[Natural history of HCV infection and risk of death in a cohort of patients on long-term hemodialysis]. / Storia naturale dell'infezione da HCV e rischio di morte in una coorte di pazienti in emodialisi da lungo tempo.

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.

[On-line hemodiafiltration without acetate]. / L'emodiafiltrazione on-line senza acetato.

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.

Double-chamber on-line hemodiafiltration: a novel technique with intra-treatment monitoring of dialysate ultrafilter integrity.

On-line hemodiafiltration is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this treatment modality depends on the quality of dialysate and, mainly, on the integrity of the ultrafilter(s) employed. Double-chamber on-line hemodiafiltration is a new technique where re-infusion takes place inside the dialyser by means of dialysate backfiltration. The peculiar geometry of the dialyser allows intra-treatment assessment of its fibre integrity. In this paper, we tested feasibility and safety of this new modality of on-line treatment. The extracorporeal blood and infusate pressure values resulted well inside the safety range. Blood urea clearances and beta(2) removal were consistent with the figures usually found in standard hemodiafiltration. Whole blood production of cytokines was similar when blood was exposed to saline or infusate, both values being comparable to the spontaneous whole blood cytokine release. The on-line dialyser fibre integrity check showed a great sensitivity even for minimal dialyser damage. We conclude that double-chamber on-line hemodiafiltration is a feasible and safe procedure. Our preliminary results encourage the undertaking of multicentre, prospective, randomised studies.

Cardiovascular stability during haemodialysis, haemofiltration and haemodiafiltration.

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.

Blood pressure measurement in haemodialysis patients.

Several studies suggest that the 24 hour ambulatory blood pressure monitoring (ABPM) predicts left ventricular hypertrophy more accurately than conventional blood pressure measurement (CBPM) with mercury sphygmomanometer. We estimated the left ventricular mass by M-mode echocardiography in 58 patients on regular haemodialysis treatment during the midweek haemodialysis (HD) interval. ABPM was recorded during the 24 hours preceding the dialysis session and the average of values were compared with the average of the 13 pre HD CBPM recorded by nurses during the month preceding the echocardiography study. The two types of BP measurements correlated significantly with each other, (systolic BP r = 0.62; p < 0.001 and diastolic BP r = 0.74; p < 0.001). The correlation of left ventricular mass with pre-HD systolic BP was stronger (r = 0.54; p < 0.001) than with 24h-systolic BP (r = 0.33; p < 0.01). The overall accuracy of prediction was also similar (68% for pre HD-CBPM; 67% for 24h-ABPM). Measurements of diastolic BP did not correlate significantly with LVM. Our data suggest that 24h-ABPM does not offer any advantage over pre HD-CBPM in predicting left ventricular hypertrophy in HD patients.

Impaired sympathetic response before intradialytic hypotension: a study based on spectral analysis of heart rate and pressure variability.

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.

Results of a national epidemiological investigation on HCV infection among dialysis patients. (Survey by the Italian Branch of EDTNA/ERCA).

The Italian Branch of EDTNA-ERCA organised a retrospective epidemiological investigation on the spread of HCV infection in dialysis. A questionnaire was sent to 830 Italian dialysis centres to collect information about prevalence and incidence of HCV infection among patients and staff, anti-HCV testing, presumed sources of infection, sanitation procedures and dialysis strategies adopted to prevent or reduce the transmission of HCV infection. Twenty-seven percent of the dialysis centres responded to the questionnaire. The answers confirmed the decline in HCV prevalence and incidence. At variance with official health organisation recommendations, isolation of anti-HCV-positive patients is still used in many centres (25%) despite the fact that it is not advisable in view of the high cost and uncertain benefit. Dedicated machines for anti-HCV-positive patients should be adopted, at least in units with a high prevalence of these cases.

Results of a national epidemiological investigation of HCV infection in dialysis patients.

The Italian Branch of EDTNA/ERCA organised a national, epidemiological, retrospective study to collect data and implement preventative measures for the spread of HCV infection in dialysis units. A questionnaire was sent to staff in 830 dialysis centres to collect information relating to 1996. Data are presented on incidence/prevalence of HCV infection, antibodies, viraemia and mortality, and comparison of the management of HCV between centres. At variance with the recommendations of the Official Health Organisations, dedicated machines and separate rooms are used in many centres and this paper concludes with recommendations for units, in particular those units with a low prevalence of anti HCV positive patients.

Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.

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.

Convective treatments with on-line production of replacement fluid: a clinical experience lasting 6 years.

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.

Universal precautions and dedicated machines as cheap and effective measures to control HCV spread.

Haemodialysis patients are at great risk for HCV infection, and a strict relationship is clear between anti-HCV positivity and dialysis age or hospital dialysis, irrespective of previous blood transfusions. Notwithstanding that, the precise root of its nosocomial nontransfusional diffusion among haemodialysis patients is not clear yet. As isolation is a very expensive policy, we evaluated whether simpler measures such as the observance of the Universal Precautions (UP), and the use of anti-HCV positive patient dedicated monitors can stop the diffusion of HCV infection in a hospital haemodialysis centre. Since January 1990 to December 1991 (1st phase), the patients shared the monitors irrespective of their serological status for HCV, and training of the dialysis care staff was not performed with regard to the UP. Since January 1991 to June 1996 (2nd phase), according to the UP, strictly personal dialysis-tools were used for all patients, anti-HCV positive patients were assigned to dedicated monitors in defined (not separated) areas of the dialysis rooms and the dialysis care staff was trained to the strict observance of the UP. In the first phase of the follow-up 5 seroconversions occurred; none occurred in the second one. Our study shows that isolation is not required for such patients. We believe that measures such as the application of UP, dedicated machines and continuous training of the care staff, instead of the isolation of positive patients, result in the same efficacy and are cheaper than isolation of positive patients. Therefore they are mandatory for all haemodialysis centres.

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

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.

Thermal balance and dialysis hypotension.

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.

Hepatitis B vaccination in dialysis patients and nutritional status.

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.

[Functional relationships between plasma renin activity and hemodynamic indices in essential arterial hypertension]. / Correlazioni funzionali tra attivita' reninica del plasma e indici emodinamici nell'ipertensione arteriosa essenziale.

Vasoconstriction-volume analysis postulates that arteriolar vasoconstriction is the mechanism of blood pressure elevation in patients with "high-renin" essential hypertension while a volume expanded state with relatively dilated arterioles sustains "low renin" essential hypertension. To test this hypothesis we carried out hemodynamic and PRA studies in 43 essential hypertensives. Cardiac index was directly related to PRA (r=0,41; p less than 0,01), by contrast, peripheral vascular resistances and plasma volume were unrelated to PRA. The data do not support the bipolar hypothesis since vasoconstriction and volume expansion are associated with unpredictable changes in PRA. The direct relationship between CI and PRA may be interpreted as the result of a common factor (presumably sympathetic nervous system) governing both functions.

[Cardiac output and pulmonary blood volume in arterial hypertension of chronic uremia]. / La portata cardiaca e il volume di sangue polmonare nell'ipertensione arteriosa dell'uremia cronica.

To investigate the mechanisms that sustains arterial hypertension in chronic uremia we performed hemodynamic studies in 13 dialysed uremics by means selective radiocardiography (Donato-Giuntini method). The 5 dialysed patients with dialysis controllable hypertension (GROUP B) had higher cardiac indexes (CI) respect to the 8 dialysed normotensive controls (GROUP A) (CI: Group B 4,250 l/min/m2, Group A 3,610 l/min/m2; p less than 0,05). The higher CI in group B appeared independent from the degree of anemia because the two groups had comparable hematocrit values (Hct:Group B 26,2% Group A 26,4%); On the other hand the slight blood volume expansion we observed in group B (7%) respect to group A hardly explains the observed difference in CI. It is interesting that pulmonary blood volume/total blood volume ratio (PBV/TBV) was significantly higher in dialysed hypertensives (PBV/TBV: Group B 14,26%, Group A 11,15%; p less than 0,05) The higher PBV/TBV can be the result of a decrease in venous compliance and could explain the higher CI in group B; further studies however are warranted to elucidate this point.