Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients.

Vascular calcifications are frequent in chronic renal disease and are associated to significant cardiovascular morbidity and mortality. The long term predictive value of coronary artery calcifications detected by multi­layer spiral computed tomography for major cardiovascular events was evaluated in non­diabetic Caucasian patients on maintenance hemodialysis free of clinical cardiovascular disease. Two­hundred and five patients on maintenance hemodialysis were enrolled into this observational, prospective cohort study. Patients underwent a single cardiac multi­layer spiral computed tomography. Calcium load was quantified and patients grouped according to the Agatston score: group 1 (Agatston score: 0), group 2 (Agatston score 1­400), group 3 (Agatston score 401­1000) and group 4 (Agatston score >1000). Follow­up was longer than seven years. Primary endpoint was death from a major cardiovascular event. Actuarial survival was calculated separately in the four groups with Kaplan­Meier method. Patients who died from causes other than cardiovascular disease and transplanted patients were censored. The "log rank" test was employed to compare survival curves. One­hundred two patients (49.7%) died for a major cardiovascular event during the follow­up period. Seven­year actuarial survival was more than 90% for groups 1 and 2, but failed to about 50% for group 3 and to <10% for group 4. Hence, Agatston score >400 predicts a significantly higher cardiovascular mortality compared with Agatston score <400 (p<0.0001); furthermore, serum Parathyroid hormone levels > 300 pg/l were associated to a lower survival (p < 0.05). Extended coronary artery calcifications detected by cardiac multi­layer spiral computed tomography, strongly predicted long term cardiovascular mortality in nondiabetic Caucasian patients on maintenance hemodialysis. Moreover, it was not related to conventional indices of atherosclerosis, but to other non­traditional risk factors, as serum Parathyroid hormone levels. A full cost­benefit analysis is however necessary to justify a widespread use of cardiac multi­layer spiral computed tomography in clinical practice.

Renal resistive index and long-term outcome in chronic nephropathies.

PURPOSE: To assess the clinical validity of renal resistive index (RI) to determine prognosis and guide therapy over a long-term follow-up in patients with chronic nephropathies and to verify the commonly used threshold value of 0.70. MATERIALS AND METHODS: Of patients referred to the nephrology center since 1995, 177 were initially enrolled and 86 were followed up for RI and renal function annually for 2-11 years (mean, 5.93 years +/- 2.92 [standard deviation]). All patients gave informed consent for the institutional review board-approved study. Correlations were determined between initial RI and age, estimated glomerular filtration rate (eGFR), proteinuria, hematuria, blood pressure, and biopsy scores. The sample was categorized in four groups on the basis of whether initial values of RI and eGFR were normal, and progression to renal failure was compared. With grouping of the sample by using initial RI (< or =0.61, 0.62-0.69, and > or =0.70), Kaplan-Meier analysis was used to obtain survival curves. RESULTS: Initial RI correlated with final eGFR (R = -0.4, P < .001), systolic blood pressure (R = 0.39, P < .001), proteinuria (R = 0.28, P = .009), and age (R = 0.28, P = .007). In stepwise multiple regression analysis, RI emerged as the only independent risk factor for the progression to renal failure (P < .001). Among the four groups of patients with different initial RIs and eGFRs, the group with an initial RI of 0.70 or higher showed a worse outcome, independent of initial eGFR. In the Kaplan-Meier analysis by using initial RI, only the group with a value of 0.70 or higher showed a rapid decline of renal function (>50% decrease in eGFR in 6 years). CONCLUSION: An RI of 0.70 or higher is predictive of an unfavorable outcome in patients with chronic nephropathies.

Homocysteinemia correlates with plasma thiol redox status in patients with end-stage renal disease.

BACKGROUND/AIMS: In end-stage renal disease (ESRD), hyperhomocysteinemia is a common finding associated with increased cardiovascular risk. However, the pathogenic role of homocysteine is still unclear. In vitro studies show that thiol redox status affects endothelial cell functions. We therefore investigated the possible association between homocysteinemia and plasma thiol redox status in ESRD patients. METHODS: Total plasma homocysteine (Hcy), cysteine (Cys) and free thiols (SH) were measured both before and after a dialytic session in 54 ESRD patients receiving (n = 15) or not receiving (n = 39) folate supplementation, and 17 control subjects. RESULTS: High predialysis levels of both Hcy and Cys were found to be negatively correlated with low SH levels both in supplemented (r = -0.680, p < 0.01 and r = -0.624, p < 0.02, respectively) and unsupplemented (r = -0.698, p < 0.001 and r = -0.445, p < 0.01, respectively) patients. Following dialysis, SH values returned to normal and the above correlations were no longer appreciable. CONCLUSION: A strong, folate therapy-insensitive association between homocysteinemia and plasma free thiol levels was found in ESRD patients. These results support a role for oxidative stress in ESRD-related hyperhomocysteinemia and suggest the plasma thiol redox status alteration as a possible pathogenic mechanism underlying the cardiovascular toxicity of hyperhomocysteinemia in these patients.

Reliability of oxidative stress biomarkers in hemodialysis patients: a comparative study.

BACKGROUND: Oxidative stress (OS) is considered to play a major role in the development of end-stage renal disease (ESRD) complications. However, conflicting and inconsistent data have been reported on OS in ESRD patients. Our aim was to investigate the reliability of the most popular non-enzymatic plasma OS biomarkers in ESRD. METHODS: Vitamins A (VitA), E and C (VitC), uric acid, plasma antioxidant and ferric-reducing potential (PAP and PRP), thiols (SH), malondialdehyde (MDA) and lipid hydroperoxides (HPO) were determined before and after dialysis in plasma from 33 ESRD patients on hemodialysis, hemodiafiltration or peritoneal dialysis and 20 control subjects. RESULTS: In ESRD patients, high PRP and normal PAP values were positively correlated with VitC levels. After dialysis, PRP levels decreased, while unchanged PAP levels correlated positively with high VitA and transiently recovered SH values. All patients showed high levels of both MDA and cholesterol-normalized HPO. However, while the former significantly decreased after dialysis, the latter were unaffected by treatment. Paradoxical correlations of MDA with both VitA and HPO were found. CONCLUSIONS: Plasma PRP and MDA levels may be dramatically affected by both uremia and dialysis; their use in ESRD patients may therefore lead to OS misevaluation and should be avoided. More reliable results can be obtained using physiologically relevant OS functional tests, such as PAP, and early biomarkers of OS damage, such as SH and HPO.

Are PTH serum levels predictive of coronary calcifications in haemodialysis patients?

BACKGROUND: Cardiac calcifications are a frequent occurrence in uraemic subjects and are probably connected to the increased cardiovascular mortality of haemodialysis patients. There is substantial support to the hypothesis that low levels of serum PTH in haemodialysis patients are associated with increased vascular and cardiac calcium deposits, due to decreased buffering capacity of bone in low turnover osteodystrophy. The present study has been carried out on a cohort of patients on haemodialysis, with exclusion of previously parathyroidectomized patients, with the aim to evaluate the association between PTH serum levels and coronary calcifications. METHODS: The study has been carried out in a cohort of 197 haemodialysis patients. There were 133 males and 64 females. Twenty-two patients had diabetes mellitus. Average age was 58.6 +/- 12.9 years. Patients were divided into groups of intact PTH levels, 0-150 (A), 150-300 (B), 300-600 (C) and >600 (D) pg/ml. RESULTS: The values of coronary scores in the PTH groups were as follows: (A) 624.7 +/- 939, (B) 866.4 +/- 1080, (C) 1202.8 +/- 1742.3 and (D) 1872.7 +/- 2961.9. The difference between coronary calcium scores was significant (P < 0.01). A general linear model identified serum calcium and dialysis age as independent factors of calcium deposits in the high PTH group. CONCLUSIONS: No prominent association between low PTH serum levels and the severity of coronary calcium deposits in haemodialysis patients was found while increased levels of PTH, with special regard to very elevated levels, associated with more frequent hypercalcaemia and hyperphosphataemia, should be considered a major risk factor of coronary calcifications and cardiac events.

Cardiac calcifications: Fetuin-A and other risk factors in hemodialysis patients.

Cardiac calcifications are a frequent finding in hemodialysis for chronic renal failure. Several factors may play a role in the intimal and medial calcification of coronary arteries such as age and some known atherogenetic factors. In addition, Fetuin-A has been proposed as a protective agent through solubilization of calcium phosphate salt. Fetuin-A is also a marker of inflammatory-nutritional state, and its changes could be an expression of this condition. The aim of this cross-sectional study is to evaluate the relative importance of risk factors of calcifications with special regard to Fetuin-A. The study was conducted with 132 hemodialysis patients. They were subjected to multislice computed tomography for evaluation of calcium deposits in the heart. In addition, the patients were sampled for evaluation of calcium-phosphate parameters, lipid profile, nutritional and inflammatory markers, and also Fetuin-A. There was a wide variability of the extent of calcium deposits expressed as Agatston score, with only 9.3% of patients without calcifications. Age, hemodialysis age, sex, calcium-phosphate parameters, and lipid profile were important risk factors, together with nutritional and inflammatory status of the patients. An inverse correlation between coronary calcium score and Fetuin-A emerged from a multiple regression analysis. However, there was no significant difference in serum Fetuin-A among different grades of calcium score. By dividing the patients in tertiles of serum Fetuin-A, an association between low levels of Fetuin-A and high calcification score was found. Fetuin-A as dependent variable was strictly linked to prealbumin serum levels. In addition, there was a clear link between cardiac calcification scores and inflammatory-nutritional markers. Serum calcium and treatment with calcitriol emerged as predictive variables of coronary score.Fetuin-A could be involved in the process of calcification both in the case of markedly low serum levels, due to decreased prevention of calcium phosphate precipitation, and also as a marker of inflammation, a well-known risk factor of atherogenesis. Treatment with intravenous calcitriol could marginally enhance cardiac calcifications, probably through its hypercalcemic effect.

Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes.

BACKGROUND: Treatment with folic acid and vitamin B12 appears to be effective in lowering total plasma homocysteine (tHcy) concentrations, but whether vitamin B12 alone lowers tHcy in patients with normal vitamin B12 status is unknown. The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B12 on tHcy concentrations in hemodialysis (HD) patients and to compare changes in tHcy concentrations with MTHFR genotype. METHODS: We recruited 200 HD patients (119 men) from the "Umberto I" Hospital (Frosinone, Italy) and the Dialysis Unit of University Hospital "Tor Vergata". These patients were randomized blindly into 2 groups of 100 each. Unfortunately, during the study, 36 patients in the first group and 16 in the second group died. The first group was treated initially with vitamin B12 for 2 months and with folic acid for a following 2 months. The second group was treated initially with folic acid and then with vitamin B12. Samples were drawn before administration of either, after the first and second periods, and again 2 months after treatment. RESULTS: The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies, and the decrease was genotype-dependent. The decrease was greater for the T/T genotype (P <0.05) and was more significant when the treatment was started with folic acid (P <0.01). CONCLUSION: The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B12 in lowering tHcy in HD patients.

Selective adsorption of homocysteine using an HFR-ON LINE technique.

HFR-ON LINE (double chamber HDF with reinfusion of ultrafiltrate regenerated through a charcoal-resin cartridge) is a novel method which combines the processes of diffusion, convection, and adsorbance. We have investigated the effect of such a treatment on the homocysteine (Hcy) levels in ten patients with a mean Hcy level of 57.6 micromol/L (range 24.1-119.7 micromol/L). We have measured the Hcy, folate, and vitamin B12 predialysis and postdialysis, and in the ultrafiltrate precartridge and postcartridge at 10, 120, and 240 min. The mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3 micromol/L) (P = 0.005) predialysis and postdialysis, respectively, while folate and vitamin B12 were unchanged. Precartridge and postcartridge Hcy levels were 11.6 vs. 2.5 micromol/L (P = 0.005), 9.3 vs. 3.9 micromol/L (P = 0.005), and 7.7 vs. 4.6 micro mol/L (P = 0.012) at the three time points considered, while folate and vitamin B12 were essentially undetectable. These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR-ON LINE is able to reduce Hcy levels not only through a likely reduction of uremic toxins, but also through an actual removal of Hcy by adsorbance onto the charcoal-resin cartridge.

Cardiac troponin I (2nd generation assay) in chronic haemodialysis patients: prevalence and prognostic value.

BACKGROUND: Elevated serum cardiac troponin T (cTnT) levels are frequently observed in chronic dialysis patients and have been shown to be associated with increased morbidity and mortality. The aim of this study was to determine whether cardiac troponin I (cTnI), which is less frequently elevated, has similar clinical significance. METHODS: We studied 101 asymptomatic patients with no clinical evidence of coronary artery disease who were undergoing chronic dialytic treatment. We measured their serum cTnI levels immediately before the start of their dialysis sessions by a second-generation assay (OPUS-DADE). Our study included a year-long follow-up with trimestrial cTnI assays as well as clinical, X-ray and echocardiographic surveillance. We considered patients with serum cTnI > or =0.15 ng/ml as positive and those with levels <0.15 ng/ml as negative. RESULTS: Among the 14 patients with high serum cTnI levels, nine (64%) suffered acute cardiac events during the 12-month follow-up. In contrast, among the 72 patients with low cTnI levels only seven (9.7%) had acute events. In another group of 15 patients with variable cTnI levels, three patients (20%) had cardiac events. CONCLUSION: Based on these results, serum cTnI appears to be a valuable predictive marker of cardiovascular events in asymptomatic dialysis patients. For those patients who might benefit from thorough cardiac investigation and treatment, information on cTnI could be useful in preventing cardiac events.