Antonio Gesuete

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study

Background Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. Methods Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. Results Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. Conclusions HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na+ measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Comprehensive geriatric assessment in the hemodialysis elderly population

The aim of this study was to assess the usefulness of a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) in defining comorbidity and the need for a multidisciplinary approach in older patients with end-stage renal disease. This was a cross-sectional study that included 162 patients, 103 aged 65 and over with a diagnosis of end-stage renal disease and ongoing chronic hemodialysis treatment. Results were compared with a group of 250 geriatric patients without renal impairment. A standardized CGA that included information on clinical, cognitive, functional and nutritional aspects, as well as comorbidity, medications and social support network, was used to calculate MPI. Among the dialysis patients, the vast majority showed a moderate (58.3%) or high risk score (19.4%). MPI score was clearly correlated with Charlson index (P = .001) both in the global population and the dialysis patients aged over 65. Compared to geriatric patients without renal failure, all MPI score domains were more compromised in the dialysis population. These preliminary findings strongly suggest that MPI may be very useful to assess the clinical picture of older patients undergoing renal replacement therapy (RRT). Its use in the dialysis population under 65 needs to be investigated.

Adsorption Dialysis: From Physical Principles to Clinical Applications

The uremic syndrome is characterized by the retention of various solutes that would normally be excreted by the kidneys. The substances that interact negatively with biologic functions are called uremic toxins. Over the past five decades, the membranes used for the treatment of chronic kidney disease have continuously evolved. The exposure of blood to any extracorporeal artificial surface results in the activation of several pathways within the body, including those involving coagulation and complement activation. One of the by-products of this generalized activation process is protein adsorption to the membrane surface, another phenomenon which can have a significant impact on solute removal. In fact, an array of studies showed that with increasing size of middle-sized proteins and other compounds, relatively more clearance is achieved by membrane adsorption compared with loss into the dialysate. A high adsorptive capacity, one of the main features of polymethylmethacrylate (PMMA) membranes, is very helpful and may both increase the total amount of solutes removed and remove different kinds of solutes. In this setting, a few studies have shown a variety of efficient clinical implications for adsorption hemodialysis, such as uremic pruritus, anemia, carpal tunnel syndrome and renal amyloidosis, immune dysfunction and improved response to vaccination. In addition, nutrition and survival were also improved using PMMA membranes.

Review: the effect of polymethylmethacrylate dialysis membranes on uraemic pruritus

Despite improvements in dialysis technology, including the development of novel biocompatible membranes and ultrapure dialysate, uraemia-associated pruritus (UP) remains a common and significant public health issue [1]. Not only does this distressing symptom profoundly impact on the quality of life and sleep, but recent evidence shows that pruritus is also associated with poor patient outcome. In the international Dialysis Outcomes and Practice Patterns Study (DOPPS) [2], which evaluated more than 18 000 patients on haemodialysis (HD) therapy, pruritus was associated with a 17% greater mortality risk, an effect that was no longer significant after adjustment for measures of sleep quality. Nonetheless, nephrologists and other health care professionals often fail to recognize and adequately address the pruritus associated with chronic uraemia. The prevalence of chronic kidney disease (CKD)-associated pruritus varies substantially, ranging from 22 to 90% [2– 6]. In the largest and most recent epidemiological study to date, the prevalence of CKD-associated pruritus was 42% [2]. Although this is a lower prevalence than initially reported, pruritus in patients with CKD remains frequent and continues to be a significant public health concern.

The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity

BACKGROUND Polymorphisms in the FTO (fat-mass and obesity-associated) gene have been associated with the body mass index, cancer, type 2 diabetes and hypertension. METHODS We investigated the relationship between 17 tag single-nucleotide polymorphisms (SNPs) and all-cause mortality in three cohorts of dialysis patients (CREED-1, North Apulian and CREED-2 cohorts; n = 783) and in one cohort of stage 2-5 CKD patients (n = 757). RESULTS We first explored the association between the 17 tag SNPs and all-cause mortality in the CREED-1 cohort and found that patients with the A allele of the FTO rs708259 polymorphism had an elevated risk of mortality (hazard ratio, HR: 1.52, 95% confidence interval (CI) 1.11-2.08; P = 0.008). Similarly, the A allele was associated with an increased risk of death also in the other two dialysis cohorts (North Apulian cohort, risk: +23%; CREED-2 cohort, risk: +21%). The elevated risk portended by this allele was even higher in the stage 2-5 CKD cohort (+97%). However, the risk of mortality associated with the A allele in the three confirmatory cohorts failed to achieve formal statistical significance. In a meta-analysis including the four cohorts (n = 1540; total deaths, n = 381), individuals with the A allele had a 42% excess risk of death (HR: 1.42, 95% CI 1.14-1.76, P = 0.002). CONCLUSION The A allele of the FTO rs708259 polymorphism is an independent predictor of all-cause mortality in patients with CKD of various severity. These data support our hypothesis that the FTO gene may be a relevant genetic risk factor for mortality in this population.

Hepatitis E in hemodialysis and kidney transplant patients in south-east Italy

AIM To investigate the serovirological prevalence and clinical features of hepatitis E virus (HEV) infection in end-stage renal failure patients and in the healthy population. METHODS HEV infection is a viral disease that can cause sporadic and epidemic hepatitis. Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects, including hemodialysis (HD) patients and patients who had undergone kidney transplant. A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy (Foggia and S. Giovanni Rotondo, Apulia). The seroprevalence of HEV was determined in 801 subjects; 231 HD patients, 120 renal transplant recipients, and 450 health individuals. All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy, and were included progressively in this study. Serum samples were tested for HEV antibodies (IgG/IgM); in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA, and the HEV genotypes were determined. RESULTS A total of 30/801 (3.7%) patients were positive for anti-HEV Ig (IgG and/or IgM) and by Western blot. The healthy population presented with a prevalence of 2.7%, HD patients had a prevalence of 6.0%, and transplant recipients had a prevalence of 3.3%. The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%. The rates of exposure to HEV (positivity of HEV-IgG/M in the early samples) were lower in the healthy controls, but the difference among the three groups was not statistically significant (P > 0.05). Positivity for anti-HEV/IgM was detected in 4/30 (13.33%) anti-HEV Ig positive individuals, in 2/14 HD patients, in 1/4 transplant individuals, and in 1/12 of the healthy population. The relative risk of being HEV-IgM-positive was significantly higher among transplant recipients compared to the other two groups (OR = 65.4, 95%CI: 7.2-592.7, P < 0.001), but the subjects with HEV-IgM positivity were numerically too few to calculate a significant difference. No patient presented with chronic hepatitis from HEV infection alone. CONCLUSION This study indicated a higher, but not significant, circulation of HEV in hemodialysis patients vs the healthy population. Chronic hepatitis due to the HEV virus was not observed.

A "nephrological" approach to physical activity.

Despite consensus among nephrologists that exercise is important and probably beneficial for their patients, assessment of physical function or encouragement of physical activity is not a part of the routine management of patients with CKD. In order to plan an useful strategy for exercise training we need to clearly define some questions. First of all, nephrologists need to be aware of physical exercise benefits; lack of motivation and increased perceived risk by health care professionals have been identified as contributing factors to physical inactivity. Moreover, the main elements necessary for sustaining exercise programs in this population have to take in account, such as the requirement of exercise professionals, equipment and space, individual prescription, adequate commitment from dialysis and medical staff. When PA may not be implemented, a comprehensive, individualized occupational therapy program may improve functional independence and activity of daily living. Finally, physical function has to be careful monitored and assesses by medical staff.