[Relationship between pre-dialysis period and mortality and morbidity; the importance of timely pre-dialysis care]. / Relatie predialyseduur met mortaliteit en morbiditeit; het belang van een tijdige voorbereiding op dialyse.

OBJECTIVE: To investigate if the duration of pre-dialysis nephrology care is a predictive factor for mortality and morbidity in the first year of renal replacement therapy (RRT). DESIGN: Cohort study. METHOD: We included all patients with chronic or acute-on-chronic renal failure whose estimated glomerular filtration time (eGFR) was < 30 ml/min/1.73 m2 6 months before starting RRT and in whom RRT was initiated in 2005-2006 or 2009-2010. Depending on the duration of the pre-dialysis period we allocated patients to the short (< 6 months) or the long (≥ 6 months) pre-dialysis group. Data regarding mortality and morbidity were registered at the initiation of RRT (T0), after 3 (T3), 6 (T6) and 12 (T12) months. RESULTS: Thirty-nine patients with a short pre-dialysis period and 49 patients with a long pre-dialysis period were included. Patients with a short pre-dialysis period had higher mortality (T6: 23.1% vs. 8.2%; p = 0.05), more hospital stays (2 vs. 1 stay; p = 0.02), and longer hospital stays (16 vs. 3 days; p < 0.01). Additionally, in this group RRT more often had to be started through an acute route of administration for dialysis, which was associated with a higher mortality at T6 (23.8% vs. 6.5%; p = 0.02). CONCLUSION: A too short pre-dialysis period is predictive for higher mortality and morbidity in the first year after initiation of RRT. The necessity for an acute route of administration for dialysis seems to be the most important predictor.

The hemodynamic effect of different ultrafiltration rates in patients with cardiac failure and patients without cardiac failure: comparison between isolated ultrafiltration and ultrafiltration with dialysis.

OBJECTIVE: The increasing number of dialysis patients with cardiovascular diseases will lead to an increase in the incidence of intradialytic hypotension. Intradialytic hypotension is determined by changes in plasma volume, changes in vascular reactivity and structural cardiovascular changes. In this study the effect of two different ultrafiltration rates (UF-rate), i. e. 500 and 1000 ml/h, on plasma volume, extracellular volume and arterial blood pressure was studied during different treatments of 2 hours combined ultrafiltration + hemodialysis (UF+HD) and 2 hours isolated ultrafiltration (i-UF). PATIENTS AND METHODS: 15 Patients, 8 patients with cardiac failure, CFpts (NYHA classification III and IV) and 7 patients without cardiac failure (NCFpts) were investigated during a standardized dialysis treatment. RESULTS: The decrease in plasma volume and decrease in extracellular volume was comparable both between i-UF and UF+HD and comparable between CFpts and NCFpts and was only dependent on the UF-rate. i-UF resulted in minor blood pressure changes in both CFpts and NCFpts. In CFpts UF+HD resulted in a significant decrease in systolic blood pressure (SBP) at both UF-rates while in NCFpts SBP decreased significantly only at the higher UF-rate during UF-HD. Although there were no significant differences in hemodynamic stability during the different treatment modalities between CFpts and NCFpts, the decrease in SBP in CFpts at the higher UF-rate during UF+HD was much more pronounced. CONCLUSION: From this clinical study we conclude that differences in hemodynamic stability between i-UF and UF+HD and between CFpts and NCFpts are not related to differences in plasma volume preservation. Other factors like different changes in vascular reactivity and in CFpts structural cardiovascular changes might be responsible for the observed differences.

Effect of dialysate calcium concentrations on intradialytic blood pressure course in cardiac-compromised patients.

To prevent hypercalcemia in the treatment of secondary hyperparathyroidism, low calcium (L-Ca) dialysate is advocated. However, changes in ionized calcium (i-Ca) levels have a pivotal role in myocardial contraction and could influence blood pressure stability during dialysis. Recently, our group found in patients with normal cardiac function a significant decrease in blood pressure (decrease in systolic blood pressure [DSBP]: -13 mm Hg and decrease in mean arterial pressure [DMAP]: -7 mm Hg) during dialysis with L-Ca dialysate compared with high calcium (H-Ca) dialysate, and this was mainly related to a decreased left ventricular contractility with use of L-Ca dialysate. On the basis of these data, it could be expected that changes in i-Ca levels during dialysis are of more clinical importance in cardiac-compromised patients (CCpts), New York Heart Association classifications III and IV. In this study, the effects of L-Ca dialysate (1.25 mmol/L) and H-Ca dialysate (1.75 mmol/L) on arterial blood pressure parameters (systolic [SBP], diastolic [DBP], and mean arterial blood pressure [MAP]), heart rate, stroke distance (SDist), and minute distance (MDist) during 3 hours of a standardized ultrafiltration/hemodialysis (UF+HD) in nine CCpts was investigated. i-Ca levels increased significantly with H-Ca dialysate UF+HD, whereas there was no change with L-Ca dialysate. SBP, DBP, and MAP decreased statistically and clinically significantly during UF+HD with L-Ca dialysate and were significantly lower with the use of L-Ca dialysate compared with H-Ca dialysate. SDist and MDist decreased significantly with L-Ca dialysate, whereas there were no changes in SDist and MDist with H-Ca dialysate. The predialysis and postdialysis index of systemic vascular resistance (SVRI) was similar between L-Ca dialysate and H-Ca dialysate use. Between the two groups, there were no significant differences in changes in SVRI. From this study, we can conclude that changes in i-Ca levels are a very important determinant of the blood pressure response during UF+HD in CCpts, and this response is mediated by changes in myocardial contractility.

Effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients.

The influence of hypervolemia on hemodynamics and interdialytic blood pressure, as well as in relation to vascular compliance, was investigated in 10 hemodialysis patients who were not receiving vasoactive medication. All subjects were studied during a relative normovolemic interdialytic period (from 1 kg below dry weight postdialytic until dry weight predialytic) and a hypervolemic interdialytic period (from 1 kg above dry weight postdialytic until 3 kg above dry weight predialytic). Interdialytic blood pressure was measured with an ambulatory blood pressure monitor. Cardiac output was echographically measured and total peripheral resistance calculated postdialytic, mid-interdialytic, and predialytic. At the same time, a blood sample was drawn for analyzing vasoactive hormones, sodium, and hematocrit. In all patients, ideal dry weight was estimated by echography of the caval vein. Arterial and venous compliance were measured with an ultrasound vessel wall movement detector system and a strain-gauge plethysmograph. After fluid load, an increase in intravascular volume, an increase in caval vein diameter and cardiac output, and a decrease in peripheral resistance was observed. No significant influence of a 3-L fluid load was found on interdialytic blood pressure course (153+/-24 mm Hg/90+/-19 mm Hg in the hypervolemic period and 146+/-27 mm Hg/89+/-22 mm Hg in the normovolemic period). Sodium and osmolality were similar in the hypervolemic and normovolemic interdialytic periods. After fluid load, a decrease in arginine vasopressin and angiotensin II was observed, which probably contributed to the decreased systemic vascular resistance. Catecholamines were not influenced by fluid load, but increased during the interdialytic period, suggesting accumulation after dialysis. Three of the 10 patients had higher systolic but not diastolic blood pressures after fluid load (159+/-13 mm Hg/81+/-22 mm Hg in the hypervolemic period and 135+/-16 mm Hg/81+/-22 mm Hg in the normovolemic period). No correlation could be found between arterial or venous compliance and blood pressure changes. We concluded that a 3-L interdialytic fluid load does not result in higher blood pressure in most hemodialysis patients.

Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration.

Impaired vascular reactivity during combined ultrafiltration-hemodialysis (UF+HD) compared with hemofiltration (HF) remains a rather enigmatic problem, the causes of which are still not well understood. Although a number of factors have been claimed to be responsible, most recent studies point to a major role of the extracorporeal blood temperature, which is usually lower during HF compared with UF + HD. However, previous studies in which hemodynamics were studied during UF + HD and HF in relation to the extracorporeal blood temperature are limited by the use of acetate in UF + HD, and measurements were often confined to BP and heart rate. Therefore, arterial BP, as well as forearm vascular resistance (FVR) and venous tone (strain-gauge plethysmography), was measured in 11 hemodialysis patients during 3 h UF + HD (37.5 degrees C) and predilution HF (39.0 degrees C = warm HF), resulting in equivalent extracorporeal blood temperatures. Patients were also studied during cold HF at an infusate temperature of 36.0 degrees C. UF + HD and HF were matched with respect to the dialysate and infusate composition (bicarbonate), bio-compatibility factors, and small molecule clearance. At equivalent temperatures, UF + HD and HF were associated with a comparable vascular and BP response. Only cold HF was associated with a significant increase in FVR. In addition, FVR and venous tone, as well as arterial BP, were all significantly higher during cold HF compared with both UF + HD and warm HF. These results indicate that the disparity in vascular reactivity between UF + HD and HF is primarily related to differences in the extracorporeal blood temperature.

Influence of changes in ionized calcium on cardiovascular reactivity during hemodialysis.

In order to prevent hypercalcemia due to the treatment of secondary hyperparathyroidism the use of low calcium dialysate is advocated. However, as calcium ions play a pivotal role in both myocardial and vascular smooth muscle contraction, lowering the dialysate calcium concentration might result in a further impairment of the cardiovascular response during dialysis. Therefore, arterial blood pressure, forearm vascular resistance (FVR) and venous tone (VT) (straing-gauge plethysmography) as well as cardiac dimensions and output (echocardiography) were measured in 10 hemodynamically stable dialysis patients (ejection fraction > 30%) during two standardized sessions of three-hour combined ultrafiltration-hemodialysis (UF + HD) at two different dialysate calcium concentrations: 1.25 and 1.75 mmol/l. High calcium UF + HD resulted in a significant increase in plasma ionized calcium (+0.19 +/- 0.11 mmol/l; p < 0.01) while ionized calcium remained unchanged during low calcium UF + HD (-0.02 +/- 0.07 mmol/l). As a result, systolic, diastolic and mean arterial blood pressure were respectively 14 +/- 10, 5 +/- 7 and 9 +/- 9 mmHg higher during high calcium UF + HD as compared to low calcium UF +/- HD (p < 0.05). There were no significant differences in FVR and VT between the two treatments. During both treatments FVR increased while VT decreased. In addition, there were no differences in calculated systemic vascular resistance. However, with comparable end-diastolic dimensions, stroke volume (-18 +/- 13 ml) and cardiac output (-1.3 +/- 1.5 l/min) decreased significantly (p < 0.05) only during low calcium UF + HD. We conclude that even in hemodynamically stable patients changes in plasma ionized calcium are an important determinant of the blood pressure response during dialysis therapy. Whereas peripheral vascular reactivity is unaffected by changes in ionized calcium, myocardial contractility is improved with higher dialysate calcium concentrations.

Vascular reactivity during combined ultrafiltration-hemodialysis: influence of dialysate-derived contaminants.

It has been suggested that hemodynamic instability and impaired vascular reactivity during combined ultrafiltration-hemodialysis are related to bioincompatibility factors such as dialysate-derived contaminants or the dialyzer. The study presented here investigated whether vascular reactivity could be improved by the use of sterile dialysate. Forearm vascular resistance and venous tone (measured by strain-gauge plethysmography) as well as arterial blood pressure (by Dinamap) and heart rate (by electrocardiogram) were measured in ten stable dialysis patients (age range, 28 to 71 yr) during 2 h of combined ultrafiltration-hemodialysis (bicarbonate; ultrafiltration rate 1.0 L/h). In addition, a dialysate sample was obtained for culture and limulus amebocyte lysate testing while blood was withdrawn for the estimation of plasma bactericidal/permeability increasing factor (measured by ELISA) and the soluble tumor necrosis factor receptor p75 (measured by ELISA). Patients served as their own control, comparing dialysis with nonsterile and sterile dialysate. No bacterial growth was observed in sterile dialysate, whereas all samples were positive for Pseudomonas in culture in nonsterile dialysis. All limulus amebocyte lysate tests were negative. Bactericidal/permeability increasing factor tended to increase during nonsterile dialysis (P = 0.063) and remained unchanged during sterile dialysis. In both treatments, tumor necrosis factor receptor p75 increased significantly (P < 0.01). There were no significant differences in hemodynamic parameters between the treatment modalities. Despite use of sterile dialysate, forearm vascular resistance remained unchanged whereas venous tone decreased significantly. These results indicate that vascular reactivity during combined ultrafiltration-hemodialysis is not improved by the use of sterile dialysate.

Vascular reactivity during combined ultrafiltration-haemodialysis: influence of dialysate sodium.

BACKGROUND: It is well known that vascular reactivity is impaired during combined ultrafiltration-haemodialysis as compared to isolated ultrafiltration and haemofiltration, which might be related to differences in plasma osmolality. Therefore vascular reactivity was studied during combined ultrafiltration-haemodialysis in relation to sodium-related differences in plasma osmolality/tonicity. METHODS: With each patient serving as his or her own control, nine stable dialysis patients (23-71 years) were studied during 2 h of combined ultrafiltration-haemodialysis (bicarbonate; UF rate 1.0 l/h)) at two different dialysate sodium concentrations: 134 and 144 mmol/l. Before dialysis as well as every 20 min during dialysis, blood pressure (Dinamap), heart rate (ECG), and forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured. Relative blood volume was monitored continuously by an optical reflection method (Haemoguard 2000), while before and after dialysis blood was obtained for the estimation of plasma prostaglandin E2. RESULTS: High-sodium dialysis resulted in a significantly higher post-dialysis plasma sodium concentration (139. 9 vs 135.0 mmol/l; P<0.01) while the decrease in relative blood volume was significantly smaller as compared to low-sodium dialysis (-8.4 vs -18.4%; P<0.01). There were no significant differences in the different haemodynamic parameters between the two treatment modalities. Both high- and low-sodium dialysis were associated with a significant increase in forearm vascular resistance while venous tone remained unchanged. Although there was no significant difference in plasma PGE2 between the two treatment modalities, PGE2 increased significantly only during low-sodium dialysis. We found no relationship between changes in PGE2 and vascular reactivity. CONCLUSIONS: We conclude that vascular reactivity during combined ultrafiltration-haemodialysis is not directly influenced by sodium-related changes in plasma tonicity. Although not directly studied, the reported improved haemodynamic stability with high-sodium dialysis is probably only mediated through a better preservation of plasma volume. Finally, an increase in plasma PGE2 as observed during low-sodium dialysis does not lead to a decrease in vascular tone.

Preventing haemodynamic instability in patients at risk for intra-dialytic hypotension.

Although as yet no major breakthroughs have occurred to improve long-term survival of haemodialysis patients with impaired cardiovascular function, it is possible to reduce morbidity by intra-dialytic hypotension in these patients by the use of relatively simple manoeuvres. In our experience, this can be achieved using the following approach (Table 1). First, the decline in plasma volume can be reduced by adequate estimation of the optimal dry weight by objective methods, such as echography of the inferior caval vein or bioimpedance measurements. Furthermore, the ultrafiltration rate during haemodialysis should be moderate and should be limited to a maximum value, which has to be defined empirically for each individual patient. Especially in patients with excess inter-dialytic weight gain, isolated ultrafiltration should be used when the required amount of fluid cannot be removed during haemodialysis. The use of low-sodium dialysate should be avoided. Probably it is best to use a physiological sodium concentration of the dialysate because a greater sodium concentration may result in increased thirst and intra-dialytic weight gain. Sodium profiling should be based on further studies concerning plasma volume changes during haemodialysis in different patient groups. Because of the deleterious impact of acetate on vascular reactivity, it should never be used in patients prone to hypotensive periods. Vascular reactivity can also be impaired by the use of vasoactive medication prior to haemodialysis treatment. Therefore, in patients prone to hypotensive periods, vasoactive medication should be withheld the morning before haemodialysis, if possible. Also, one should be very cautious with the use of low-calcium dialysate in patients with frequent hypotensive periods, and ideally it should be avoided. If the use of these manoeuvres fails to control intra-dialytic hypotension, one should consider the use of cold dialysate. Switching to haemofiltration or to continuous treatment modes such as CAPD are other options. Future studies should address haemodynamics during other treatment modes, such as haemodiafiltration or acetate-free biofiltration.

Vascular reactivity during haemodialysis and isolated ultrafiltration: thermal influences.

BACKGROUND: The present study was performed to assess the role of the extracorporeal blood temperature in the disparate cardiovascular response between isolated ultrafiltration and combined ultrafiltration-haemodialysis. METHODS: In twelve stable dialysis patients (21-77 years), blood pressure and heart rate (Finapres) as well as forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured during 1-h isolated ultrafiltration and 1-h combined ultrafiltration-haemodialysis (bicarbonate, sodium 141 mmol/l) at a fixed ultrafiltration rate of 0.91 l/h. The sequence of both treatment modalities was randomly defined within each patient. Serving as his or her own control, each patient was studied at two different dialysate temperatures: 37.5 and 35.0 degrees C. RESULTS: At a dialysate temperature of 35.0 degrees C extracorporeal blood cooling during combined ultrafiltration-haemodialysis was comparable to isolated ultrafiltration. The cardiovascular response in isolated ultrafiltration was characterized by a significant increase in both forearm vascular resistance and venous tone, while heart rate even decreased. As a result, blood pressure remained unchanged or even increased. In contrast, during combined ultrafiltration-haemodialysis at a dialysate temperature of 37.5 degrees C the increase in forearm vascular resistance was only small and insignificant, while venous tone decreased significantly. Heart rate tended to increase. Combined ultrafiltration-haemodialysis at a dialysate temperature of 35.0 degrees C was also associated with a small increase in forearm vascular resistance. However, venous tone remained stable while heart rate decreased. At both dialysate temperatures, blood pressure was well maintained. CONCLUSIONS: We conclude that differences in cardiovascular reactivity between isolated ultrafiltration and combined ultrafiltration-haemodialysis are only partially explained by differences in the extracorporeal blood temperature. In addition, especially venous reactivity is improved by lowering the dialysate temperature.

Long-term effects of recombinant human erythropoietin on macro- and microcirculation in chronic hemodialysis patients.

Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an increase in systemic vascular resistance and to a decrease in cardiac index and skin microcirculatory flow. Long-term adaptive changes might occur. We studied the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8 normotensive and normovolemic hemodialysis patients before and after, respectively, 4 and 14 months of treatment. The reported macrocirculatory changes at short term were at long term not significantly different as compared with the initial values. The mean arterial pressure remained unaltered, as might be explained by the slow correction of the hematocrit and the decrease in cardiac output in all initially long-lasting normotensive patients who were maintained normovolemic. Left ventricular end-diastolic dimensions decreased, and also the left ventricular muscle mass decreased, depending on the initial left ventricular muscle mass. The skin oxygenation improved, whereas the maximal capillary flow decreased both at short- and long-term ReHuEpo treatment. The number of capillaries in the nail fold remained unchanged. However, the percentage of tortuosity decreased significantly during ReHuEpo therapy.