Seroprevalence of IgG against conformational and linear capsid antigens of parvovirus B19 in Italian blood donors.

Serum samples from 446 Italian blood donors between 18 and 65 years of age were analysed for the presence of IgG against parvovirus B19 capsid proteins VP1 and VP2 including conformational and linear epitopes. The overall prevalence of IgG against parvovirus B19 capsid proteins VP1 and VP2 against at least one antigen type was 79.1 %. No significant difference was found between men and women. In the 18-27 years age group, 77.0 % of the population had experienced infection with the virus, reaching 88.5 % in the 48-57 years age group. The overall prevalence of IgG was 78.0 % against conformational VP1 + VP2 antigens, 74.9 % against conformational VP2, 70.9 % against linear VP1 and 23.3 % against linear VP2 in the analysis of the IgG response against different conformational and linear epitopes of VP1 and VP2. Although IgG against conformational VP1+VP2, conformational VP2 and linear VP1 was present in more than 60 % of subjects in all age groups, IgG against VP2 linear antigens was present in only 32% of subjects in the 18-27 years age group and then decreased to 20.5 % in the 28-37 years age group. A different trend was noted when IgG positivity against linear and conformational epitopes was analysed separately in men and women. A significant increase was found in seroprevalence of IgG against VP2 conformational antigens with increasing age in males and a significant decrease in seroprevalence of IgG against VP2 linear antigens in women with increasing age.

Production and use of fibrin glue at blood transfusion service of Bellaria-Maggiore Hospital Bologna.

FG is created by combining the two principal clotting factors found in plasma, fibrinogen and thrombin, whose natural function is to halt bleeding and seal tissues. We determined the safety, and efficacy of autologous FG by an automated device CryoSeal FS System. This procedure allows the blood transfusion center to produce a standardized product having similar characteristics of the pharmaceutical products available on the market and to produce a consistent amount of FG components from a single unit of autologous blood. The study involved a retrospective controlled evaluation of urologic patients compared with a control group operated of radical perineal prostatectomy. Blood loss difference is not significant. The hospital stay of the study group is shorter then the control group. The control group received more unit of homologous blood compared to the study group. This acquisition is suggestive for hypothetical blood saving.

Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.

PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

Effect of Lisinopril on the progression of renal insufficiency in mild proteinuric non-diabetic nephropathies.

BACKGROUND: The aim of the study was to determine whether Lisinopril, an ACE-inhibitor (ACEi), was more effective than other antihypertensive agents in slowing the progression of non-diabetic chronic renal diseases in patients with baseline proteinuria < or =1.0 g/day. METHODS: In an open, multicentre study all eligible patients entered a 3 months run-in phase during which antihypertensive therapy (with exclusion of ACEi) was adjusted in order to obtain a supine diastolic blood pressure < or =90 mmHg and urinary protein excretion and renal function stability were verified. One hundred and thirty-one patients with chronic renal insufficiency (Clcr between 20-50 ml/min) because of primary renoparenchymal diseases and proteinuria < or =1.0 g/day, were randomized to Lisinopril (L=66) or alternative antihypertensive therapy (C=65). Changes in renal function were assessed by inulin (Clin) clearance. RESULTS: During the follow-up period of 22.5+/-5.6 months, Clin did not change significantly in group L (-1.31+/-0.6 ml/min/1.73 m(2)) differing significantly from group C in which it declined markedly (-6.71+/-3.6 ml/min/1.73 m(2)) (P<0.04). Seven patients experienced adverse events that prompted discontinuation of treatment: four in group L and three in group C; in addition seven patients showed severe deterioration in renal function requiring dialysis: two in group L and five in group C. The overall risk of the combined end-points: need for dialysis or halving of GFR was significantly higher in group C versus group L. During the study the mean value for systolic blood pressure was 137.8+/-14.6 SD mmHg in group L and 140.8+/-14.1 SD mmHg in group C; the mean difference between groups, during and at the end of the study, was 2 mmHg (NS). The mean diastolic blood pressure during the study was 83.8+/-8.6 SD mmHg in group L and 84.3+/-7.56 SD mmHg in group C; during and at the end of the study the mean diastolic difference between groups was 1 mmHG: CONCLUSION: This study, employing a sensitive measurement of renal function and with similar blood pressure in both groups, provides support to the hypothesis that ACEi have a specific renoprotective effect, in addition to blood pressure control, also in patients with mild proteinuria.

Dry weight in hemodialysis: volemic control.

In dialysis patients the chronic fluid overload may represent a nonphysiologic condition which brings both arterial hypertension and hemodynamic instability. Volume expansion is significantly correlated to casual predialysis blood pressure and 24-hour arterial pressure. The normalization of the patient hydration status is not only followed by a reduction in pressure values but also by an improvement of the circadian blood pressure rhythm. On the other hand, hypovolemia and underhydration combined with an impaired cardiovascular regulatory response may generate the dialysis-related hypotension. Many techniques have been introduced to obtain an objective measurement of the hydration status: postdialysis radiological chest examination, plasma atrial natriuretic peptide (ANP), and plasma cyclic guanidine monophosphate (cGMP) levels, multifrequency electrical bioimpedance and the continuous plasma volume measurement. The latter, alone or in combination with provocative tests (stop and go of the ultrafiltration), may help in optimizing plasma volume contraction. The plasma volume monitoring avoids the risk of hypovolemic hypotension and facilitates the achievement of a correct dry body weight. The biofeedback system, exploiting the automatic control of the intradialytic variations, may represent an additional advantage in the formulation of an ideal postdialysis blood volume that overlaps the patient's dry weight.

Continuous urea monitoring in hemodialysis: a model approach to forecast dialytic performance. Results of a multicenter study.

BACKGROUND: A urea biosensor, inserted into the ultrafiltrate collection-line of paired filtration dialysis (PFD), not only allows on-line dialysis quantification, but also forecasts final (Cend) and 30 min equilibrated urea concentration (Ceq), the most reliable value for calculating dialysis efficiency. The urea biosensor processes plasma ultrafiltrate continuously, delivering a large amount of data to the computer, which estimates the parameters by a mathematical model, thus predicting the whole urea profile with rebound. METHODS: A multicenter randomized trial on 41 patients was conducted to ascertain the ability of a two-pool variable-volume urea model to forecast Cend and Ceq at 60 and 90 min after the start of dialysis. Two alternative dialytic treatments, A or B, were chosen, the latter being more efficient. Each treatment included six serial PFD. The accuracy of forecasting was evaluated through four indices based on forecast errors, calculated as the difference between observed and forecasted urea values: mean percent error (MPE) (%), mean absolute deviation (MAD) (mg/dl), mean absolute percent error (MAPE) (%) and root mean squared error (RMSE) (mg/dl). RESULTS: Forecasted urea concentrations were lower than those measured by the biosensor. MPE for Cend was negligible in A (+1.2%) and much higher in B (+7.2%); both values improved at 90 min, +1.0% and +5.8%, respectively. MAD for Cend was similar in both treatments and improved slightly at 90 min, ranging from 4.9 to 5.9 mg/dl. MPE for Ceq was +4% in A and and more than doubled in B (+11.5%); both values improved at 90 min, +3.7% and +9.7%, respectively. MAD for Ceq was 7.5 mg/dl in A and 8.5 mg/dl in B; both improved at 90 min, 6.7 and 7.4 m g/dl, respectively. The other indices, MAPE and RMSE, showed similar results. Comparison between the errors of the two treatments with analysis of variance (ANOVA) for repeated measures gave no significant results. CONCLUSIONS: Our model forecasts of urea concentrations were overall lower than the measured ones: the bias was negligible for A-Cend, greater for the A-Ceq and when the more efficient treatment B was used. The 60 min predictions improved at 90 min. The comparison between the prediction errors in the two treatments were not statistically significant. The recirculation measurement would probably reduce the bias if it were properly incorporated into the model.

The careful correction of renal insufficiency abnormalities: early is good.

Cardiovascular disease in end-stage renal disease (ESRD) patients starts early in the course of renal insufficiency and may be aggravated by renal replacement therapy. Many potential reversible risk factors are present in renal insufficiency. The identification and correction of these risk factors, in part delaying progression of renal failure, may reduce their role in ESRD cardiovascular disease significantly. Early referral of renal insufficiency patients to a nephrologist may be the real answer to the cardiovascular morbidity and mortality of ESRD patients.

The impact of haemofiltration on the systemic cardiovascular response.

Convective transport across the dialysis membrane has long been known to be a good alternative to diffusion. Among the advantages of haemofiltration over conventional haemodialysis is a better cardiovascular stability. Haemofiltration has a more physiological response to fluid removal than haemodialysis: (i) blood volume may be better preserved, especially in patients with a compromised cardiac function; (ii) arterial peripheral resistances and venous tone increase; and (iii) myocardial contractility is neither depressed nor altered. We discuss the role of the different pathophysiological mechanisms in the disparity in cardiovascular reactivity between haemofiltration and haemodialysis.

3 R study: renal outcome in renal ischemia: revascularisation or medical treatment.

Ischemic nephropathy refers to the kidney damage following stenosis or an obstructive lesion in the main kidney arteries. This disorder has been overlooked in the past and a more rational and specific use of clinical criteria, and the development of not very invasive techniques with a good diagnostic accuracy such as spiral CT angiography, NMR angiography and echo-colour-Doppler have improved our ability to identify these patients. It is therefore likely that, in the next few years, we will find ourselves treating an increasing number of patients with renovascular ischemic disorders. Transluminal angioplasty and, more recently, the use of endovascular stents, have led to a marked improvement in the treatment of stenoses and, together with vascular surgery, allow to treat almost all patients with this disorder. There is, however, a lack of prospective and controlled studies, which demonstrate the long term benefit of revascularization treatment, as compared with optimum conservative treatment in reducing cardiovascular mortality, cardiovascular events and preserving renal function. The Ischemic Nephropathy Study Group of the Italian Society of Nephrology has organized a prospective, controlled study over a period of three years, aimed at comparing the effect of revascularization versus medical therapy in 300 patients with renal artery stenosis, ranging between 50 and 90 per cent, who will be randomly assigned to the two treatments. End point will be cardiovascular mortality and morbidity and need for renal replacement therapy.

The deletion polymorphism of the angiotensin-converting enzyme is associated with nephroangiosclerosis.

The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression. The association of this allele with nephroangiosclerosis has been scarcely investigated. We have tested this association in 45 hypertensive patients (all whites) with well defined nephroangiosclerosis (diagnosis established on the basis of renal biopsy in all cases) and moderate to severe renal failure. As studies of genetic association of small size often produce conflicting results, besides a control group of 343 Italian patients with essential hypertension and normal renal function, we elected to use also a very large control group of race-matched subjects taken from a meta-analysis of 27,565 whites. The proportion of patients with the D allele (64%) was higher in patients with nephroangiosclerosis than that in Italian hypertensives (54%) and in whites (54%). DD and DI genotypes were more prevalent in patients than in control groups. The dominant model (DD and DI v II: nephroangiosclerosis v Italian controls: chi2 = 6.19, P = .012; nephroangiosclerosis v whites chi2 = 6.86, P = .009) fitted the data better than the codominant and the recessive model (P < or = .022). The D allele is associated with nephroangiosclerosis with a dominant effect in the sample of patients studied. Although intervention studies are needed to see whether these findings imply a causal association, our data suggest that this allele may at least act as disease marker in nephroangiosclerosis.

Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency.

AIMS: To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. METHODS: Patients with congestive heart failure (CHF, NYHA Class II-IV) and chronic renal insufficiency (creatinine clearance

Clinical and prognostic value of serial renal biopsies in lupus nephritis.

Little information is available about the role of repeated renal biopsies in lupus nephritis. We analyzed retrospectively the prognostic significance of serial renal biopsies in patients with lupus nephritis. Thirty-one patients with lupus nephritis underwent two or more renal biopsies during follow-up. The indications for repeated biopsy were as follows: improvement of renal disease but persistence of nonnephrotic proteinuria (group A, 7 patients); persistent or relapsing nephrotic syndrome (group B, 12 patients); and worsening of renal function (group C, 19 patients). After a median follow-up of 10.5 years, 17 patients reached the end point (persistent doubling of plasma creatinine level). At repeated renal biopsy, there was a correlation between improved clinical and histological features for group A. In these patients, treatment was reduced or stopped successfully. Histological features remained almost unchanged in group B. All patients showed an improvement of proteinuria after reinforcement of therapy. In group C, the worsening of renal function was associated with a variable and clinically unpredictable combination of active and chronic lesions. Only the few patients with an elevated activity index and moderate chronicity index showed a favorable and persistent improvement of renal disease after reinforcement of therapy. At multivariate analysis of clinical and histological data at presentation, only male sex was predictive of an adverse outcome (P = 0.015). At repeated renal biopsy, crescents in more than 30% of glomeruli (P = 0.0009) and chronicity index of 5 or greater (P = 0.00006) were associated with the probability of reaching the end point at multivariate analysis. Repeated renal biopsy may be helpful for establishing the prognosis in patients with lupus nephritis, particularly in the presence of worsening of renal function.

The management of hypotension in dialyzed patients.

Acute hypotension is a frequent hemodialysis complication. This intra-treatment vascular instability is a multifactorial process in which procedure-related and patient-related factors may influence the decrease in plasma volume and the impairment of cardiovascular regulatory mechanisms. Identification of the most susceptible patients and of the various risk factors may contribute to significantly improving cardiovascular stability during dialysis. In some high-risk patients, continuous monitoring of the various parameters can predict the appearance of symptomatic hypotension and help to prevent its onset.

Angiotensin-converting enzyme inhibitors and kidney protection: the AIPRI trial. The ACE Inhibition in Progressive Renal Insufficiency (AIPRI) Study Group.

A protective effect of angiotensin-converting enzyme (ACE) inhibitors has been shown in patients with diabetic nephropathy but has not been clearly established in nondiabetic renal disease. A multicenter European study was designed to determine whether the ACE inhibitor benazepril was safe and effective in protecting residual renal function in patients with various renal diseases and mild to moderate renal failure. The trial involved 583 patients from 49 centers in Italy, France, and Germany. The patients were randomized to receive benazepril or placebo plus other antihypertensive agents, the target being a diastolic blood pressure of less than 90 mm Hg. Thirty-one patients in the benazepril group and 57 patients in the placebo group reached the end point [the time elapsed from entry to (a) doubling of serum creatinine (SCr) concentrations and (b) start of renal replacement therapy; p < 0.001 at 3 years]. The associated reduction in the relative risk of reaching the end point was 53% in benazepril-treated patients, with actuarial renal survival probability significantly better at 3 years. The best survival of renal function was observed in patients with chronic glomerular diseases and proteinuria greater than 1.0 g/24 h. Benazepril is effective in slowing the rate of progression and improving the survival of renal function in patients with renal diseases of various origins. This protective effect is associated with a clinically relevant decrease in both blood pressure and proteinuria.

A prospective randomised European multicentre study of medium-long run mortality and morbidity comparing acetate-free biofiltration and bicarbonate dialysis.

In recent years, the progressive increase in the mean age of the population entering chronic dialysis treatment has been responsible, on the one hand, for the growing number of patients undergoing regular dialysis, and on the other, for the high number of "critical" patients, both as a result of their age and the presence of concomitant morbidity. Thus, dialysis treatment today is not only aimed at waste removal and water-electrolyte homeostasis, but also at a reduction in morbidity and mortality, and at improving the patients' quality of life, thanks to the use of biocompatible materials and the achievement of good cardiovascular tolerance to treatment. Consequently, diffusive-convective dialysis procedures have been on the increase, since they combine better depuration with the use of biocompatible high-flux membranes. Acetate-free biofiltration (AFB) is a diffusive-convective dialysis procedure which utilises a high-flux membrane, AN69, post-dilution infusion of a sodium bicarbonate solution (NaHCO3), and a dialysate which is completely free of any buffer, and thus also free of acetate, which may have various negative effects on the patient. A number of studies have already shown the better hemodynamic stability and the reduction of intradialytic side-effects during AFB. All these, however, were short-term studies. To verify the beneficial effects of AFB in the long run, a three year multicentre randomised European trial has been proposed to compare bicarbonate hemodialysis (BD), a technique used in nearly 80% of the world's dialysis population, and AFB. The specific aim of the investigation is to verify, in a large number of patients, the results of hemodialysis treatment in terms of morbidity, mortality and quality of life. The study involves 80 hemodialysis units across Italy, France, Germany, Spain, Slovenia and Croatia, with enrollment of about 400 patients considered "critical" for at least one of the following reasons: age, diabetes, dialysis cardiovascular instability. Fifty percent of the patients are to undergo AFB with the AN69 membrane and bicarbonate solution infusion (NaHCO3 145 or 167 mEq/lt), and the other fifty percent are to be treated by BD, with any membrane except the nonmodified cellulosic one. Biochemical, cardiological, and nutritional parameters will be considered throughout the study. Mortality, morbidity both in terms of intra- and interdialysis symptoms - and hospitalisation rate, as well as the patients' quality of life, evaluated by the SF36 questionnaire, will be analysed.

Ischemic nephropathy.

Ischemic nephropathy, involving stenotic lesions in the renal arteries, associated with renal insufficiency, is now recognized as a frequent disease. It may be responsible for a significant proportion of end stage renal disease, at least in the Caucasian population. Some non-invasive but reliable techniques such as echo-color-Doppler, gadolinium-enhanced magnetic resonance and spiral CT angiography are now available for diagnosis. Revascularization with either angioplasty, stent or surgery improves renal function in many patients. In the near future systemic and/or local medical therapy will provide better answers for renovascular disease.

Renovascular disease in diabetes mellitus: treatment by percutaneous transluminal renal angioplasty.

BACKGROUND: Diabetes mellitus is an important cause of end-stage renal failure (ESRF). Although classic diabetic nephropathy accounts for the majority of patients reaching ESRF, renovascular disease, which is frequent in such patients, plays an increasingly important role. Percutaneous transluminal renal angioplasty (PTRA) has been proven to be an efficacious measure for renal revascularization. METHODS: Ninety-nine patients with diabetes mellitus and renal artery stenosis, corresponding to 16.6% of the entire population of diabetic patients, were treated by PTRA or with the Palmaz-Schatz stent in our clinic. Technical success was achieved by PTRA in 92/99 patients, in 10 patients a Palmaz-Schatz stent was implanted. RESULTS: Hypertension was cured in eight and improved in 44 patients. In 47 patients, there was no impact on blood pressure. An improvement in renal function was evident 1 month after PTRA in 8/27 patients. A further improvement occurred in another four patients after 6 months. The re-stenosis rate was 22% after 5 years. Serious complications occurred in seven patients (one patient required surgery and two patients had regular dialysis treatment). CONCLUSIONS: Renovascular disease is an important cause of ESRF in diabetic patients. PTRA is a valid tool to revascularize renal artery stenosis and improve blood pressure control and renal function both in diabetic and non-diabetic patients.