The effect of 1 alpha-hydroxyvitamin D3 on cell-mediated immunity in hemodialyzed patients

The immunoregulatory effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3), a precursor form of active vitamin D3, was examined in hemodialyzed patients. Four weeks of oral administration of 0.5 micrograms/day 1 alpha OHD3 markedly enhanced the lymphoproliferative responses to mitogens without influencing lymphocyte counts or the ratios of lymphocyte subpopulations. In fact, these responses were nearly normal after treatment. These results suggest that deficiency of 1,25-dihydroxyvitamin D3 may play a role in the impairment of cellular immunity in hemodialyzed patients, and that administration of 1 alpha OHD3 may have therapeutic immunological benefit.     

Hypertension in hemodialyzed uremic patients

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.     

Utility of non-high-density lipoprotein cholesterol in hemodialyzed patients

Non-high-density lipoprotein-cholesterol (HDL-C) is proposed as a strong predictor of cardiovascular disease (CVD). Measuring non-HDL-C, as total cholesterol minus HDL-C, is convenient for routine practice because, among other advantages, fasting is not required. There are limited data of non-HDL-C in end-stage renal disease patients. We applied non-HDL-C calculation to 50 chronic renal patients receiving maintenance hemodialysis (HD) and 20 healthy subjects, apart from measurement of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) HDL, intermediate-density lipoprotein-cholesterol (IDL-C), apoprotein (apo) B, and triglycerides. HD patients presented higher plasma triglycerides and IDL-C and lower HDL-C than the control group, even after adjustment for age (P < .05). VLDL-C increased in HD patients (P < .001) while differences in non-HDL-C did not reach significance (P = .08). To detect which parameter constitutes a better marker of CVD risk among HD patients, a receiver-operating characteristic (ROC) analysis was performed considering HD patients in the highest risk group for CVD. In the ROC graphic, the plots of VLDL and IDL-C exhibited the greater observed accuracy and the best performance, while non-HDL-C showed a curve close to the 45 degrees line indicating that this parameter is a poor discriminator for evaluating CVD risk among HD patients. Non-HDL-C calculation, expressing all apo B-containing lipoproteins, may miss the significant contribution of each atherogenic lipoprotein, such as increase in IDL. This observation would not be in agreement with the currently proposed application of non-HDL-C a useful tool for risk assessment among HD patients.     

Beneficial effect of cilnidipine on morning hypertension and white-coat effect in patients with essential hypertension.

Home blood pressure has a higher predictive power for cardiovascular events than office blood pressure, and there is a particularly close association between morning blood pressure at home and the incidence of cardiovascular events and mortality in the early morning. In this study, we evaluated the efficacy of a long-acting N-type and L-type calcium channel blocker, cilnidipine, in reducing morning blood pressure at home and in ameliorating the white-coat effect. Fifty-eight subjects diagnosed with both essential hypertension and morning hypertension (43 currently being treated, 15 new patients) were prescribed cilnidipine at a dosage of 10-20 mg per day for 8 weeks. After the addition of or a change to cilnidipine, the morning systolic blood pressure (SBP) was controlled to less than 135 mmHg in 25 (58%) out of the 43 patients currently receiving antihypertensive medication. The office SBP in 24 out of those 25 patients was also maintained under 140 mmHg. In the 15 newly treated patients, the morning SBP of 12 patients (80%) was controlled to less than 135 mmHg after administration of cilnidipine. At baseline, 17 patients showed a clear white-coat effect, in which the difference between office blood pressure and home blood pressure was 20/10 mmHg or more. The white-coat effect was depressed significantly after cilnidipine administration. These results suggest that cilnidipine may serve as a useful antihypertensive medication in the treatment of morning hypertension, and also attenuate the white-coat effect in patients with essential hypertension.     

Beneficial effect of heparin in the management of patients with APL

115 patients with acute promyelocytic leukaemia (APL) were studied retrospectively to evaluate prognostic factors and assess therapeutic approaches, particularly the use of heparin in the management of disseminated intravascular coagulation (DIC). The remission rate was 86% (30/35 patients) in those who received heparin and 49% (39/80 patients) in those who received no heparin (P = 0.0002). This difference in remission rates was accounted for by a marked decrease in the number of haemorrhagic deaths, especially those due to intracranial haemorrhage (ICH), in the heparin treated group. Other factors associated with a poor remission rate were prothrombin ratio (PTR) greater than 1.3 (P = 0.008), fibrinogen less than 1.5 g/l (P = 0.02) and WCC greater than 2.0 x 10(9)/l (P = 0.03).     

Beneficial antiarrhythmic effect of beta-blockade in patients with dilated cardiomyopathy.

Antiarrhythmic effects of beta-blockade (BB) in patients with dilated cardiomyopathy were compared with those of various antiarrhythmic agents using ambulatory Holter monitoring. The BB therapy effectively suppressed ventricular extrasystoles (VEs) in 85% of patients, as evidenced by improvement in Lown's grade or a reduction in the number of the highest grade VEs greater than 50%. In contrast, conventional antiarrhythmic agents, except flecainaid and amiodarone, were poorly effective in suppressing VEs. BB therapy gradually increased left ventricular fractional shortening (16 +/- 6% to 22 +/- 12%) and improved 12-month survival rates as compared with those receiving conventional therapy (93 vs 69%). This antiarrhythmic potency seemed to be an additional therapeutic efficacy of BB in the management of patients with dilated cardiomyopathy, which frequently associated with serious VEs.     

Comparison of the circulatory effects of continuous renal replacement therapy using AN69ST and polysulfone membranes in septic shock patients: A retrospective observational study

The acrylonitrile‐co‐methallyl sulfonate surface‐treated (AN69ST) membrane is expected to improve hemodynamics in patients with sepsis through cytokine adsorption. However, the clinical literature on AN69ST membranes is very limited. We aimed to compare the circulatory effects of continuous renal replacement therapy (CRRT) between patients using the AN69ST membrane and polysulfone (PS) membrane (a nonadsorbing membrane). This retrospective observational study enrolled 38 patients with septic shock, as defined by Sepsis‐3 criteria, who required CRRT from April 2013 to March 2018. Those who died within 24 hours after CRRT initiation and received polymyxin B‐immobilized fiber column direct hemoperfusion, extracorporeal membrane oxygenation, and CRRT using other membranes were excluded. The primary outcome was the vasopressor dependency index during the 12 hours after CRRT initiation, which was calculated as (inotropic score)/(mean arterial pressure). Of 38 patients analyzed, 16 underwent CRRT with an AN69ST membrane and 22 with a PS membrane. The median patient age was 68 years, and the median Acute Physiology and Chronic Health Evaluation (APACHE) II score at intensive care unit admission was 29.5. The vasopressor dependency index decreased significantly during the 12 hours after CRRT initiation in both groups (AN69ST: from 0.50 ± 0.43 to 0.33 ± 0.27 [P < .05], PS: from 0.34 ± 0.30 to 0.21 ± 0.22 [P < .05]). The time course of the vasopressor dependency index during the 12 hours did not differ between the two groups (P = .11). The vasopressor dependency index decreased significantly after CRRT initiation in both groups. The time course of the vasopressor dependency index did not differ between the groups.     

Isolated systolic hypertension in uremic hemodialyzed patients]

Prevalence of Isolated Systolic Hypertension (ISH) defined as systolic blood pressure greater than 160 mmHg and diastolic blood pressure less than 90 mmHg was studied in a population of 148 patients treated by hemodialysis whose 80 had undergone ambulatory blood pressure (ABP) recording during the interdialytic period. All patients were treated 3 times 4 hours a week. ABP was recorded for 48 hours between two sessions of hemodialysis using a Delmar Avionic Presurometer (PIV). Prevalence of ISH was 12.5%, while that of systolic-diastolic hypertension (SDH) was 15%. Average age at the time of the study was respectively 59 +/- 13 yrs ISH and 49 +/- 11 yrs SDH (p less than 0.01) while that of patients with normal blood pressure (N) was 57 +/- 10 yrs. Mean duration of HD treatment was no different between groups: 5.3 +/- 3.5 yrs ISH, 5.0 +/- 4.2 yrs SDH and 5.0 +/- 4.3 yrs N. Causes of end-stage renal disease were similar in each group. All patients with ISH and SDH and 42% of N pts were receiving antihypertensive treatment at the time of ABP recording. Finally, level of anemia and percentage of patients treated by EPO were similar in each group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total and corrected antioxidant capacity in hemodialyzed patients

Background  

Oxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results.     

Osteomalacia and vitamin D deficiency in hemodialyzed patients

Aluminum accumulation in plasma and tissues is a well-described complication among patients undergoing hemodialysis. Although the ratio of aluminum-induced osteomalacia has been decreasing year by year, there are still considerably many problems in such patients. Sources of aluminum now include food, drugs, and cooking tools. Besides, iron and strontium accumulations also induce osteomalacia. Early and accurate diagnosis of such metal toxicities is important because effective therapy is available.     

Parathyroid interventions for secondary hyperparathyroidism in hemodialyzed patients

Although parathyroidectomy (PTX) is the ultimate treatment for secondary hyperparathyroidism (SHPT) that is resistant to medical treatment, recent advances in ultrasonographic techniques have increased the treatment options in Japan. Percutaneous ethanol injection therapy (PEIT) of the parathyroid was approved under the national health insurance system in 2004, and there have been trials of direct injection of vitamin D (VD) preparations. We followed 30 patients for at least 1 year who had undergone PEIT at the same institution. The overall mean concentration of intact parathyroid hormone (PTH) fell from 865.3+/-388.4 pg/mL to 291.9+/-277.8 pg/mL, or 34% of the pretreatment value. The effect was even more pronounced for one or two glands, with 68.4% reaching the target of intact PTH相似文献   

Enhanced methylglyoxal formation in the erythrocytes of hemodialyzed patients

Methylglyoxal (MG) contributes significantly to the carbonyl stress in uremia; however, the reason for its increased concentration is not clear. Thus, the present study was aimed to investigate the formation and degradation of MG in the erythrocytes of hemodialyzed (HD) patients with end-stage renal disease. In 22 nondiabetic patients on long-term HD, erythrocyte MG and d-lactate levels, glyoxalase activities, and whole blood reduced glutathione content were determined. The data were compared with those from 22 healthy controls. Erythrocyte MG and d-lactate production were also investigated in vitro under normoglycemic (5 mmol/L) and hyperglycemic (50 mmol/L) conditions. The erythrocyte MG levels were elevated (P < .001) in the HD patients. The blood reduced glutathione content and glyoxalase I activity were similar to the control levels, but the glyoxalase II activity was significantly (P < .005) increased. In the normoglycemic in vitro model, production of both MG (P < .001) and d-lactate (P < .002) was significantly enhanced in the HD erythrocytes relative to the controls. During hyperglycemia, the MG formation and degradation rates were further increased (P < .001). The present study demonstrated an increased formation of MG in the erythrocytes of HD patients. This seemed to be related to a glucose metabolism disturbance of the cells. The degradation system of MG was also activated; still, it was not able to counteract the high rate of MG formation. The alterations and imbalance of these metabolic processes may contribute to the carbonyl overload and stress in the HD patients.     

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.