Minako Koike

The characteristics of relapse in adult-onset minimal-change nephrotic syndrome

BackgroundAlthough minimal-change nephrotic syndrome (MCNS) is highly steroid-responsive, the frequency of relapses in some patients is high, necessitating the administration of repeated courses of prednisolone in high doses. It is, therefore, necessary to identify factors that can predict this increased risk of relapse in some patients in order to establish useful treatment methods to reduce the risk.MethodsTo clarify the factors that might increase the risk of relapses, the data of 82 Japanese adult patients with MCNS receiving treatment at our department were analyzed retrospectively. Of the total, 55 patients (67.1%) experienced relapse after showing an initial response. We divided the patients into two groups; namely, the nonrelapse group (n = 27) and the relapse group (n = 55), and compared the clinico-pathophysiological characteristics between the two groups.ResultsSignificantly increased serum immunoglobulin E (IgE) levels (P = 0.0002) and increased frequency of steroid side effects were observed in the relapse group as compared to the nonrelapse group.ConclusionsTo develop effective therapeutic modalities, it is important to have a thorough understanding of the clinico-pathophysiological characteristics of MCNS patients showing relapse.

Frequency of Renal Disease in Japan: An Analysis of 2,404 Renal Biopsies at a Single Center

Background: Evaluating the frequency of renal disease according to sex, age, time period and ethnicity is of considerable importance. Methods: Disease frequency was evaluated in a total of 2,404 cases that had undergone a renal biopsy at Tokyo Women’s Medical University between 1979 and 2008. Results: The overall frequencies of primary glomerulonephritis (GN) and secondary GN were 77.8 and 14.4%, respectively. Primary GN and nephrosclerosis occurred more frequently among men, while secondary GN was more frequent among women. Primary GN decreased and secondary GN increased with advancing age. Immunoglobulin A nephropathy was the most common form of primary GN during each time period and also gradually increased over time (44.4–57.4%). The most common form of secondary GN was lupus nephritis (59.0%); this disease was commonly observed in women (79.3%) but not as frequently among men (27.9%). Our data regarding the frequencies of each form of primary GN were almost the same as data from other regions of Japan and East Asia but were quite different from data originating in West Asia and South America. Conclusions: Our epidemiological results may be useful for analyzing the morbidity of renal disease.

Fatal diffuse pulmonary arterial thrombosis as a complication of nephrotic syndrome.

A 21-year-old man was admitted to our hospital because of leg edema. Because laboratory findings revealed massive proteinuria and hypoproteinemia, he was diagnosed as having nephritic syndrome caused by minimal change disease. He was given a continuous heparin infusion and intravenous steroid therapy, at a prednisolone dose of 1 mg/kg per day, and his condition gradually improved. Five months after discharge, the patients proteinuria relapsed. He was readmitted to our hospital and we restarted anticoagulant treatment with intravenous heparin and 60 mg prednisolone. On the third hospital day, he complained of chest pain with sudden onset and dyspnea. He quickly developed shock and died. The findings of an autopsy confirmed the presence of diffuse fibrin thrombi in bilateral pulmonary arteries, and we diagnosed the cause of death as diffuse pulmonary artery thrombosis. A coagulation test for activated partial thromboplastin time (aPTT) had already shown that aPTT was prolonged before the initiation of treatment. There may have been a deficit of antithrombin III (ATIII) – a cofactor of heparin – because of the proteinuria; thus, the continuous heparin treatment might not have been effective for the prevention of thrombosis. Alternatives to heparin treatment that do not suppress AT III, such as nafamostat mesilate or argatroban, which do not require the presence of AT III for their anticoagulant action, should be considered in cases similar to the that in the patient reported here. In patients with nephrotic syndrome who exhibit altered coagulation test results, the choice of anticoagulation therapy for treatment of the hypercoagulabilty status associated with nephrotic syndrome should be carefully considered.

Efficacy of Semiannual Single Fixed Low-Dose Rituximab Therapy in Steroid-Dependent Minimal Change Nephrotic Syndrome: A Case Series

The frequency of using rituximab to treat refractory nephrotic syndrome has recently been increasing, and the conventional dose of rituximab used to treat it, 375 mg/m2 body surface area once weekly for 4 weeks, has been modelled on the chemotherapy regimen for B-cell non-Hodgkin’s lymphoma. The dose and intervals of rituximab in refractory nephrotic syndrome remain controversial. Clear lymphoma cell hyperplasia is seen in lymphoma patients, but not in nephrotic syndrome patients. Since we thought that it might be possible to reduce the dose of rituximab if only used for the purpose of depleting CD20-positive B cells in nephrotic patients’ peripheral blood, we tried semiannually with a single fixed rituximab dose of 100 mg/body, and a complete remission was attained in 3 cases without treatment with prednisolone or cyclosporine. Our report strongly suggests considering appropriate dose and interval of rituximab therapy in the treatment of steroid-dependent nephrotic syndrome.

The Improvement of the Outcome of Osmotic Demyelination Syndrome by Plasma Exchange

A 71-year-old Japanese woman presented with progressive fatigue, lethargy, dysarthria and a gait disorder. Her laboratory data revealed hyponatremia (Na 101 mEq/L), and we started correcting her serum sodium level. Within a few days, she became comatose, bedridden, and was intubated. We diagnosed osmotic demyelination syndrome (ODS) and started performing plasma exchange (PE) on the 39th day of hospitalization. She fully recovered after starting PE, and was discharged on foot unassisted. PE can be a beneficial treatment in patients with chronic ODS.

A case of posterior reversible leukoencephalopathy syndrome caused by fibromuscular dysplasia.

A 23-year-old woman presented with disturbance of consciousness and seizure. Her blood pressure was remarkably high, and brain magnetic resonance imaging (MRI) showed high-intensity T2 signals in the bilateral basal ganglia, corpus callosum, cerebral white matter, and cortex. With the administration of angiotensin II receptor blocker, the symptoms and MRI findings improved, along with normalization of blood pressure, and a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES) was made. Plasma renin activity was high, and the right kidney was severely atrophic. Results from renal and adrenal vein sampling revealed renal vascular hypertension derived from the right renal artery stenosis. The right kidney was then removed by laparoscopic nephrectomy. Pathological examination of the kidney confirmed the diagnosis of fibromuscular dysplasia (FMD). In juvenile-onset encephalitis/encephalopathy, PRES due to FMD should be included in the differential diagnosis.

Decreased expression of vascular endothelial growth factor in glomeruli of puromycin aminonucleoside nephrosis

AbstractBackground. Vascular endothelial growth factor (VEGF) is a selective endothelial growth factor which potently enhances microvascular permeability. In the kidney, VEGF mRNA is known to be highly expressed in visceral epithelial cells in glomeruli. However, the physiological role of VEGF in glomerular function and its involvement in the pathogenesis of proteinuria are not clear. The present studies were designed to determine whether altered expression of VEGF mRNA was observed in the course of puromycin aminonucleoside (PAN) nephrosis in rats (a model of human minimal change nephrosis). Methods. The message level of VEGF in isolated glomeruli of PAN nephrosis rats was measured using a ribonuclease protection assay. Results. VEGF expression began to decrease 4 days after PAN injection and could not be detected in the nephrotic stage of PAN nephrosis (on days 8 and 16). In the remission of stage of PAN nephrosis (on day 28), mRNA was restored to the control level. Conclusions. According to our results, a functional defect in the VEGF expression of visceral epithelial cells was observed in PAN nephrosis. VEGF could be a functional marker of visceral epithelial cells, and the loss of normal expression of VEGF after damage to visceral epithelial cells could affect glomerular endothelial cell function in PAN nephrosis.