Background: The most common complication of hemodialysis (HD) access graft is thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to prevent this serious complication. Methods: A prospective study in which 24 patients on chronic HD whose vascular accesses were grafts were divided into two groups: group A (n = 12, 50%) consisted of patients who did not receive antithrombotic therapy after graft creation, and group B (n = 12, 50%) received clopidogrel 75 mg/day from 2 days after surgery onwards. Both groups were not different according to age, gender, cause of renal failure, hematocrit levels, platelet counts and Kt/V. All patients’ thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed. Finally, the patient survival difference between both groups was determined. Results: Eleven thrombotic episodes were diagnosed in group A while one event was reported in group B (p < 0.001). Graft access days of patency were significantly longer in group B compared to group A (380.8 ± 170 vs. 90.1 ± 57.2, p < 0.001). Time that elapsed from dialysis initiation to graft creation was not different (group A 18 ± 12 days, group B 20 ± 10 days). Days on HD were different between both groups (group A 208.9 ± 97.2 vs. group B 583.2 ± 287.0, p < 0.001) and all patients from group A (n = 12, 100%) and 2 patients from group B (16.7%) died (p = 0.001). Major bleeding events were not reported. Conclusions: Clopidogrel significantly decreased thrombotic graft episodes. Patients on clopidogrel had a prolonged vascular access patency, longer time on HD and better survival.

Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.

Background Hyperhomocysteinemia is a risk factor for thrombosis, a frequent complication of vascular access (VA) in hemodialysis (HD). The enzyme methylenetetrahydrofolate reductase (MTHFR) is necessary for the remethylation of homocysteine (Hcy) to methionine. It has been postulated that patients homozygous and, to a lesser extent, heterozygous for the C677T thermolabile variant of this enzyme present a reduced catalytic activity, with secondary increases in plasmatic Hcy levels (normal: 10 ± 5 μmol/L) and an elevated risk of vascular thromboses. Methods Sixty-two patients on chronic HD were divided into two groups: group A (n = 23, 37.1%) was normal for the enzyme (CC); group B (n = 39, 62.9%) was heterozygous (CT). Both groups were not different according to age, sex, time on HD, hematocrits (Hct), baseline levels of Hcy, folic acid and vitamin B12. After the 1st HD session patients were started on folic acid 10 mg/day and 500 μg/week of intravenous (i.v.) methylcobalamin. Results Two years later, thrombotic events were not different between the two groups. Group A = 5 (21.7%) vs. group B = 12 (30.7%), Hcy levels were significantly different between final and baseline measurements (group A 21.5 ± 5.2 vs. 16.6 ± 3.9 μmol/L, p = 0.02; group B 22.1 ± 8.9 vs. 16.1 ± 3.9 μmol/L, p = 0.008), folic acid (group A 22.1 vs. 346.9 ng/ml, range (r) = 166–527, p<0.001; group B 19.2 vs. 218.5 ng/ml, r = 138–298, p<0.001) and vitamin B12 (group A 1489 vs. 3192.3 pg/ml, r = 1494–4890, p = 0.01; group B 1086 vs. 1513.8 pg/ml, r = 1092–1934, p = 0.02). Conclusions HD patients heterozygous for the C677T variant of the enzyme MTHFR can present a similar risk of thrombotic events in arteriovenous fistulae (AVF) compared to patients normal for the enzyme at a 1-yr follow-up. These results could be explained by an adequate control of Hcy levels after folic acid and methylcobalamin replacement therapy.

Background: There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients. Methods: We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 µg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 µg twice/week alone. Fasting tHcy, vitamin B12, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy. Results: Final tHcy levels were significantly lower in group A (10.2 ± 3.1 µmol/l) compared to groups C (27.3 ± 9.7 µmol/l, p < 0.001) and group D (24.3 ± 11.8 µmol/l, p < 0.001) and similar to group B (11.2 ± 1.9 µmol/l, p = n.s.). Mean tHcy levels showed a significant decrease in group A from 22.5 ± 15.6 to 10.2 ± 3.1 µmol/l (p = 0.003) and in group B from 19.9 ± 4.0 to 11.2 ± 1.9 µmol/l (p = 0.012), while no significant changes were observed in groups C (25.9 ± 9.3 vs. 27.3 ± 9.7 µmol/l, p = n.s.) and D (26.6 ± 14.3 vs. 24.3 ± 11.8 µmol/l, p = n.s.). Conclusion: Oral FA (10 mg/day) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients; the addition of i.v. Me-Cbl (500 µg twice/week) to this regimen showed no benefit. Separately, FA corrected hyperhomocysteinemia (HtHcy), while Me-Cbl showed no change.

Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48% and homozygozity 4%. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.

Cytomegalovirus is the most important viral infection in kidney transplants, but rarely affects the allograft after the sixth month posttransplantation. We present a patient who developed renal failure eighteen months posttransplant; a kidney biopsy showed cytomegalovirus inclusions, acute tubular necrosis and mild interstitial nephritis. After intravenous ganciclovir, renal function transiently improved. Cytomegalovirus pp65 antigen was weekly reported as negative. One month later another biopsy was performed due to renal failure. The findings were consistent with tubular atrophy and severe interstitial nephritis. No cytomegalovirus cellular inclusions were found on histology, including immunohistochemical and polymerase chain reaction studies; pp65 antigen studies were persistently negative. Despite an attempt to recover renal function with steroid therapy, the patient restarted hemodialysis 20 months posttransplantation. This report suggests that cytomegalovirus should be considered as a late cause of kidney failure even in the absence of infection-related symptoms. The irreversible allograft damage can be caused despite the successful eradication of the virus with intravenous ganciclovir.

A woman on daclizumab developed thrombotic microangiopathy secondary to cyclosporine after a living-unrelated kidney transplant. Despite cyclosporine discontinuation, hemolysis persisted. The second dose of daclizumab was postponed 24 h, and after a maximum of two sessions of plasmapheresis (to avoid further modifications in daclizumab schedule) with plasma exchange, daclizumab was administered. Plasma infusions were prescribed until D-dimer and fibrinogen-degradation products normalized; thereafter, FK-506 was started without recurrence of the hemolytic picture and renal function restored. This observation suggests that in patients on daclizumab who develop thrombotic microangiopathy secondary to immunosuppressants, if discontinuation of the offending drug is unsuccessful, plasmapheresis with plasma exchange can be performed when the lowest levels of daclizumab exist, followed by daclizumab infusion. Plasma prescription must be continued thereafter until D-dimer and figrinogen-degradation products normalize. However, if hemolysis persists when daclizumab levels are high, plasma infusions are useful and plasmapheresis avoided. FK-506 administration did not result in recurrence of hemolysis during daclizumab induction.