are not reliable markers of CVD in dialysis patients, and support the hypothesis that dialysis per se does not accelerate the atherosclerotic process in uremic patients.

[Therapeutic effectiveness of bamifylline in elderly patients with COPD]. / Valutazione dell'efficacia terapeutica della bamifillina in pazienti anziani affetti da BPCO.

We studied the clinical and instrumental modifications of 20 patients (mean age: 67.95 +/- 1.23 years; 13 males, 7 females) suffering from COPD (less than 65% theoretical FEV1), during treatment with bamiphylline. At basal time, and after 1, 2, 3, 4, and 6 months of therapy we performed a clinical and spirometric examination. All spirometric parameters (FEV1, VC, MEF25-75, Tiffeneau Index) increased significantly (p less than 0.01 - ANOVA1) since the first control performed after 1 month of treatment. This trend was confirmed in the successive controls. Analogue results were observed for emogasanalytical (P-CO2-PO2) and clinical (cough and dyspnoea) parameters. During the experimental research we did not observe side effects due to the xanthine-derivative (bamiphylline) under study or modifications of the main haematochemical tests. Therefore we believe that bamiphylline must be considered an effective therapeutic tool for COPD therapy.

Chronic hemodynamic effects of propranolol treatment in dialysis-refractory hypertension.

The hemodynamic mechanism of the hypotensive effect of propranolol was studied by quantitative radiocardiography in 8 patients with dialysis-resistant hypertension. Propranolol treatment brought about a decrease in mean arterial pressure and peripheral vascular resistances. The cardiac index was slightly reduced only in the early stage of the treatment. No significant difference was found between patients on treatments lasting longer than 3 months and patients with dialysis-controlled hypertension. The results show that propranolol can be used safely as the sole antihypertensive agent in patients with dialysis-resistant hypertension.

The value of ultrasound as a screening procedure for urological disorders in renal failure.

Renal ultrasound was evaluated as a screening procedure for urological conditions (hydronephrosis or space-occupying lesions) in 175 patients (316 kidneys) with renal failure. The final diagnosis of renal disease was based on excretory urography, ascending or translumbar pyelography, open surgical findings, clinical and laboratory test results or renal biopsies. Ultrasonic images suggestive of renal disease requiring surgery were obtained in 83 kidneys and subsequently confirmed in 67. There were 16 falsely positive and 2 falsely negative results. Assuming a 22 per cent prevalence of renal disease requiring surgery in the azotemic population, Bayes' theorem predicts that an abnormal ultrasonic test will increase the probability of surgery in a patient with renal failure from 0.22 to 0.81, while a negative test will reduce the probability from 0.22 to 0.013. Renal ultrasound is a highly effective method to screen for patients with renal failure who require contrast studies. With this means the risks and cost of contrast investigations can be reduced markedly.

[Pulmonary tuberculosis in an immigrant population: the epidemiological aspects and clinical picture]. / La tubercolosi polmonare nella popolazione extracomunitaria: aspetti epidemiologici e quadri clinici di presentazione.

The number of extra European subjects coming to our country, in the last twenty years, is increased. This fact has contributed to enlarge the number of new cases of tuberculosis. In the present work we analyzed 54 extra European and 116 Italian patients with pulmonary tuberculosis observed in the last six years in our institute. The diagnosis was established by finding acid-fast bacilli in sputum and by clinical and radiographic patterns. We found that extra European subjects show disseminated and ulcerated forms in about 89% against approximately 40% viewed in Italian patients; while the cases of noncavitary tb in immigrants were about 11% against 60% in Italian population.

Leukocytes, eosinophils and complement function during hemodialysis with polysulphone and polymethylmethacrylate membranes: comparison with cuprophan and polyacrylonitrile.

The biocompatibility of the two new dialysis membranes, polysulphone (PS) and polymethylmethacrylate (PMMA), was evaluated versus cuprophan (CUP) and polyacrylonitrile (PAN) by studying the in vivo effects of the four different membranes on leukocyte counts, eosinophil levels and complement function both in the presence and absence of dialysis fluid. Complement function was also examined in vitro by studying the generation of chemotactic factors, whole complement activity and C3d serum conversion. Passive absorption of complement fractions by membranes has completed in vitro studies. PS, PMMA and PAN showed a higher biocompatibility than CUP, even if slight differences can be observed: PS showed a PAN-like biocompatibility pattern with a relatively high absorption of complement factors by the membrane and without complement activation. On the other hand, PMMA showed a CUP-like pattern and caused complement activation, even though to a lower intensity than CUP. PMMA biocompatibility appears to stand in-between CUP and the other two synthetic membranes PS and PAN. Our results confirm the important role played by membrane-induced complement activation on hemodialysis leukopenia. Dialysis fluid does not have a significant influence on membrane biocompatibility, but represents the major factor in determining intradialytic eosinopenia. Eosinophils seem to represent a more important marker of dialysis than of membrane biocompatibility.

Total antioxidant capacity (TAC): is it an effective method to evaluate the oxidative stress in uraemia?

Lipoprotein abnormalities are common in uraemia and are considered important factors for development of atherosclerosis and progression of renal disease. Reduction of total antioxidant capacity (TAC) and lipid peroxidation (LP) probably play a major role in both processes. The aim of this study was to assess the effect of renal function, dietary manipulation and lipids on TAC of uraemic patients with different chronic renal failure (CRF). Sixty patients (36M, 24F), aged 60 +/- 12 years were divided into five groups according to serum creatinine levels (sCr,mg/dl)--CRFI, 1.5-3; CRFII, > 3-5.5; CRFIII, > 5.5; CRFIV, > 3 on vegetarian supplemented diet (SD); CRFV haemodialysis patients (HD)- and investigated for TAC by enhanced chemiluminescent assay, autoantibodies against oxidized LDL (oxLDLAb), lipids, apolipoprotein AI, B, Lp(a) and uric acid (UA). The results were compared to a control group of 19 people (8M, 11F), aged 52 +/- 11 years with sCr < 1.5. TAC increased significantly with the progression of CRF and was strongly related to both sCr and UA. Lipids and SD did not show any influence on TAC. Unexpectedly, lipid peroxidation did not correlate to TAC, neither to sCr or UA. HD accounted for a mild reduction of both TAC and LP. Patients on SD showed a marked reduction of LP as compared to patients with a similar degree of renal failure (CRF-III) but on conventional diet. Our results suggest that elevated TAC in uraemia is likely to be dependent on increased UA levels and does not seem to induce an effective protection in vivo from oxidative stress. In conclusion, TAC does not appear to be a reliable method for assessing the oxidative susceptibility of CRF patients.

Autoantibodies against oxidized LDL in chronic renal failure: role of renal function, diet, and lipids.

Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure. The aim of this study was to evaluate the influences of renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in uremic patients either on conservative or replacement therapy. Seventy-one patients (42 males, 29 females) aged 60 +/- 19 years with chronic renal failure (CRF) of different etiology and degree were divided into four groups according to serum creatinine levels [sCr(mg/dl)] and diet: CRF I > or = 1.5-3.0, CRF II > 3.0-5.5, and CRF III > 5.5 were all patients on a conventional low-protein diet, while a fourth group included patients on a vegetarian diet supplemented with keto analogues and amino acids (CRF SD >3.0). A further group was represented by patients on dialysis therapy. All patients were examined for Ox-LDLAb, triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of 20 controls (9 males and 11 females) aged 52 +/- 11 years with sCr <1.5 mg/dl. Ox-LDLAb increased, although not significantly, with TG and Lp(a) from the early stages of CRF along with the deterioration of renal function. However, TG and Lp(a) levels were significantly higher in all groups of patients except those on vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No relationship was observed between lipids or apolipoproteins and Ox-LDLAb. Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics. Our results show a progressive increase of LP as the renal function declines, which may account for the increased risk of cardiovascular disease reported in uremia. Dialysis does not correct significantly the oxidative state observed in patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a), is supposed to decrease the risk of cardiovascular disease and worth being reconsidered as an alternative effective therapeutic tool in patients with advanced CRF.

Renal involvement in IgD myeloma.

Nine patients affected from IgD myeloma were studied retrospectively in order to elucidate the incidence and peculiar traits of related nephropathy. Eight patients developed chronic renal failure, and as many as 5 were already suffering from renal failure since first admission to the hospital. In 3 cases acute renal failure was the major presenting symptom of the disease. Five patients underwent a regular dialytic treatment. We suggest that the high incidence of renal involvement found in IgD myeloma is related to the high incidence of Bence-Jones proteinuria observed in this disease. Presenting atypical symptoms, among which renal failure is the most important, are misleading and characteristic of the disease. Survival time seems to be negatively influenced by the presence of renal failure at the time of diagnosis.

Hyperparathyroidism: is it really the major factor affecting glucose tolerance in uremia?

The effects of secondary hyperparathyroidism (sHPTH) on immunoreactive insulin (IRI) release and glucose (G) tolerance were studied in two groups of dialysis patients with normal (NPTH, n = 9) or elevated PTH levels (HPTH, n = 8), 27 +/- 24 and 660 +/- 440 pg/ml, respectively. The patients received an intravenous glucose tolerance test (IVGTT) using 0.33 g/kg of glucose solution. G, IRI and C-peptide (C-p) levels were determined calculating the G constant decay (K) and the relative incremental areas for each study. Regardless of PTH levels, all patients showed an impaired glucose tolerance (GT). IRI secretion and K values were not significantly different between the two groups. However, a significantly lower K value with a reduced (although not significant) early and late IRI secretion was found in the subgroup of patients with more severe. sHPTH (PTH: 560-1,500 pg/ml, n = 5) as compared to patients with moderate sHPTH (PTH: 87-341 pg/ml, n = 4) or normal (5-32 pg/ml, n = 8) PTH levels. No relationship was found between PTH and G, IRI or C-p levels. Our results point to a threshold limit for PTH's inhibitory effect on IRI secretion and suggest that other factors, known to affect IRI secretion and GT besides PTH levels, may modulate the role played by excess PTH levels on carbohydrate metabolism of dialysis patients.

Lipoprotein abnormalities in chronic renal failure and dialysis patients.

Lipoprotein abnormalities are common in patients with chronic renal failure (CRF) on either dialysis or conservative therapy. In order to investigate the changes in lipid and apolipoprotein pattern from early CRF to dialysis treatment, plasma lipids with apoproteins AI, B, E, CII, CIII, CII/CIII ratio, E/CIII ratio, parathyroid hormone (PTH) and insulin levels were examined in 72 patients with different degrees of CRF and 31 patients on hemodialysis (HD), and compared the values of 28 controls. A significant decrease in the Apo CII/CIII ratio was the earliest lipoprotein abnormality to occur in CRF. Hypertriglyceridemia (HTG) with reduced high-density lipoprotein cholesterol levels, increased Apo CIII and decreased Apo E/Apo CIII ratio only occurred in more advanced renal failure (creatinine clearance < 31 ml/min). HD patients showed a general worsening of the lipoprotein profile with elevated Apo E levels and indirect evidence of remnant accumulation. While PTH did not have any significant influence on lipoprotein pattern, increased insulin levels during HD might partly account for the HTG of these patients. Our results point to elevated Apo CIII, reduced Apo CII/Apo CIII and Apo E/ Apo CIII ratios as typical features of uremic hyperlipidemia and show that a defective triglyceride removal is the major pathogenetic mechanism of uremic HTG. HD treatment seems generally to worsen the lipid and apolipoprotein pattern observed in the predialytic stage of CRF.