Background Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia, lipid abnormality and cardiac ...dysfunction. The therapeutic value of carnitine supplementation on left ventricular hypertrophy (LVH) in patients with normal cardiac systolic function remains uncertain. Methods and Results The cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally, immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients. Using echocardiography, left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) were measured before and after the study period. As a result, amounts of serum-free carnitine increased from 28.4±4.7 to 58.5±12.1 μmol/L. The LVMI decreased significantly from 151.8±21.2 to 134.0±16.0 g/m2 in treated patients (p<0.01), yet the LVMI in untreated control patients did not change significantly (ie, from 153.3±28.2 to 167.1±43.1 g/m2). However, LVFS values remained unchanged in both groups. Although L-carnitine promoted a 31% reduction in erythropoietin requirements, hematocrit and blood pressure did not change during the study period. Conclusions Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis, even for those with normal systolic function. (Circ J 2008; 72: 926 - 931)
Switch from conventional to high-flux membrane reduces the risk of carpal tunnel syndrome and mortality of hemodialysis patients. The use of a high-flux membrane, which eliminates larger molecular ...weight solutes with better biocompatibility, has steadily increased since the discovery of beta-2 microglobulin (β2m) amyloidosis in 1985. The long-term effects of a dialyzer membrane on morbidity and mortality are not completely understood. To examine the membrane effect as a factor of carpal tunnel syndrome onset and mortality, multivariate Cox regression analysis with time-dependent covariate was conducted on 819 patients from March 1968 to November 1994 at a single center. Two hundred and forty-eight of the patients were either switched from the conventional to high-flux membrane or treated only with a high-flux membrane. Fifty-one patients underwent a CTS operation and 206 died. Membrane status (on high-flux or on conventional) was considered as time-dependent covariate and risk was adjusted for age, gender, type of renal disease and calendar year of dialysis initiation. The relative risk of CTS was reduced to 0.503 (P < 0.05) and mortality 0.613 (P < 0.05) by dialysis on the high-flux membrane, compared to the conventional membrane. Serial measurements of β2m indicated significantly lower β2m to persist in patients on the high-flux membrane. The high-flux membrane decreased the risk of morbidity and mortality substantially. Larger molecule elimination was shown important not only for preventing β2m amyloidosis, but for prolonging survival of dialysis patients as well.
Transferrin saturation versus reticulocyte hemoglobin content for iron deficiency in Japanese hemodialysis patients.
Iron deficiency is a frequent cause of recombinant human erythropoietin ...(rhEPO)-resistant anemia in hemodialysis patients. Both reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) have been proposed as markers of iron deficiency, but it is unclear which parameter is superior.
To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency, we conducted a single-center, open-label, prospective, randomized, controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis. After 4 weeks of run-in period during which iron supplementation was suspended, 100 patients who were randomized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg, and 97 patients who were randomized to the TSAT group received the same doses of iron colloid when TSAT less than 20%. We measured the rhEPO dose needed to maintain prestudy hematocrit levels, hematocrit, CHr, TSAT, serum ferritin, percentage of hypochromic red blood cells, and total iron administered.
Sixteen weeks later, 94 patients in the CHr group and 89 patients in the TSAT group finished the study. The doses of rhEPO required decreased by 35.8% (4081 to 2629 U/week, P < 0.005) in the TSAT group, but not significantly in the CHr group (4121 to 3606 U/week). Although CHr increased promptly after the iron administration in both groups, TSAT increased only in the TSAT group.
Although CHr reflects the iron status more sensitively, TSAT is a better clinical marker for iron supplementation therapy.
Dialysis-related amyloidosis of the heart in long-term hemodialysis patients.
Dialysis-related amyloidosis (DRA) predominantly occurs in the osteoarticular structures, but it also systemically ...appears in the extra-articular tissues as well. However, the pathological characteristics of DRA in the hearts of hemodialysis (HD) patients have rarely been reported.
We studied the pathological characteristics of DRA in the hearts of 18 HD patients, including its relationship to calcification. Furthermore, we studied the immunohistochemical localization of advanced glycation end products (AGEs) using monoclonal anti-imidazolone and anti-Nε-(carboxymethyl)lysine (CML) antibodies.
β2-microglobulin (β2m) amyloid deposits were detected in the hearts of seven patients who had undergone HD for more than 10 years. β2m amyloid deposits in the left atrium were localized in the endocardium, the myocardium, and the walls of small blood vessels, whereas in the left ventricle, they were localized only in the walls of small blood vessels. The extent and prevalence of DRA in the heart were severe in the patients on HD for more than 15 years. Most calcification areas near mitral valve were dotted with β2m amyloid deposits, while diffuse fine calcification was localized within the β2m amyloid tissues in some cases. Imidazolone and CML were localized not only in massive β2m amyloid deposits, but also in cardiac myocytes.
DRAs were localized extensively in the hearts of long-term HD patients. A strong affinity was observed between β2m amyloid deposits and calcification.
The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, ...administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, (123)I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 +/- 6.5 micromol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 +/- 7.7 micromol/l, p < 0. 0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 +/- 0.19 vs. 1.52 +/- 0.24, p < 0.005), and the patients' washout rate (WOR) of BMIPP was lower (17.2 +/- 6.0 vs. 22.8 +/- 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 +/- 27.0 micromol/l (p < 0.0001). Although the H/M ratio did not change (1.89 +/- 0.20) with this treatment, their WOR increased to 21.9 +/- 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.
Background. In congenital or acquired antithrombin III-deficient patients undergoing haemodialysis, coagulation or residual blood in the blood circuit and dialyser is commonly observed under ...anticoagulation with heparin. Argatroban, a synthetic thrombin antagonist, directly inhibits thrombin activity in a manner that is different from that of heparin, thereby displaying an anticoagulating effect without the activation of antithrombin III. For this reason, the anticoagulating effect of argatroban in haemodialysis patients with antithrombin III deficiency was investigated. Methods. A retrospective nationwide survey was conducted among patients with congenital or acquired antithrombin III deficiency who had undergone haemodialysis with argatroban as an anticoagulant from April 1996 to April 2000. Inclusion criteria were patients with antithrombin III activity <70% of normal, and patients in whom blood coagulation or residual blood in the extracorporeal circuit could not be prevented by the use of heparin during haemodialysis. Results. Of 80 patients who underwent haemodialysis with argatroban, 59 met the inclusion criteria. Compared with the data before the administration of argatroban, significant improvements of residual blood in the dialyser and arterial and venous drip chambers were observed at the last administration of argatroban. A significant rise in antithrombin III activity was also observed. Among 80 safety analysis cases, no adverse events were reported in 66 patients (82.5%). As severe adverse events, one showed bleeding tendency and one had prolongation of prothrombin time. Conclusion. Argatroban was an effective and safe anticoagulant for haemodialysis in patients with congenital or acquired antithrombin III deficiency.
Lipoprotein(a) is a predictor for cardiovascular mortality of hemodialysis patients.
Although hemodialysis (HD) patients have been associated with elevations in serum lipoprotein(a) Lp(a) levels, ...relatively little has been published on the link between Lp(a) and the risk for atherosclerotic cardiovascular death in HD patients.
Lipoprotein(a) was measured in 390 HD patients. The relationship between Lp(a) and mortality (overall and cardiovascular) was determined during 28 months of prospective follow-up.
Hemodialysis patients demonstrated Lp(a) concentrations that were approximately two times as high as that of healthy controls (median, 16 vs. 8 mg/dl, P < 0.001; mean, 22.9 vs. 12.1 mg/dl, P < 0.01). Lp(a) showed a significant correlation between albumin, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. The high-Lp(a) group Lp(a) ≥ 30 mg/dl showed significantly higher mortality than the low-Lp(a) group Lp(a) < 30 mg/dl in a Kaplan–Meier survival analysis (P < 0.05). Multiple logistic regression analysis demonstrated albumin, age, and diabetic state as significant risk factors for overall death. However, if confined to atherosclerotic cardiovascular death, Lp(a) (P < 0.01), age, and diabetic state were the only independent contributors.
Lp(a) is an independent risk factor for atherosclerotic cardiovascular death in Japanese patients receiving chronic dialysis therapy.
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