Are traditional risk factors valid for assessing cardiovascular risk in end-stage renal failure patients?

Aim: Cardiovascular diseases (CVD) are the major cause of morbidity and mortality in end-stage renal failure (ESRF). Establishing whether traditional risk factors are valid predictors of CVD in ESRF is important in order to devise preventive and interventional strategies for the ESRF populations. Methods: In this retrospective cohort study, a cohort of patients on dialysis were examined between September 2000 and February 2001. Only those without previous CVD events at baseline were included. For each individual, 5 year CVD risk was calculated using the New Zealand 5 year CVD risk prediction charts based on the Framingham Heart Study prognostic algorithm. The subsequent 5 year CVD outcome for each patient was determined and the observed rate of first CVD events was compared to the predicted risk. Relation of individual risk factors with the CVD outcome was also assessed. Results: Of the patients, 274 were without previous CVD events at baseline and 27% experienced CVD events during the subsequent 5 years. Observed CVD risk was more than twofold that of predicted risk although there was a linear correlation between the two. Among individual risk factors, increasing age, diabetes and smoking were significantly related to the incidence of the CVD events but, unlike in the general population, systolic blood pressure, total cholesterol/high-density lipoprotein ratio and body mass index were not significantly related to CVD events. Conclusion: The very high incidence of CVD in ESRF patients suggest that non-traditional risk factors present in the uraemic state are independent risk factors for CVD in ESRF patients. Nevertheless, the application of traditional cardiovascular risk profiles does allow risk stratification of the ESRF population.     

Are conventional cardiovascular risk factors predictive of two-year mortality in hemodialysis patients?

BACKGROUND: In general population hypertension, diabetes mellitus, overweight, hyperlipidemia and smoking are well-established risk factors for cardiovascular disease. However, the effect of these conventional risk factors on cardiovascular disease and mortality of patients on hemodialysis is not well understood. Indeed, some risk factors such as high blood pressure, hyperlipidemia and excess weight have been recently claimed to correlate with improved survival. OBJECTIVE: This study was undertaken to define the prevalence of these conventional risk factors in 453 hemodialysis patients, predominantly African-Americans, to determine their influence on two-year survival. RESULT: High cholesterol was found in 30% of the patients, high LDL-cholesterol in 25% and high triglycerides in 16%. Lipoprotein(a) (LP(a)) was elevated in 68% of the patients. 31% of our patients had predialysis mean arterial blood pressure (MAP) over 114, and 25% were obese based on a body mass index (BMI) over 30, 26% were diabetic and 25% were active smokers. Smoking was more common among our male and Caucasian patients. The aggregate score for the risk factors were 2.4+/-0.1 per patient, which increased to 3.2+/-0.1 in patients with obesity or diabetes, to 3.0+/-0.1 with hypertension and to 2.8+/-0.1 with active smoking. In multivariate Cox model analysis, prealbumin, body weight and blood pressure showed a positive correlation with two-year survival whereas diabetes mellitus had a negative correlation. Hyperlipidemia did not correlate to patients' two-year mortality. Smoking was associated with higher mortality, but that did not reach statistical significance. CONCLUSION: Conventional risk factors at least over a two-year period do not readily account for the higher mortality of a group of predominantly African-American patients on hemodialysis. The lack of prediction is speculated to be partly due to the overriding beneficial effects of better nutrition and due to the presence of other yet to be well-defined factors such as hyperhomocysteinemia, oxidative stress, coronary calcification, hitherto unidentified uremic toxins or a combination of these factors.     

Male–female differences in the risk of tuberculosis in dialysis patients

Aim  To define any gender-related differences in the prevalence and risk for tuberculosis (TB) in hemodialysis (HD) patients. Methods  All active TB cases were recorded during a 36-month follow-up of 272 (193 male and 79 female) HD patients. Entering the study, HD patients were tested with tuberculin and 2,4-dinitrochlorobenzene, and a cell-mediated immunity (CMI) index was estimated. Relative risks (RR) for TB were calculated considering subjects from the background general population as a reference group. The independent effect of age, BMI and tuberculin sensitivity was determined using Cox’s proportional hazard model. Results  Female HD patients presented significantly lower CMI indices and rates of positive Mantoux tests, but higher rates of DM, as compared to males. The male:female ratio in TB for the general and HD patients population was 1.8 and 0.6, respectively. There was a significantly lower TB prevalence in male as compared to female HD patients (7.7% vs. 11.3%), and a subsequent female predominance in risk for TB in those HD patients aged <49 and 50–69 years (M:F adjusted relative risk 0.67 and 0.53) was recorded. Conclusions  In contrast to the general population, there is a female predominance among dialysis TB patients younger than 70 years associated with the coexistence of DM. Female gender should always be considered as a risk factor when evaluating diabetic HD patients for active TB.     

A green light for troponin T in the cardiovascular risk stratification of continuous ambulatory peritoneal dialysis patients?

Troponin T is specifically qualified as a predictor of circulatory overload in peritoneal dialysis (PD) patients. Given the good standardization and the high reproducibility of the troponin T assay, this measurement may prove useful in the clinical management of PD patients. It still remains to be tested whether clinical policies incorporating troponin T may actually produce better outcomes in PD patients.     

Intima–media thickness measurements in children with cardiovascular risk factors

Measuring intima–media thickness (IMT) is now a standard diagnostic procedure in assessing cardiovascular risk and hypertensive target-organ damage (TOD) in adults. There is also an increasing number of pediatric publications evaluating IMT in children from high-risk groups, such as those with arterial hypertension, diabetes, chronic kidney disease, obesity, dyslipidemia, and homocystinurias. It has been shown that carotid IMT is strongly related with other markers of TOD in children with arterial hypertension and with metabolic cardiovascular risk factors. In children with coarctation of the aorta, carotid IMT correlated both with blood pressure and even with mild residual aortic gradient. On the other hand, studies in children with high cardiovascular risk have shown that normalization of blood pressure and metabolic abnormalities led to regression of arterial changes and decrease of IMT. Although not yet accepted as standard pediatric procedure, IMT measurement is emerging as a promising method of assessing TOD and cardiovascular risk and monitoring treatment efficacy. From a practical point of view, clinical utility of IMT measurements seems to be similar to use of echocardiography in assessing left ventricular mass. However, IMT measurements in children and adolescents should be standardized to avoid bias caused by the use of different measurement methods.     

Apelin: a peptide involved in cardiovascular risk in hemodialysis patients?

Inflammation, oxidative stress, and obesity are important features associated with pathogenesis of cardiovascular disease, a major contributor to the mortality of hemodialysis (HD) patients. Apelin is an adipokine involved in a variety of physiological functions; however, little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyze apelin plasma levels in HD patients and verify whether there is any relationship with inflammation, oxidative markers, and obesity. Twenty-four HD patients [53.6 ± 14.4 years, 14 men, and body mass index (BMI) of 25.0 ± 4.2 kg/m(2)] were studied and compared with 15 healthy subjects (51.3 ± 13.5 years, 7 men, and BMI of 26.3 ± 3.7 kg/m(2)). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay method. Plasma electronegative low-density lipoprotein [LDL(-)] levels were measured using ELISA method, and tumor necrosis factor-α, interleukin-6, leptin, and plasminogen activator inhibitor-1 levels were measured by a multiplex assay kit. C-Reactive protein (CRP) was determined by immunoturbidimetry. Anthropometric data were also evaluated. There was no difference between apelin-36 levels in HD patients (0.82 ± 0.60 ng/mL) and healthy subjects (0.83 ± 0.23 ng/mL). In contrast, apelin-12 levels were significantly higher in patients (0.34 ± 0.15 ng/mL vs. 0.24 ± 0.13 ng/mL in healthy subjects). TNF-α, CRP, and LDL(-) levels were higher in patients; however, there was no correlation among apelin-12 or -36 and inflammatory or oxidative markers. The adiposity parameters were also not associated with apelin-12 or -36. In conclusion, plasma apelin seems to be not associated with cardiovascular risk in HD patients.     

Cardiac medications and their association with cardiovascular events in incident dialysis patients: cause or effect?

BACKGROUND: There are no large randomized, controlled trials evaluating the efficacy of common cardioprotective medications on cardiovascular outcomes in the dialysis population. We aimed to determine the association between cardioprotective medications and a composite end point of cardiovascular events or death in an incident dialysis cohort. METHODS: Medicare claims data were utilized to determine outcomes in participants of the Dialysis Morbidity and Mortality Wave 2 cohort. Information was gathered at baseline regarding demographics, comorbidities, medication use, and lab data. Cox proportional hazard models were developed to determine the association between cardioprotective medication use at baseline and the subsequent development of a composite of cardiovascular events or death. RESULTS: Two thousand two hundred thirty-four of 3044 individuals experienced a cardiovascular event or death. Use of the following medications at baseline was associated with an increased event rate: nitrates, antiplatelet agents, and warfarin. There was no association between the use of angiotensin-converting enzyme inhibitors, beta-blockers, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and a composite cardiovascular outcome or death. Only use of a calcium channel blocker at baseline was associated with a reduced risk of events. This beneficial association did not persist when death was excluded as an outcome. Many of the associations observed varied substantially depending on the outcome utilized. CONCLUSION: Use of cohort data to determine an association between medication use and outcome is difficult because the indication for the medication confounds the observed association. Before widespread practice changes, rigorous clinical trials of common cardioprotective medications on cardiovascular morbidity and mortality in dialysis should be performed.     

Can the DOQI guidelines be met by peritoneal dialysis alone in pediatric patients?

DOQI guidelines recommend minimal standards for automated peritoneal dialysis (APD), with a weekly Kt/V of 2.1 and creatinine clearance (C _Cr) of 63 l/1.73 m². The purpose of this study was to assess if the DOQI guidelines could be met by dialysis alone in children on PD. Dialysis clearance studies were retrospectively analyzed in 20 pediatric patients on APD, all with a dwell volume of at least 1,000 ml/m². Mean dialytic Kt/V was 2.0; only 45% had a Kt/V above the recommended 2.1. Mean dialytic C _Cr was 43.5 l/week per 1.73 m²; only 10% achieved a C _Cr above the recommended 63 l/week per 1.73 m². Despite the significant correlation between total therapy volume (TTV) and both Kt/V and C _Cr, only 2 of 10 patients with a TTV over 10 l/m² per day reached the target C _Cr. All patients had currently recommended dwell volumes, therapy times, and nocturnal cycles, but DOQI guidelines were difficult to achieve with dialysis alone. Strict adherence to DOQI guidelines in anephric pediatric PD patients may result in changing dialysis modality. However, without evidence of a correlation between delivered dose of dialysis and improved outcome, adequate dialysis should not be assessed by only measuring Kt/V and C _Cr. Received: 24 June 1999 / Revised: 2 November 1999 / Accepted: 2 November 1999     

Do cardiovascular risk factors influence cardiac allograft vasculopathy?

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of heart transplant failure after the first year. The etiological factors involved are currently a controversial matter. Intravascular ultrasound (IVUS) is considered the diagnostic procedure of choice. We assessed the relationship of cardiovascular risk factors with CAV. MATERIALS: We analyzed prospectively 22 patients. We conducted a first study with coronary angiography and IVUS at 36 +/- 3 days and a second at 598 +/- 49 days. We performed an average of 5.6 clinical revisions per patient, assessing the effect of the classic cardiovascular risk factors, the cause of heart failure, and the age of the patient and donor. The statistics used were chi(2), Fisher exact test, and Student t test. RESULTS: CAV was found in 10 subjects (45.5%). Univariate analysis showed statistically significant differences in the assessment of the presence of diabetes and dyslipidemia posttransplantation, but not pretransplantation. Among the patients with CAV there was a higher percentage of diabetics (32.8% vs 12%, P < .01). The patients with CAV also had higher levels of total cholesterol (211 +/- 40 mg/dL vs 195 +/- 35 mg/dL, P = .02), triglycerides (172 +/- 108 mg/dL vs 136 +/- 66 mg/dL, P = .03), low-density lipoprotein (133 +/- 35 mg/dL vs 117 +/- 30 mg/dL, P = .01), and lower high-density lipoprotein levels (46 +/- 15 mg/dL vs 52 +/- 12 mg/dL, P = .03). CONCLUSIONS: Only the diabetes and dyslipidemia present in the posttransplantation period were associated with CAV, which highlights the fact that it is a condition that both shares and has different features with atherosclerosis and probably requires a different diagnostic-therapeutic approach.     

Low nephron number—a new cardiovascular risk factor in children?

There is increasing evidence that primary hypertension, coronary heart disease, and other aspects of the so-called metabolic syndrome that develop in adulthood are primed in fetal life or early postnatally. The identification of this phenomenon, also known as prenatal or fetal programming, and the detailed characterization of the underlying pathomechanisms will greatly influence the understanding of these diseases. The present paper reviews recent experimental and clinical evidence that low nephron number, found in patients with renal dysplasia and low birth weight, is a risk factor for cardiovascular disease in later life. Therefore, it is important to identify children at risk as early as possible in order to treat them early and to prevent the development of end-organ damage. This could be an important goal for pediatrics in the near future.     

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

Background: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.

Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.

Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64?±?3.6 and 70?±?5.3?ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36?±?2.5; pHMGB1:30.5?±?7.0?ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5?±?7.0 versus 6.9?±?3.6; p?p?=?0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = ?0.83; p?=?0.03).

Conclusion: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.     

Aortic pulse wave velocity is a strong predictor of all – cause and cardiovascular mortality in chronic dialysis patients

Background/Aims: The aim of this study was to investigate all-cause and cardiovascular mortality in chronic hemodialysis patients (CHP) and to identify the determinants of mortality predictors. Methods: In this study with 3 years of follow-up period, we studied a cohort of 80 CHPs. Mean age at entry was 59.3?±?11.8 years (duration of dialysis 5.47?±?5.16 years). At entry, together with standard clinical and biochemical analyses, pulse wave velocity (PWV) was determined from time diversity propagation of the common carotid artery and common femoral artery flow signals by Doppler ultrasound. Results: The mean PWV (m/s) was presented at entry: in survived (12.5?±?2.01) and deceased (13.13?±?1.70) patients. The PWV cutoff point (by ROC curves) was 11.8. The regression coefficients (b) and Exp (b) hazard ratio coefficients of covariates in Cox-regression survival analysis in all-cause and CV outcomes was: PWV (b?=?0.2617, Exp[b]?=?1.2992, p?=?0.0027; b?=?0.3569, Exp[b]?=?1.4289, p?=?0.0005), CRP (b?=?0.0776, Exp[b]?=?1.0807, p?=?0.0001; b?=?0.0832, Exp[b]?=?1.0868, p?=?0.0001) and albumin (b?=??0.1302, Exp[b]?=?0.8779, p?=?0.0089; b?=??0.1881, 0.8285, p?=?0.0030), respectively. Relative risk for exposed groups according to all-cause and CV events was 4.2976 (95% CI?=?1.6051–11.5071) and 14.3590 (95% CI?=?1.6051–11.5071), p?=?0.0037, respectively. Conclusions: We conclude that PWV, CRP and serum albumin are strong independent predictors of overall and CV mortality in patients undergoing dialysis.     

Metabolic risk factors in pediatric and adult calcium oxalate urinary stone formers: is there any difference?

OBJECTIVES: Urolithiasis in children is recognized with an increasing frequency, while exact etiological factors remain to be determined. The aim of this study is to compare the metabolic risk factors and saturation of urine in pediatric and adult calcium oxalate (Ca-Ox) stone formers. METHODS: A total of 33 pediatric (mean age: 6.8 +/- 3.1 years) and 120 adult patients (mean age: 39.7 +/- 5.7 years), with documented Ca-Ox urinary stone disease, underwent a comprehensive metabolic evaluation at our institution. Beside a broad serum analysis, concentrations of calcium, oxalate, magnesium, uric acid and citrate were measured in 24-hour collected urine. Saturation of urine was calculated by Marshall-Robertson's nomograms. RESULTS: Hypocitraturia, observed in 60.6%, and hypomagnesuria, detected in 39.4%, but not hypercalciuria, were the most common metabolic risk factors in the pediatric group. In adults, hypercalciuria still represented one of the major metabolic risk factors, detected in 44.1%, although hypocitraturia, observed in 45.8%, was the most prevalent metabolic risk factor, as it was in the pediatric group. Pediatric cases had significantly (p < 0.05) higher prevalence of hypocitraturia, hypomagnesuria and supersaturated urine when compared to adults. Metabolic abnormalities could be detected in a high percentage (82%) of primary and recurrent pediatric Ca-Ox stone formers, but not in primary adult stone formers. CONCLUSIONS: Metabolic risk factors significantly differ in pediatric and adult Ca-Ox stone formers. Hypocitraturia and hypomagnesuria seem to play a major role in stone formation, and metabolic abnormalities can be detected in a significant percentage of both primary and recurrent pediatric stone formers. Thus, a comprehensive metabolic evaluation is of utmost importance for all children with Ca-Ox stones.     

Hormonal changes in hemodialysis patients: Novel risk factors for mortality?

Patients with end‐stage renal disease undergoing dialysis commonly experience derangements in the hypothalamic‐pituitary‐gonadal axis together with alterations at the level of synthesis and clearance of many hormones. This hormonal imbalance, even if asymptomatic, has recently been associated with increased mortality in these patients. In this review, we summarize observational and mechanistic evidence linking hormonal alterations at the level of the thyroid and sex‐hormone systems with this mortality risks.