Acute renal failure complicating high-dose intravenous immunoglobulin therapy for acquired haemophilia

Acquired haemophilia is a rare disorder requiring therapy to control bleeding and to suppress the inhibitory antibody. High-dose intravenous immunoglobulin is commonly used as part of immunosuppressive regimens for this condition. We describe the case of an elderly patient who developed acute oliguric renal failure as a result of intravenous immunoglobulin therapy. All patients receiving such treatment should have renal function carefully monitored both during and after the infusion.     

Incidence and associations of acute renal failure complicating high-dose intravenous immunoglobulin therapy

In a formal study, we have identified increasing age, pretreatment renal impairment and diabetes mellitus as risk factors for the development of intravenous immunoglobulin-induced renal failure. Identification of these characteristics in potential recipients should alert clinicians to the associated increased risk of this serious complication.     

Method of dialysis therapy and selected markers of oxidative stress and endothelial injury in patients with chronic renal failure

Cardiovascular diseases (CVD), being mostly a clinical manifestation of atherosclerosis, are the main cause of mortality in patients with chronic renal failure (CRF). It is now generally accepted that the first step in atherosclerosis is endothelial dysfunction. Recently, oxidative stress (SOX) has been implicated as an important etiologic factor in atherosclerosis and vascular dysfunction both in general and uremic populations. The aim of the present study was to establish the effect of two different method of dialysis therapy: hemodialysis (HD) and continuous peritoneal dialysis (CAPD) on the markers of SOX: lipid peroxides, Cu/Zn superoxide dismutase (Cu/Zn SOD) and autoantibodies against oxidized LDL (OxLDL-Ab), and endothelial injury: antigen of the von Willebrand factor (vWF : Ag), soluble thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) in 43 patients with CRF. Compared with the control subjects, patients with CRF showed a significant increase in plasma concentrations of Cu/Zn SOD, which was more elevated in HD than in CAPD group. The lipid peroxide levels were increased only in the post-HD samples, whereas OxLDL-Ab were more elevated in HD than in CAPD group. Markers of endothelial injury were significantly higher in dialyzed patients relative to controls, and were positively correlated themselves as well as with Cu/Zn SOD levels. The patients on HD and CAPD are exposed to increased SOX as well as to endothelial injury. The association between Cu/Zn SOD and the endothelial injury markers suggests the possible effect of oxidative stress on endothelial dysfunction in CRF patients.     

Bradycardia after high-dose intravenous methylprednisolone therapy

In 5 consecutive patients with rheumatoid arthritis who received intravenous high-dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high-dose MP is recommended. High-dose MP may be contraindicated in patients with known heart disease.     

慢性心力衰竭伴铁缺乏患者静脉补充铁剂有效性和安全性的meta分析

目的 用meta分析的方法评价慢性心力衰竭伴铁缺乏患者静脉补充铁剂的有效性和安全性。方法 收集国内外关于慢性心力衰竭伴铁缺乏患者静脉补充铁剂的随机对照临床试验（RCT）,按照纳入与排除标准筛选文献,评价文献质量并提取有效数据,对其有效性和安全性进行meta分析。结果 共纳入相关英文研究5篇,其方法学质量较高,2篇文献的质量等级为A级,余为B级。Meta分析结果显示:①有效性:静脉注射铁剂能够改善患者血清铁蛋白［SMD=2.15,95%CI(0.84,3.45),P<0.01］、TSAT［MD=7.97,95%CI(5.71,10.23),P<0.01］、NYHA［MD=-0.56,95%CI(-0.97,-0.15),P<0.01］,减少因心力衰竭住院的人数［OR=0.27,95%CI(0.15,0.47),P<0.01］,但不能降低全因病死率［OR=0.83,95%CI(0.43,1.60),P>0.05］;②安全性:静脉注射铁剂未增加胃肠道不良反应［OR=1.11,95%CI(0.36,3.47),P>0.05］和总不良反应［OR=0.81,95%CI(0.26,2.46),P>0.05］。结论 静脉补充铁剂能够改善慢性心力衰竭伴铁缺乏患者的心衰症状,并具有良好的安全性,但不能改善临床预后。     

Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis.

A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine.     

Dialysis-dependent renal failure in patients with myeloma can be reversed by high-dose myeloablative therapy and autotransplant

To evaluate the role of high-dose melphalan and autologous transplant (AT) in reversing dialysis-dependent renal failure, 59 patients still on dialysis at the time of AT were analyzed. A total of 37 patients had been on dialysis < or =6 months. A 5-year event-free and overall survival rate of all patients after AT was 24 and 36%, respectively. Of 54 patients evaluable for renal function improvement, 13 (24%) became dialysis independent at a median of 4 months after AT (range: 1-16). Dialysis duration < or =6 months prior to first AT and pre-transplant creatinine clearance >10 ml/min were significant for renal function recovery: 12 of 36 (33%) < or =6 months vs one of 18 patients (6%) >6 months on dialysis recovered renal function; 10 of 26 (38%) with >10 ml/min vs three of 28 (11%) with < or =10 ml/min of creatinine clearance (both P<0.05). Quality of response after autotransplant was also significant: 12 of 31 (39%) being greater than partial remission after AT vs one of 21 patients (5%) attaining partial remission or less became independent of dialysis (P<0.05). Our data suggest that significant renal failure can be reversible and AT should be considered early in the disease course.     

Treatment of acute obstructive renal failure with high-dose methylprednisolone

High-dose methylprednisolone sodium succinate (Solu-Medrol) therapy was administered to two patients with acute renal failure and anuria secondary to cancer-related urinary tract obstruction. Following the administration of intravenous methylprednisolone, obstruction was relieved, as evidenced by increased urinary flow and improvement of renal function. The salutary effect of methylprednisolone is probably related to the relief of obstruction secondary to a decrease in tumor-associated edema similar to the effect obtained in patients with brain tumors and spinal cord compression by epidural metastases. The temporary improvement in renal function allowed time for more definitive therapy to be instituted under more favorable clinical conditions.     

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone pulse therapy

This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired.     

Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis

A 45-year-old man developed fulminant myocarditis for which ventricular assist devices (intra-aortic balloon pumping and percutaneous cardiopulmonary support) were required for hemodynamic support. Echocardiography showed left ventricular akinesis and, since no improvement was noted on the following day, immunoglobulin (70 g/day for 2 days) was added to the therapy. The left ventricular ejection fraction increased to 25% and 40% at 12 and 36 h, respectively, representing a marked improvement in wall motion within a very short period. An endomyocardial biopsy specimen revealed focal lymphomononuclear infiltrate with adjacent myocytolysis, and acute lymphocytic myocarditis was diagnosed. Two days after administration of immunoglobulin, the serum level of interleukin-6 decreased rapidly from 180 to 5.9 pg/ml. In this patient, cardiac function improved immediately after immunoglobulin administration, suggesting the usefulness of this therapy. Three years after the diagnosis the patient is in good health, with steady normal left ventricular ejection fraction. We conclude that there are cases of acute myocarditis in which high-dose intravenous immunoglobulin therapy is effective.     

Cardiovascular risk in patients with chronic renal failure. Patients in renal replacement therapy

Dialysis patients constitute a high-risk subset of patients for developing cardiovascular disease, which accounts for nearly 50% of deaths. After stratification for age, race and gender, cardiovascular mortality is 10-20 times higher in dialysis patients than in the general population. Cardiovascular disease in this population cannot be fully explained by the high prevalence of classical cardiovascular risk factors (age, hypertension, diabetes, hyperlipidemia, smoking, etc.). Thus, the involvement of "new" cardiovascular risk factors (hyperhomocysteinemia, hyperfibrinogenemia, high lipoprotein (a) levels, oxidative stress, inflammation, etc.), and uremia-related factors (anemia, impaired calcium-phosphorus metabolism, hyperparathyroidism, accumulation of endogenous inhibitors of nitric oxide synthesis, etc.) has been also invoked to play a role in the increased cardiovascular risk in these patients. Endothelial dysfunction is the initial event in the development of atherosclerosis. Uremic patients exhibit an endothelial dysfunction, even before starting dialysis, which persists o is even aggravated under dialysis treatment. Uremic patients must be considered at high risk of developing cardiovascular disease. Thus cardiovascular risk factors in these patients should be managed early, aggressive and multifactorially in order to reduce their high cardiovascular morbidity and mortality.     

Single high-dose intravenous immunoglobulin therapy for kawasaki disease increases plasma viscosity.

BACKGROUND: Intravenous immunoglobulin therapy, widely used for various autoimmune and systemic inflammatory diseases including Kawasaki disease (KD), is occasionally associated with thromboembolic adverse effects caused by an abrupt increase in blood viscosity. Scarce information is available, however, regarding the effect of single high-dose immunoglobulin therapy for KD on blood viscosity. METHODS AND RESULTS: Eleven boys and 5 girls (mean age: 2.1 years) with acute-phase KD underwent single high-dose immunoglobulin therapy. Plasma viscosity before the treatment was 1.18 centipoises (SD = 0.06), but it significantly rose to 1.34 centipoises (SD = 0.06) (p < 0.001). Multiple regression analysis revealed that, among various factors including hematocrit, plasma concentrations of total protein, immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM), only plasma IgG concentration was included in the model to explain plasma viscosity (R2 = 0.59, p < 0.001). CONCLUSIONS: Single high-dose regimen for acute-phase KD increases blood viscosity and therefore might increase the risk of thromboembolism.     

Macrophage-megakaryocyte interaction in bone marrow after high-dose intravenous immunoglobulin therapy

Localization of IgG in bone marrow after high-dose intravenous immunoglobulin therapy (IVIG) was investigated via light and electron microscopy. IgG was incorporated into the cytoplasm of various types of bone marrow cells of all the three lineages, particularly in reticulum cells, fat cells, and megakaryocytes. In addition, both reticulum cells and fat cells showed many elongated cytoplasmic protrusions, which were in contact with the various types of blood cells, especially the megakaryocytes. A filamentous structure was also seen near the point of contact between the cells. Ultrastructural changes of macrophages in bone marrow after IVIG suggest that these cells were activated by IVIG. © 1993 Wiley-Liss, Inc.