Francis Verbeke

The uremic syndrome, which is the clinical expression of chronic kidney disease (CKD), is a complex amalgam of accelerated aging and organ dysfunctions, whereby cardio-vascular disease plays a capital role. In this narrative review, we offer a summary of the current conservative (medical) treatment options for cardio-vascular and overall morbidity and mortality risk in CKD. Since the progression of CKD is also associated with a higher cardio-vascular risk, we summarize the interventions that may prevent the progression of CKD as well. We pay attention to established therapies, as well as to novel promising options. Approaches that have been considered are not limited to pharmacological approaches but take into account lifestyle measures and diet as well. We took as many randomized controlled hard endpoint outcome trials as possible into account, although observational studies and post hoc analyses were included where appropriate. We also considered health economic aspects. Based on this information, we constructed comprehensive tables summarizing the available therapeutic options and the number and kind of studies (controlled or not, contradictory outcomes or not) with regard to each approach. Our review underscores the scarcity of well-designed large controlled trials in CKD. Nevertheless, based on the controlled and observational data, a therapeutic algorithm can be developed for this complex and multifactorial condition. It is likely that interventions should be aimed at targeting several modifiable factors simultaneously.

Low plasma adiponectin concentration was recently recognized as a novel risk factor for new-onset diabetes after transplantation. Pharmacological modulation of the renin-angiotensin system activity and genetic predisposition were shown to have an influence on plasma adiponectin level. Therefore the aim of this study is to analyze the association between angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT1R) A1166C and angiotensinogen (AGT) M235T genotypes and plasma adiponectin concentration as well as insulin resistance in a cohort of kidney transplant patients.

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659–0.776) for pulse wave velocity, 0.670 (95% CI 0.604–0.736) for central augmentation pressure, and 0.595 (95% CI 0.529–0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104–1.649; P =0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219–1.814; P <0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.

Summary: Background and objectives: Radiographic calcification and arterial stiffness each individually are predictive of outcome in dialysis patients. However, it is unknown whether combined assessment of these intermediate endpoints also provides additional predictive value. Design, setting, participants, & measurements: Scoring of abdominal aortic calcification (AAC) using plain lateral abdominal x-ray and measurement of carotid-femoral pulse wave velocity (PWV) were performed in a cohort of 1084 prevalent dialysis patients recruited from 47 European dialysis centers. Results: During a follow-up of 2 years, 234 deaths and 91 nonfatal cardiovascular (CV) events occurred. Compared with the lowest tertile of AAC, the risk of an event was increased by a factor 3.7 in patients with a score of 5 to 15 (middle tertile), and by a factor 8.6 in patients with scores of 16 to 24. Additionally, each 1-m/s increase in PWV was associated with a 15% higher risk. At higher AAC (scores ≥5), the effect of PWV was attenuated because of a negative PWV × AAC interaction (hazard ratio [HR]: 0.895 and 0.865 for middle and upper AAC tertiles). After accounting for age, diabetes, and serum albumin, AAC and PWV remained independent predictors of outcome. Conclusions: AAC and central arterial stiffness are independent predictors of mortality and nonfatal CV events in dialysis patients. The risk associated with an increased PWV is less pronounced at higher levels of calcification. Assessment of AAC and PWV is feasible in a clinical setting and both may be used for an accurate CV risk estimation in this heterogeneous population.

Background. Susceptibility to infection and thrombosis of intravascular catheters is increased by surface irregularities, which might be prevented by coating. Methods. BaSO4 release from conventional haemodialysis catheters (CC) and modified catheters (MC) which had been coated with a surface-modifying additive (SMA) was assessed in vivo and in vitro. For the in vivo part, patients were randomized to receive a temporary CC or MC, with crossover after 1 week. After retrieval, catheters were examined using scanning electron microscopy to assess surface integrity, and an in vitro model of catheter exposure to the bloodstream was used to evaluate surface morphology and susceptibility to bacterial adhesion and proliferation. Results. BaSO₄ moieties covered 14.7 ± 3.7% of the surface of unused CC. After in vivo use in 16 patients, 62.7 ± 32.9 × 10³ holes/mm² were detected, indicating BaSO₄ detachment from 3.3 ± 1.7% of the catheter surface. No defects were observed in unused CC and in MC, whether used or unused. After incubation of four catheters (two of each type) with Staphylococcusepidermidis, the two degraded CC showed an immediate and strong bacterial growth as indicated by an increase in medium impedance of 0.512%/10 min compared to −0.021%/10 min in MC (P < 0.001). Conclusions. Short-term exposure of CC to the bloodstream causes BaSO₄ particle release, resulting in surface irregularities predisposing to bacterial proliferation. BaSO₄ release can be prevented by SMA coating.

Background: Although peritoneal dialysis is considered to offer more hemodynamic stability than hemodialysis, the acute hemodynamic effects of peritoneal dialysis have only been investigated scarcely. The present study assesses the central hemodynamic impact of volume infusion using pH-adjusted icodextrin, thus avoiding interference of glucose, pH, and osmolarity. Methods: Patients were randomized to 3 different starting volumes (A: 1000 mL, B: 1500 mL, and C: 2500 mL) of icodextrin, followed by addition (A and B) or drainage (C) of 200 mL every 10 minutes for 50 minutes. Local carotid systolic blood pressure (BP; as a surrogate for central BP), augmentation index, and augmentation pressure were measured by applanation tonometry before and after infusion of the starting volumes and after each volume change. Results: We included 13 patients (median age 57 years). Baseline brachial BP was 126/77 mmHg. After infusion of the starting volume, carotid systolic BP and augmentation pressure increased by 4.7 mmHg ( p = 0.006) and 3.1 mmHg ( p = 0.015). Augmentation index increased by 5.7% ( p = 0.04) and heart rate decreased by 2.6/minute ( p = 0.006). Intraperitoneal pressure increased by 2.3 cm H₂O ( p = 0.03). No additional hemodynamic changes except for a rise in diastolic BP with increasing volume ( p = 0.004) were observed after subsequent addition or removal of volumes. Conclusions: Infusion of peritoneal dialysis fluids causes an acute increase in carotid systolic B P, followed by a progressive rise in diastolic BP. These effects persist until complete drainage of the abdomen and may be due to an enhanced preload, resulting from intraperitoneal venous compression, and/or increased wave reflection.

Background. Arterial stiffness predicts cardiovascular disease (CVD) events and has been well documented in haemodialysis patients. Information in renal transplant recipients (RTR), however, remains limited despite their higher CVD risk compared to the general population. We aimed to assess arterial stiffening and wave reflections in RTR and healthy controls and to evaluate which factors could explain potential differences.

The advocated SphygmoCor procedure uses a radial-to-aorta transfer function with calibration on brachial instead of radial artery pressure to assess the central pulse pressure. We compared these values with carotid artery pulse pressures obtained from a validated calibration method, assuming mean minus diastolic blood pressure constant throughout the large artery tree. From 44 healthy subjects (21 males; 22 to 68 years) pressure waves were obtained at the radial, brachial, and carotid artery with applanation tonometry. Using the calibration method, radial and carotid artery pressures were assessed from brachial artery waves and pressures. The effect of brachial-to-radial pulse pressure amplification, brachial pulse pressure, mean pressure, age, gender, height, body mass index, and smoking on differences between the 2 methods was assessed. Brachial artery pressure was 118±12/72±10 mm Hg. SphygmoCor central pulse pressure was 9.7±4.6 mm Hg lower ( P P P =0.005). After calibration of the radial pressure wave with radial instead of brachial artery pressures, the difference between SphygmoCor central pulse pressure and carotid pulse pressure decreased with 4 mm Hg. The advocated SphygmoCor procedure systematically underestimates the central pulse pressure with brachial-to-radial pulse pressure amplification as important determinant. Therefore, calibration of radial artery pressure waves on brachial artery pressures should be avoided. The underestimation of central aortic pulse pressure caused by the radial-to-aorta transfer function itself is much less than previously reported.