Thrice-weekly in-center nocturnal hemodialysis: an effective strategy to optimize chronic dialysis therapy.

OBJECTIVES: Daily nocturnal hemodialysis (NHD) has been proposed as a valuable strategy to improve outcomes for patients on conventional hemodialysis (CHD), but it is burdened by high costs and logistic issues. Thrice NHD might represent a more affordable approach to improve hemodialysis patient outcome. METHODS: Here we retrospectively analyzed the data on blood pressure, body weight, and hematochemical parameters in a cohort of 7 patients (mean age 50.4-/+11.0 years, duration of CHD 14.3-/+11.5 years) who registered in the NHD program at the dialysis unit of Ospedali Riuniti, Bergamo, Italy. Data for the 2 first years of NHD were compared with those of the last year on CHD. RESULTS: At 2 years after start of NHD, we found a significant decrease in systolic (149.4-/+16.6 vs. 128.4+/-26.0 mm Hg, p<0.001) and diastolic (87.7-/+11.1 vs. 79.6-/+16.7 mm Hg, p<0.05) blood pressure, along with a significant reduction in the use of per-patient antihypertensive agents (1.17-/+1.19 vs. 0.47-/+0.89, p<0.05 and an increase in dry body weight (61.4-/+21.8 vs. 67.1-/+16.4 kg, p<0.001). Moreover, patients had a significant reduction in phosphate levels (6.2-/+2.4 vs. 5.4-/+3.0 mg/dL, p<0.01). The procedure was safe and well tolerated and did not require extra cost for ad hoc facilities. CONCLUSION: NHD is an effective approach to optimize chronic dialysis therapy.

[Daily/nocturnal hemodialysis: only for the happy few or a real alternative for many?]. / La emodialisi lunga e/o quotidiana: solo speranze o qualche certezza? Una dialisi per pochi o reale alternativa?

After the negative results of the HEMO study there is renewed interest in alternative, more ''physiological'' dialysis schemes, such as short daily or nocturnal dialysis. Considerable experience has been acquired with short daily hemodialysis, especially in Italy and the Netherlands. Nocturnal daily hemodialysis is mostly performed in Canada, the USA and Australia. Long hemodialysis three times a week is used in Tassin, France. Many observational studies and the prospective controlled London Study have suggested improvements in many intermediate patient outcomes such as dialysis-related symptoms, blood pressure and volume control, phosphate control (only for nocturnal daily dialysis), nutritional status, and quality of life. These studies are, however, too small and underpowered to evince differences in the primary outcomes, mortality and morbidity. An International Registry of Daily Dialysis has been created to obtain further information, and the US National Institutes of Health have sponsored two large-scale trials to compare short and nocturnal daily dialysis with conventional schemes. Organizational problems, higher costs especially initially, and the unavailability of simpler dialysis machines are the main factors that hamper the widespread use of these new schemes. Long nocturnal hemodialysis either in hospital or at home, three times a week or every other night, appears overall the best arrangement and the most attractive solution at present. It provides significant advantages with a minimal increase in cost. It would be interesting if the Italian National Health Service would prioritize funding for these promising schemes of hemodialysis.

[Health related quality of life (HRQoL) assessment in uremic patients: a qualitative review of concepts, methods, available instruments and results]. / Misurare la Qualità della Vita correlata alla Salute (QdV-S) nel paziente uremico: una review dei concetti, dei metodi, degli strumenti disponibili e dei risultati.

The health related quality of life (HRQoL) assessment is a complex and multidimensional concept usually defined as the perception by individuals of the impact of diseases and medical treatments on physical, psychological and social aspects of health and life. HRQoL has become more popular in the last 20 yrs as an important indicator of the effectiveness of the medical care in clinical research protocols, and as part of so-called patient-reported outcomes (PRO), which are concepts concerning aspects of health perceived, reported and rated by study subjects or patients. Generic and disease specific questionnaires are usually used to assess the individual's perceptions about health and life, and more valid and reliable instruments are now available to use in research settings. Instruments that can be useful in daily clinical practice, in the management of the single patient, are not yet available. A large portion of the scientific literature dealing with HRQoL is actually focused on many aspects of uremic syndrome, renal transplantation and dialysis therapies, probably because several reasons make this clinical setting particularly favorable for HRQoL assessment. Early referral to a nephrologist, anemia treatment with epoetin, daily and nocturnal dialysis, kidney transplantation, a program of physical exercise and the treatment of some co-existent conditions and symptoms (i.e. depression, pain, erectile dysfunction and restless leg symptoms) are the most effective ways to ameliorate HRQoL in renal patients. Moreover, HRQoL is a reliable prognostic factor for morbidity and mortality in uremic patients.

Clinical pharmacokinetics of oral buspirone in patients with impaired renal function.

12 patients with mild to moderate impairment of renal function and 12 healthy subjects each received 20mg buspirone as a single dose in this acute study. Six anuric patients with chronic renal failure were given two 20mg doses of buspirone, the first 2 days before haemodialysis (between dialyses) and the second during hemodialysis (2 hours before dialysis began). The differences between the median pharmacokinetic values of buspirone for healthy subjects, patients with mild to moderate renal impairment, and anuric patients were not statistically significant. Similarly, there were no significant differences between values in mild to moderate renal failure vs healthy subjects. Some of the median pharmacokinetic values for the active buspirone metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), however, differed significantly for anuric patients, compared with healthy subjects or patients with mild to moderate renal impairment. When assessed between and during haemodialysis, the anuric patients had significantly (p less than 0.05) greater pharmacokinetic median values: half-life (t 1/2) = 15.2 vs 9.8 hours; area under the concentration-time curve (AUC) = 604 vs 404 nmol/L.h; and mean residence time (MRT) = 9.28 vs 6.96 hours. No firm recommendation for specific dosage can be made based on the present data. However, it does appear that in patients with mild to moderate renal impairment, the pharmacokinetics of buspirone and its active metabolite 1-PP are similar to those in individuals with normal renal function. For anuric patients higher concentrations of the 1-PP metabolite are attained while they are not undergoing haemodialysis. A dosage reduction of 25 to 50% might be necessary when buspirone is given to anuric patients.

Carnitine balance in hemodialyzed patients.

1-Carnitine was assayed before and after dialysis in plasma, dialyzate and muscle of four patients undergoing hemodialysis. The findings suggest that plasma carnitine losses occurring during hemodialysis may be at the expense of the carnitine present in extracellular fluid. Carnitine concentrations in muscle of hemodialyzed patients and controls did not differ significantly. Chronic carnitine administration did prevent plasma carnitine from falling below base levels, but did not affect muscle concentration.

Quality of life and end stage renal disease therapeutic programs. DIA-QOL Group. Dialysis quality of life.

Because patients with ESRD cannot be cured of their underlying conditions and because the therapeutic programs have an important impact on the patients' life style, the patient's own assessment of health should have a central place in clinical care. Until now, attention has almost exclusively focused on technical and clinical outcomes, and survival. Functional status, well-being and quality of life, satisfaction with care, or in other words "patient's experience", have been only marginally considered. There is a growing recognition that use of mortality data alone is not the most effective way to asses the quality of care provided to these patients. Generic and disease-specific health issues can be investigated with the use of questionnaires, by asking questions that cover physical, psychological and social domains. Health related quality of life data regarding chronic renal failure, dialysis and transplantation are briefly presented and discussed. These data show differences between patient's subjective feelings and physician's opinions about patients, between objective quality of life indexes and subjective quality of life scores. A more comprehensive view of our patients seems possible and useful.

Biofiltration: an effective and simple method to reduce dialysis time.

Biofiltration: an effective and simple method to reduce dialysis time. Six stable anuric patients, on maintenance hemodialysis, were treated for 10 weeks with a parallel flow 1 m2 cuprophan filter, for 20 weeks with a parallel flow 1.2 m2 polyacrylonitrile filter using the biofiltration (BF) technique and again 10 weeks with the cuprophan filter. Usual monitors were used, without automatic control of ultrafiltration. Biochemical and hematological profile, urea kinetic parameters, incidence of hypotensive episodes, body weight and blood pressure did not change throughout the study. We conclude that three hours of BF, at least for 20 weeks, are as effective and well tolerated as four hours standard hemodialysis and could be of value in reducing dialysis time, to permit better utilization of dialysis beds.

Factors affecting plasma free fatty acids rise during hemodialysis.

We studied the mechanisms responsible for causing acute changes in plasma lipids during hemodialysis. Dialysis decreased plasma triglycerides to the same extent as when heparin was given without dialysis. Cholesterol increased in proportion to hemoconcentration. Plasma free fatty acids (FFA) levels were also increased, but more so than with heparin alone. Glucose and acetate did not play a role, nor did carnitine loss, and hemofiltration elicited similar effects. The rise in plasma FFA is therefore likely to be caused by other as yet unknown mechanism.

Heparin for hemodialysis: practical guidelines for administration and monitoring.

Anticoagulation of extracorporeal circuit still represents a major problem for hemodialysis units. Uraemic patients are at risk of hemorrhages, so anticoagulant could increase such a risk. On the other hand clotting of extracorporeal circuit may complicate inadequate heparin administration or hemostatic activation by the foreign surfaces. In this article we propose a simple standard for heparin administration and monitoring which allows the theoretical best anticoagulation for extracorporeal circuit. Our data also indicate that the effect of our proposed schedule is not influenced by the type of membrane or dialyser used.

Management of myeloma kidney: an anti-light-chain approach.

This report describes the course of 23 patients with multiple myeloma and severe renal failure treated with a combination of plasmapheresis, chemotherapy, and supportive measures. Eight of ten patients with acute renal failure (ARF) obtained recovery of renal function, and in five of them serum creatinine concentration returned to normal. The remaining two patients died before the effect of treatment could be evaluated. Eleven of 13 patients with chronic renal failure (CRF) had substantial, albeit incomplete, improvement in renal function. The extent of functional recovery appeared to depend on the type of renal lesions, probably related to the duration of exposure to light chains. The median survival of the whole series of patients was 9 months, and five patients lived longer than 3 years. No clear-cut difference in survival was found between the group with ARF and that with CRF, although the latter presented higher values of serum creatinine at the time of diagnosis and residual renal insufficiency after the completion of treatment. Moreover, no significantly different survival times were found when the group with complete recovery of renal function was compared to that with minor improvement. Thus, renal failure, with the availability of effective forms of treatment of uremia, did not play a major prognostic role in our series. In contrast, the response to chemotherapy appeared to be the outstanding factor conditioning the duration of survival in these patients.

Outbreak of non-A, non-B hepatitis in centre haemodialysis patients: a retrospective analysis.

We reviewed the medical records of 177 patients who at 31 December 1985 had been on dialysis treatment for at least one year. Fifty cases of non-A, non-B hepatitis were found: 33 in 70 patients dialysed at the centre and 17 in 107 outpatients (P less than 0.0001). The difference was not related to blood transfusions but to the high prevalence of non-A, non-B in hospital patients who had not been transfused. The time on dialysis before the onset of non-A, non-B hepatitis became gradually shorter, from an average of 82 months before 1980 to 5.7 months in the patients starting haemodialysis after 1983. At follow-up, 7% of patients had abnormal hepatic enzymes 5 years from the onset of acute illness. The epidemiology of non-A, non-B hepatitis in haemodialysis patients appears to be similar to that of hepatitis B. Apart from blood transfusions, contamination of hospital environmental surfaces seems to be the major route of transmission. Our results strongly support a preventive programme for non-A, non-B hepatitis similar to that for hepatitis B, and a separate section for any patient with suspected non-A, non-B hepatitis must be considered.

Accelerated recovery of post-dialysis plasma carnitine fall by oral carnitine.

Plasma free carnitine in 6 chronic uremic patients fell 73% during hemodialysis. The recovery time was 6 h with placebo and only 2 h when dl carnitine (3 g oral) was taken at the end of dialysis.

Recombinant human erythropoietin to correct uremic bleeding.

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.

Health-related quality of life in dialysis patients. A report from an Italian study using the SF-36 Health Survey. DIA-QOL Group.

BACKGROUND: Interest in measuring health-related quality of life (HRQoL) has increased together with an awareness that such humanistic outcomes require valid and reliable measures. In the last decade short, simple and multidimensional generic and disease-specific questionnaires have been developed. Among the several generic questionnaires available, the Short Form 36 Items Health Survey (SF-36) was translated and validated in several languages, and applied to different settings and diseases. METHODS: Within the framework of a larger, prospective, multicentre study (DIA-QOL project) the SF-36 was administered to 304 patients to test its characteristics in terms of patient acceptability, and psychometric and clinical validity. Standard psychometric techniques were used to evaluate its validity in terms of convergence, divergence and internal consistency reliability (Cronbach's alpha). Correlations between clinical variables and HRQoL scores were performed to test the questionnaire's capability to capture differences across patients groups. RESULTS: Overall, the findings show that, in this sample, the SF-36's performance was very good. Acceptability was satisfactory, with a response rate higher than 80%. All the questionnaire scales met the psychometric standards suggested in terms of grouping and scaling assumptions. The internal reliability coefficients actually replicate the satisfactory findings reported previously for the original SF-36. In terms of the ability of the questionnaire scales to discriminate between groups expected to differ in a given health concept in relation to clinical variables, the results were also good. On average, females reported lower scores, the impact of ageing was more evident for physical scales. Diabetic patients score significantly worse on the physical function scale and patients with mental health problems score significantly lower on the mental health scale. No significant association was found with the index KtV, haemoglobin levels, body mass index, parathyroid hormone and type of dialysis. A strong association was indeed found between SF-36 scales measuring physical health concepts and the serum albumin level. This association held after adjusting for the confounding effect of age. Comparison of the health profile of the present sample with others from the US and UK and from a representative sample of the Italian general population highlights the potential of such questionnaire in dialysis setting. CONCLUSIONS: The SF-36 questionnaire is easy to use in Italian dialysis patients and SF-36 scores are related to important clinical aspects. This approach can help in caring for dialysis patients and can be useful in outcome assessment programmes.

Ventricular arrhythmias and four-year mortality in haemodialysis patients. Gruppo Emodialisi e Patologie Cardiovascolari.

127 randomly selected patients on haemodialysis showed a high prevalence of ventricular arrhythmias, the frequency of which rose significantly during and after dialysis. These patients have now been followed up for 4 years. Only age and ischaemic heart disease correlated independently with mortality. Although ventricular arrhythmias are often associated with cardiac disease in patients on chronic haemodialysis, they do not seem to predict overall mortality.

Conjugated estrogens for the management of bleeding associated with renal failure.

Bleeding is a major complication of uremia. Both cryoprecipitate and desmopressin effectively shorten the prolonged bleeding time and favorably influence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases, and both cryoprecipitate and desmopressin have a short duration of action. Preliminary evidence has suggested that estrogens may be useful, and we therefore performed a randomized, double-blind, crossover trial comparing the effect of conjugated estrogens with that of placebo on hemorrhagic tendencies and the bleeding time in six patients with uremia who were on maintenance hemodialysis. Five daily infusions of placebo or conjugated estrogens were administered at the beginning of one-month trial periods. Estrogen shortened the bleeding time in all six patients. The effect was detectable six hours after the first infusion, reached its maximum in all patients between days 5 and 7, and lasted for 14 days. By day 16 after the last infusion, the bleeding time had returned to base line in four of the six patients. No side effects were noted during or after estrogen infusion. Estrogens did not influence the circulating level of von Willebrand factor or change its multimeric structure. Moreover, the defective platelet aggregation and thromboxane formation observed in the patients were not corrected by estrogens. We conclude that conjugated estrogens are an adequate alternative to cryoprecipitate or desmopressin for the treatment of bleeding associated with renal failure, especially when a longer duration of action is needed and immediate onset of the effect is not essential. The mechanism of action of estrogens remains to be clarified.