Comparison of blood volume biofeedback hemodialysis and conventional hemodialysis on cardiovascular stability and blood pressure control in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Despite the improvements in hemodialysis (HD) technology, 20-30% of sessions are still complicated by hypotension or hypotension-related symptoms. Biofeedback systems have proven to reduce the occurrence of such events, but no conclusive findings can lead to wider adoption of these systems. We conducted this systematic review and meta-analysis of randomized clinical trials to establish whether the use of blood volume tracking systems compared to conventional hemodialysis (C-HD) reduces the occurrence of intradialytic hypotension. METHODS: The PRISMA guidelines were used to carry out this systematic review. Randomized clinical trials that evaluated the incidence of intradialytic hypotension during C-HD and blood volume tracking-HD were searched in the current literature. PROSPERO registration number: CRD42023426328. RESULTS: Ninety-seven randomized clinical trials were retrieved. Nine studies, including 347 participants and 13,274 HD treatments were considered eligible for this systematic review. The results showed that the use of biofeedback systems reduces the risk of intradialytic hypotension (log odds ratio = 0.63, p = 0.03) in hypotension-prone patients (log odds ratio = 0.54, p = 0.04). When analysis was limited to fluid overloaded or hypertensive patients, it did not show the same effect (log odds ratio = 0.79, p = 0.38). No correlation was found in systolic blood pressure drop during dialysis and in post-dialysis blood pressure. CONCLUSIONS: The use of blood volume tracking systems may be effective in reducing the incidence of intradialytic hypotension and allowing for easier attainment of the patients' ideal dry body weight. New studies to examine the long-term effects of the use of blood volume tracking systems on real hard endpoints are needed.

Sotrovimab in SARS-COV-2 chronic hemodialysis patients in the Omicron era. Is intradialytic administration feasible? Report of 4 cases.

Chronic hemodialysis patients are at high risk of morbidity and mortality in case of SARS-CoV-2 infection and they may need to be treated with monoclonal antibodies, either because they have not been vaccinated, or because they have a low anti spike antibody titer. Administration of Sotrovimab has recently been proposed for hemodialysis patients, but data are on the results lacking. We report on four cases of chronic dialysis patients who received Sotrovimab during intermittent dialysis sessions. In our series, no adverse reactions were recorded; intradialytic administration resulted safe and allowed an adequate observation time without prolonging hospital stay in chronic hemodialysis outpatients.

A novel double parameters based biofeedback system to prevent intradialytic hypotension in clinical practice: Case report.

Intradialytic hypotension (IDH) still represents the main complication during dialysis treatment. Patient's discomfort, reduced dialysis efficiency, reduced treatment time are only some of the main problems that could derive from the need to stop or temporarily interrupt the treatment because of IDH. Up to now, different types of treatment (HDF, HF, or AFB) have been considered to prevent IDH as well as the use of biofeedback systems (Blood Volume Monitoring, Temperature control, Sodium profiling, Blood Pressure monitoring). Recently a new biofeedback system (Biologic Fusion®) controlling simultaneously blood pressure (BP) and relative blood volume changes (RBV) has been developed to prevent IDH. This system runs according to fuzzy logic. We describe how this system works and to a better understanding, we report a clinical case of a patient with frequent IDH treated with the use of this system.

Flash Glucose Monitoring to Assess Glycemic Control and Variability in Hemodialysis Patients: The GIOTTO Study.

Background: Flash glucose monitoring (FGM) is a technology with considerable differences compared to continuous glucose monitoring (CGM), but it has been scarcely studied in hemodialysis patients. Thus, we aimed assessing the performance of FGM in such patients by comparison to self-monitoring of blood glucose (SMBG). We will also focus on estimation of glycemic control and variability, and their relationships with parameters of glucose homeostasis. Methods: Thirty-one patients (20 with type 2 diabetes, T2DM, 11 diabetes-free, NODM) collected readings by FGM and SMBG for about 12 days on average. Readings by FGM and SMBG were compared by linear regression, Clarke error grid, and Bland-Altman analyses. Several indices of glycemic control and variability were computed. Ten patients also underwent oral glucose tolerance test (OGTT) for assessment of insulin sensitivity/resistance and insulin secretion/beta-cell function. Results: Flash glucose monitoring and SMBG readings showed very good agreement in both T2DM and NODM (on average, 97 and 99% of readings during hemodialysis in A+B Clarke regions, respectively). Some glycemic control and variability indices were similar by FGM and SMBG (p = 0.06-0.9), whereas others were different (p = 0.0001-0.03). The majority of control and variability indices were higher in T2DM than in NODM, according to both FGM and SMBG (p = 0.0005-0.03). OGTT-based insulin secretion was inversely related to some variability indices according to FGM (R < -0.72, p < 0.02). Conclusions: Based on our dataset, FGM appeared acceptable for glucose monitoring in hemodialysis patients, though partial disagreement with SMBG in glycemic control/variability assessment needs further investigations.

COVID-19 incidence and mortality in non-dialysis chronic kidney disease patients.

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.

Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.

Clinical, electromyographical, histopathological characteristics of COVID-19 related rhabdomyolysis.

Rhabdomyolysis is an uncommon complication of the coronavirus disease 2019 (COVID-19) infection. Previous reports have described its management and treatment in medical units, but have not discussed confirmatory tests or differential diagnosis. We report a case of a 58 year-old male patient, who was admitted for COVID-19 pneumonia and subsequently developed severe weakness, inability to move limbs, acute renal failure, significantly elevated myoglobin and creatinine kinase, and was diagnosed with rhabdomyolysis. Continuous renal replacement therapy, the treatment modality of choice over hyperhydration due to ongoing mechanical ventilation, was effective in resolving symptoms. No direct viral invasion of muscles was noted on biopsy. Here, we describe his symptoms, electromyography, and muscular biopsy results, and further discuss the possible differential diagnoses. Neuromuscular symptoms related to COVID-19 require careful clinical analysis. In addition, detailed reports of patients' course of illness and diagnoses will assist in improving care for affected patients.

Central venous catheter management prior to the start of the dialysis session: a new device to improve a critical procedure.

BACKGROUND: Central venous catheter (CVC) preparation for a haemodialysis (HD) session is a critical non-standardized manoeuvre. METHODS: We compared the procedure in use at our centre (C) versus the use of Haemocatch® (H), a device recently presented for the management of CVC, in 12 patients, with C during 7 dialysis sessions and H during the subsequent 7 sessions. RESULTS: Out of 75 HD sessions with C and 75 with H, both the number of connections and disconnections of the CVC via a syringe and the amount of blood wasted during the manoeuvres proved significantly lower with H (2.19 ± 0.59 for H vs. 4.23 ± 0.78 for C, p = 0.00093; 5.97 ± 2.77 ml for H vs. 14.57 ± 6.3 ml for C, p = 0.000078, respectively). CONCLUSIONS: The new device could improve the quality of care in the HD patients carrying a CVC: standardization of the procedure, reduced blood wasting and infection risk.

Sodium concentration measurement during hemodialysis through ion-exchange resin and conductivity measure approach: in vitro experiments.

Sodium measurement during hemodialysis treatment is important to preserve the patient from clinical events related to hypo- or hyper-natremia Usually, sodium measurement is performed through laboratory equipment which is typically expensive, and requires manual intervention. We propose a new method, based on conductivity measurement after treatment of dialysate solution through ion-exchange resin. To test this method, we performed in vitro experiments. We prepared 40 ml sodium chloride (NaCl) samples at 280, 140, 70, 35, 17.5, 8.75, 4.375 mEq/l, and some "mixed samples", i.e., with added potassium chloride (KCl) at different concentrations (4.375-17.5 mEq/l), to simulate the confounding factors in a conductivity-based sodium measurement. We measured the conductivity of all samples. Afterwards, each sample was treated for 1 min with 1 g of Dowex G-26 resin, and conductivity was measured again. On average, the difference in the conductivity between mixed samples and corresponding pure NaCl samples (at the same NaCl concentration) was 20.9%. After treatment with the exchange resin, it was 14.7%, i.e., 42% lower. Similar experiments were performed with calcium chloride and magnesium chloride as confounding factors, with similar results. We also performed some experiments on actual dialysate solution during hemodialysis sessions in 15 patients, and found that the correlation between conductivity measures and sodium concentration improved after resin treatment (R=0.839 before treatment, R=0.924 after treatment, P<0.0001). We conclude that ion-exchange resin treatment coupled with conductivity measures may improve the measurement of sodium compared to conductivity measures alone, and may become a possible simple approach for continuous and automatic sodium measurement during hemodialysis.

The prevalence of peripheral neuropathy in hemodialysis patients.

BACKGROUND/AIMS: Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work. METHODS: We studied 225 prevalent dialysis patients from two Italian Centers. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluation (MNSI_P). Patients without any disease possibly inducing secondary neuropathy and with MNSI score ≥ 3 have been diagnosed as affected by UN. Electroneurographic (ENG) lower limbs examination was performed in these patients to compare sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) with the MNSI results. RESULTS: 37 patients (16.4%) were identified as being affected by UN, while 9 (4%) presented a score < 3 in spite of neuropathic symptoms. In the 37 UN patients a significant correlation was found between MNSI_P and SCV (r2 = 0.1959; p < 0.034) as well as SNAP (r2 = 0.3454; p = 0.027) both measured by ENG. CONCLUSIONS: UN is an underestimated disease among the dialysis population even though it represents a huge problem in terms of pain and quality of life. MNSI could represent a valid and simple clinical-instrumental screening test for the early diagnosis of UN in view of an early therapeutic approach.

[Arterial hypertension in dialysis: up to what point should it be corrected? It depends]. / Ipertensione in dialisi: fino a che punto trattarla? Dipende...!

It is well known that blood pressure values <130/80 mmHg in high-risk patients (diabetics, heart patients) reduces the cardiovascular risk, and it is equally well known that the same target is advised for patients with renal insufficiency. In view of the elevated prevalence of postural hypotension, autonomic dysfunction and peripheral, cerebral and cardiac vasculopathy in kidney patients, the maintenance of this pressure target can, however, be harmful in this category of patients. Indeed, some studies have shown that lower pressure values are associated with more cardiovascular events in dialysis patients. The increased incidence of organ damage consequent to the hypotensive episodes that may occur in these patients should also be taken into account. Hypotension during dialysis, especially when occurring repeatedly, has indeed been indentified as the cause of the increased risk of intestinal, cardiac and cerebral ischemia in such patients. Antihypertensive treatment must therefore be seen in a different light compared with that of the general population, and we should consider the anatomic and physiopathological peculiarities of dialysis patients. It thus becomes of primary importance to assess the presence of comorbidities and cardiovascular risk factors that may favor the maintenance of pressure values that are not necessarily extremely low. A carefully reasoned use of antihypertensive drugs which takes these aspects into account could reduce the incidence of ischemic events with consequent organ damage that can increase dialysis patient mortality.

A continuous and non-invasive arterial pressure monitoring system in dialysis patients.

BACKGROUND: As symptomatic intradialytic hypotension in the hemodialysis (HD) patient is often a sudden event whose onset cannot be predicted by means of extemporary measures, continuous blood pressure (BP) measurement would be far more useful. We tested a new continuous noninvasive BP monitoring system, Harmonized Alert Sensing Technology (HASTE), which, by means of the analysis of the finger pulse wave, obtained from an O2 sensor, estimates a beat-to-beat systolic pressure value (Esys) and supplies a continuous read-out. The study aim sought to verify the reliability of this non-invasive instrument in continuously providing systolic pressure values during HD. METHODS: We studied 18 patients during HD treatment, initially comparing the Esys with the invasive blood pressure measurement (SYS). Subsequently, the Esys derived from the O2 sensor in the arm with the shunt (S) and the arm without (N), respectively, were both compared with the cuff measurement. RESULTS: The mean difference between SYS and Esys was 0.7 +/- 13.3 mm Hg (p < 0.01; r = 0.80). There was a mean difference of 0.2 +/- 21.9 mm Hg (p = NS; r = 0.67) between Esys(N) and Esys(S). The correlation was not statistically significant even between Esys(N) or Esys(S) versus the cuff measurement, respectively. Patient movement compromised the accuracy of the estimations made using the O2 sensor in the non-fistula arm. CONCLUSIONS: A good correlation between the data estimated by HASTE compared with invasive BP suggests that the instrument may prove useful for continuously monitoring the blood pressure trends during the dynamic hemodialysis situation. However, its sensibility needs to be improved in order to be used indifferently in both arms with a view to achieving real intradialytic hypotension prevention.

Severe ticlopidine-induced cholestatic syndrome.

A patient with chronic renal insufficiency undergoing dialysis treatment presented with a clinical picture of acute intrahepatic cholestasis and alterations in liver function indices. Liver biopsy showed a histological picture of hepatitis with cholestatic signs. A causal correlation with the recent administration of ticlopidine was hypothesized, which led to the drug being discontinued. Four months after drug withdrawal no improvement in the biochemical parameters had yet occurred and the patient's clinical conditions were indeed worsening so we proceeded with extracorporeal selective plasmapheresis treatments to reduce the bilirubin. As the cholestatic syndrome was unresolved and owing to the progressive worsening in the clinical picture, the patient was submitted to combined liver and kidney transplant followed by a rapid functional recovery in both organs. Regular monitoring of the hepatic function indices during the therapy with ticlopidine is therefore indispensable for the early detection of unpredictably severe hepatotoxicity.

Prevention of dialysis hypotension episodes using fuzzy logic control system.

BACKGROUND: Automatic systems for stabilizing blood pressure (BP) during dialysis are few and only control those variables indirectly related to BP. Due to complex BP regulation under dynamic dialysis conditions, BP itself appears to be the most consistent input parameter for a device addressed to preventing dialysis hypotension (DH). METHODS: An automatic system (ABPS, automatic blood pressure stabilization) for BP control by fluid removal feedback regulation is implemented on a dialysis machine (Dialog Advanced, Braun). A fuzzy logic (FL) control runs in the system, using instantaneous BP as the input variable governing the ultrafiltration rate (UFR) according to the BP trend. The system is user-friendly and just requires the input of two data: critical BP (individually defined as the possible level of DH risk) and the highest UFR applicable (percentage of the mean UFR). We evaluated this system's capacity to prevent DH in 55 RDT hypotension-prone patients. Sessions with (treatment A) and without (treatment B) ABPS were alternated one-by-one for 30 dialysis sessions per patient (674 with ABPS vs 698 without). RESULTS: Despite comparable treatment times and UF volumes, severe DH appeared in 8.3% of sessions in treatment A vs 13.8% in treatment B (-39%, P=0.01). Mild DH fell non-significantly (-12.3%). There was a similar percentage of sessions in which the planned body weight loss was not achieved and dialysis time was prolonged. CONCLUSIONS: In conclusion, FL may be suited to interpreting and controlling the trend of a determined multi-variable parameter like BP. The medical knowledge of the patient and the consequent updating of input parameters depending on the patient's clinical conditions seem to be the main factors for obtaining optimal results.

Thermal balance in convective therapies.

Among the factors causing intradialytic haemodynamic instability, dialysate temperature has been shown to play a relevant role. An improved cardiovascular response during isolated ultrafiltration or with cooled dialysate has been described in the past. Cold dialysate may increase the external heat loss compensating for the increase in core temperature, thus avoiding vasodilatation, but it also increases myocardial contractility. However, a better haemodynamic response to dialysis treatment has long been known in convective therapies as well, and the hypothesis of a leading role for thermal balance is under discussion. In conventional haemofiltration (HF), venous blood cooling is expected, on the basis of the infusate temperature and the filtration fraction. In on-line HF, the infusate temperature and its volume may have a different impact on thermal balance depending on the site of infusion (pre- or post-dialyser). In an in vitro study comparing haemodialysis (HD) (conventional HD, dialysate 37 degrees C; and cold HD, dialysate 35.5 degrees C) with HF (pre- and post-dilution, 37 degrees C), we observed a more negative thermal balance with cold HD (-130 kJ/h) and with post-dilution HF (-75 kJ/h). The beneficial pressor effects of HF have been confirmed even in on-line HF, which actually has very few differences in the thermal balance compared with conventional HD (dialysate 37 degrees C). In on-line HF, the amount of warm infusion, often exceeding the blood flow, makes the achievement of a negative thermal balance highly unlikely. Thus, there is not sufficient evidence that vascular stability in on-line HF is solely related to different thermal energy balances. Other factors playing a relevant role in the cardiocirculatory response to convective dialysis should thus be considered.

Biofeedback in dialysis.

The traditional control of the dialysis session comes about by means of an open-loop system. At the beginning of the session some parameters are set, such as the kind of dialyzer, the blood flow, the ultrafiltration rate, the dialysate conductivity and the dialysate temperature. Generally speaking, these parameters are not modified unless there occur complications in the patient that call for adjustments to be made. The biofeedback concept, which is synonymous with a closed-loop control of biological variables, presupposes, on the other hand: the continuous measurement of a variable thanks to a specific sensor its evaluation by a sort of expert system--the so-called controller and a series of means--the actuators--that allow the behavior of the variable to be directly or indirectly influenced. In clinical practice, different biofeedback systems are emerging, addressed to the control of blood volume, body temperature, and blood pressure. Each one of these systems has been successfully deployed, especially in the management of "difficult" patients unstable from the hemodynamic point of view. However, the future will be an integrated system that sees a complex adaptive, multi-input, multi-output controller which, with a great simplicity of use and low costs, will allow renal replacement therapy to be increasingly physiological and more efficient.