Prognostic Value of Serum Uric Acid in Patients on the Waiting List before and after Renal Transplantation.

Background. High serum uric acid (UA) is associated with increased cardiovascular (CV) risk in the general population. The impact of UA on CV events and mortality in CKD is unclear. Objective. To assess the relationship between UA and prognosis in hemodialysis (HD) patients before and after renal transplantation (TX). Methods. 1020 HD patients assessed for CV risk and followed from the time of inception until CV event, death, or TX (HD) or date of TX, CV event, death, or return to dialysis (TX). Results. 821 patients remained on HD while 199 underwent TX. High UA (≥428 mmol/L) was not associated with either composite CV events or mortality in HD patients. In TX patients high UA predicted an increased risk of events (P = 0.03, HR 1.6, and 95% CI 1.03-2.54) but not with death. In the Cox proportional model UA was no longer significantly associated with CV events. Instead, a reduced GFR (<50 mL/min) emerged as the independent risk factor for events (P = 0.02, HR 1.79, and % CI 1.07-3.21). Conclusion. In recipients of TX an increased posttransplant UA is related to higher probability of major CV events but this association probably caused concurrent reduction in GFR.

A new risk score model to predict the presence of significant coronary artery disease in renal transplant candidates.

BACKGROUND: Renal transplant candidates are at high risk of coronary artery disease (CAD). We sought to develop a new risk score model to determine the pre-test probability of the occurrence of significant CAD in renal transplant candidates. METHODS: A total of 1,060 renal transplant candidates underwent a comprehensive cardiovascular risk evaluation. Patients considered at high risk of CAD (age ≥50 years, with either diabetes mellitus (DM) or cardiovascular disease (CVD)), or having noninvasive testing suggestive of CAD were referred for coronary angiography (n = 524). Significant CAD was defined by the presence of luminal stenosis ≥70%. A binary logistic regression model was built, and the resulting logistic regression coefficient B for each variable was multiplied by 10 and rounded to the next whole number. For each patient, a corresponding risk score was calculated and the receiver operating characteristic (ROC) curve was constructed. RESULTS: The final equation for the model was risk score = (age × 0.4) + (DM × 9) + (CVD × 14) and for the probability of CAD (%) = (risk score × 2) - 23. The corresponding ROC for the accuracy of the diagnosis of CAD was 0.75 (P <0.0001) in the developmental model. CONCLUSIONS: We developed a simple clinical risk score to determine the pre-test probability of significant CAD in renal transplant candidates. This model may help those directly involved in the care of patients with end-stage renal disease being considered for transplantation in an attempt to reduce the rate of cardiovascular events that presently hampers the long-term prognosis of such patients.

Which patients are more likely to benefit from renal transplantation?

BACKGROUND: We evaluated whether the advantages conferred by renal transplantation encompass all individuals or whether they favor more specific groups of patients. METHODS: One thousand and fifty-eight patients on the transplant waiting list and 270 receiving renal transplant were studied. End points were the composite incidence of CV events and death. Patients were followed up from date of placement on the list until transplantation, CV event, or death (dialysis patients), or from the date of transplantation, CV event, return to dialysis, or death (transplant patients). RESULTS: Younger patients with no comorbidities had a lower incidence of CV events and death independently of the treatment modality (log-rank=0.0001). Renal transplantation was associated with better prognosis only in high-risk patients (p=0.003). CONCLUSIONS: Age and comorbidities influenced the prevalence of CV complications and death independently of the treatment modality. A positive effect of renal transplantation was documented only in high-risk patients. These findings suggest that age and comorbidities should be considered indication for early transplantation even considering that, as a group, such patients have a shorter survival compared with low-risk individuals.

Unexplained sudden death in patients on the waiting list for renal transplantation.

BACKGROUND: The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known. METHODS: We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list. RESULTS: Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease. CONCLUSIONS: Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates.

BACKGROUND: We validated a strategy for diagnosis of coronary artery disease (CAD) and prediction of cardiac events in high-risk renal transplant candidates (at least one of the following: age > or =50 years, diabetes, cardiovascular disease). METHODS: A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. RESULTS: The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29-2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. CONCLUSION: The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures.

Underuse of American College of Cardiology/American Heart Association Guidelines in hemodialysis patients.

Patients with end-stage renal disease (ESRD) are at high risk for cardiovascular disease (CVD) and therefore should be treated according to ACC/AHA Guidelines. Scant data are available concerning the actual use of cardioprotective drugs in this population. The use of angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, aspirin, and statins was assessed in 271 (72% males, 66% Caucasians) high-risk ESRD patients on hemodialysis. The study population comprised 27% smokers, 95% with hypertension, 38% with diabetes, and 44% with dyslipidemia; 44% of patients had overt CVD at baseline, including 9% with heart failure, 9% with prior myocardial infarction, and 3% with previous myocardial revascularization. One-third of all patients were not receiving any cardioprotective drugs; among those patients who were, 42% were on one drug, 21% were on two, 3.7% were on three, and 1.5% were on four. The most prescribed agent was ACE-I (35.8%), followed by aspirin (30.6%), and beta-blockers (28.0%). The use of statins was remarkably and significantly low (4.1%) (p < 0.001), even in the higher risk subgroups (patients with diabetes or macrovascular disease). ACE-I plus aspirin was the most prescribed combination (8.5%). Cardioprotective agents recommended for risk-factor modification by the ACC/AHA Guidelines for their well-established efficacy in the general population were underutilized in this cohort of high-risk hypertensive hemodialysis patients, despite an elevated prevalence of clinically evident CVD. Speculatively, this fact may be relevant to better understand the known increased cardiovascular morbidity-mortality associated with chronic renal disease.

Diabetes and coronary artery disease impose similar cardiovascular morbidity and mortality on renal transplant candidates.

BACKGROUND: In renal transplant candidates (RTC), diabetes and coronary artery disease (CAD) are commonly observed. However, whether diabetes imparts a cardiovascular risk equivalent to that of CAD and whether CAD adds to the cardiovascular risk associated with diabetes is unknown. METHODS: To assess the interplay between diabetes and CAD as a determinant of major adverse cardiovascular events (MACE), 288 high-risk RTC (56.4+/-8.1 years old, 72% males) underwent a comprehensive cardiovascular evaluation including coronary angiography. Patients were divided into four groups based on the diagnoses of diabetes and CAD (>70% narrowing), and followed up for 1-60 months (median, 17). The primary endpoint was the composite incidence of fatal/non-fatal MACE. RESULTS: During follow-up, 80 MACE occurred. Patients with diabetes (P=0.03) or CAD (P<0.0001) had a worse long-term prognosis. However, only in patients without diabetes was CAD associated with an increased incidence of MACE (10.6% vs 45.9%, P<0.0001). In patients with diabetes, the endpoints were not different between those with and without CAD. No difference occurred in the long-term prognosis of patients with diabetes (with or without CAD) and patients without diabetes with CAD. CONCLUSIONS: We concluded that in high-risk RTC, diabetes confers a cardiovascular risk comparable to that of CAD in patients without diabetes, independent of coronary obstruction. In patients with diabetes, concomitant CAD does not add to the already very high cardiovascular risk of this population.