Ikuyo Narita

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy

BackgroundMyeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined.Case presentationA 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN.ConclusionCombination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection.

Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression.

Abstract: Enhanced renin–angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1–7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of blood pressure, and evaluated the potential mechanisms. The 3- to 4-month-old male mice overexpressing renin in the liver (Ren-Tg) were given Olm (5 mg/kg/d) and hydralazine (Hyd) (3.5 mg/kg/d) orally for 2 months. Systolic blood pressure was higher in the Ren-Tg mice than in wild-type littermates. Olm and Hyd treatments lowered systolic blood pressure to the same degree. However, cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression, was inhibited by only Olm treatment, but not by Hyd. Olm treatment reversed decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibited enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species, whereas Hyd treatment had no influence on them. These findings indicate that Olm treatment inhibits cardiac hypertrophy independently of blood pressure, not only through its original AT1R blockade but partly through enhancement of ACE2/Ang(1–7)/Mas axis and suppression of Nox4 expression.

An adult case of nephrotic syndrome presenting with pulmonary artery thrombosis: a case report

IntroductionPulmonary artery thrombosis is one of the most important complications in patients with nephrotic syndrome. It is well known among nephrologists, however, that this possibly lethal complication very rarely occurs before the diagnosis of nephrotic syndrome.Case presentationA 21-year-old Japanese woman who had no specific medical history consulted a primary care clinic. Although she had been aware of the edema of her lower extremities for 2 weeks, her chief complaints were palpitations and chest pain, which had started the day before. An electrocardiogram and chest radiograph did not reveal any specific abnormalities. Because her etiology was not clear, she was referred to an emergency division in a hospital 2 days later. Although arterial blood gas analysis did not reveal hypoxemia, computed tomography revealed thrombi of the bilateral pulmonary arteries and left iliac vein. At this point, a laboratory examination confirmed the diagnosis of nephrotic syndrome. Subsequently, she was admitted, and anticoagulant therapy was initiated immediately. The next day, oral corticosteroid therapy was initiated, and an inferior vena cava filter was placed internally. Her proteinuria resolved after 3 weeks of treatment. The prompt and complete response to corticosteroid therapy suggested that minimal change disease was the etiology of the nephrotic syndrome and pulmonary artery thrombosis.ConclusionsAn awareness regarding the complication of pulmonary artery thrombosis in nephrotic syndrome is important not only for nephrologists but for all clinicians. Contrast-enhanced computed tomography is crucial to detect pulmonary artery thrombosis.

Blood Pressure-Independent Effect of Olmesartan on Albuminuria in Mice Overexpressing Renin: Its Beneficial Role in the ACE2/Ang (1-7)/Mas Axis and NADPH Oxidase Expression

Enhanced renin-angiotensin activity contributes to hypertension, albuminuria, and glomerular hypertrophy. The angiotensin (Ang)-converting enzyme (ACE) 2/Ang (1-7)/Mas axis pathway acts against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits albuminuria independently of blood pressure and elucidated the potential mechanisms.Three- to 4-month-old male mice overexpressing renin in the liver (Ren-TG) were given olmesartan (5 mg/kg/day) or hydralazine (Hyd) (3.5 mg/kg/day) orally for 2 months. Ren-TG mice had higher systolic blood pressure (SBP) than wild-type (WT) mice (158.2 ± 6.3 versus 112.8 ± 8.8 mmHg, n = 3-4, P < 0.01). Ren-TG mice treated with Olm or Hyd for 2 months had lower SBP than untreated Ren-TG mice. Urinary albumin excretion (UAE) was significantly increased in Ren-TG mice compared with WT mice (78.2 ± 31.2 versus 28.6 ± 13.8 μg/day, n = 5-6, P < 0.01). Olm treatment for 2 months reduced UAE, whereas Hyd treatment did not. Olm treatment reversed decreased gene and protein expressions of ACE2 and Mas receptor (Mas 1) in the kidney of Ren-TG mice and inhibited enhanced NADPH oxidase (Nox) 4 expression, whereas Hyd treatment had no influence. Furthermore, increased reactive oxygen species (ROS) in the kidney of Ren-TG mice were decreased by Olm treatment but not by Hyd treatment.Olm treatment inhibits albuminuria and glomerular hypertrophy independently of blood pressure not only through its original AT1R blockade but also partly through the enhancement of the ACE2/Ang (1-7)/Mas axis and suppression of ROS generation.

Successful Resuscitation of a Patient with Life-Threatening Metabolic Acidosis by Hemodialysis: A Case of Ethylene Glycol Intoxication

Background Ethylene glycol intoxication causes severe metabolic acidosis and acute kidney injury. Fomepizole has become available as its antidote. Nevertheless, a prompt diagnosis is not easy because patients are often unconscious. Here we present a case of ethylene glycol intoxication who successfully recovered with prompt hemodialysis. Case Presentation A 52-year-old Japanese male was admitted to a local hospital due to suspected food poisoning. The patient presented with nausea and vomiting, but his condition rapidly deteriorated, with worsening conscious level, respiratory distress requiring mechanical ventilation, hypotension, and severe acute kidney injury. He was transferred to the university hospital; hemodialysis was initiated because of hyperkalemia and severe metabolic acidosis. On recovering consciousness, he admitted having ingested antifreeze solution. Thirty-seven days after admission, the patient was discharged without requiring HD. Conclusions We reported a case of ethylene glycol intoxication who presented with a life-threatening metabolic acidosis. In a state of severe circulatory shock requiring catecholamines, hemodialysis should be avoided, and continuous hemodiafiltration may be a preferred approach. However, one should be aware of the possibility of intoxication by unknown causes, and hemodialysis could be life-saving with its superior ability to remove toxic materials in such cases.

Enhanced p122RhoGAP/DLC-1 Expression Can Be a Cause of Coronary Spasm

Background We previously showed that phospholipase C (PLC)-δ1 activity was enhanced by 3-fold in patients with coronary spastic angina (CSA). We also reported that p122Rho GTPase-activating protein/deleted in liver cancer-1 (p122RhoGAP/DLC-1) protein, which was discovered as a PLC-δ1 stimulator, was upregulated in CSA patients. We tested the hypothesis that p122RhoGAP/DLC-1 overexpression causes coronary spasm. Methods and Results We generated transgenic (TG) mice with vascular smooth muscle (VSM)-specific overexpression of p122RhoGAP/DLC-1. The gene and protein expressions of p122RhoGAP/DLC-1 were markedly increased in the aorta of homozygous TG mice. Stronger staining with anti-p122RhoGAP/DLC-1 in the coronary artery was found in TG than in WT mice. PLC activities in the plasma membrane fraction and the whole cell were enhanced by 1.43 and 2.38 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT mice. Immediately after ergometrine injection, ST-segment elevation was observed in 1 of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (p<0.05, WT versus TGs). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in TG, but not in WT mice, despite of the similar response to prostaglandin F2α between TG and WT mice (n = 5). Focal narrowing of the coronary artery after ergometrine was documented only in TG mice. Conclusions VSM-specific overexpression of p122RhoGAP/DLC-1 enhanced coronary vasomotility after ergometrine injection in mice, which is relevant to human CSA.

Lack of Awareness among Renal Transplant Recipients Regarding Consumption of Phosphate- containing Processed Food and Drinks

In the chronic kidney disease (CKD), adequate phosphate control is critical to reduce mortality rate and cardiovascular risks, besides, it may improve renal prognosis. We surveyed the awareness of the high phosphate content in the commercially processed food and drinks among renal transplant recipients, since they usually have reduced kidney function. Thirty seven subjects were provided with a questionnaire to evaluate their awareness of food and drinks containing phosphate. Most of the subjects (91.9%) were aware of the presence of sugar in soda drinks, but only 13.5% were aware of the presence of phosphate. Only 29.7% understood that phosphate is present in processed food, such as hamburgers and pizza, and 64.9% were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. In this survey, 24.3%