Kinetics of hepatitis B virus load and haemodialysis: a prospective study.

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.

Reduction in urea distribution volume over time in clinically stable dialysis patients.

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

[Acute renal failure and thrombotic microangiopathy (TM)]. / Insufficienza renale acuta e microangiopatia trombotica.

BACKGROUND: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia. HUS is more frequent in children and is mainly characterized by renal symptoms, whereas PTT is dominated by neurologic abnormalities. However, in many patients, the clinical distinction between HUS and PTT is not clear; therefore, some authors consider the two syndromes as manifestations of the same entity. In children, the most common cause of HUS is an enteric infection caused by cytotoxin-producing bacteria (mainly Escherichia coli with serotype O157:H7). This toxin--the Shiga toxin--can bind to glomerular endothelial cells and stimulate the production of cytokines and the secretion of von Willebrand factor (vWf). TM may be caused by drugs such as cyclosporin, tacrolimus, mytomicin C, ticlopidine, quinine, and oral contraceptives. It may be associated with disorders of pregnancy (severe pre-eclampsia and postpartum HUS) or with systemic disorders such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, systemic sclerosis, and human immunodeficiency virus (HIV) infection. Abnormalities of the gene of complement factor H have been found in familial HUS and in some sporadic cases of HUS not associated with diarrhea. Factor H abnormalities induce an uncontrolled complement activation that can activate the coagulation cascade. In familial PTT, genetic abnormalities of the cleaving metalloproteinase of fWf ADAMTS 13 have been identified. In other patients with TTP, antibodies inhibiting this enzyme have been found. As a consequence of plasma ADAMTS 13 deficiency, unusually large vWf multimers are produced. This abnormality, in the presence of an increased shear stress, stimulates platelet adhesion and aggregation. CONCLUSIONS: Knowledge of the type of causative abnormality is relevant to a therapeutic approach. Children with diarrheal HUS usually do not benefit from plasma infusion or exchange, whereas in patients with factor H or ADAMTS 13 deficiency procedures that include the administration of the lacking product and removal of the inhibiting or toxic factors, such as ultralarge vWfs, are mandatory. Potentially renal transplantation candidates should be screened for genetic defects to avoid the recurrence of TM in the graft.

Conductivity: on-line monitoring of dialysis adequacy.

Cardiovascular disease and the inadequacy of delivered dialysis are the main factors determining morbidity and mortality in dialysis patients. We have already demonstrated that a conductivity kinetic model makes it possible to match interdialytic sodium loading and intradialytic sodium removal (the main factor determining cardiovascular morbidity) without the need for blood samples and, thus, in routine clinical practice. The aim of the present study was to test the possibility of using the conductivity method also to determine Kt/v without blood or dialysate sampling. In 18 steady-state patients, the urea distribution volume (V) was kinetically determined once using ionic dialysance (D) values instead of those of effective urea clearance. One month later, the Kt/V was determined by using the current D and T values and the predetermined V (Dt/V), then compared with the equilibrated Kt/V computed by means of the SPVV kinetic model (eqKt/V). The mean value of Dt/V was 1.18+/-0.15; while of eqKt/V it was 1.18+/-0.16, with a mean difference of 0.00+/-0.07. The conductivity method therefore seems to be very promising not only for monitoring the sodium balance, but also for quantifying delivered dialysis. Since its simplicity and low-cost make it suitable for use at each dialysis session, the conductivity method could therefore lead to significant progress in dialytic practice by contributing to the elimination of the two main causes of morbidity and mortality in dialysis patients.