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Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early. In certain situations, such as bleeding, urgent invasive procedures, and surgical settings, the evaluation of anticoagulant levels and the monitoring of reversal therapy appear essential. Standard coagulation tests (i.e., activated partial thromboplastin time (aPTT) and prothrombin time (PT)) can be normal, and the turnaround time can be long. While the role of viscoelastic hemostatic assays (VHAs), such as rotational thromboelastometry (ROTEM), has successfully increased over the years in the management of bleeding and thrombotic complications, its usefulness in detecting anticoagulants and their reversal still appears unclear.

Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide "dynamic" data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions. In patients with severe COVID-19 infection VETs can supply to clinicians more information about the CAC, identifying the presence of hypercoagulable and hypofibrinolysis states. In the last year, many studies have proposed to explain the underlying characteristics of CAC; however, there remain many unanswered questions. We tried to address some of the important queries about CAC through VETs analysis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: CKD is associated with a reduction of patients' health-related quality of life. Considering the time spent in dialysis, satisfaction with care is essential for patients QOL., Objective: Since the possible association between satisfaction with the dialysis care and QOL has never been studied, in this study, we explore this plausible link., Methods: One hundred three patients on hemodialysis (HD) and peritoneal dialysis (PD) filled-in patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). QOL was assessed by Kidney Disease Quality of Life-36 and satisfaction by Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire. The analysis was conducted on patient-level, considering for single patient sociodemographic characteristics and presence of depression/anxiety. One-way ANOVA was used to compare QOL mean scores for patients who answered "excellent" and for those who answered "other ratings" in CHOICE questionnaire and the Pearson χ2 test to compare the patients' characteristics between these 2 groups of patients., Results: The analysis showed a significant positive association between PREM and PROM scores for 8 out of 23 CHOICE items. Six of them were related to the figure of nephrologist, 1 to dialysis access site, and 1 to the social worker support. Significant association (p < 0.05) were between frequency of seeing nephrologist and physical component plus mental component, accuracy of information from nephrologist and burden of disease, accuracy of instructions from nephrologist and burden of disease, coordination between nephrologist and other physicians plus mental component, attention to cleanliness of access site and mental component, amount of dialysis information from staff and burden of disease, information from staff when choosing between HD or PD and physical component plus burden of disease, and ease of seeing social worker and burden of disease., Conclusions: The study provides support for the relationship between the care satisfaction and QOL, highlighting the central role of the nephrologist-patient communication in the QOL of dialysis patients., (© 2020 S. Karger AG, Basel.)

Background: Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients., Methods: We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet (<100 mmol/day) as measured by 24-h urine Na (UNa) excretion and 24-h ambulatory blood pressure (ABPM) monitoring., Results: In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8-58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI -5.6-50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69-0.99; Month 6, P = 0.73-0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial., Conclusions: The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background:: Estimated glomerular filtration rate (eGFR) is a predictor of outcome among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), but which estimation formula provides the best long-term risk stratification in this setting is still unclear. We compared the prognostic performance of four creatinine-based formulas for the prediction of 10-year outcome in a NSTE-ACS population treated by percutaneous coronary intervention., Methods:: In 222 NSTE-ACS patients submitted to percutaneous coronary intervention, eGFR was calculated using four formulas: Cockcroft-Gault, re-expressed modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-Epi), and Mayo-quadratic. Predefined endpoints were all-cause death and a composite of cardiovascular death, non-fatal reinfarction, clinically driven repeat revascularisation, and heart failure hospitalisation., Results:: The different eGFR values showed poor agreement, with prevalences of renal dysfunction ranging from 14% to 35%. Over a median follow-up of 10.2 years, eGFR calculated by the CKD-Epi and Mayo-quadratic formulas independently predicted outcome, with an increase in the risk of death and events by up to 17% and 11%, respectively, for each decrement of 10 ml/min/1.73 m 2 . The Cockcroft-Gault and MDRD equations showed a borderline association with mortality and did not predict events. When compared in terms of goodness of fit, discrimination and calibration, the Mayo-quadratic outperformed the other formulas for the prediction of death and the CKD-Epi showed the best performance for the prediction of events (net reclassification improvement values 0.33-0.35)., Conclusions:: eGFR is an independent predictor of long-term outcome in patients with NSTE-ACS treated by percutaneous coronary intervention. The Mayo-quadratic and CKD-Epi equations might be superior to classic eGFR formulas for risk stratification in these patients.

Aim: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings., Methods: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL)., Results: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age., Conclusion: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.

Background and Objectives: The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients., Design, Setting, Participants and Measurements: We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m(2). Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula., Results: In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r -0.27, p = 0.000). During conservative follow-up 55 subjects (18%) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66%) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95% confidence interval [CI] 1.04-1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g. <5.7 ml/min, showed a better survival (HR for mortality 0.52, 95% CI 0.30-0.89, p 0.016) than the other group., Conclusions: A well-organized nephrological outpatient clinic for conservative follow-up of CKD stage five patients can delay dialysis entry as long as 1 year. Starting dialysis with eGFR lower than 6 ml/min does not confer any increased risk of death in selected early-referral patients.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase implicated in several age-related biological mechanisms such as telomere shortening and cell senescence. We tested the hypothesis that ADMA blood level is an independent predictor of mortality in elderly. This is a longitudinal population-based cohort study. Participants are a representative cohort of 1,025 men and women (age range 65-102 years) living in Chianti area, Tuscany, Italy. The plasma ADMA was measured by liquid chromatography-tandem mass spectrometry. During the follow-up (95 ± 32 months), 384 individuals died, of whom 141 (37 %) died of cardiovascular (CV) causes. In adjusted analyses, the plasma ADMA was the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10-1.44, P < 0.001) with a non-significant trend for CV mortality (HR 1.22, P = 0.07). The predictive effect of the ADMA level on mortality was statistically significant among participants with low to low-normal L-arginine levels (≤ 60 μMol/L), but not in those with L-arginine >60 μMol/L. Notwithstanding the association of ADMA with all-cause mortality was robust, this biomarker failed to add predictive power to a simple model based on the risk factors in the elderly (area under the ROC curve 0.85 ± 0.01 vs. 0.84 ± 0.01). ADMA is a strong independent predictor of mortality in the older population, and L-arginine modifies the effect of ADMA on survival. The mechanisms for this association should be targeted by future studies.

Wilms' tumour suppressor gene-1 (WT1) plays a critical role in kidney development and function. Several WT1 mutations can occur in exons 7, 8 and 9 and they have been associated with Denys-Drash syndrome. WT1 mutations of intron 9 have been reported too and associated with Frasier syndrome. However, overlapping and incomplete forms of both the syndromes have been described. We report a novel sequence variant (c.1012A>T) of the WT1 gene in exon 6 (p.R338X) in a 18-year-old girl with a history of Wilms' tumour, minor gonadal changes and relatively late-onset nephropathy. WT1-related nephropathies should be suspected in every patient with proteinuria not associated to immunological changes when a congenital neoplasia or minor gonadal anomalies are present.

Multiple solitary plasmacytoma (MSP) is a rare plasma cell dyscrasia, characterised by multiple lesions of neoplastic monoclonal plasma cells. It differs from multiple myeloma by the lack of hypercalcaemia, renal insufficiency, anaemia and pathological monoclonal plasmocytosis on a random bone biopsy. We present the case of an MSP described for the first time in a patient on peritoneal dialysis. There are only few cases of MSP described in literature, and we performed a review of these cases trying to systematise the topic. The increasing clinical use of CT, MRI and positron emission tomography will enhance in the future the correct diagnosis of MSP.

Calcimimetics are effective in lowering serum parathyroid hormone (PTH) levels in hyperparathyroidism (HPT). However, they failed to reduce PTH levels in the long term in the setting of primary malignant HPT. A haemodialysis patient suffering from severe longstanding secondary HPT underwent total parathyroidectomy with autotransplantation of parathyroid tissue in her left arm. In the following years, she developed a severe HPT sustained by cancerous transformation of the parathyroid transplanted tissue and resistant both to pharmacological and repeated surgical treatments. The calcimimetic 'cinacalcet' was able to effectively reduce serum PTH levels over a 3-year follow-up and to induce disappearance of the neoplastic lesion on radionuclide imaging. Biochemical control of HPT was associated with a remarkable improvement in cardiac function.

The discovery of hepatitis C viruses in the 1990s started a new era in hemodialysis. Hepatotropic RNA viruses are able to infect the immune cell populations of the host and show high viral persistence and chronicity rates. Although, like the HIV viruses, they can change inside the host, they are less resistant than hepatitis B viruses both to environmental conditions and common disinfection tools. The clinically subtle course of chronic and acute infections has pivotal importance in the spread of HCV and can explain its prevalence rates of 2-3% in the general population and about 9% in hemodialysis patients. Among the risk factors for transmission, the nosocomial risk is of primary importance in the hemodialysis setting but it is present in every health-care environment. Though low, also the occupational risk is important, particularly for nurses, in whom accidental pricks are responsible for a mean incidence of HCV infection of 1.8%. In the dialysis setting both these risk factors are essentially imputable to sanitary malpractice. In the last 30 years, the most important agencies for the prevention of infection have developed a set of "special" precautions for particular settings such as hemodialysis. In this review we report and recommend these precautions because their regular adoption is fundamental and a sufficient requisite to prevent the spread of hematogenous infections, including HCV.

Background: HCV infection represents the major cause of chronic liver disease in hemodialysis and renal transplant patients. The clinical course of liver disease in hemodialysis patients is generally asymptomatic. Only few studies describe the natural history of HCV infection in haemodialysis patients, showing an association between HCV infections and poor survival., Methods: A prospective cohort study of our haemodialysis population was conducted to define the natural history of HCV infection and its relation to mortality. 77 patients on haemodialysis were enrolled, 24 (31%) of whom were anti-HCV and 53 (69%) anti-HCV-negative., Results: The HCV-RNA was positive in 18 of the 24 anti-HCV-positive subjects (75%). None of the anti-HCV-negative subjects was HCV-RNA-positive. Eight of the 18 HCV-RNA-positive patients (40%) developed cirrhosis with portal hypertension and ascites within 7 years after the first increase of GPT. Seven of these died, nobody developed hepatocarcinoma (HCC). During 58+/-37-follow-up months mortality rate was higher among anti-HCV-positive patients than among anti-HCV-negative. Besides, the 6 deaths occurred only among anti-HCV-positive and HCV-RNA-positive patients., Conclusion: in our haemodialysis patient population the presence of antibodies anti-HCV and HCV-RNA is associated with an increased risk of developing liver cirrhosis and of death, in comparison to anti-HCV-negative patients. Our data show that anti-HCV-positive patients have an accelerated course towards chronic hepatopathy and cirrhosis.

Background: In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation., Methods: To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients., Results: In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5-6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%. Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate., Conclusions: Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.

Background: Reports have shown that well-defined histological patterns do not always correspond to equally clear clinical pictures, particularly so in elderly patients., Methods: With the aim of assessing clinicopathological correlations in the population aged >65 years with that of lower age, we retrospectively analyzed computerized records of renal needle biopsies consecutively performed in the decade 1991-2000 in our unit., Results: Among the 392 eligible subjects, there were 150 patients 65 years of age and more, 76 of whom were over 70. The average serum creatinine was 2.9 mg/dl, with values > 3.5 mg/dl in 25% of cases. The major indication to biopsy was nephrotic syndrome followed by chronic renal failure both in the young adult and the elderly population. The rapidly progressive form led more often to renal biopsy in the elderly patients, and the different prevalence was statistically significant (p < 0.05), as was the higher prevalence of urinary anomalies in the young-adult population. Regarding renal histology, the crescentic necrotizing forms were significantly more frequent in the elderly patients, while IgAN, minimal change disease and SLE predominate in young adults. The most relevant result is the greater prevalence of crescentic necrotizing glomerulonephritis in elderly patients, not only in the cases presenting clinically as rapidly progressive renal failure and acute renal failure, but also in those with the clinical picture of chronic renal failure., Conclusions: Re-evaluation of our case files verifies the importance of the bioptic approach in selected cases with stages 3-4 chronic kidney damage. This holds true especially for elderly patients.

Background: Autopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics. Changes in tissue structure are detectable by ultrasound as changes in echo reflectivity., Methods: We studied 96 dialysis patients, 18 hypertensive subjects with normal renal function and 52 healthy subjects. The echo pattern of interventricular septum was assessed by videodensitometry (VDT) (i.e., a computer-assisted quantitative analysis of gray levels). For each pixel a numerical value from 0 (black) to 255 (white) was assigned. From the resulting histogram of gray level frequency distribution, we obtained indexes of central tendency (reflectivity) and of homogeneity of distribution (uniformity)., Results: For the same septum thickness, dialysis patients showed a significantly greater reflectivity (87 +/- 19 and 70 +/- 17) (P < 0.001) and lower uniformity (137 +/- 32 and 184 +/- 71) (P < 0.007) compared with hypertensives. Hypertensive patients showed VDT parameters similar to control subjects in spite of significantly higher septum thickness (P < 0.003). Followed up after 5 years, dialysis patients with a reduced homogeneity of distribution of gray levels (lower uniformity) showed a significantly shorter survival (HR by Cox 2.5, 95% CI 1.21-5.27)., Conclusion: For a similar degree of cardiac hypertrophy, dialysis patients differed widely from hypertensives in their VDT parameters. By contrast, the hypertensive heart differed from the normal heart in the degree of hypertrophy but not in terms of VDT parameters. VDT parameters are independent predictors of all-cause mortality in dialysis patients.

Background: The use of 24-hour ambulatory blood pressure monitoring is increasing in end-stage renal disease (ESRD) patients but the prediction power for cardiovascular complications of time-averaged ambulatory blood pressure components has been little investigated in these patients., Methods: We analyzed the prognostic power of 24-hour ambulatory blood pressure monitoring for all-cause and cardiovascular mortality in 168 nondiabetic, events-free hemodialysis patients selected from a total dialysis population of about 450 patients., Results: During the follow-up period (38 +/- 22 months), 48 patients died, 29 of them of cardiovascular causes. On univariate Cox regression analyses, the night/day systolic ratio resulted to be the sole blood pressure indicator to be associated with all-cause and cardiovascular mortality while left ventricular hypertrophy (LVH) was a strong predictor of these outcomes. In multivariable Cox models not including LVH, the night/day systolic ratio maintained an independent prognostic value for incident outcomes. However, when both risk factors, LVH and night/day systolic ratio, were introduced into Cox models, LVH was no longer a significant predictor while the night/day systolic ratio became a predictor of marginal statistical significance., Conclusion: The night/day ratio emerges as the sole ambulatory blood pressure monitoring-derived indicator providing significant prognostic information in patients with ESRD. However, this indicator as well as LVH loses substantial prediction power in statistical models including both risk factors. The results suggest that the night/day systolic ratio and LVH provide overlapping prognostic information, a phenomenon in keeping with the hypothesis that they represent a common pathway leading to adverse outcomes in ESRD.

Purpose: The suitably filtered dialysate which is currently reinfused during on-line hemodiafiltration (HDF-OL) contains bicarbonate and small doses of acetate. The trend of acetataemia During "forced" convective treatments has never been studied. The gain in acetate secondary to the considerable quantities of fluids infused might have clinical significance in relation to the well-known side effects of this anion., Methods: In this pilot study 12 patients underwent HDF-OL with reinfusion in predilution of 40 L of substitution fluids containing or not 3 mmol/L of acetate. Apart from this variable, all the other treatment parameters were the same in both procedures. The treatments were carried out in two short consecutive intervals in a random sequence., Results: During HDF-OL the use of dialysate containing small doses of acetate is associated with levels of acetataemia 5-6 times higher compared to the basal. HDF-OL without acetate cancels out this increase. The acetate gained by the patients is significant, on average 75 mmol, and accounts for over 1/3 of the global base gain. Consequently, the bicarbonataemia levels at the end of treatment are significantly higher in HDF-OL with acetate than in the treatment without. Two hours after the end of the treatments the IL-6 levels tend to grow in both methods, but numerically less in HDF-OL without acetate; the difference verges on meaningfulness., Conclusions: The acetate gain is significant during forced convective treatments carried out with standard dialysate. This acetate gain can trigger cytokinin activation. These events are cancelled out by eliminating the acetate from the dialysate. The absence of this anion will be compensated with appropriate increases in the concentration of bicarbonate in the dialysis fluid.

Many studies have demonstrated that left ventricular hypertrophy is the most frequent cardiac alteration in patients on chronic hemodialysis. Autopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics, namely deposition of calcium salts, intermyocytic fibrosis, sometimes amyloid. None of the parameters obtainable from conventional echocardiografic images provides information on myocardial tissue structure. Analysis of "texture" originated as analysis of images sent by satellites for military or agricultural purposes and subsequently was applied to medicine for studying various organs like mainly and widely heart. Videodensitometry is a method for in vivo analysis of myocardial structure using computer-assisted quantitative assessment of grey levels of conventional echocardiographic images. In dialysis patients quantitative ultrasonic analysis of myocardial texture appears a promising technique for an observer-independent assessment of myocardial tissue characteristics. Although it may be hampered by many potentially confounding factors, quantitative echocardiography may offer useful parameters for the follow-up of myocardial structural changes in chronic uremia. Further studies are ongoing to completely understand the prognostic significance of myocardial ultrasonic textural alterations in dialysis population.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrasonically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23-87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 x 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23-40 years; II, age 41-65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Several comparative studies have claimed that procedures based substantially or exclusively on pressure-driven water-solute transport, such as haemodiafiltration or haemofiltration, afford better protection of the cardiovascular tolerance to fluid removal than conventional haemodialysis. During each depurative modality, several factors are set in motion that might impact, each in its own right, upon the haemodynamic response to fluid withdrawal. To explore the haemodynamic effect of each of them singularly, one needs to keep all other components unvaried. However, this is very difficult to accomplish. For instance, to confirm the alleged greater protection of cardiovascular stability by pure convection vs diffusion, one needs to keep unvaried all the other factors potentially affecting haemodynamic tolerance, i.e. the rate of body fluid removal, the membrane, the buffer, the blood temperature in the extracorporeal circuit, depuration efficiency, the sodium balance, the fluid sterility and so on. Such studies are still awaited. However, clinical trials published to date have not resolved the question of whether haemofiltration and haemodiafiltration provide a better haemodynamic tolerance to fluid removal. If we limit our consideration to controlled trials only, most prospective studies have adopted a cross-over design implemented on very small patient samples and for very short periods. Such an approach is liable to generate misleading results because the incidence of dialysis hypotension often fluctuates from time to time. Owing to such fluctuations, results can be strongly affected by the 'order effect' of the cross-over from one technique to the other. The negative results provided by parallel comparisons of procedures should be taken with caution because patients samples did not include a suitable proportion of unstable patients.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R-R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30-150 mHz) and high-frequency (HF, 150-400 mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R-R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R-R interval and systolic blood pressure (7.9 versus 0.9 ms/mmHg, P<0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2+/-1 for R-R LF/HF ratio, +2.4+/-0.6 mmHg2 and +7.2+/-2 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9+/-1.4 for R-R LF/HF ratio, -2.7+/-1.4 mmHg2 and -8.6+/-4.0 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7+/-1.4 for R-R LF/HF ratio, +5.9+/-2.7 mmHg2 and +13.3+/-6.2 mmHg2 for LF of diastolic and of systolic blood pressure, P<0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

Background: The relationship between hepatitis C virus (HCV) infection and acute or chronic glomerulonephritis (GN) is not well understood., Methods: Two hundred and eighty-four patients with biopsy-proven GN and other renal diseases were studied in a multicentre survey performed during the period 1992-1995. Several clinical parameters were collected for each patient at the time of renal biopsy. We made a multivariate analysis by logistic regression model to evaluate the independent association of clinical and histological patient characteristics with HCV infection, as detected by anti-HCV antibody testing. In addition, three patients with HCV-related liver disease, membranous nephropathy, and proteinuria in the nephrotic range received therapy with interferon-alpha in standard doses., Results: The prevalence of anti-HCV positivity was 13% (38/284). The frequency of anti-HCV positivity ranged between 0 and 100% in the different types of renal diseases, the difference was statistically significant (P = 0.0001). The anti-HCV rate was significantly higher in patients with cryoglobulinaemic membranoproliferative and mesangioproliferative GN than among the other individuals (14/14 (100%) vs 24/270 (9%), P = 0.0002). Our multivariate analysis by logistic regression model showed that age (P = 0.0017) and type of renal diseases (P = 0.0007) were independently and significantly associated with anti-HCV antibody. At the completion of treatment with interferon-alpha, 67% (2/3) of patients with membranous nephropathy had lowering of hepatic enzyme levels into the normal range whereas 100% (3/3) of these did not show significant reduction of proteinuria., Conclusions: We observed strong association between HCV infection and cryoglobulinaemic GN. Age and type of renal disease were important independent predictors of anti-HCV positivity in our cohort of patients. Three anti-HCV-positive patients with membranous nephropathy did not show significant remission of nephrotic proteinuria after treatment with interferon-alpha. Our data do not appear to support an association between HCV and non-cryoglobulinaemic GN. Further epidemiological surveys, experimental studies and clinical trials are warranted to fully elucidate the role of HCV in non-cryoglobulinaemic GN.

Background: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients., Methods: SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV., Results: LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001)., Conclusions: LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.

Background: The introduction of techniques with on-line (OL) production of replacement fluid by filtration of dialysis fluid raises concerns about exposure of dialysis patients to pyrogenic substances. This work was undertaken to evaluate safety and feasibility of OL preparation of replacement fluid for haemodiafiltration (HDF)., Methods: OL HDF was carried out with commercially available monitors without any adjustment in the operational organization of our Centre. Bicarbonate dialysis fluid was filtered twice before being reinjected into the patients. The effects of acute load of OL fluid were assessed by very sensitive in vitro and in vivo tests; the chronic effects were assessed by monitoring the patients for the appearance of any untoward clinical manifestations and by measuring their cytokine response., Results: In a pilot study the membrane filter culture technique of replacement fluid yielded no bacteria or mycetes growth, while LAL test was < 0.01 EU/ml. The normal human monocyte production of TNF alpha, IL-1 beta and IL-1Ra was not significantly different when cells were incubated with OL or commercial replacement fluid. The patients' body temperature profile (continuous recording during treatments and the following 24 h) overlapped with that of the control procedure. Over 6 years we performed 4284 OL treatments (total amount reinjected fluid 102,900 litres) on 13 patients treated for 26 +/- 9 months. In none of these treatments did we observe pyrogenic reactions. In comparison with the previous period on standard bicarbonate haemodialysis, OL HDF afforded significantly better cardiovascular tolerance to fluid removal and higher Kt/V values. The nutritional status did not deteriorate, while the acute-phase reactants and serum beta 2M levels did not increase. Moreover, no translucent cysts or destructive arthropathy were observed on bone X-rays. The patients' plasma cytokine levels and monocytes cytokines production, measured either before or after a single OL HDF, were comparable with the values obtained in controls treated with standard HDF., Conclusions: We conclude that OL-prepared replacement fluid is as safe as that of the commercial bags with regard to sterility and non-pyrogenicity. OL HDF can be readily implemented in any dialysis centre without bringing any further burden on the staff.

The uremic state affects myocardial structure, bringing about, among other things, interstitial calcium deposition. Abnormalities of myocardial structure can be assessed quantitatively and noninvasively during life by the analysis of the gray-level distribution of conventional two-dimensional echocardiograms. The aim of this study was to evaluate the role of quantitative echocardiography in providing information on myocardial structure in patients under maintenance hemodialysis and to relate the ultrasonic findings with abnormalities in calcium-phosphate metabolism. Forty patients undergoing dialysis without abnormalities in left ventricular regional and global function and 17 hypertensive patients with comparable left ventricular hypertrophy were studied. The distribution of the gray levels within a region of interest in the interventricular septum was analyzed off-line by an array processor-based computer. Compared with hypertensive patients, patients undergoing dialysis showed a greater myocardial echogenicity (mean 92 +/- 20 versus 72 +/- 15; p = 0.004) and a reduced homogeneity of distribution of gray levels (entropy 4.5 +/- 0.2 versus 4.2 +/- 0.2, p < 0.01; uniformity 0.010 +/- 0.003 versus 0.020 +/- 0.004, p < 0.005). In the same patients, a significant negative linear relation was found between entropy and calcium-phosphate product (r = -0.66; p = 0.001). Quantitative analysis of conventional two-dimensional echocardiograms allows the detection of a pathologic myocardial structure in patients under maintenance hemodialysis with normal left ventricular function. These abnormalities are related to disorders of calcium-phosphate metabolism and bear no relationship to the degree of left ventricular hypertrophy.

Many studies have confirmed our original observation that dialysate T set at about 35 degrees C affords a better hemodynamic protection than the standard dialysate T of 37-38 degrees C. In this review we present some new data on the hemodynamic mechanism of the protective effect of cold dialysis on blood pressure. The study was based on serial assessment of the percent changes occurring during dialysis treatment in estimated stroke volume (aortic blood flow determined by Doppler echocardiography), blood volume (hemoglobinometry), arterial pressure (Dynamap), and heart rate (ECG), from which cardiac output (CO) indexes and total peripheral vascular resistances (TPVR) were derived. Of the 14 pts studied, 7 showed a drop in mean arterial pressure (MAP) of 25% or greater during standard dialysis (unstable patients). Compared with the 7 patients having more stable intradialysis MAP, unstable pts showed greater reduction in CO which was disproportionately greater than the reduction in blood volume, and a paradoxical decrease in TPVR, the difference being highly significant (p < 0.01 for both changes). When crossed-over to cold dialysis, along with a significantly lower reduction in MAP (p < 0.01) the unstable pts showed a lower decrease in CO which paralleled the reduction in blood volume, and an increase in TPVR. These changes were highly significant (p < 0.01). Data suggest that dialysis hypotension is characterized by an impaired venous return, probably due to the peripheral blood pooling (increased ratio between the 'unstressed' and 'stressed' blood volume) associated with the decrease in TPVR. Exposure of extracorporeal blood to cold dialysate favours the venous return to the heart by increasing TPVR and the 'stressed' blood volume.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypothensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC.

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

35 dialysis patients underwent anti-HBV vaccination. We classified patients in responders or non-responders using an anti-HBs titer of 50 UI/l as the discriminating serum level and tried to assess whether the antibody response bears any relationship with the nutritional status. 26 patients (74%) reached the target atb titer, which was maintained during follow-up (average 360 UI/l). The weak response in the other 9, with values never exceeding 20 UI/l, was short-lived. Anthropometric and impedenziometric parameters were higher in responders than in nonresponders, but the difference did not reach statistical significance. We conclude that the atb titer which discriminates uremics in responders or not must be greater than 50 UI/l and that the nutritional status may interfere with the seroconversion rate, but this conclusion needs to be validated in a wider population.