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1.
CEN Case Rep ; 11(3): 386-390, 2022 08.
Article in English | MEDLINE | ID: mdl-35124791

ABSTRACT

Acute focal bacterial nephritis (AFBN) refers to the bacterial infection of the renal parenchyma without abscess formation. Although AFBN has mainly been reported in pediatric patients, it may be underdiagnosed in adults as it resembles acute pyelonephritis in its clinical presentation. However, the symptoms suggesting acute abdomen is an important clue to diagnose AFBN, which requires additional imaging studies such as contrast-enhanced computed tomography (CECT). Here, we present the case of a 49-year-old female presenting to our emergency room with acute abdomen as well as acute kidney injury (AKI). CECT was performed to rule out critical etiologies of severe abdominal pain and the results revealed multifocal wedge-shaped shadows in the right kidney and diffuse enlargement of bilateral kidneys. We diagnosed the patient with AFBN and treated her through temporal hemodialysis (two sessions) and antibiotics for 23 days. Although AKI associated with AFBN has rarely been reported, her renal dysfunction and other symptoms were completely improved. In conclusion, clinicians should be aware of AFBN and be cautious to avoid the unnecessary invasive interventions.


Subject(s)
Abdomen, Acute , Acute Kidney Injury , Nephritis , Pyelonephritis , Abdomen, Acute/diagnosis , Abdomen, Acute/etiology , Acute Disease , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adult , Child , Female , Humans , Middle Aged , Nephritis/complications , Pyelonephritis/complications , Pyelonephritis/diagnosis , Pyelonephritis/microbiology
2.
BMC Cardiovasc Disord ; 20(1): 89, 2020 02 24.
Article in English | MEDLINE | ID: mdl-32093607

ABSTRACT

BACKGROUND: Acute coronary syndrome (ACS) with high-grade atrioventricular block (HAVB) still has a poor mortality risk, even in the current percutaneous coronary intervention (PCI) era. However, early PCI for ACS with HAVB is associated with improved in-hospital survival and a 6-month survival similar to that of ACS without HAVB. CASE PRESENTATION: A 70-year-old man was admitted to our hospital for ACS with HAVB. ECG showed complete AV block, complete right bundle branch block (CRBBB), and left axis deviation. Cardiac enzymes were elevated. He underwent temporary pacemaker insertion and coronary angiography, which showed severe stenosis of the proximal right coronary artery (RCA), 99% stenosis of the distal RCA with Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow, and total occlusion of the proximal left anterior descending artery (LAD). We performed primary PCI in both the RCA and LAD, which resulted in TIMI grade 3 flow in both. After PCI, the HAVB recovered to normal sinus rhythm with CRBBB; a normal QRS interval returned within three days. The patient was discharged from the hospital without complications. CONCLUSION: In this case of ACS with HAVB, early intensive coronary artery reperfusion resulted in long-term patient survival. The blood supply to the AV node and bilateral bundle branches is complex. Multivessel ischemia may compromise both primary and collateral blood flows to the AV node and septum, resulting in severe conduction impairment. Clinicians performing PCI should be aware of this anatomy and physiology.


Subject(s)
Acute Coronary Syndrome/therapy , Atrioventricular Block/diagnosis , Bundle-Branch Block/diagnosis , Electrocardiography , Heart Rate , Percutaneous Coronary Intervention , Action Potentials , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/physiopathology , Aged , Atrioventricular Block/complications , Atrioventricular Block/physiopathology , Bundle-Branch Block/complications , Bundle-Branch Block/physiopathology , Collateral Circulation , Coronary Angiography , Coronary Circulation , Drug-Eluting Stents , Humans , Male , Percutaneous Coronary Intervention/instrumentation , Predictive Value of Tests , Time Factors , Treatment Outcome
3.
Case Rep Nephrol Dial ; 7(3): 154-160, 2017.
Article in English | MEDLINE | ID: mdl-29457020

ABSTRACT

The risk of infective endocarditis in chronic hemodialysis patients is markedly higher than that in the general population. We report the first case of a hemodialysis patient with infective endocarditis caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE) who presented with streptococcal toxic shock syndrome. In the last decade, there has been an increase in the incidence of SDSE infections. Therefore, it is important to recognize SDSE as a possible causative agent of infective endocarditis in an immunocompromised population, such as hemodialysis patients.

4.
BMC Cardiovasc Disord ; 16: 71, 2016 Apr 22.
Article in English | MEDLINE | ID: mdl-27102232

ABSTRACT

BACKGROUND: Takotsubo cardiomyopathy (TC) is a cardiomyopathy that shows distinctive clinical conditions first described more than 20 years ago. Because clinical features of TC mimic those of anterior acute myocardial infarction (AMI), the differential diagnosis is important in selecting the appropriate treatment strategy in the acute phase. But it was difficult to differentiate those two diseases because the TC-like findings; such as the electrocardiogram (ECG) changes and left ventricular wall motion abnormality can occur in AMI especially with the anatomical variance of the coronary artery. CASE PRESENTATION: A 63-year-old man was admitted due to sudden onset of chest pain and was in a cardiogenic shock state. His ECG showed ST-segment elevation in precordial (V2-6) and inferior leads (II, III, and aVF) and ST-segment depression in lead aVR. Blood biochemistry showed that cardiac enzymes were not elevated. Ultrasonic cardiography showed that the left ventricular apical level was akinetic, papillary muscle level was severely hypokinetic, and basal level was hyperkinetic, mimicking TC. However, coronary angiogram showed total occlusion of his right coronary artery wrapping around the cardiac apex. Successful percutaneous coronary intervention reversed his critical status. CONCLUSION: To our knowledge, the present case is the first report described AMI with wrap-around RCA, mimicking TC. Although TC is increasingly recognized as a true but relatively infrequent clinical entity, it is still important to carefully rule out obstructive coronary artery disease.


Subject(s)
Coronary Angiography , Coronary Occlusion/diagnostic imaging , Coronary Vessel Anomalies/diagnostic imaging , Myocardial Infarction/etiology , Takotsubo Cardiomyopathy/diagnosis , Coronary Occlusion/complications , Coronary Occlusion/therapy , Coronary Vessel Anomalies/complications , Diagnosis, Differential , Echocardiography , Electrocardiography , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Predictive Value of Tests
5.
CEN Case Rep ; 4(2): 119-125, 2015 Nov.
Article in English | MEDLINE | ID: mdl-28509086

ABSTRACT

A 70-year-old woman developed anemia and kidney injury 10 months after mitral valve (MV) repair. Serological findings and Doppler echocardiography suggested hemolytic anemia due to mitral regurgitation jet collision with an annuloplasty ring (MRCR). Since kidney injury persisted even without exacerbation of anemia over 10 months, we performed an MV replacement. The anemia improved rapidly after the surgery; however, the renal function remained chronic kidney disease (CKD) after reoperation. Kidney injury was thought to be due to iron deposition and decreased renal perfusion that caused tubular injury. A comprehensive literature review shows that hemolysis due to MRCR in the early postoperative phase (within 3 postoperative months) can be often ameliorated with endothelialization without the need for reoperation; however, hemolysis in the late postoperative phase can persist even for a long period without reoperation. Chronic hemolysis can lead to kidney injury and progress to CKD even without clinical evidence of exacerbation of anemia. Therefore, in cases of late postoperative phase hemolysis, reoperation should be considered for better management of kidney injury and hemolytic anemia.

7.
Am J Physiol Heart Circ Physiol ; 305(5): H667-75, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23812390

ABSTRACT

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis.


Subject(s)
Adipose Tissue/physiopathology , Aorta, Thoracic/physiopathology , Apolipoproteins E/deficiency , Atherosclerosis/physiopathology , Nephrectomy/adverse effects , Renal Insufficiency, Chronic/physiopathology , Renin-Angiotensin System/physiology , Adipocytes/drug effects , Adipocytes/metabolism , Adipose Tissue/metabolism , Angiotensin II/metabolism , Angiotensinogen/metabolism , Animals , Aorta, Thoracic/metabolism , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Atherosclerosis/etiology , Atherosclerosis/metabolism , Cholesterol, Dietary/adverse effects , Disease Models, Animal , Insulin/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , PPAR gamma/metabolism , Renal Insufficiency, Chronic/etiology
8.
Ren Fail ; 35(4): 551-5, 2013.
Article in English | MEDLINE | ID: mdl-23473081

ABSTRACT

A 69-year-old man was admitted to our hospital with severe hypertension and rapidly worsening renal function. He presented with a 10-year history of chronic renal failure caused by bilateral ureteral obstruction due to retroperitoneal fibrosis. Magnetic resonance angiography and Doppler ultrasonography suggested severe right renal artery stenosis (RAS). Renal angiography revealed 99% stenosis at the ostium of the right renal artery. We performed percutaneous transluminal renal angioplasty (PTRA) with the support of intravascular ultrasound to decrease the amount of contrast agent needed. In addition, to prevent distal atheroembolism, a distal protection device was used. The procedure was completed without any adverse effects. After PTRA, renal function and blood pressure improved remarkably and remained stable for one year. PTRA for RAS remains controversial, especially in patients with renal insufficiency. Use of new devices should be considered to decrease catheterization-related adverse effects.


Subject(s)
Angioplasty , Hypertension, Renal/therapy , Kidney/physiopathology , Renal Artery Obstruction/therapy , Renal Artery/physiopathology , Renal Insufficiency/therapy , Aged , Humans , Hypertension, Renal/physiopathology , Male , Renal Artery Obstruction/physiopathology , Renal Insufficiency/physiopathology , Treatment Outcome
9.
BMC Nephrol ; 14: 16, 2013 Jan 16.
Article in English | MEDLINE | ID: mdl-23324110

ABSTRACT

BACKGROUND: S100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined. METHODS: In a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels. RESULTS: Higher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (<18.79 ng/mL; P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195-4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017-3.781; P = 0.044), serum albumin levels <3.5 g/dL (HR, 2.198; 95%CI, 1.218-3.968; P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146-3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656-0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627-0.815)]. CONCLUSION: The results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels.


Subject(s)
Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Proportional Hazards Models , Renal Dialysis/mortality , S100 Proteins/blood , Survival Analysis , Aged , Biomarkers/blood , Female , Humans , Incidence , Japan/epidemiology , Kidney Failure, Chronic/diagnosis , Male , Middle Aged , Prognosis , Reproducibility of Results , Risk Assessment/methods , S100A12 Protein , Sensitivity and Specificity , Survival Rate
10.
Clin Nephrol ; 80(3): 218-22, 2013 Sep.
Article in English | MEDLINE | ID: mdl-22541678

ABSTRACT

MYH9 disorders are autosomal dominant diseases characterized by giant platelets, thrombocytopenia, and granulocyte inclusion bodies. These diseases are caused by mutations in the MYH9 gene that encodes nonmuscle myosin heavy chain IIA. We describe the case of a 27-year-old male who presented with macrothrombocytopenia and leukocyte inclusion bodies. Chronic kidney disease, probably due to progressive glomerulosclerosis, and high-tone sensorineural deafness were evident. Although deterioration of renal function necessitated renal replacement therapy in the form of peritoneal dialysis, we reconsidered the etiology of the kidney disease due to the patient's clinical history. We identified an in-frame deletion mutation in exon 24 of the MYH9 gene that resulted in the removal of 21 nucleotides. The patient was diagnosed with an MYH9 disorder. We report this novel abnormality of the nucleotide sequence and compare it with previous cases and their associated phenotypes.


Subject(s)
Hearing Loss, Sensorineural/genetics , Kidney Failure, Chronic/genetics , Molecular Motor Proteins/genetics , Myosin Heavy Chains/genetics , Sequence Deletion , Thrombocytopenia/congenital , Adult , DNA Mutational Analysis , Exons , Genetic Predisposition to Disease , Hearing Loss, Sensorineural/blood , Hearing Loss, Sensorineural/pathology , Humans , Inclusion Bodies/pathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/therapy , Leukocytes/pathology , Male , Peritoneal Dialysis , Phenotype , Thrombocytopenia/blood , Thrombocytopenia/genetics , Thrombocytopenia/pathology
11.
Case Rep Nephrol Urol ; 2(1): 15-9, 2012 Jan.
Article in English | MEDLINE | ID: mdl-23197950

ABSTRACT

We report the case of a Japanese family suffering from familial juvenile hyperuricemic nephropathy (FJHN) due to a rare missense mutation of the uromodulin (UMOD) gene. An 18-year-old male presented with gout, hyperuricemia, and stage 3 chronic kidney disease. Mostly, FJHN is caused by a mutation altering the cystine residue of UMOD/Tamm-Horsfall protein. However, in the present case, a T688C mutation was identified in exon 4, resulting in amino acid substitution with arginine replacing tryptophan at position 230 (Trp230Arg). This mutation was also found in his brother and father with the same phenotype, indicating autosomal dominant inheritance. The affected amino acid was conserved in 200 healthy Japanese controls. Therefore, mutation T688C most likely causes rare structural and/or functional abnormalities in UMOD/Tamm-Horsfall protein.

12.
Clin Exp Nephrol ; 16(6): 903-20, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23053590

ABSTRACT

BACKGROUND AND OBJECTIVES: Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed. RESULTS: The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life. CONCLUSIONS: Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.


Subject(s)
Age Factors , Kidney Diseases/epidemiology , Kidney Diseases/pathology , Kidney/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Female , Glomerulonephritis/epidemiology , Glomerulonephritis/pathology , Glomerulonephritis, IGA/epidemiology , Glomerulonephritis, IGA/pathology , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Nephrotic Syndrome/epidemiology , Nephrotic Syndrome/pathology , Registries
13.
Kidney Int ; 81(5): 449-57, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22157654

ABSTRACT

Unilateral ureteral obstruction is a well-established experimental model of progressive renal fibrosis. We tested whether mechanical stretch and subsequent renal tubular distension might lead to renal fibrosis by first studying renal tubular epithelial cells in culture. We found that mechanical stretch induced reactive oxygen species that in turn activated the cytoplasmic proline-rich tyrosine kinase-2 (Pyk2). This kinase is abundantly expressed in tubular epithelial cells where it is activated by several stimuli. Using mice with deletion of Pyk2 we found that the expression of transforming growth factor-ß1 induced by mechanical stretch in renal tubular epithelial cells was significantly reduced. The expression of connective tissue growth factor was also reduced in the Pyk2(-/-) mice. We also found that expression of connective tissue growth factor was independent of transforming growth factor-ß1, but dependent on the Rho-associated coiled-coil forming protein kinase pathway. Thus, Pyk2 may be an important initiating factor in renal fibrosis and might be a new therapeutic target for ameliorating renal fibrosis.


Subject(s)
Connective Tissue Growth Factor/metabolism , Focal Adhesion Kinase 2/metabolism , Kidney Tubules/metabolism , Kidney/metabolism , Kidney/pathology , Stress, Mechanical , Animals , Cells, Cultured , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fibrosis , Focal Adhesion Kinase 2/deficiency , Focal Adhesion Kinase 2/genetics , Kidney Tubules/pathology , MAP Kinase Signaling System/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Phosphorylation , Reactive Oxygen Species/metabolism , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Ureteral Obstruction/complications
14.
Clin J Am Soc Nephrol ; 6(4): 718-23, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21258041

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/blood , Renal Dialysis , S100 Proteins/blood , Aged , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Prevalence , Receptor for Advanced Glycation End Products , Receptors, Immunologic/blood , S100 Proteins/physiology , S100A12 Protein
15.
Metabolism ; 60(5): 735-9, 2011 May.
Article in English | MEDLINE | ID: mdl-20817213

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common features. Both are associated with visceral obesity, type 2 diabetes mellitus, metabolic syndrome, and insulin resistance. However, the relationship between NAFLD and CKD is poorly understood. We examined the prevalence of and risk factors for CKD in patients with NAFLD. We analyzed 174 Japanese patients with liver biopsy-proven NAFLD using a cross-sectional design. Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1.73 m(2) and/or overt proteinuria. Of 174 NAFLD patients, 92 (53%) exhibited histologic characteristics of nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD; and 82 (47%) had non-NASH NAFLD. Chronic kidney disease was present in 24 (14%) of 174 NAFLD patients. The prevalence of CKD was significantly higher in NASH patients (19 of 92; 21%) than non-NASH patients (5 of 82; 6%). The presence of CKD was associated with a higher body mass index and the presence of hypertension and NASH. Our results demonstrated a high prevalence of CKD among patients with NASH.


Subject(s)
Kidney Diseases/etiology , Adolescent , Adult , Aged , Asian People/statistics & numerical data , Body Mass Index , Chronic Disease , Comorbidity , Cross-Sectional Studies , Fatty Liver/complications , Fatty Liver/epidemiology , Female , Glomerular Filtration Rate/physiology , Humans , Hypertension/epidemiology , Japan/epidemiology , Kidney Diseases/epidemiology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease , Obesity/epidemiology , Prevalence , Proteinuria/epidemiology , Risk Factors , Young Adult
16.
Nephron Extra ; 1(1): 242-50, 2011 Jan.
Article in English | MEDLINE | ID: mdl-22470398

ABSTRACT

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.

17.
Proc Natl Acad Sci U S A ; 107(45): 19308-13, 2010 Nov 09.
Article in English | MEDLINE | ID: mdl-20966350

ABSTRACT

Klotho is a circulating protein, and Klotho deficiency disturbs endothelial integrity, but the molecular mechanism is not fully clarified. We report that vascular endothelium in Klotho-deficient mice showed hyperpermeability with increased apoptosis and down-regulation of vascular endothelial (VE)-cadherin because of an increase in VEGF-mediated internal calcium concentration ([Ca(2+)]i) influx and hyperactivation of Ca(2+)-dependent proteases. Immunohistochemical analysis, the pull-down assay using Klotho-fixed agarose, and FRET confocal imaging confirmed that Klotho protein binds directly to VEGF receptor 2 (VEGFR-2) and endothelial, transient-receptor potential canonical Ca(2+) channel 1 (TRPC-1) and strengthens the association to promote their cointernalization. An in vitro mutagenesis study revealed that the second hydrolase domain of Klotho interacts with sixth and seventh Ig domains of VEGFR-2 and the third extracellular loop of TRPC-1. In Klotho-deficient endothelial cells, VEGF-mediated internalization of the VEGFR-2/TRPC-1 complex was impaired, and surface TRPC-1 expression increased 2.2-fold; these effects were reversed by supplementation of Klotho protein. VEGF-mediated elevation of [Ca(2+)]i was sustained at higher levels in an extracellular Ca(2+)-dependent manner, and normalization of TRCP-1 expression restored the abnormal [Ca(2+)]i handling. These findings provide evidence that Klotho protein is associated with VEGFR-2/TRPC-1 in causing cointernalization, thus regulating TRPC-1-mediated Ca(2+) entry to maintain endothelial integrity.


Subject(s)
Glucuronidase/metabolism , TRPC Cation Channels/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Binding Sites , Calcium/metabolism , Calcium Channels , Glucuronidase/deficiency , Klotho Proteins , Mice , Protein Binding
18.
Ther Apher Dial ; 14(3): 303-7, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20609183

ABSTRACT

Eicosapentaenoic acid (EPA), which is purified from fish oil, attenuates inflammatory responses by decreasing eicosanoid and cytokine production. EPA reportedly improves renal survival in patients with immunoglobulin (Ig)A nephropathy; however, this is unconfirmed. We studied the effects of EPA on IgA nephropathy patients. Eighteen biopsy-confirmed IgA nephropathy patients (aged 31 +/- 3 years) were enrolled. The prognoses based on glomerular findings were good (N = 5), relatively poor (N = 12), and poor (N = 1). EPA was administered at 1.8 g/day for 12 months. Five biopsy-confirmed IgA nephropathy patients were enrolled as control subjects. Administration of other drugs used to treat IgA nephropathy was not changed. The estimated creatinine clearance (eCCr), serum creatinine (Cr) concentration, urinary protein creatinine ratio (U/P), and other clinical parameters were checked. In the EPA group, the Cr went from 0.8 +/- 0.2 mg/dL to 0.7 +/- 0.2 mg/dL after 12 months of EPA treatment, and the U/P went from 550 +/- 580 mg/g Cr to 330 +/- 920 mg/g Cr. The values did not differ significantly; however, Cr and U/P tended to improve, with no adverse effects from the EPA. The eCCr improved significantly (99 +/- 7-110 +/- 8 mL/min, P = 0.001) in the EPA group, but not in the control group (126 +/- 12-120 +/- 13, P > 0.05). The effect of EPA in patients with IgA nephropathy is not pronounced, but these results suggest that EPA is a safe and worthwhile supplement to the drugs used to treat this disease.


Subject(s)
Creatinine , Eicosapentaenoic Acid/therapeutic use , Glomerulonephritis, IGA/drug therapy , Adolescent , Adult , Biopsy , Creatinine/blood , Creatinine/urine , Female , Glomerulonephritis, IGA/physiopathology , Humans , Male , Prognosis , Proteinuria/etiology , Young Adult
19.
Arzneimittelforschung ; 59(9): 435-9, 2009.
Article in English | MEDLINE | ID: mdl-19856789

ABSTRACT

INTRODUCTION: A long-acting erythropoiesis-stimulating agent named "darbepoetin alfa" (CAS 11096-26-7) was recently developed. Though it is already in use worldwide, especially in western countries, its efficacy and safety for Asian patients have not been well evaluated yet. The purpose of this study was to evaluate the efficacy and safety of short-term darbepoetin alfa administration for Japanese hemodialysis patients. METHODS: Patients who had undergone maintenance hemodialysis were enrolled in this study. The erythropoiesis-stimulating agent was switched from epoetin alfa (CAS 113427-24-0) to darbepoetin alfa so as to control the hemoglobin (Hgb) value between 10 and 12 g/dl. The initial conversion ratio was made according to the manufacturer's recommendations. The factors relevant to the responsiveness to erythropoiesis were analyzed. RESULTS: One hundred and fifty-nine patients with a mean age of 67.6 years were enrolled. Two months after switching to darbepoetin alfa, the Hgb value had increased significantly (10.3 +/- 1.2 to 10.6 +/- 1.4 g/dl). Only iron supplementation correlated positively with the change of Hgb. In addition, 14.3% of patients had excess Hgb (Hgb > 12 g/dl) at the end of the study period, but only 5.6% patients at the run-in. Serious cardiovascular disease did not occur during the study period; however, the mean systolic blood pressure at the start of hemodialysis increased significantly and there was no correlation between the change of Hgb value and blood pressure. CONCLUSION: Darbepoetin alfa increases the Hgb value effectively in Japanese hemodialysis patients. Although no serious adverse events were apparent in our short-term analysis, the incidence of hypertension and excessive increase of the Hgb value must be noted.


Subject(s)
Anemia/drug therapy , Erythropoietin/analogs & derivatives , Kidney Failure, Chronic/blood , Renal Dialysis , Aged , Anemia/etiology , Blood Pressure/drug effects , Darbepoetin alfa , Dose-Response Relationship, Drug , Erythropoietin/adverse effects , Erythropoietin/therapeutic use , Female , Hematocrit , Hemoglobins/metabolism , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged
20.
Clin Transplant ; 23 Suppl 20: 58-61, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19594599

ABSTRACT

A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.


Subject(s)
Graft Rejection/prevention & control , Kidney Transplantation , Kidney/cytology , Living Donors , Preoperative Care/methods , Biopsy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies
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