Noriko Kishimoto

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.

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

BACKGROUND AND OBJECTIVES S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. RESULTS Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). CONCLUSIONS These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

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.

Membranous Nephropathy Associated with Donor Lymphocyte Infusion following Allogeneic Bone Marrow Transplantation

Nephrotic syndrome after hematopoietic stem cell transplantation (HSCT) followed by donor lymphocyte infusion (DLI) has never been described. We report the case of a myelodysplastic syndrome (MDS) patient who developed nephrotic syndrome with membranous nephropathy 18 months after allogeneic HSCT and 4 months after DLI. A 50-year-old woman with MDS underwent allogeneic bone marrow transplantation from her HLA-matched brother. MDS relapsed 55 days after transplantation, donor lymphocytes were infused as adoptive immunotherapy, and complete remission was achieved. Four months after the third DLI, the patient developed nephrotic syndrome with proteinuria up to 9 g/day. Renal biopsy revealed granular deposits of immunoglobulin G along the glomerular basement membrane, and subepithelial electron-dense deposits. A diagnosis of membranous nephropathy was made. For maintenance of the immunotherapeutic effect of DLI, minimum doses of immunosuppressive therapy for decreasing proteinuria were administered, and improvement of nephrotic syndrome and persistent complete remission of MDS were achieved.

Plasma S100A12 Levels and Peripheral Arterial Disease in End-Stage Renal Disease

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29–25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40–0.74; p < 0.001). Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.

'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.