Elena Mancini

Blood Volume Regulation During Hemodialysis

Hemodialysis (HD)-induced hypotension may be precipitated by severe hypovolemia. To avoid the appearance of destabilizing hypovolemias, we have developed a biofeedback control system for intradialytic blood volume (BV)-changes modeling. The system, incorporated in a dialysis machine, is based on a multivariable closed-loop control with a dependent output variable, the BV changes, and two independent control variables, the ultrafiltration rate (Qf) and dialysate conductivity (DC). The relative BV changes occurring during HD are measured by an optical device. The Qf and DC are continuously adjusted by the control model during the treatment to minimize any discrepancies between the ideal targets for the BV, the patients body weight reductions, and the experimentally obtained results. The system manages three kinds of errors: in BV changes, the total weight loss, and the sodium balance. The latter is controlled by a dedicated kinetic model that continuously calculates the equivalent DC and, by the end of the session, tends to make the sodium balance the same as the one obtained in conventional HD with constant DC. This systems capacity to improve intradialytic hemodynamic tolerance has been assessed in a crossover study of eight highly symptomatic patients. Conventional HD (CHD; period A) was compared with blood volume-controlled dialysis sessions (BV-CHD; period B) following a protocol with an A1-B-A2 sequence, with each period lasting 1 month. A lower decrease in BV (-10.6%) was obtained during BV-CHD (period B) compared with CHD (-12.3% in period A1 and -12.5% in period A2). The predialysis to postdialysis systolic arterial pressure changes were lower in period B (-12.4%) than in period A (-20% in A1 and -17.5% in A2; P < 0.05) despite similar total Qf and mean treatment times. A significant reduction in the number of severe hypotensive episodes (three in period B v 26 in period A1 and 16 in period A2; P < 0.05) and the overall incidence of complaints, especially of muscular cramps, was found in BV-CHD. These results were reflected in a reduced need for therapeutically administered isotonic saline in each session (60 mL in B v160 mL in A1 and 95 mL in A2; P < 0.05). In conclusion, the proposed biofeedback system for intradialytic BV control may be useful to avoid severe hypovolemic states, to stabilize BV by modeling its trend, and to avoid reaching individual critical BV thresholds in hypotension-prone patients.

The effect of on-line high-flux hemofiltration versus low-flux hemodialysis on mortality in chronic kidney failure: a small randomized controlled trial.

BACKGROUND Given the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD). STUDY DESIGN An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle. SETTING & PARTICIPANTS Prevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers. INTERVENTIONS Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32). OUTCOMES & MEASUREMENTS All-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method. RESULTS There was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06 versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54 mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 +/- 0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03). LIMITATIONS This is a small preliminary intervention study with a high dropout rate and problematic generalizability. CONCLUSION On-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index. A larger study is required to confirm these results.

Hemoscan: a dialysis machine-integrated blood volume monitor.

We describe an opto-electronic device capable of measuring the hemoglobin concentration (Hgb) non-invasively and continuously, hence the percentage changes in blood volume (BV) during dialysis treatment by means of the optical absorption of monochromatic light by the blood in the arterial line. This method has been validated during several in vitro and in vivo tests, during which the system has shown a low sensitivity to all the common intra-dialytic interference factors, such as oxygen saturation (max. err.=1.6%), blood flow (max. err. =1.8%), osmotic pressure (max. err.=0.7°) and hydraulic pressure (max. err.=0.6°), a high precision (std. err.≤0.1 g/dl) and a good accordance (Hgb mean err.=0.1 g/dl; std. err.=0.38 g/dl; BV mean err.=0.1%; std. err.=1.6%) with the corresponding values derived from standard laboratory tests.

Automatic control of blood volume trends during hemodialysis.

Dialysis induced hypovolemia plays an important role in triggering intradialytic hypotension. The authors developed an automatic system (BVAC) with feedback changes in the ultrafiltration rate (UFR) and dialysate conductivity (DC) to match blood volume (BV) intradialytic profiles with the desired trajectories. The system consists of three subunits: (1) an optical probe to continuously detect the BV changes derived from hemoglobin changes, and (2) a dialysis machine interfaced with (3), a personal computer in which a time-dependent model is implemented. The model is based on a dynamic regulator that can set the actual BV changes against the corresponding desired values. Any discrepancy is offset by changes in UFR and DC. To verify the efficacy of the BVAC system in reducing intradialytic cardiovascular instability, five hypotension-prone patients were studied during a three period protocol (A1-B-A2) that lasted six sessions per period per patient. During periods A1 and A2, the dialysis procedure was conventional hemodialysis (HD) with linear UFR and constant DC. During period B, both UFR and DC were automatically regulated by the BVAC system. Mean BV reduction and its variability were lower during period B than during periods A1 and A2 (-10.2%, -11.3%, and -11.5, respectively). Episodes of hypotension were significantly (P < 0.05) fewer during period B (n = 1) than during periods A1 (n = 8) and A2 (n = 5). The therapeutic interventions defined as infused milliliters of isotonic and hypertonic solution were fewer during period B compared with periods A1 and A2. Total UF and end-dialysis plasma sodium concentrations did not differ in the three study periods. BVAC was effective in improving cardiovascular tolerance to treatment.

Liver support systems.

Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity of toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile acids or mercaptans) ar

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Renal ultrasonography in critically ill patients.

Acute renal failure is a sudden and sustained decrease in the glomerular filtration rate associated with a loss of excretory function and the accumulation of metabolic waste products and water. It leads to an increase in serum urea and creatinine, usually with a decrease in urine output. Although routine surveillance of patients by means of laboratory examinations has been well defined, very little is known about renal imaging. Modern technology has provided a large number of sophisticated monitoring systems. Ultrasonography with color-Doppler study of the kidneys may be indicated as a possible monitor of renal perfusion. Ultrasonography is often used as the initial imaging procedure in the examination of patients with renal failure. Aside from excluding hydronephrosis, it is well recognized in characterizing the type of renal disease, especially in an acute setting. This article describes the use of ultrasound to achieve the proper diagnosis of acute renal diseases and to enable the appropriate and early assessment of these patients in intensive care units.

MARS and Prometheus: Our Clinical Experience in Acute Chronic Liver Failure

INTRODUCTION In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Body mass index trend in haemodialysis patients: The shift of nutritional disorders in two Italian regions

BACKGROUND In the USA, the increase in the prevalence of obesity in the general population has been accompanied by a marked increase in the prevalence and incidence of obesity in the dialysis population. However, secular trends of body mass index (BMI) have not been investigated in European renal registries. METHODS We investigated the secular trend of BMI across 18 years (1994-2011) in two haemodialysis (HD) registries (Calabria in southern Italy and Emilia in northern Italy) on a total of 16 201 prevalent HD patients and in a series of 3559 incident HD patients. We compared trends in BMI for HD patients with those in the background general population of the same regions. RESULTS The average BMI rose from 23.5 kg/m(2) in 1994 to 25.5 (+8.5%) in 2011 in the Calabria registry and from 23.7 in 1998 to 25.4 (+7.1%) in 2011 in the Emilia registry (P < 0.001). The proportion of obese patients (i.e. with BMI >30 kg/m(2)) rose from 6 to 14% in Calabria and from 6 to 16% in Emilia (P < 0.001). These patterns were fully confirmed in incident patients and were mirrored by a substantial decline in the prevalence of underweight-normal and underweight (P < 0.001) patients. Of note, the steepness of the increase in BMI in haemodialysis patients was 3.7 times more pronounced than that in the coeval, age- and sex-matched general population of Calabria and Emilia. CONCLUSIONS In two regional haemodialysis registries in Italy a steady increase in overweight and obese patients is observed. These patterns are more pronounced than those found in the general population. If further confirmed in other European haemodialysis cohorts, these findings may have relevant public health implications.

Bortezomib-based therapy combined with high cut-off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influences the prognosis. Several studies demonstrated that bortezomib can improve both renal function and outcome. We prospectively evaluated 21 newly diagnosed MM patients with severe renal impairment secondary to tubular‐interstitial damage, most of them due to myeloma kidney, who were primarily treated with bortezomib‐based therapy combined with high cut‐off hemodialysis (HCOD). The median serum creatinine level at baseline was 6.44 mg dL−1 and calculated median estimated glomerular filtration rate (eGFR), according to Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) creatinine equation, was 8 mL/min/1.73 m2. Serum free light chain (sFLC) median concentration was 6,040 mg L−1. Post induction and best stringent complete response rates were 19 and 38%, respectively. Responses were fast, occurring within a median of 1.4 months. The combination of bortezomib and HCOD led to a prompt and remarkable (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis independent within a median of 32 days. With a median follow up of 17.2 months, the 3‐year PFS and OS were 76 and 67%, respectively. No early deaths were observed. This study demonstrates that incorporation of bortezomib into induction therapy combined with HCOD is a highly effective strategy in rescuing renal function and improving outcomes in patients with MM and RI. Am. J. Hematol. 90:647–652, 2015.