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C Zoccali

Publications and source records attributed to C Zoccali.

At least 37 records · Page 2Linked to original sources
PubMed2001

Autonomic neuropathy is linked to nocturnal hypoxaemia and to concentric hypertrophy and remodelling in dialysis patients.

BACKGROUND: Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients. METHODS: To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day. RESULTS: Twenty-five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of concentric remodelling or hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term. CONCLUSIONS: Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to concentric hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one.

Adult↗
PubMed2001

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.

Anemia↗
PubMed2001

Long-term CAPD patients are volume expanded and display more severe left ventricular hypertrophy than haemodialysis patients.

BACKGROUND: Whether hypertension and left ventricular hypertrophy (LVH) are more prevalent in CAPD than in haemodialysis (HD) patients is still under discussion. METHODS: To examine this problem we compared a group of 51 CAPD patients, with a group of 201 HD patients. The evaluation included the measurement of atrial natriuretic peptide (atrial natriuretic factor (ANF)), taken as indicator of volume status, and echocardiographic measurements. RESULTS: CAPD patients were older, had been treated for a shorter time, and had lower serum albumin and phosphate than HD patients. Plasma ANF was higher (P<0.01) in CAPD (median 33.8 pmol/l (interquartile range 18.2-63.0)) than in HD patients (22.7 pmol/l (14.9-38.7)). Similarly, the left atrial volume was substantially higher (P<0.0001) in CAPD patients (49+/-22 ml) than in HD patients (37+/-17 ml), while the left ventricular end-diastolic diameter was similar in the two groups (CAPD 51+/-7 mm; HD 50+/-7 mm). Furthermore, left ventricular hypertrophy was more severe (P<0.0001) in CAPD (157+/-37 g/m(2)) than in HD patients (133+/-39 g/m(2)). The proportion of CAPD patients requiring antihypertensive drugs was markedly higher than that of HD patients (65 vs 38% P<0.001). Multivariate modelling showed that volume expansion and pressure load as well as serum albumin were independent predictors of left ventricular mass. CONCLUSIONS: Left ventricular hypertrophy is more severe in long-term CAPD patients than in HD patients. This finding is associated with evidence of more pronounced volume expansion, hypertension, and hypoalbuminaemia. Volume and pressure load along with factors associated with hypoalbuminaemia may aggravate LVH in uraemic patients on CAPD.

Aged↗
PubMed2001

Left ventricular hypertrophy and nocturnal hypoxemia in hemodialysis patients.

OBJECTIVE: Nocturnal hypoxemia has recently been proposed as a cardiovascular risk factor in patients with chronic renal failure. In this study we have tested the hypothesis that this disturbance is associated with left ventricular hypertrophy (LVH) in dialysis patients. METHODS: During a mid-week non-dialysis day, 38 hemodialysis patients underwent continuous monitoring of arterial O2 saturation (SaO2) during night-time as well as 24 h ambulatory blood pressure monitoring and echocardiography. RESULTS: Eighteen patients had one or more episodes of O2 desaturation during night-time (average: 21 episodes; range 1 to 120) while the other 20 had no episode. Neither day-time arterial pressure nor heart rate were significantly associated with nocturnal hypoxemia. However there was a significant correlation between the night/day systolic ratio and the severity of hypoxemia during night-time (r = 0.36, P = 0.03). On multivariate analysis, nocturnal hypoxemia proved to be the stronger independent predictor of relative wall thickness, mean wall thickness and left ventricular mass index, suggesting that nocturnal O2 desaturation is linked to concentric hypertrophy and to concentric geometry of the left ventricle. Accordingly, the proportion of patients with such geometric alteration was higher (chi2 = 4.1, P = 0.04) in patients with a pulse oximetry severity score > 50th percentile [15 of 19 (79%)] than in those below this threshold [nine of 19 (47%)]. CONCLUSIONS: Nocturnal hypoxemia is an important correlate of LVH in hemodialysis patients. Such an association is largely independent of arterial pressure. These data further underscore the importance of disturbed respiratory control as a cardiovascular risk factor in dialysis patients.

Adult↗
PubMed2001

Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.

Adolescent↗
PubMed2000

Gender-dependent differences in plasma leptin in essential hypertension.

Leptin, the gene product of the ob gene, is influenced by gender and insulin sensitivity. Because in human hypertension there are important endocrine-hemodynamic gender-dependent differences, we compared plasma leptin in 39 essential hypertensives (EH) and in 27 normotensive healthy subjects (HS) matched for gender, age, and fat mass. Fat mass was measured by bioelectrical impedance analysis (BIA), plasma leptin by a sensitive radioimmunoassay RIA (intraassay CV < 6%), and insulin sensitivity by the HOMA-R index. Both in essential hypertensives and in normotensive subjects plasma leptin was consistently higher in females than in males and was strictly related to fat mass. Gender differences in plasma leptin were not explained by differences in fat mass. Separate analysis of data by gender showed that leptin was significantly higher (P < .05) in hypertensive men (median, 5.4 ng/mL; interquartile range, 4.1-9.5) than in normotensive men (4.6 ng/mL, 2.6-7.4) whereas it was identical in hypertensive and normotensive women. In essential hypertensives, in a multiple regression model only fat mass, gender, and the HOMA-R index were independently linked to plasma leptin. Similarly, fat mass and gender were independent predictors of plasma leptin in normotensive subjects. In the combined group of hypertensive and normotensive men, heart rate as well as systolic and diastolic pressure were univariate predictors of leptin. However, in a multivariable model only heart rate was independently related to leptin, and neither systolic nor diastolic pressure contributed significantly to explain the variability in plasma leptin. No relationship was found between leptin and heart rate or systolic or diastolic pressure in women. These results support the notion that leptin may participate in the gender-dependent variability of human hypertension.

Female↗
PubMed2000

The deletion polymorphism of the angiotensin-converting enzyme is associated with nephroangiosclerosis.

The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression. The association of this allele with nephroangiosclerosis has been scarcely investigated. We have tested this association in 45 hypertensive patients (all whites) with well defined nephroangiosclerosis (diagnosis established on the basis of renal biopsy in all cases) and moderate to severe renal failure. As studies of genetic association of small size often produce conflicting results, besides a control group of 343 Italian patients with essential hypertension and normal renal function, we elected to use also a very large control group of race-matched subjects taken from a meta-analysis of 27,565 whites. The proportion of patients with the D allele (64%) was higher in patients with nephroangiosclerosis than that in Italian hypertensives (54%) and in whites (54%). DD and DI genotypes were more prevalent in patients than in control groups. The dominant model (DD and DI v II: nephroangiosclerosis v Italian controls: chi2 = 6.19, P = .012; nephroangiosclerosis v whites chi2 = 6.86, P = .009) fitted the data better than the codominant and the recessive model (P < or = .022). The D allele is associated with nephroangiosclerosis with a dominant effect in the sample of patients studied. Although intervention studies are needed to see whether these findings imply a causal association, our data suggest that this allele may at least act as disease marker in nephroangiosclerosis.

Adult↗
PubMed2000

ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1.

UNLABELLED: ACE genotype and ACE induced renoprotection in chronic proteinuric nephropathies. BACKGROUND: Whether angiotensin-converting enzyme (ACE) gene polymorphism affects disease progression and response to ACE inhibitor therapy in nondiabetic proteinuric nephropathies is not clearly established. METHODS: The relationship between insertion/deletion (I/D) genotypes and proteinuria, rate of glomerular filtration rate decline (DeltaGFR)-centrally evaluated by repeated measures of iohexol plasma clearance-and incidence of end-stage renal disease (ESRD) was prospectively evaluated in 212 patients with nondiabetic proteinuric chronic nephropathies enrolled in the Ramipril Efficacy in Nephropathy (REIN) trial, where patients were randomly assigned to ramipril or conventional treatment. RESULTS: The DeltaGFR +/- SEM (-0.38 +/- 0.09 vs. -0.50 +/- 0.08 vs. -0.36 +/- 0.06 mL/min/1.73 m2 per month) and incidence of ESRD (19 vs. 22 vs. 25%) in the three subgroups with the II, ID, and DD genotypes, respectively, were comparable. Of note, DeltaGFR (-0.28 +/- 0.07 vs. -0.43 +/- 0.09 mL/min/1.73 m2 per month) and incidence of ESRD [14% vs. 36%, P = 0.04, RR (95% CI), 2.62 (1.02 to 6.71)] were lower in ramipril than in conventionally treated patients in the DD genotype, but not in the II and ID genotype. Either at univariate (P = 0.04) or at multivariate (P = 0.01) analysis, ramipril significantly predicted a lower incidence of events in DD, but not in II and ID patients. At three months, ramipril decreased proteinuria more effectively in DD (-38.2%) than in the II (-26.7%) or ID (-19.2%) genotype. In DD (but not in II or ID) ramipril-treated patients, a short-term reduction in proteinuria correlated with DeltaGFR over the entire follow-up period (P = 0.02, r = -0.41). CONCLUSIONS: In nondiabetic proteinuric nephropathies, the ACE I/D polymorphism does not predict disease progression, but is a strong predictor of ACE inhibition-associated renoprotection in that proteinuria, DeltaGFR, and progression to ESRD are effectively reduced in patients with the DD, but not in those with the II or ID genotype.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Hepatocyte growth factor predicts survival and relates to inflammation and intima media thickness in end-stage renal disease.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in tissue protection and repair in the endothelium and various organ systems. The serum concentration of this protein is markedly increased in patients with chronic renal diseases, but the clinical and pathophysiological correlates of this substance in renal failure are scarcely understood. Serum HGF, lipid, albumin, hemoglobin, C-reactive protein (CRP), and immunoglobulin G (IgG) were measured in fasting conditions in a cohort of 244 dialysis patients. In addition, the relationship between HGF and severity of carotid atherosclerosis was studied in a subgroup of 105 patients. The entire cohort was followed up for a median of 31 months (interquartile range, 21 to 34 months). Serum HGF level was directly related to duration of dialysis treatment, CRP level, age, IgG level, and hemoglobin level and inversely related to systolic and diastolic arterial blood pressure. In a multiple regression model, only duration of dialysis treatment (r = 0.38), age (r = 0.26), hemoglobin level (r = 0.17), IgG level (r = 0.15), and CRP level (r = 0.14) were independent correlates of serum HGF level (R = 0.54; P < 0.0001), suggesting that increased levels of serum HGF may be the expression of a chronic inflammatory process. HGF levels were greater in hemodialysis than continuous ambulatory peritoneal dialysis patients, independent of the type of dialysis membrane, and slightly increased in patients seropositive for hepatitis C virus. In the subgroup of patients who underwent echo color Doppler studies, serum HGF level was an independent correlate of intima media thickness (IMT; partial r = 0.23; P = 0.02). In the entire cohort, increased HGF levels predicted shorter survival in a multivariate Cox regression model. These results support the hypothesis that in patients with chronic renal failure, increased serum HGF level is linked to an inflammatory state. The relationships between HGF level and survival and IMT suggest that this cytokine might be a marker of a process that has a major impact in the high mortality and morbidity of the dialysis population.

Analysis of Variance↗
PubMed2000

AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.

Advanced glycation end products (AGEs) may be involved in the pathogenesis of complications of chronic renal failure. Pentosidine, a carbohydrate-derived AGE, is considerably elevated in uraemic patients. This compound per se has no biological activities but is highly correlated to the levels of precursors of carbonyl compounds, and for this reason is considered a reliable surrogate marker for AGEs. The modification of proteins in uraemia is not limited to AGEs, since advanced lipoxidation end products are also demonstrable in plasma proteins in uraemia. The accumulation of these compounds does not seem to be dependent only on the decline of renal function. Carbonyl precursors of AGEs and advanced lipoxidation end products are markedly elevated in uraemic patients. On this basis, the 'carbonyl stress' theory has been formulated. This theory holds that increased oxidation of carbohydrates and lipids and/or inadequate detoxification of carbonyl compounds may contribute to long-term complications of end-stage renal disease such as dialysis amyloidosis and cardiovascular diseases. Preliminary cross-sectional studies in haemodialysis patients seem to indicate that the AGEs and carbonyl stress may be involved in the pathogenesis of alterations in left ventricular geometry and function in these patients.

Arginine↗
PubMed2000

ACE and alpha-adducin genotypes and renal disease progression.

In the REIN study of non-diabetic proteinuric nephropathies, renal disease progression was independent of the angiotensin-converting enzyme (ACE) and alpha-adducin genotypes. However, the ACE genotype predicted the renoprotective effect of ACE inhibition. Subgroup analysis in patients with Berger disease showed a tendency (NS) for a faster progression in DD homozygotes.

Calmodulin-Binding Proteins↗
PubMed2000

Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators. Cardiovascular Risk Extended Evaluation in Dialysis Patients.

OBJECTIVE: To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis. DESIGN: A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis). METHODS: Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient RESULTS: One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers. CONCLUSIONS: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

Adult↗
PubMed2000

The salt epidemic: old and new concerns.

Salt is the most suspected environmental factor which may influence arterial pressure. The recent demonstration that in the chimpanzee there is a strict dose-response relationship between salt added to food and arterial pressure and that the large majority of these animals are "salt-sensitive" is solid proof that salt has a central importance in arterial hypertension. The behavioral complexity of mankind is such that the issue of salt sensitivity is very difficult to study in man. This is probably the main reason why all attempts to validate the arterial pressure response to tests of salt sensitivity based on changes in salt intake have produced negative or inconclusive results. However our inability to reliably identify salt-sensitive individuals in no way implies that the pressor effect of salt is evenly distributed in the population or that it is intrinsically so variable that the scientific efforts aimed at defining its nature are bound to fail. We envisage that in the near future the individual "salt-sensitive risk profile" will be calculated on the basis of new scientific knowledge about hypertension genes and environmental risk factors influencing the pressor response to salt. The link between target organ damage and salt is even stronger than that between arterial pressure and salt. Left ventricular mass is closely related to salt intake. In the kidney there is evidence that high salt intake induces hyperfiltration and raises glomerular pressure. Of note the damaging potential of salt to the heart and the kidney seems to be largely independent of the ongoing arterial pressure response. A widespread reduction in salt intake at population level might in theory produce major health benefits but it seems unlikely that major public health actions will be undertaken in the near future.

Blood Pressure↗