Journal of Human Hypertension (2005) 19, 425–427 & 2005 Nature Publishing Group All rights reserved 0950-9240/05 $30.00 www.nature.com/jhh COMMENTARY Acute vs chronic volume overload on arterial stiffness in haemodialysis patients

Y-P Lin1,W-CYu1 and C-H Chen1,2,3 1Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; 3Department of Social Medicine, National Yang-Ming University, Taipei, Taiwan

Journal of Human Hypertension (2005) 19, 425–427. doi:10.1038/sj.jhh.1001842 Published online 10 March 2005

Volume overload is a cardinal feature of end-stage in the various vascular parameters monitored. renal disease (ESRD) patients. Acute volume over- Each vascular parameter may be affected variably load, as represented by interdialytic weight gain, is by factors such as and rate. associated with increased aortic wave velocity For instance, augmentation index may be under- (aPWV) and independently related to total mortality estimated for approximately 4% per 10 beats/min in haemodialysis patients.1,2 Based on the Laplace’s increase of .9 aPWV may increase 41 m/s law, volume expansion increases arterial stiffness (or by an increase in heart rate of 40 beats/min.10 The reduces arterial compliance) by increasing arterial existence of multiple arteriovenous shunts may also distension. Therefore, it would appear intriguing that affect systemic compliance. aPWV is proportional to acute volume reduction by ultrafiltration does not the square root of the product of wall elastance and always acutely improve arterial stiffness.3–7 Dialysis thickness. As a result of this square root relation- with a ‘low-calcium’ dialysate (1.50 mmol/l) did not ship, aPWV may not be a sensitive measure of a change aPWV, while dialysis with a ‘high-calcium’ change in physical arterial properties.8 On the other dialysate (1.75 mmol/l) even induced a significant hand, aortic compliance describes arterial stiffness increase in aPWV.6 Haemodialysis with polysul- as an absolute volume expansion over a given phone but not polyamide membranes may acutely pressure increment, and may therefore be more increase aPWV, probably due to membrane bioin- straightforward to reveal the effect of absolute compatibility.7 In contrast, by combining carotid volume reduction from ultrafiltration.8 pulse contour analysis with aortic outflow measure- (2) Timing of measurements: Large swing of ments, Le et al8 was able to demonstrate that acute volume status could affect vascular parameters. volume removal improved aortic compliance in Taken the thrice-weekly haemodialysis schedule, haemodialysis patients who had already attained for example, the impacts of volume removal on dry weight and had normal systolic and diastolic vascular functions are expected to be more conspic- function. While aPWV was not different after uous at the first dialysis session of the week due to haemodialysis in the study, the results suggested larger volume accumulation over the weekend. that the increase in aortic stiffness in haemodialysis Measurements immediately at the start of haemo- patients is partly caused by a reversible reduction of dialysis may be subject to biases from the white coat aortic compliance due to volume expansion.8 effect on blood pressure due to the anticipatory Why has it been difficult to demonstrate an acute anxiety with cannulation of the fistula or graft.11 beneficial effect of volume removal by haemodia- Those measured immediately after haemodialysis lysis on arterial stiffness? Possible reasons are as may also be confounded by the incomplete inter- follow: compartmental fluid shift. (1) Methodology of assessment of vascular func- (3) Status of cardiac function: Left ventricular tion: Dialysis may exert different effects on the stiffness at end- is coupled to arterial heterogeneous vascular beds and reflect differently mechanical properties and is associated with the enhanced volume dependency of blood pressure in ESRD patients.12 The presence of may Correspondence: Dr C-H Chen, Division of Cardiology, Depart- also increase the sensitivity of volume change on ment of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. , , and arterial mechan- E-mail: [email protected] ical property. Furthermore, the frequently seen Published online 10 March 2005 calcific degeneration of the mitral annulus and Acute vs chronic volume overload Y-P Lin et al 426 aortic valve may influence the interpretations of ultrafiltration rate is often required for adequate vascular parameters. chronic volume removal. Due to the intolerance of (4) Neurohumoral response to ultrafiltration: The intradialysis haemodynamic instability and the activation of the sympatho-inhibitory cardiodepres- nonadherence to salt and fluid restriction, a sig- sor reflex (Bezold-Jarisch reflex) could cause sudden nificant proportion of haemodialysis patients re- intradialytic hypotension. The removal of nitric main chronic volume overloaded. By applying the oxide inhibitors during haemodialysis coupled with more intensive dialysis modalities as the 8-h thrice- increased production of nitric oxide induced by weekly schedule19 or the nocturnal haemodialysis cytokines activated via blood–dialyzer interaction with 8–10 h of dialysis during sleep and five to could also change the sites of arterial wave reflec- seven nights per week,20 patients could tolerate tion. The beneficial effect of acute volume reduction better to volume removal and also have better may be obscured by the increased vasoconstrictor clearance of uraemic toxin. They also have im- activity through the activation of the renin–angio- proved blood pressure control and normalization of tensin system.3 Therefore, combined volume reduc- the left ventricular geometry. tion and angiotensin-converting enzyme inhibition We should emphasize that it is of paramount may have an enhanced effect in decreasing aortic importance to define precisely the volume status in compliance.3 the individual ESRD patient in order to prescribe (5) Dialysate electrolytes: Vascular tone could optimal ultrafiltration volume. Further investiga- be influenced by changes of magnesium13 and tions are also needed to explore to what extent that calcium6,14 during dialysis. Sodium can modify volume removal can improve arterial function vascular muscle tone through sympathetic nervous instead of compromising tissue . system, insulin sensitivity, and endothelium-depen- dent factors.15 The increased vascular muscle tone could affect the arterioles as well as the elastic properties of large arteries, and consequently the References arterial stiffness. Salt restriction, and instead of the 1 Foley RN, Herzog CA, Collins AJ. Blood pressure and lengthening of dialysis, may result in improved long-term mortality in United States hemodialysis cardiac geometry as regression of left ventricular patients: USRDS Waves 3 and 4 Study. Kidney Int hypertrophy, decreased left atrial and left ventri- 2002; 62: 1784–1790. cular systolic and diastolic dimensions, and 2 Saran R et al. Nonadherence in hemodialysis: also better blood pressure control without anti- associations with mortality, hospitalization, and hypertensive agents under the 4-h thrice-weekly practice patterns in the DOPPS. Kidney Int 2003; 64: haemodialysis.16 254–262. (6) Miscellaneous: Patient’s chronic volume status 3 Tycho VJL et al. Contribution of volume overload and and nutritional condition may exert effects on the angiotensin II to the increased pulse wave velocity of plasma refilling rate and affect arterial compliance. hemodialysis patients. J Am Soc Nephrol 2002; 13: 177–183. As mentioned above, membrane incompatibility 4 Covic A et al. Analysis of the effect of hemodialysis on may cause repetitive endothelial damage and peripheral and central arterial pressure waveforms. 7 acutely alters aortic stiffness during haemodialysis. Kidney Int 2000; 57: 2634–2643. Acute volume load reflected from the interdialytic 5 Kosch M et al. Acute effects of haemodialysis weight gain abruptly influences cyclic tensile stress on endothelial function and large artery elasticity. and/or shear stress and may induce change of Nephrol Dial Transplant 2001; 16: 1663–1668. vascular tone. On the other hand, chronic volume 6 Marchais S et al. Arterial compliance in uraemia. overload may also induce alterations of mechanical J Hypertens Suppl 1989; 7: S84–S85. forces and lead to changes in the geometry and 7 Mourad A et al. Acute effect of haemodialysis composition of the vessel walls.17 Although volume on arterial stiffness: membrane bioincompatibility? Nephrol Dial Transplant 2004; 19: 2797–2802. withdrawal in the study had an acute, albeit small, 8 Ie EHY et al. Ultrafiltration improves aortic compliance impact on arterial wall characteristics, high aPWV in hemodialysis patients. J Hum Hypertens 2005; values and marked augmentation continued to be 19: 439–444 (this issue). present afterhaemodialysis.8 This indicates that the 9 Wilkinson IB et al. The influence of heart rate on acute large swing in volume status before and after augmentation index and central arterial pressure in haemodialysis affects arterial stiffness on top of a humans. J Physiol 2000; 525(Part 1): 263–270. more permanent alteration in arterial structure and 10 Lantelme P et al. Heart rate: an important confounder function, which is likely to be caused by chronic of pulse wave velocity assessment. Hypertension 2002; volume overload.8 The deranged body fluid distri- 39: 1083–1087. bution in haemodialysis patients has been demon- 11 Agarwal R. Assessment of blood pressure in hemo- dialysis patients. Semin Dial 2002; 15: 299–304. strated to be significantly related to structural and 12 Chen CH et al. Volume status and blood pressure functional alterations of the large arteries related to during long-term hemodialysis: role of ventricular chronic volume overload and/or body fluid distribu- stiffness. Hypertension 2003; 42: 257–262. tion.18 With the intermittent and brief nature of 13 Kyriazis J et al. Dialysate magnesium level and blood routine 4-h thrice-weekly dialysis schedule, high pressure. Kidney Int 2004; 66: 1221–1231.

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