Roel M. Huisman

Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis

Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra‐HD hemodynamic stability. We first questioned whether BVT also improves post‐HD blood pressure stability in hypotension‐prone patients and second, whether BVT is effective in reducing the post‐HD weight as many hypotension‐prone patients are overhydrated because of an inability to reach dry weight. After a 3‐week period on standard HD, 12 hypotension‐prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post‐HD target weight was kept identical compared with the standard HD period (BVT‐constant weight; BVT‐cw). During the second BVT period of 6 weeks, we gradually tried to lower the post‐HD target weight (BVT‐reduced weight; BVT‐rw). In the last week of each period, we studied intra‐HD and 24 hr post‐HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre‐ and post‐HD weight did not differ between standard HD and either BVT‐cw or BVT‐rw. Heart size on a standing pre‐dialysis chest X‐ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post‐HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension‐prone patients is associated with higher systolic blood pressures for as long as 16 hr post‐HD. BVT was not effective in reducing the post‐HD target weight in this patient group.

Determination of protein catabolic rate in patients on chronic intermittent hemodialysis: Urea output measurements compared with dietary protein intake and with calculation of urea generation rate

We assessed the agreement between different methods of determining protein catabolic rate (PCR) in hemodialysis patients and the possible influence of postdialysis urea rebound and the length of the interdialytic interval on the PCR determination. Protein catabolic rate derived from measured total urea output was compared with recorded daily protein intake (DPI) and calculated urea generation rate (G), calculated by the interdialytic increase in serum urea and an estimated urea distribution volume using either the Watson equation or 58% of postdialysis body weight, and by single-pool urea kinetic modelling. In 16 patients PCR derived from calculated G by fixed urea distribution volume showed a significant decrease with blood samples obtained 10 minutes after dialysis onward as compared with immediately after dialysis, leading to an approximately 6% decrease at 60 minutes. Protein catabolic rate values derived from blood samples taken 15 to 60 minutes after dialysis were not significantly different. Urea kinetic modelling led to a significant increase in calculated PCR with samples from 5 minutes after dialysis onward and a total increase by 11.5% at 60 minutes. Different methods for determining PCR were compared in 13 clinically stable outpatients treated with conventional hemodialysis on cellulose acetate membrane dialyzers during 1 week. The mean PCR calculated from measured total urea output was 61.3 g/24 hr (range, 43.7 to 83.2 g/24 hr). Assessment of DPI as compared with PCR calculated from measured total urea output was lower by 7.5% (95% confidence intervale [CI], 1.4 to 17.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of ultrafiltration volume on blood volume changes during hemodialysis as observed in day-of-the-week analysis of hemodialysis sessions

Monitoring of relative blood volume changes (&Dgr;RBV) has been propagated for the prevention of hemodialysis hypotension. Although the influence of ultrafiltration volume on &Dgr;RBV is well-known, there is no mention in the literature that &Dgr;RBV results should be interpreted differently for the first, second, or third hemodialysis session of the week. To elucidate whether &Dgr;RBV and its derivative, &Dgr;RBV normalized for ultrafiltration volume (&Dgr;RBV/ultrafiltration ratio), vary systematically over the week, we separately analyzed these parameters for the first, second, and third hemodialysis session of the week in 13 chronic hemodialysis patients over a 17-week period. As expected, mean (±SD) ultrafiltration volume was significantly (p < 0.001) higher during the first session than during the second and third hemodialysis sessions (3163 ± 615, 2622 ± 674 and 2607 ± 638 ml, respectively). &Dgr;RBV was significantly (p < 0.01) more negative at the first session than at the second and third hemodialysis sessions (−10.1 ± 2.7, −9.3 ± 3.0 and −9.3 ± 3.1%, respectively). The &Dgr;RBV/ultrafiltration ratio was significantly (p < 0.01) less negative at the first session than at the second and third hemodialysis sessions (−3.2 ± 0.6, −3.5 ± 0.8 and −3.6 ± 0.6%/l, respectively). In conclusion, &Dgr;RBV and the &Dgr;RBV/ultrafiltration ratio differ systematically between the first and other hemodialysis sessions in patients on a thrice-weekly hemodialysis schedule, most likely as a result of different ultrafiltration volumes.

Effects of relative blood volume-controlled hemodialysis on blood pressure and volume status in hypertensive patients

In hypertensive hemodialysis (HD) patients, dry weight reduction to normalize blood pressure (BP) often results in increased frequency of HD hypotension. Because HD with blood volume tracking (BVT) has been shown to improve intra-HD hemodynamic stability, we performed a prospective, randomized study to test whether BVT is more effective than standard hemodialysis (SHD) in the management of hypertension by dry weight reduction. After a run-in period of 4 weeks on SHD, 28 patients were randomly assigned for a 12-week treatment period with either SHD (n = 14) or BVT (n = 14). The mean pre-HD and post-HD weight did not change over time in either group. In the BVT group, pre-HD systolic and diastolic BP decreased on average 22.5 mm Hg and 8.3 mm Hg, respectively (both p < 0.05), whereas BP did not change in the SHD group. Extracellular water and cardiothoracic ratio decreased significantly (all p < 0.05) in the BVT group but not in the SHD group. Brain natriuretic peptide levels declined only in the BVT group, without reaching statistical significance. The frequency of HD hypotensive episodes decreased significantly (p < 0.05) in the BVT group and was unchanged in the SHD group. HD with BVT was associated with a significant reduction in pre-HD BP. At the same time, the frequency of intra-HD hypotensive episodes decreased. Although the mean weight did not change, the reductions in cardiothoracic ratio and extracellular water suggest that HD with BVT resulted in optimization of volume status.

Changes in Renal Function Induced by ACE-lnhibition in the Conscious Two-Kidney, One-Clip Goldblatt Hypertensive Dog

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)

ANGIOTENSIN CONVERTING ENZYME-INHIBITION IMPROVES DIAGNOSTIC PROCEDURES FOR RENOVASCULAR HYPERTENSION IN DOGS

In renovascular hypertension adaptive mechanisms in the poststenotk kidney are a probable cause of the 20 to 25% false-negative findings during rapid sequence urography or [123I]oiodohippurate renography. We blocked the renin-angiotensin system in an effort to increase the yield of these diagnostic procedures. Chronically instrumented, salt-depleted conscious dogs were used in which a light (n = 5), moderate (n = 4), or severe (n = 2) renal artery stenosis was induced. Before stenosis 10 of the dogs showed no left-right differences with either diagnostic procedure, and angiotensin converting enzyme (ACE) inhibition did not change this result. Two to 3 weeks after induction of a renal artery stenosis, all dogs showed signs of renovascular hypertension. However, only 50% of the renograms and 22% of the urograms showed differences between the two kidneys indicative of the presence of stenosis. After ACE inhibition, all previously negative test results became positive (abnormal) and previously existing left-right differences became more evident. Ekctromagnetically measured renal blood Bow on the stenotic side did not change during ACE inhibition (146 ± 13 vs 145 ± 21 ml/mm), whereas contralateral blood flow showed a distinct increase (207 ± 18 vs 282 ± 20 ml/min, p < 0.01). In conclusion, ACE Inhibition markedly improves the sensitivity of rapid sequence urography and hlppurate renography in the diagnosis of renovascular hypertension in the two-kidney, one clip Goldblatt hypertensive dog. The effects of ACE inhibition on the handling of the different tracers do not appear to be related to its effects on renal blood flow or systemic blood pressure.

Effect of high and low ultrafiltration volume during hemodialysis on relative blood volume

Achieving an optimal posthemodialysis hydration status may be difficult because objective criteria for dry weight are lacking. Both relative blood volume changes (&Dgr;RBV) at the end of hemodialysis and &Dgr;RBV normalized for ultrafiltration volume (&Dgr;RBV/UF ratio) have been reported to indicate posthemodialysis volume status. A parameter for volume status should not be influenced by variations in ultrafiltration volume. However, if the volume that has to be ultrafiltrated to reach dry weight varies as a result of variations in prehemodialysis weight, either &Dgr;RBV or the &Dgr;RBV/UF ratio (or both) must change. To elucidate the relation between intradialytic ultrafiltration volume versus &Dgr;RBV and its derivative, the &Dgr;RBV/UF ratio, we studied the effect of a relatively high (mean ± SD, 2.7 ± 0.5 l) and low (1.5 ± 0.3 l) intradialytic ultrafiltration volume on these parameters in eight patients. Posthemodialysis weight was comparable in low and high ultrafiltration volume sessions. The average end-hemodialysis &Dgr;RBV did not differ between high (–6.7 ± 2.5%) and low ultrafiltration volume sessions (–7.3 ± 1.0%; NS), but the intraindividual variation was considerable. The &Dgr;RBV/UF ratio differed markedly (p < 0.001) between high (–2.4 ± 0.8 %/l) and low (–4.9 ± 1.3 %/l) ultrafiltration volume sessions. In conclusion, the considerable random intraindividual variation of &Dgr;RBV and the systematic change of the &Dgr;RBV/UF ratio with variations in intradialytic ultrafiltration volume limit the use of these parameters as an aid to assess hydration status in hemodialysis patients.

PHARMACOLOGICAL ZERO FOR ELECTROMAGNETIC RENAL BLOOD-FLOW MEASUREMENT

Measurement of blood flow in chronically instrumented laboratory animals using electromagnetic flow probes depends on a reference “zero flow” value. The latter is usually obtained by mechanical vessel occlusion. We tested an alternative method: a bolus of angiotensin II was injected in the abdominal aorta resulting in an immediate decrease of renal blood flow. Diastolic blood flow at this stage appeared to be identical to the zero level obtained by mechanical occlusion. Thus, pharmacological interruption of renal blood flow may serve as a zero reference in the dog.

Membrane Biocompatibility Does Not Affect Whole Body Protein Metabolism during Dialysis

Background: Protein-calorie malnutrition is present in 30–50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. Methods: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-13C]-valine was used during a 4-hour dialysis session. Results: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (–15 ± 3) and cuprophan (–13 ± 2 µmol/kg/h) dialysis. Conclusion: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.

Angiotensin converting enzyme inhibition induces alterations to hippuran renography despite unchanged ipsilateral renal blood flow in conscious two-kidney, one clip Goldblatt hypertensive dogs

We performed experiments in the two-kidney, one clip Goldblatt hypertensive dog to see whether angiotensin converting enzyme (ACE) inhibition could improve the sensitivity of hippurate renography in detecting renal artery stenosis. Ten dogs on a sodium-restricted diet were studied before and after induction of a renal artery stenosis. In the absence of renal artery stenosis nine dogs showed normal renograms before ACE inhibition, and one was false positive. During ACE inhibition all 10 renograms were normal. With a renal artery stenosis 50% of the renograms were false negative, whereas a 100% sensitivity was reached during ACE inhibition. The alterations induced by the ACE inhibition on the renograms were not related to changes in renal blood flow. In conclusion, ACE inhibition markedly improved the sensitivity of hippurate renography in the two-kidney, one clip dog.