Cardiovascular risk reduction with periodontal treatment in patients on the waiting list for renal transplantation.

BACKGROUND: Cardiovascular mortality is increased in chronic kidney disease, a condition with a high prevalence of periodontal disease. Whether periodontitis treatment improves prognosis is unknown. METHODS: The effect of periodontal treatment on the incidence of cardiovascular events and death in 206 waitlist hemodialysis subjects was compared with that in 203 historical controls who did not undergo treatment. Patients were followed up for 24 months or until death or transplantation. RESULTS: The prevalence of moderate/severe periodontitis was 74%. Coronary artery disease correlated with the severity of periodontal disease (P = .02). Survival free of cardiovascular events (94% vs 83%, log-rank 0.009), coronary events (97% vs 89%, log-rank = 0.009), and cardiovascular death (96% vs 87%, log-rank = 0.037) was higher in the evaluated group. Death by any cause did not differ between groups. Multivariate analysis showed that treatment was associated with reduction in cardiovascular events (HR 0.43; 95% CI 0.22-0.87), coronary events (HR 0.31; 95% CI 0.12-0.83), and cardiovascular deaths (HR 0.43; 95% CI 0.19-0.98). CONCLUSION: Periodontal treatment reduced the 24-month incidence of cardiovascular events and cardiovascular death, suggesting that periodontal treatment may improve cardiovascular outcomes. We suggest that periodontal screening and eventual treatment may be considered in patients with advanced renal disease.

The role of therapy with aminoglycoside in the outcomes of kidney transplant recipients infected with polymyxin- and carbapenem-resistant Enterobacteriaceae.

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (blaKPC, blaNDM, and blaOXA-48), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.

Evaluation of a protocol for coronary artery disease investigation in asymptomatic elderly hemodialysis patients.

BACKGROUND: Coronary artery disease (CAD) is prevalent in older patients on dialysis, but the prognostic relevance of coronary assessment in asymptomatic subjects remains undefined. We tested the usefulness of a protocol, based on clinical, invasive, and noninvasive coronary assessment, by answering these questions: Could selecting asymptomatic patients for coronary invasive assessment identify those at higher risk of events? Is CAD associated with a worse prognosis? METHODS: A retrospective study including 276 asymptomatic patients at least 65 years old on the waiting list, prospectively evaluated for CAD and followed up until death or renal transplantation, were classified into two groups: 1) low-risk patients who did not undergo coronary angiography (n=63) and 2) patients who did undergo angiography (n=213). The latter group was reclassified into patients with significant CAD or normal angiograms/nonsignificant CAD. RESULTS: CAD (≥70% stenosis) occurred in 124 subjects (58%). The incidence of death by any cause, coronary death, and major cardiovascular (CV) events were similar in patients selected or not for angiography and in those with or without significant CAD. Myocardial revascularization (surgical/percutaneous) was performed in only 21/276 patients (7.6%) and did not result in a reduction in mortality. CONCLUSION: In older patients on renal replacement therapy, the prevalence of CAD was high, but coronary investigation was not useful as a risk stratification tool and also resulted in a rather small proportion of patients eligible for intervention. Therefore, in the elderly, coronary investigation should not be considered routine in asymptomatic patients.

The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed "de novo" Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p < 0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

Coronary Artery Disease Assessment and Intervention in Renal Transplant Patients: Analysis from the KiHeart Cohort.

BACKGROUND: The value of coronary artery disease (CAD) assessment and coronary intervention in the prognosis of patients who undergo renal transplantation is controversial. We investigated whether pretransplant identification of patients with CAD is helpful for defining prognosis and whether preemptive coronary intervention reduces the incidence of cardiovascular events and death after engraftment. METHODS: We analyzed the impact of coronary assessment by clinical stratification and coronary angiography and of coronary intervention on prognosis in 535 chronic kidney disease patients on the transplantation waiting list who underwent renal transplantation. RESULTS: Patients with 70% or greater narrowing experienced more coronary events than patients with less significant lesions (P = 0.01) and subjects at low risk (P = 0.001). Coronary assessment did not discriminate between the risk of death in patients with or without significant CAD, and the independent predictors of death were age (hazards ratio, 1.04; 95% confidence interval, 1.01-1.06, P = 0.001) and diabetes (hazards ratio, 1.63; 95% confidence interval, 1.11-2.39, P = 0.01). No difference occurred in events and mortality between patients treated medically or by intervention, but the severity of CAD was higher in the latter. CONCLUSIONS: Coronary assessment identified patients at increased risk of posttransplant coronary events and was also useful to define a low-risk population that may be safely transplanted without in-depth cardiovascular evaluation. However, it did not differentiate between the risk of death in patients with and those without significant CAD. Survival was similar in patients undergoing either medical or interventional treatment for CAD.

Coronary events in obese hemodialysis patients before and after renal transplantation.

We examined the impact of obesity (BMI ≥30 kg/m(2) , n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End-points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 ± 9.2 vs. 54.2 ± 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 ± 52 vs. 169 ± 47), and triglycerides (219 ± 167 vs. 144 ± 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 ± 56 vs. 172 ± 48), and triglycerides (237 ± 190 vs. 149 ± 100). Obesity was independently associated with coronary events (log-rank = 0.008, HR 2.55% CI 1.27-5.11) and death (log-rank 0.046, HR 1.52, % CI 1.007-2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death.

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.

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade.

BACKGROUND: Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. METHODS: Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. RESULTS: Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. CONCLUSION: Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.

Recipient of kidney from donor with asymptomatic infection by Paracoccidioides brasiliensis.

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.

Diagnosis and treatment of coronary artery disease in hemodialysis patients evaluated for transplant.

We present a review of current strategies for the diagnosis and treatment of coronary artery disease (CAD) in patients with advanced chronic kidney disease who are on the waiting list for transplants, based on data from the literature and originated from a single-center cohort of 1,250 patients with maximum follow-up of 12 years. We discuss the best way to select patients to be tested for CAD, how to choose the more adequate screening test for CAD and cardiovascular disease, how to select patients for invasive treatment studies and how to treat patients with significant CAD. We also suggest new research avenues to be explored to resolve some problems in this area.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients.

UNLABELLED: BACKGROUND: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. METHODS: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. RESULTS: Asymptomatic patients with normal myocardial scans (n=57) had significantly fewer cardiac events (log-rank=0.0002) and deaths (log-rank=0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n=76) and individuals with CAD (n=34) documented angiographically. CAD increased the probability of events (HR=2.27, % CI 1.007-5.11; p=0.04). The incidence of cardiac events (log-rank=0.349) and deaths (log-rank=0.588) was similar among patients treated medically (n=23) or by intervention (n=11). CONCLUSION: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support preemptive myocardial revascularization for renal transplant candidates.

Cardiac MRI for detection of unrecognized myocardial infarction in patients with end-stage renal disease: comparison with ECG and scintigraphy.

OBJECTIVE: The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS: We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS: Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION: Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BACKGROUND: Renal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis > or =70%) in high-risk renal transplant candidates. METHODS: Clinical evaluation and coronary angiography were performed in 301 patients (57+/-8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age > or =50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). RESULTS: Significant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08-3.07], PAD (OR=2.50; 95% CI=1.44-4.37), and previous MI (OR=7.75; 95% CI=3.03-23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). CONCLUSIONS: In high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Coronary angiography is the best predictor of events in renal transplant candidates compared with noninvasive testing.

Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (>or=70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (>or=50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P=0.007) and CA (P=0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with >or=70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P=0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.