Oxygen Extraction and Mortality in Patients Undergoing Chronic Haemodialysis Treatment: A Multicentre Study.

Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% group showed a higher incidence of death (60% vs. 30%; p = 0.005). The survival curve (log-rank-test: p = 0.0001) and multivariate analysis (p = 0.0002) confirmed a ΔOER ≥ 40% as a mortality risk factor. This study showed the intradialytic ΔOER ≥ 40% was a mortality risk factor able to highlight critical hypoxic damage. Using a ΔOER ≥ 40% could be clinically applicable to characterise the most fragile patients.

[Between old and new targets: blood pressure control in hypertensive outpatients].

OBJECTIVE: In developed countries, blood pressure (BP) control has increased over the past few decades and is now approaching 70% of patients. Herewith we report the results of a cross-sectional study carried out on hypertensive outpatients. DESIGN AND METHODS: In a cohort of 1,412 consecutive hypertensive outpatients (790 females, 622 males; mean age: 60.3±12.2 years) evaluated from January 2015 to December 2016, the following parameters were assessed: age, gender, body mass index (BMI), waist circumference (WC), smoking habits, BP in the sitting position, estimated glomerular filtration rate (eGFR), serum glucose, lipid profile, antihypertensive drugs prescribed. In agreement with the European guidelines, hypertension was defined as sitting BP ≥140/90 mmHg or use of antihypertensive drugs. Patients whose BP was <140/90 mmHg were considered as having achieved BP control. Furthermore, in compliance with the redefinition of hypertension suggested by the American College of Cardiology/American Heart Association (ACC/AHA), a second level of BP control (BP <130/80 mmHg) was evaluated. RESULTS: Overall, 75.7% of hypertensive patients achieved BP levels <140/90 mmHg, while 50.5% achieved BP levels <130/80 mmHg. In both contexts, compared with patients whose BP was not controlled, those achieving the BP targets were mainly younger and females with a lower prevalence of obesity, diabetes and chronic kidney disease. Furthermore, they also had a lower WC and a higher eGFR. CONCLUSIONS: Nearly 76% of patients achieved the BP target of <140/90 mmHg, a result which is higher than the 70% achieved in Europe, and 50.6% achieved that of <130/80 mmHg, a result which is slightly higher than the 47% recently reported in USA.

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.

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.

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.

[Bone ultrasonography in kidney disease: applications and limitations]. / L'ultrasonografia ossea in nefrologia: applicazioni e limiti.

Quantitative ultrasound (QUS) of the bone is a technique that is generating great interest among bone structure researchers because of its intrinsic features. Its safety and low cost make it an ideal technique for repeated measurements over time such as in chronic disease or when it is necessary to monitor the effects of prescribed therapies. The method was developed for the study of osteoporosis and the sites of measurement are all peripheral, including the distal diaphyses and metaphyses of the phalanges, calcaneus, radius and tibia. QUS parameters, however, cannot be used directly for the diagnosis of osteoporosis according to the WHO criteria, although many authors have shown that ultrasound parameters, particularly those of calcaneal QUS, can predict the risk of osteoporotic fractures independently of MBD. Very promising results with the use of QUS have been obtained in corticosteroid-induced osteoporosis, rheumatoid arthritis, Cushing's syndrome, cystic fibrosis, osteomalacia, thalassemia and osteopenia related to parenteral nutrition. QUS can also monitor the effectiveness of therapy in various pathological conditions. In nephrology the combined use of phalangeal QUS and biochemical markers of bone turnover allows adequate follow-up of patients on dialysis and renal transplant recipients with alterations or disorders of the bone.

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.

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.

Uraemic itching: do polymethylmethacrylate dialysis membranes play a role?

BACKGROUND: Patients undergoing chronic renal replacement therapy by haemodialysis (HD) suffer from chronic itching, the prevalence of which is very high. Many of the available treatment options are ineffective, but, as it has been shown that Polymethylmethacrylate based dialysis membranes (PMMA) membranes remove a wide range of 'middle molecules' and improve such long-term complications of HD as carpal tunnel syndrome and malnutrition, they may also have an effect on uraemic itching. METHODS: This prospective study enrolled eight patients undergoing standard HD with low-flux synthetic membranes and suffering from chronic itching. The strength and duration of itching was evaluated by the patients themselves at each study time-point using a visual analogue scale (VAS). After a baseline evaluation, the patients were switched to a PMMA membrane for 6 months during which their pre-dialysis haemoglobin, haematocrit, total protein, albumin, urea, creatinine, phosphate, intact parathyroid hormone (i-PTH), serum bile acid, beta2-microglobulin, C-reactive protein (CRP) levels, and eKt/V were measured, and any general complaints were recorded. RESULTS: The self-assessed VAS itching strength scores decreased by 15% after 1 month, 30% after 2 months, and 55% after 6 months, and itching duration decreased by, respectively, 10, 22 and 44% at the same time; 2 months after the end of the study, both scores had slightly increased. There were no statistically significant differences in the pre-dialysis blood chemistry values or eKt/V at the four study time-points, but beta2-microglobulin levels significantly decreased (P < 0.03); the decrease in CRP levels was not significant (P < 0.06). Furthermore, four patients showed a trend towards a lower incidence of intradialytic hypotension. CONCLUSIONS: These findings support the hypothesis that a PMMA dialyser may improve renal itching in ESRD patients. This effect is not mediated by increased dialysis efficiency or an improvement in other biochemical parameters, but we can speculate that ionic substances may be directly or indirectly adsorbed into the polymer composition of BG-U series (PMMA membrane dialyser). We are currently undergoing further studies using a proteomic approach.