Junko Chinda

A newly estimated glomerular filtration rate is independently associated with arterial stiffness in Japanese patients.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, and thus is a major worldwide public health problem. Recently, an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation for Japanese patients was proposed by the Japanese Society of Nephrology. However, the role of eGFR in the assessment of atherosclerosis is not well understood in Japanese patients. We analyzed the relationship between eGFR and severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 647 adult Japanese patients. baPWV correlated significantly and positively with age, hypertension, diabetes, prior cardiovascular disease, blood pressure, pulse pressure and heart rate, and negatively with eGFR (r=−0.405, p<0.0001). A multiple regression analysis revealed that baPWV correlated independently with eGFR. Furthermore, there was a stepwise increase in baPWV, corresponding to advances in CKD through stages 1 to 5. When CKD stage 3 was divided at eGFR 45 mL/min/1.73 m2, the baPWV of stage 3b (eGFR 30 to 44) was significantly higher than that of stage 3a (eGFR 45 to 59) independent of traditional risk factors, suggesting that an eGFR of 45 mL/min/1.73 m2 may be a critical cut off value to predict arterial stiffness in CKD. In conclusion, the newly proposed eGFR is significantly associated with arterial stiffness, independent of traditional risk factors for cardiovascular disease.

Minimal Change Nephrotic Syndrome Associated with Gefitinib and a Successful Switch to Erlotinib

Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome (NS). We herein present the case of a 57-year-old woman with advanced lung adenocarcinoma treated with the tyrosine kinase inhibitor (TKI) gefitinib who developed NS. A renal biopsy revealed minor glomerular abnormalities, and the patients symptoms improved exclusively with the discontinuation of gefitinib. Therefore, we diagnosed her with MCNS associated with gefitinib treatment. A few months later, however, she developed recurrent lung tumors. Following the challenging initiation of the TKI erlotinib, she achieved remission without proteinuria. We thus conclude that erlotinib is a potential treatment option in patients with NS associated with gefitinib therapy.

Diagnosis of IgG4-related systemic disease by cytology of large pericardial effusion with fine needle aspiration

IgG4-related disease has characteristic features as follows; Serum IgG4 is prominently elevated, IgG4-positive plasma cells infiltrate in involved tissues and various mass-forming lesions with fibrosis, such as the autoimmune pancreatitis, salivary gland and retroperitoneum. As this disease comes to attention, the reports of IgG4-related disease have been increasing, but the pathogenesis and exact frequency of the disease remain unknown. We present the case of a 69 year-old male who was admitted to our hospital for evaluation of lower legs edema in July, 2010. He first noticed lower legs edema in 2009 and visited a local clinic, and was diagnosed deep vein thrombosis, received anti-coagulation therapy. However, his edema was getting worth and hydrocele testis was appeared. When he visited our office, he complained of trouble in walking with lower legs edema. On physical examination, his body temperature was 36.2 °C, blood pressure 152/82 mm Hg, and pulse rate 60 per minute. There was no murmur in his cardiac sounds and lungs were clear. On abdominal examination, it was slightly swelling but not any mass were noted. His trunk was edematous, especially in lower legs. The thyroid gland, salivary glands and lymph nodes were not palpable. He had never experienced dry eye and dry mouth. Laboratory findings were as follows: WBC 4390/μL, hemoglobin 10.6 g/dL, platelet 27.3×10/μL, BUN 10 mg/dL, creatinine 1.04 mg/dL, BNP 119.0 pg/mL, CRP b0.10 μg/L. Liver function test was normal. Urinalysis did not demonstrate any protein on dipstick. Rheumatoid factor, anti-nuclear antibody, anti SS-A and anti SS-B, antibodies and antineutrophil cytoplasmic antibody were all negative. IgG, IgA, IgM and IgE were 1769.0 mg/dL, 272.7 mg/dL, 74.8 mg/dL and 276 mg/dL, respectively. Serum level of IgG4 was elevated by 408 mg/dL. A chest radiograph revealed marked cardiomegaly. Echocardiography revealed marked pleural effusion with slightly collapsed right atrium. Computed tomography (CT) revealed also large pericardial effusion (Fig. 1A) and low density area around the aorta (Fig. 1B). The mass, which was suspected retroperitoneal fibrosis (RPF), compressed inferior vena cava and right urinary duct, and induced lower legs edema and right hydronephrosis. After admission, a ureteral stent was placed in order to treat the hydronephrosis. Lip biopsy was done, but there was no significant pathological change. Gallium scintigraphy showed no hot lesions. Autoimmune pancreatitis was ruled out by magnetic resonance pancreatic cholangiopancreatography. Then,we performedpericardiocentesis byfineneedle aspiration on 9 days after admission. The specimen was light yellow, cloudy, TP 5.2 g/dL, albumin 3.0 g/dL, IgG 1604.3 mg/dL, IgG4 451 mg/dL and abundant small sized lymphocytes, rich in IgG4-positive cells (Fig. 2). There was no malignancy. Culture of the pericardial fluid revealed no bacterial infection. Therefore, we diagnosed this case as IgG4-related disease and treated with prednisolone 50 mg/day. Then his edema was rapidly improved. One month after starting steroid therapy, the CT revealed disappearance of pericardial effusion and regression of retroperitoneal mass (Fig. 1C and D). To our knowledge, this is the first case report diagnosed by fine needle aspiration cytology of large pericardial effusion. The pathological characteristic of this disease is rich in IgG4-positive plasma cells with typical fibrosis or sclerosis in the tissue [1]. IgG4related disease sometimes shows retroperitoneal fibrosis (RPF) and caused hydronephrosis as in our case. A biopsy for the retroperitoneal mass is necessary to provide a definitive diagnosis, but is considerably invasive. The major reasons of pericardial effusion are idiopathic pericarditis, infection included tuberculosis and malignancy [2,3]. Secondary to malignancy are frequently observed in lung cancer, breast cancer, and malignant lymphoma. Malignant lymphoma is considered of differential diagnosis in both RPF and pericardial effusion. Fine needle aspiration of pericardial effusion is less invasive compared to retroperitoneal biopsy. Although Sugimoto et al. reported IgG4-related disease caused constrictive pericarditis diagnosed by pericardiectomy [4], pericardial effusion is not a major complication. We showed that the cytology of pericardial effusion was rich in IgG4-positive cells similar to serum, suggesting that IgG4-related disease caused pericardial exudation of the plasma cell. Thus, it is necessary to consider the possibility of IgG4-related disease in the differential diagnosis of pericardial effusion. A pericardiocentesis will be useful to diagnose a IgG4related disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].

Angiotensin II receptor blocker and long-acting calcium channel blocker combination therapy decreases urinary albumin excretion while maintaining glomerular filtration rate

Microalbuminuria is a recognized risk factor and predictor for cardiovascular events in patients with hypertension. We analyzed changes in hypotensive effect, urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) in subjects with hypertension and microalbuminuria as a subanalysis of the results of the Nifedipine and Candesartan Combination (NICE-Combi) Study. A total of 86 subjects with essential hypertension with microalbuminuria (UAE <300 mg g−1 creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg per day plus controlled-release (CR) nifedipine 20 mg per day) (n=42) or an up-titrated monotherapy group (candesartan 12 mg per day) (n=44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg per day) monotherapy for 8 weeks (initial treatment). After 8weeks, blood pressure (BP) was significantly reduced in both groups compared with at the end of initial treatment. UAE also showed a significant decrease in the combination therapy group, while there was no significant change of eGFR in either group. A significant positive correlation was seen between BP reduction and UAE after 8 weeks of double-blind treatment in both groups, whereas no significant association was found between ΔUAE and ΔeGFR in either group. These findings show that combination therapy with standard-dose candesartan and nifedipine CR is more effective than up-titrated candesartan monotherapy for reducing BP and improving UAE while maintaining eGFR, and strongly suggest that the combination of an angiotensin II receptor blocker and long-acting calcium channel blocker is beneficial in patients with hypertension and microalbuminuria.

Hemocholecyst complicated in a hemodialysis patient with microscopic polyangiitis.

Microscopic polyangiitis (MPA) is a systemic vasculitis associated with antineutrophil cytoplasmic antibodies, and it involves multiple organs, including the kidneys and lungs. We report on the case of a 72-year-old woman with MPA who developed hemocholecyst in addition to alveolar hemorrhage and rapidly progressive glomerulonephritis. Although her renal function was not salvaged, the alveolar hemorrhage and hemocholecyst were treated conservatively. Clinicians should consider the possibility of hemocholecyst in patients with MPA complaining of abdominal pain.

A Sporadic Case of Fabry Disease Involving Repeated Fever, Psychiatric Symptoms, Headache, and Ischemic Stroke in an Adult Japanese Woman.

Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. This case suggests that Fabry disease should be considered in young patients who exhibit central nervous system symptoms such as ischemic stroke, even if there is no family history of the condition. The episodes of aseptic meningitis and stroke experienced by our patient suggest that persistent inflammation might be the mechanism underlying Fabry disease.

Successful percutaneous transluminal angioplasty for the treatment of renovascular hypertension with an atrophic kidney

Renovascular hypertension is an important cause of secondary hypertension. We present the case of a 61-year-old man with renovascular hypertension caused by chronic total occlusion of the left renal artery resulting in an atrophic kidney. Although renography indicated almost no residual function of the left kidney, renal vein sampling showed a significant increase of renin secretion in the left kidney. The endocrine function of the left kidney was believed to be preserved; thus, we performed percutaneous transluminal renal angioplasty with stent placement. After the procedure, the patient’s blood pressure decreased gradually to within the normal range without adverse events. The laboratory data on endocrine function and the renography findings drastically improved. Percutaneous transluminal renal angioplasty is a promising therapeutic procedure for renovascular hypertension with an atrophic kidney.

Monitoring with serum SP-A, SP-D, and KL-6 in a patient with interstitial pneumonia complicated with ANCA-associated glomerulonephritis

A 69-year-old woman was admitted to hospital, complaining of fatigue and dry cough. Her renal function deteriorated rapidly, and the laboratory findings showed elevated myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (ANCA). Renal biopsy examination revealed crescentic glomerulonephritis (pauci-immune type), and linear opacities and a honeycomb appearance in both lower lobes was evident on the chest computed tomography scan. The patient was diagnosed as having ANCA-associated glomerulonephritis complicated with mild interstitial pneumonia (IP). Treatment with methylprednisolone pulse therapy improved both her renal function and IP, but her lung lesions worsened during the course of tapering the prednisolone doses. After careful observation, her IP improved gradually without specific treatment. Worsening or improvement of her lung lesions was accompanied by changes in the serological markers of IP, namely, surfactant protein-A, surfactant protein-D, and KL-6. We found that monitoring these markers was helpful in diagnosing and managing IP in our patient with ANCA-associated vasculitis.

Mizoribine for crescentic glomerulonephritis with sarcoidosis : effectiveness not only for urinalysis abnormalities but also for hilar lymph node enlargement

Sarcoidosis is a multisystem disease related to helper T cell responses. We recently experienced the case of a 57-year-old woman with sarcoidosis complicated by crescentic glomerulonephritis with low levels of myeloperoxidase-antineutrophil cytoplasmic antibody. We herein describe the details of her clinical course and discuss the effectiveness of mizoribine, which has an immunosuppressive effect equivalent to that of mycophenolate mofetil, not only for urinalysis abnormalities but also for hilar lymph node enlargement.