Hideki Yamahara

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Comparison of the Effects of Quinapril and Losartan on Carotid Artery Intima-Media Thickness in Patients with Mild-to-Moderate Arterial Hypertension

Background: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. Methods: 57 hypertensive patients were randomly assigned to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB (losartan; n = 18, group L). Results: After 1 year of treatment, a similar decrease in mean blood pressure was observed in all groups. Carotid IMT was decreased significantly in group Q (10% decrease, p < 0.05) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups. Conclusion: Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients. This effect appears unrelated to the drug’s antihypertensive action or to traditional atherosclerotic factors.

Direct Aldosterone Action as a Profibrotic Factor via ROS-Mediated SGK1 in Peritoneal Fibroblasts

Background/Aims: Peritoneal fibrosis leads to discontinuation of peritoneal dialysis. Although aldosterone promotes tissue fibrosis in many organs, its contribution to peritoneal fibrosis and the underlying mechanism are poorly understood. The present study investigated the direct effect of aldosterone on cultured rat peritoneal fibroblasts (RPFs). Methods: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors (MRs), 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), serum- and glucocorticoid-inducible protein kinase 1 (SGK1), and connective tissue growth factor (CTGF) mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). To determine the role of reactive oxygen species (ROS) induced by aldosterone, an active oxygen assay with several inhibitors was used. The ability of RPFs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA (siRNA) of SGK1 was transfected into cultured cells using lipofectamine. Results: CYP11B2, MRs, and 11β-HSD2 were expressed in RPFs. The release of aldosterone from RPFs into the culture medium was confirmed. Aldosterone increased the expression of SGK1 mRNA via ROS generation. Spironolactone, apocynin, and tempol significantly reduced SGK1 expression. Aldosterone upregulated CTGF transcripts significantly. SGK1 gene silencing suppressed aldosterone-induced CTGF expression. Conclusion: The local aldosterone system acts directly as a profibrotic factor via ROS-mediated SGK1 in RPFs.

'Takotsubo' cardiomyopathy in a maintenance hemodialysis patient.

Abstract:  An 84‐year‐old woman undergoing maintenance hemodialysis presented with chest discomfort lasting several days and electrocardiographic abnormalities. She had stopped smoking 2 weeks earlier and was experiencing irritability. Upon admission, electrocardiography showed ST‐segment elevation in leads I, II, aVF, and V2‐6 and an abnormal Q wave in leads II, III, and aVF. Ultrasound cardiography showed left ventricular anteroapical akinesia and basal hyperkinesia. The chest discomfort disappeared without specific therapy. During hospital days 1–5, the ST‐segment elevation gradually improved. Giant negative T waves then developed. The left ventricular asynergy resolved by day 8. Radionuclide imaging with iodine‐123‐beta‐methyl‐p‐iodophenyl pentadecanoic acid, but not with technetium‐99 m‐sestamibi, showed an apical defect. Elective coronary angiography showed no stenosis. ‘Takotsubo’ cardiomyopathy was diagnosed. After discharge, the patient continued regular dialysis without cardiac symptoms. We concluded that endogenously activated sympathetic nerve action in hemodialysis patients, especially those under emotional or physical stress, might be a causative factor for Takotsubo cardiomyopathy.

Peritoneal Mesothelial Cells as a Target of Local Aldosterone Action: Upregulation of Connective Tissue Growth Factor Expression via Serum- and Glucocorticoid-Inducible Protein Kinase 1

Background/Aims: Peritoneal fibrosis can lead to the discontinuation of continuous ambulatory peritoneal dialysis. The present study investigated the direct effect of aldosterone, which influences tissue fibrosis, and its cellular mechanism using cultured rat peritoneal mesothelial cells (RPMCs). Materials andMethods: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors, 11β-hydroxysteroid dehydrogenase 2, serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and connective tissue growth factor (CTGF) was evaluated using reverse transcriptase-polymerase chain reaction and Western blot. The ability of RPMCs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA of SGK1 was transfected to determine the role of SGK1. Results: CYP11B2, mineralocorticoid receptors and 11β-hydroxysteroid dehydrogenase 2 were expressed in RPMCs. The release of aldosterone from RPMCs into the culture medium was confirmed. Stimulation of RPMCs with the addition of aldosterone significantly increased SGK1 expression and phosphorylation and CTGF upregulation, and these effects were completely inhibited by the mineralocorticoid receptor antagonist spironolactone. SGK1 gene silencing abrogated aldosterone-induced CTGF expression. Conclusion: The local aldosterone system exists and acts directly as a profibrotic factor in the peritoneal mesothelium.

A Case Report of Interferon β Monotherapy for High Hepatitis C Viral Load in Dialysis Patients

Abstract:  A 42‐year‐old male dialysis patient was infected with hepatitis C virus (HCV), and treated with interferon β (IFN‐β) for a rapid increase in viral load. After dialysis three times a week, 3 million units of IFN‐β were intravenously infused for 1 h. The treatment was markedly effective, and the virus was eliminated in the sixth week. Therapy was continued for 24 weeks, and HCV negativity has been maintained for more than 6 months after the completion of administration. The blood IFN level slowly decreased immediately after administration. The mean trough level was 37 U/mL, and the half‐life was 65 min. No adverse event requiring discontinuation of the treatment occurred, showing that IFN alone may safely eliminate the virus in dialysis patients with high hepatitis C viral load. Many dialysis patients are latently infected with HCV, and the infection affects the prognosis. Therefore, establishment of a therapeutic method is urgently needed.