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.
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.
We started dialysis treatment in our institution in 1966, and have improved hemodialysis (HD) treatment through the induction of a biocompatible dialysis membrane, recombinant human erythropoietin, ...activated vitamin D and purification of the dialysate. We verified improvement of the prognosis for survival of patients with ESRD during this forty-year period, retrospectively. A total of 1,690 patients who began dialysis therapy in our hospital between January 1966 and December 2005 was studied (men: 1,047, women: 643, age: 58.6 +/- 17.4 years. They were divided into four groups (A: patients who started dialysis in the period from 1966 to 1975; n = 280, B: 1976-1985; n = 455, C: 1986-1995; n = 499, D: 1996-2005; n = 456). The mean follow-up period was 8.48 +/- 8.53 years. Of the patients 1,588 were treated with HD, 78 with peritoneal dialysis (PD), and 24 with PD or HD. Age at the initiation of dialysis increased gradually (A: 40.1 +/- 14.2 y-o, B: 53.2 +/- 15.8 y-o, C: 60.0 +/- 16.0 y-o, D: 66.4 +/- 13.8 y-o), and diabetics increased (A: 6.4%, B: 19.5%, C: 25.6%, D: 33.4%). A total of 1,180 patients died; 48.5% of these patients died of cardiovascular disease, 21.3% of infectious disease, and 6.4% of malignancy. Only 13 patients had kidney-transplants. With the Cox proportional hazard model for HD cases, age at the initiation of dialysis, gender, cause of renal disease, and the periods were significant predictors of mortality. The relative risk of mortality compared with that in A was reduced progressively: 0.796 in period B (95% confidence interval CI: 0.659-0.961, p = 0.0178), 0.505 in period C (95% CI: 0.409-0.623, p < 0.0001), and 0.286 in period D (95% CI: 0.223-0.366, p < 0.0001).
Although the number of high-aged patients or diabetics with ESRD increased in these 40 years, the survival of the patients with ESRD improved.
In K/DOQI guideline, albumin adjusted serum calcium concentrations between 8.4 to 9.5 mg/dL and serum phosphorus concentrations between 3.5 to 5.5 mg/dL are recommended. But without clinical symptoms ...relating to hypocalcemia, medication for increasing serum calcium levels is not needed even less than 8.4 mg/dL. To clarify this guideline, we examined the data of 271 patients who started dialysis at Shinrakuen Hospital, their medication before renal replacement therapy and life prognosis. Medication made higher serum calcium concentrations (p< 0.005) at first renal replacement therapy. Concerning serum calcium concentrations, the lower group (<8.4 mg/dL) showed significantly better prognosis than the middle group (8.4 to 9.5 mg/dL) and the higher group (>9.5 mg/dL) (p< 0.05). When serum calcium levels were adjusted for the level of serum albumin, this tendency was stronger (p< 0.0001). We concluded that although serum calcium concentrations might not need control, nutritional states are far more important before starting dialysis.
Purpose: For the first step to investigate the blood volume change during hemodialysis, we studied it without ultrafiltration. Methods: Ten chronic hemodialysis patients were studied. We measured the ...hematocrit during hemodialysis and calculated the blood volume (BV) change continuously using CRITLINE (IN-LINE DIAGNOSTICS). We approximated the time-sequential changes in BV (ΔBV) to the equation: ΔBV(%)=a×{1-exp-b×TIME (hr)}-c×TIME (hr) and determined the relationship between the coefficients (a, b, c) and clinical parameters. Results: 1) In all patients, BV was increased during hemodialysis and could be approximated to the equation very well (0.92<r<0.99, p<0.0001). 2) Coefficient (a), the degree of increase of BV, was 8.66±2.92 and almost equal to the percentage of the lost BV for the extracorporeal circuit to the whole By. Coefficient (a) was significantly related to the cardio-thoratic ratio of the chest X-ray film (CTR) (r=0.88, p=0.0008) and serum albumin concentration before hemodialysis (r=0.80, p=0.03). 3) Coefficient (b), the speed of increase of BV, was 2.02±0.77, 99.9% of the total increase was achieved by 2 hours after the beginning of hemodialysis. 4) Coefficient (c) varied from -1.64 to 1.06, and was related to no clinical parameters. Conclusions: BV was increased during hemodialysis without ultrafiltration. The mechanism of the BV increase was thought to cover the lost BV for the extracorporeal circuit. Coefficient (a) could be the indices of hydration and plasma refilling.
Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a ...possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0±16.9 μmol/L, a significantly higher amount than that of healthy subjects (11.0±3.1μmol/L, p<0.0001). The patients' carotid maximum IMT was 1.79±1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r=0.417, p<0.0001), systolic blood pressure (r=0.262, p=0.0043), smoking (r=0.177, p=0.0076), duration of hemodialysis (r=0.083, p=0.0045), and tHcy (r=0.195, p=0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients. (Jpn Circ J 1999; 63: 692 - 696)
Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual ...irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients.
We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era.
The mean duration of HD was 6 years, the mean duration of the patients' marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery.
The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.
An useful procedure for the synthesis of 2-substituted 1, N6-etheno-adenosine-3', 5'-cyclic phosphates by ring closure of 3-β-D-(3', 5'-cyclic ...phospho)-ribofuranosyl-4-amino-5-(imidazol-2-yl)-imidazole (II), under relative mild conditions, is reported. Treatment of the compound II with bromine cyanide, triethyl orthoacetate, 1, 1'-carbonyldiimidazole and carbon disulfide gave 2-amino-, 2-methyl-, 2-hydroxy-, and 2-mercapto-1, N6-etheno-adenosine-3', 5'-cyclic phosphate (c-AMP), respectively. Moreover, several 2-alkylmercapto-, 2-benzylmercapto-, and 2-bromo-1, N6-etheno-c-AMP were synthesized from 2-merc apto-1, N6-etheno-c-AMP. 2-Methoxy-, 2-azido-, 2-dimethylamino-1, N6-etheno-c-AMP were synthesized from 2-bromo-1, N6-etheno-c-AMP. The fluorescent and ultraviolet spectra of 2-substituted 1, N6-etheno-c-AMP are tabulated.
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