Tissue-advanced glycation end product concentration in dialysis patients.

BACKGROUND AND OBJECTIVES: Tissue-advanced glycation end products (AGE) are a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluoresence (AF) correlates well with cardiovascular outcomes in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGE levels in HD and peritoneal dialysis (PD) patients and to evaluate the impact of systemic PD glucose exposure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Tissue AGE were measured in 115 established dialysis patients (62 HD and 53 PD) using a cutaneous AF device (AGE Reader; DiagnOptics). Values were compared with an age-matched non-chronic kidney disease database. Review of all previous PD solution delivery/prescription data determined PD glucose exposure. RESULTS: PD patients were similar in age to HD patients but had a shorter dialysis vintage. There were no differences in ischemic heart disease or smoking history, statin or angiotensin-converting enzyme inhibitor (ACEi) use, lipids, biochemistry, or prevalence of diabetes. More than 90% of both groups had met current dialysis adequacy targets. Skin AF values in PD and HD patients were similar and strongly correlated with historical PD glucose exposure. Skin AF correlated with age in both groups but with dialysis vintage only in PD patients CONCLUSIONS: Cumulative metabolic stress and transient hyperglycemia results in grossly elevated levels of tissue AGE in dialysis patients. In PD patients, this high level of AGE deposition is associated with historical glucose exposure. This observation provides a previously unappreciated potential link between PD exposure to glucose and systemic cardiovascular disease.

Categorization of the hemodynamic response to hemodialysis: the importance of baroreflex sensitivity.

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. The baroreflex arc is under autonomic control and regulates blood pressure. This study aimed to investigate the contribution of impaired baroreflex sensitivity (BRS) to the pathophysiology of IDH. Thirty-four chronic HD (12 IDH-prone, 22 IDH-resistant) patients underwent BRS measurement during HD with relative blood volume monitoring. During analysis, patients were separated into four age-matched groups according to resting BRS>or=4.5 ms/mmHg and hemodynamic stability. Resting BRS was extremely heterogenous (geometric mean BRS 5.78+/-1.41 [range 1.76-41.41] ms/mmHg). Relative blood volume reduction was well matched in all groups (mean reduction in relative blood volume for all patients -6.74%+/-0.86%, P>0.05). Thirty-seven episodes of IDH occurred in the IDH prone, reduced BRS group. Patients with impaired resting BRS and prone to IDH had markedly different responses to HD as compared to the preserved BRS group, but the total peripheral resistance response was significantly lower than in the IDH-resistant patients (15.9%+/-2.1% vs. 42.4%+/-3.0%, respectively, P<0.001). In those patients prone to IDH and with impaired resting BRS, percentage reduction in cardiac output at the end of HD highly correlated with reduction in relative blood volume (r=0.94, P=0.006). Hypotension during dialysis may be an important source of recurrent cardiac injury and early recognition of those patients prone to relative symptomatic and asymptomatic hypotension remains important. Impaired resting BRS and recognition of a suboptimal peripheral pressor response, appear to predict those patients most likely to undergo hemodynamic instability and may assist in the pursuit of this elusive goal.

Cool dialysate reduces asymptomatic intradialytic hypotension and increases baroreflex variability.

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in chronic hemodialysis (HD) patients and can be ameliorated by cool temperature HD. The baroreflex arc is under autonomic control and is essential in the short-term regulation of blood pressure (BP). This study aimed to investigate if the baroreflex sensitivity (BRS) response to HD differed between standard and cool-temperature dialysate. Ten patients (mean age 67+/-2 years) prone to IDH were recruited into a randomized, crossover study to compare BRS variation at dialysate temperatures of 37 degrees C (HD(37)) and 35 degrees C (HD(35)). Each patient underwent continuous beat-to-beat BP monitoring during a dialysis session of HD(37) and HD(35). During HD(37) 2 patients developed symptomatic IDH, as opposed to 1 with HD(35). However, asymptomatic IDH occurred with a frequency of 0.4 episodes per session with HD(35) and 6.2 episodes per session during HD(37) (odds ratio15.5; 95%CI 5.6-14.2). Although absolute BRS measurements did not differ between the 2 modalities, BRS variability increased during HD(35). Our study has demonstrated that in IDH-prone patients, cool HD resulted in a reduction in heart rate and a greater reduction in cardiac output and stroke volume. Mean arterial pressure was maintained through a significantly greater increase in total peripheral resistance. Furthermore, although absolute BRS values during HD were not significantly altered by a reduction in dialysate temperature, there was a greater percentage increase in BRS values during cool HD. Understanding the varied causes of, and categorizing impaired hemodynamic responses to HD will enable further individualization of HD prescriptions according to patient need.

Myocardial contractile function and intradialytic hypotension.

Dialysis-induced hypotension remains a significant problem in hemodialysis (HD) patients. Numerous factors result in dysregulation of blood pressure control and impaired myocardial reserve in response to HD-induced cardiovascular stress. Episodic intradialytic hypotension may be involved in the pathogenesis of evolving myocardial injury. We performed an initial pilot investigation of cardiovascular functional response to pharmacological cardiovascular stress in hypotension-resistant (HR) and hypotension-prone (HP) HD patients. We studied 10 matched chronic HD patients (5 HP, 5 HR). Dobutamine-atropine stress (DAS) was performed on a nondialysis short interval day, with noninvasive pulse-wave analysis using the Finometer to continuously measure hemodynamic variables. Baroreflex sensitivity was assessed at rest and during DAS. Baseline hemodynamic variables were not significantly different. The groups had differing hemodynamic responses to DAS. The Mean arterial pressure was unchanged in the HR group but decreased in HP patients (-13.6 +/- 3.5 mmHg; P<0.001). This was associated with failure to significantly increase cardiac output in the HP group (cf. increase in cardiac output in the HR group of +33.4 +/- 6%; P<0.05), and a reduced response in total peripheral resistance (HP -10.3 +/- 6.8%, HR -22.7 +/- 2.9%, P=NS). Baroreflex sensitivity was not significantly different between groups at baseline or within groups with increasing levels of DAS; however, the mean baroreflex sensitivity was higher in HR cf. HP subjects throughout pharmacological stress (P<0.05). Hypotension-prone patients appear to have an impaired cardiovascular response to DAS. The most significant abnormality is an impaired myocardial contractile reserve. Early identification of these patients would allow utilization of therapeutic strategies to improve intradialytic tolerability, potentially abrogating aggravation of myocardial injury.

Continuous online monitoring of ionic dialysance allows modification of delivered hemodialysis treatment time.

Considerable intrinsic intrapatient variability influences the actual delivery of Kt/V. The aim of this study is to examine the feasibility of using continuous online assessment of ionic dialysance measurements (Kt/V(ID)) to allow dialysis sessions to be altered on an individual basis. Ten well-established chronic hemodialysis (HD) patients without significant residual renal function were studied (mean age 65+/-4.3 [38-81] years, mean length of time on dialysis 66+/-18 [14-189] months). These patients had all been receiving thrice-weekly 4-hr dialysis using Integra dialysis monitors. Dialysis monitors were equipped with Diascan modules permitting measurement of Kt/V(ID). Predicted treatment time required to achieve a Kt/V(ID) > or = 1.1 (equivalent to a urea-based method of 1.2) was calculated from the delivered Kt/V(ID) at 60 and 120 min. Treatment time was reprogrammed at 2 hr (ensuring all planned ultrafiltration would be accommodated into the new modified session duration). Owing to practical issues, and to avoid excessively short dialysis times, these changes were censored at no more than+/-10% of the usual 240-min treatment time (210-265 min). Data were collected from a total of 50 dialysis sessions. Almost all sessions (47/50) required modification of the standard treatment time: 13/50 sessions were lengthened and 34/50 shortened (mean length of session 232.2+/-2.5 [210-265] min). A Kt/V(ID) of > or = 1.1 was achieved in 39/50 sessions. The difference in mean urea-based Kt/V poststudy (1.3+/-0.05 [1.1-1.6]) and mean achieved Kt/V(ID) (1.16+/-0.02 [0.7-1.37]) was significant (p = 0.002). The use of individualized variable dialysis treatment time using online ionic dialysance measurements of Kt/V(ID) appears both practicable and effective at ensuring consistently delivered adequate dialysis.

Dialysis-induced regional left ventricular dysfunction is ameliorated by cooling the dialysate.

Dialysis patients who develop cardiac failure have a poor prognosis. Recurrent subclinical myocardial ischemia is important in the genesis of heart failure in nondialysis patients. It has previously been demonstrated that subclinical ischemia occurs during hemodialysis; therefore, this study examined whether the improved stability of cool-temperature dialysis lessens this phenomenon. Ten patients who were prone to intradialytic hypotension entered a randomized, crossover study to compare the development of dialysis-induced left ventricular (LV) regional wall motion abnormalities (RWMA) at dialysate temperatures of 37 and 35 degrees C. Serial echocardiography with quantitative analysis was used to assess ejection fraction and regional systolic LV function. BP and hemodynamic variables were measured using continuous pulse wave analysis. The severity of thermal symptoms was scored using a simple questionnaire. Forty-nine new RWMA developed in nine patients during hemodialysis with dialysate at 37 degrees C (HD(37)), compared with thirteen RWMA that developed in four patients during HD(35) (odds ratio 3.8; 95% confidence interval 2.1 to 6.9). The majority of RWMA displayed improved function by 30 min after dialysis. Overall, regional systolic LV function was significantly more impaired during HD(37) (P < 0.001). BP was higher during HD(35), with fewer episodes of hypotension as a result of a higher peripheral resistance and no difference in stroke volume. The development of thermal symptoms was heterogeneous, with most patients tolerating HD(35) well. This study confirms previous findings of reversible LV RWMA that develop during hemodialysis. It also shows that this phenomenon can be ameliorated by reducing dialysate temperature, a simple intervention with no cost implications.

The assessment of baroreflex sensitivity in patients with chronic kidney disease: implications for vasomotor instability.

PURPOSE OF REVIEW: Autonomic dysfunction is well recognized in chronic kidney disease. The baroreflex arc is an important component of the autonomic nervous system and influences vasodilatation and heart rate in response to information derived from baroreceptors located in the aorta and common carotid arteries. Appropriate regulation of systemic blood pressure is therefore dependent upon the integrity and normal function of the baroreflex arc. Vasomotor instability during haemodialysis has traditionally been identified as a pathophysiological state largely due to the failure of compensatory mechanisms during ultrafiltration. This review article discusses autonomic dysfunction as a key factor contributing to the systemic haemodynamic instability that may occur during dialysis. RECENT FINDINGS: Relationships have begun to be established between markers of reduced baroreflex sensitivity and abnormal cardiovascular structure, such as left ventricular dysfunction, left ventricular hypertrophy and arterial stiffness. SUMMARY: Pathological relationships between cardiovascular structure and function remain important in the understanding of both haemodynamic instability and cardiovascular mortality in chronic kidney disease patients. Understanding the associations between conventional markers of haemodynamic instability and autonomic function will allow early identification of patients likely to benefit from individualizing dialysis therapy.

Reduced baroreflex sensitivity is associated with increased vascular calcification and arterial stiffness.

INTRODUCTION: Vascular calcification is a critical determinant of cardiovascular morbidity and mortality in chronic haemodialysis (HD) patients. The pathophysiology underlying this observation remains obscure. Baroreceptor sensitivity (BRS) is important in the maintenance of an appropriate cardiovascular status both at rest and under the physiological stress of HD. BRS is determined by both the mechanical properties of the vascular wall, mediating the transfer of transmural pressure, and afferent and efferent autonomic function. We aimed to study the association between arterial structure, function and BRS in chronic HD patients. METHODS: We studied 40 chronic HD patients mean age 62+/-2 (26-86) years who had received HD for a mean 40+/-4 (9-101) months. Spontaneous BRS was assessed using software studying the relationship between inter-beat variability and beat to beat changes in systolic blood pressure. Functional characteristics of conduit arteries (pulse wave analysis) were studied with applanation tonometry at the radial artery. Arterial calcification was assessed in lower limbs using reconstructed multi-slice computed tomography and quantified with volume-corrected calcification scores within the superficial femoral artery. RESULTS: Mean BRS was 4.43+/-0.44 ms/mmHg, with a wide range from 1.0 to 11.5 ms/mmHg. This correlated with arterial stiffness as measured by time to shoulder calculated from the central pulse wave analysis (r = 0.4, P = 0.01). BRS was also associated with vascular calcification (P = 0.01) but not by other factors such as dialysis vintage, age or pre-dialysis systolic/diastolic blood pressure. CONCLUSION: The reduction in BRS and the resulting aberrant blood pressure response to the physiological stress and volume changes of HD may be important in the further understanding of the pathophysiology of the increased mortality in HD patients with vascular calcification.

Venography at insertion of tunnelled internal jugular vein dialysis catheters reveals significant occult stenosis.

BACKGROUND: Tunnelled catheters are widely used to provide vascular access for haemodialysis. Percutaneous insertion of these catheters requires large calibre tissue dilators with the potential to cause trauma to central veins, particularly if anatomical abnormalities are present. METHODS: We evaluated the use of venography to identify central vein anatomical abnormalities in 69 consecutive patients undergoing percutaneous placement of tunnelled right internal jugular vein catheters. The internal jugular vein was entered under ultrasound guidance and venography was performed prior to insertion of a guide-wire. Images were evaluated on-screen by the operator and a decision made regarding the need for additional fluoroscopy during insertion of the catheter. RESULTS: In 29 cases (42%), venography showed evidence of unexpected stenosis and/or angulation of the central veins of sufficient severity to warrant additional fluoroscopy during insertion of the dilators, or abandonment of the procedure. Patients who had previously had tunnelled internal jugular catheters had more than double the incidence of such abnormalities than those who had not [15/23 (65%) vs 14/46 (30%); P = 0.009]. In two patients the procedure was abandoned due to severe stenosis. No patient suffered central vein trauma or pneumothorax. There were no adverse reactions to contrast injection. CONCLUSIONS: Venography performed immediately prior to tunnelled internal jugular dialysis catheter insertion detects unexpected, clinically significant anatomical abnormalities of the central veins in a substantial proportion of patients, particularly those with a history of previous tunnelled catheter insertion. We suggest that the use of venography may help to minimize the risk of complications from this procedure.