Methylprednisolone pulse therapy combined with mizoribine following tonsillectomy for immunoglobulin A nephropathy: clinical remission rate, steroid sparing effect, and maintenance of renal function.

BACKGROUND: The long-term prognosis of immunoglobulin A nephropathy (IgAN) is reportedly poor. In Japan, tonsillectomy-steroid pulse therapy has frequently been used for treatment of early IgAN, with favorable outcomes. However, steroid usage is sometimes limited due to adverse reactions. To reduce the total dose of steroids, we have been using mizoribine (MZR) in combination with tonsillectomy-steroid pulse therapy since 2004. Here we report a retrospective evaluation of our protocol outcome. METHODS: Forty-two patients aged <70 years with histopathologically confirmed IgAN and an estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m(2) or higher were enrolled. After giving informed consent, all the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone (30 mg/day and tapered to 0 over 7 months) and MZR (150 mg/day for 11 months). The complete remission (CR) rate and renoprotective effect were assessed. RESULTS: The CR rate at 6, 12, and 24 months was 33.3, 69.1, and 76.2%, respectively. Despite a relatively low total steroid dose, renal function was satisfactorily maintained for 24 months or longer with no relapse. The eGFR in patients with stage 3 chronic kidney disease was significantly improved at 6 months after start of treatment. Three patients (7.1%) had mild and transient adverse events. CONCLUSION: This protocol appears to be highly effective and safe for IgAN patients with renal dysfunction.

Effects of selective LDL apheresis on plasma concentrations of ICAM-1, VCAM-1 and P-selectin in diabetic patients with arteriosclerosis obliterans and receiving maintenance hemodialysis.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a serious complication in patients with end-stage renal disease (ESRD) caused by diabetic nephropathy. Adsorption of low-density lipoprotein (LDL) has been performed to treat ASO. While efficacy of this treatment has been reported in limb ischemia, the mechanism underlying the benefit remains unclear. We investigated how LDL adsorption affected soluble adhesion molecules; P-selectin, an endothelial and platelet activation marker; inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tissue necrosis factor (TNF)-alpha; and lipids in serum. METHODS: Selective LDL adsorption by dextran sulfate columns (LDL apheresis) was performed weekly for 10 weeks to treat eight hemodialysis patients with ASO, ESRD, and type 2 diabetes mellitus. Serum was sampled before and immediately after apheresis. RESULTS: LDL apheresis was performed safely. After LDL apheresis lipid concentrations were significantly reduced and clinical findings, such as Fontaine's classification and ankle brachial pressure index values, were improved. Pretreatment concentrations of soluble intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1) and also P-selectin were higher in patients than healthy controls. After apheresis these decreased, especially P-selectin. IL-1beta, IL-6, and TNF-alpha concentrations before apheresis were similar to those in controls and were unaffected by treatment. CONCLUSION: Effectiveness of LDL apheresis against ASO may involve decreased endothelial cell and platelet activation.

A patient with idiopathic cholesterol crystal embolization: effectiveness of early detection and treatment.

A 72-year-old man was admitted to our hospital because of progressive renal dysfunction persisting for 1.5 months. Physical examination showed livedo reticularis of the toes of both feet, peripheral edema, and gait disturbance due to the toe pain. The levels of blood urea nitrogen (50.0 mg/dL) and creatinine (2.81 mg/dL) were elevated, and eosinophilia (10%, 870/µL) was noted. A biopsy of the area of livedo reticularis revealed cholesterin crystals. The patient had not undergone angiography, anticoagulation therapy, or antithrombotic treatment. Idiopathic cholesterol crystal embolization was diagnosed. Transesophageal echocardiography revealed intimal thickening of the aorta and plaque. Oral steroid therapy was started because of the progressive renal dysfunction. After steroid therapy, the symptoms improved. Early diagnosis and treatment are important. Renal dysfunction is a common symptom in elderly patients. Cholesterol crystal embolization should also be considered as a cause of unexplained renal dysfunction, especially in such patients.

Thrombosis in Japanese patients with Fabry disease.

Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme alpha-galactosidase (alpha-Gal) A. It has been postulated that the accumulation of globotriaosylceramide in the endothelial cells of blood vessels may lead to thrombosis of the brain and other tissues. Recently, enzyme replacement therapy (ERT) for Fabry disease is available. A high incidence of thrombotic accidents in Fabry disease has been postulated. However, a systemic study on thrombosis in cases of Fabry disease has not been undertaken. To clarify the incidence of thrombosis in Fabry disease, we screened 65 patients with Fabry disease (49 hemizygotes and 16 heterozygotes) from 39 unrelated Japanese families. We found that ten patients with Fabry disease (7 hemizygous males and 3 heterozygous females) had experienced thrombotic accidents, under 45-years-old in 8 cases. These 10 patients showed the gene mutations of classical Fabry disease. Nine of these thrombotic patients developed brain infarctions, one man who had the complication of recurrent thrombophlebitis, and the remaining woman showed central retinal artery occlusion and thrombophlebitis. We demonstrated a high incidence of thrombosis in Fabry disease (15%). ERT should be performed in patients not only in hemizygous males but also in heterozygous females and started at their early ages.

Severe thiamine deficiency resulted in Wernicke's encephalopathy in a chronic dialysis patient.

A 64-year-old male patient with diabetic nephropathy had been treated with maintenance hemodialysis therapy for 4 years, and had developed disturbed consciousness. The disturbance was firstly noticed by a primary care doctor who recognized slow responses in conversation. Prior to developing this symptom, the patient had noticed a loss of appetite for about 2 weeks. During a period of observation at an outpatient clinic, the symptoms became worse. He was admitted to a primary care hospital for 10 days, but his consciousness level deteriorated and he became unconscious (JCS 200). About 1 month after the onset of symptoms, the patient was transferred to our hospital. A brain computed tomography (CT) scan and magnetic resonance imaging (MRI) showed typical abnormal lesions in the aquaduct of the midbrain and thalamus, and a diagnosis of Wernicke's encephalopathy was made. In addition, the patient's serum thiamine level was extremely low (7 ng/ml). He received immediate treatment with intravenous thiamine administration (150 mg/day), and this significantly improved his symptoms (JCS 2). Dialysis patients may develop water-soluble vitamin deficiency as a result of the combination of reduced oral intake and increased loss of vitamins into the dialysate. Wernicke's encephalopathy should be considered as one of many causes of disturbed consciousness in hemodialysis patients. A rapid diagnosis and adequate treatment are essential in order to minimize long-term neurological sequelae.