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1.
Med Mol Morphol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622315

RESUMO

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochondrial dysfunction and has therapeutic potential against various diseases including kidney diseases. However, whether MA-5 is effective against peritoneal fibrosis remains unclear. Therefore, we investigated the effect of MA-5 using a peritoneal fibrosis mouse model. Peritoneal fibrosis was induced in C57BL/6 mice via intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks. MA-5 was administered daily by oral gavage. The mice were divided into control, MA-5, CG, and CG + MA-5 groups. Following treatment, immunohistochemical analyses were performed. Fibrotic thickening of the parietal peritoneum induced by CG was substantially attenuated by MA-5. The number of α-smooth muscle actin-positive myofibroblasts, transforming growth factor ß-positive cells, F4/80-positive macrophages, monocyte chemotactic protein 1-positive cells, and 4-hydroxy-2-nonenal-positive cells was considerably decreased. In addition, reduced ATP5a1-positive and uncoupling protein 2-positive cells in the CG group were notably increased by MA-5. MA-5 may ameliorate peritoneal fibrosis by suppressing macrophage infiltration and oxidative stress, thus restoring mitochondrial function. Overall, MA-5 has therapeutic potential against peritoneal fibrosis.

2.
J Clin Med ; 10(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34640403

RESUMO

We aimed to investigate the factors associated with the development of aortic stenosis (AS) in patients undergoing hemodialysis (HD), and to elucidate the prognosis of HD patients with AS. Patients on HD that had also undergone echocardiography at Nagasaki Renal Center between July 2011 and June 2012 were included. Patients with AS at the time of inclusion were excluded. The diagnosis of AS was based on an annual routine or additional echocardiography. The patients were followed up until June 2021. The association between patient background and AS was also evaluated. Of the 302 patients (mean age, 67.4 ± 13.3 years; male, 58%; median dialysis history, 4.7 years), 60 developed AS and 10 underwent aortic valve replacement. A Cox proportional hazards model revealed that age (hazard ratio (HR), 1.07; 95% confidential interval (CI), 1.04-1.10; p < 0.001) and serum phosphate levels (HR, 1.40; 95%CI, 1.16-1.67, p < 0.001) were independent risk factors for developing AS. Incidentally, there was no significant mortality difference between patients with AS and those without (p = 0.53). Serum phosphate levels are a risk factor for developing AS and should be controlled. Annual echocardiography may contribute to the early detection of AS and improves the prognosis of patients undergoing HD.

3.
Intern Med ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34565774

RESUMO

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging. Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017. Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p<0.001). Conclusion Hemodialysis patients with intracerebral hemorrhaging who were bedridden showed poor outcomes. The major causes of death were infections. Therefore, these patients should be carefully monitored for infections in order to improve their prognosis.

4.
Intern Med ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34393162

RESUMO

A 68-year-old woman developed systemic blisters while receiving treatment for nephrotic syndrome. As she also developed marked liver dysfunction and disseminated intravascular coagulation, she was admitted to our hospital. She was diagnosed with varicella zoster virus (VZV) infection. Treatment was administered in the intensive-care unit, but the patient died on day 24 post-admission after severe VZV infection. A post-mortem examination showed micro-abscesses and necrosis caused by varicella zoster infection in multiple organs, including the liver, kidneys, and gastrointestinal tract. Because VZV infection can become severe in immunocompromised patients, careful consideration is needed for the prevention and treatment of the viral infection.

5.
Medicina (Kaunas) ; 57(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207077

RESUMO

Background and Objectives: Urinary levels of dickkopf-3 (DKK-3) are associated with poor renal survival in patients with non-dialytic chronic kidney disease. However, it remains unknown whether urinary DKK-3 levels can predict residual renal function (RRF) decline in patients undergoing peritoneal dialysis (PD). Therefore, we investigated the correlation between urinary levels of DKK-3 and the subsequent rate of RRF decline in PD patients. Materials and Methods: This study included 36 PD patients who underwent multiple peritoneal equivalent tests during 2011-2021. The relationship between baseline clinical characteristics and the subsequent annual rate of Kt/V decline was investigated. Results: The annual rate of renal Kt/V decline was 0.29 (range: 0.05-0.48), which correlated with renal Kt/V (r = 0.55, p = 0.0005) and 24 h urinary DKK-3 excretion (r = 0.61, p < 0.0001). Similarly, 24 h urinary DKK-3 excretion (ß = 0.44, p = 0.0015) and renal Kt/V (ß = 0.38, p = 0.0059) were independently associated with the annual rate of renal Kt/V decline in multivariate analyses. Conclusions: Urinary DKK-3 assessment may help identify PD patients at a high risk of RRF decline.


Assuntos
Diálise Peritoneal , Insuficiência Renal Crônica , Progressão da Doença , Humanos , Rim , Testes de Função Renal
6.
Healthcare (Basel) ; 9(4)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923650

RESUMO

Percutaneous renal biopsy is an essential tool for diagnosing various renal diseases; however, little is known about whether renal biopsy performed by physicians with short nephrology experience is safe in Japan. This study included 238 patients who underwent percutaneous renal biopsy between April 2017 and September 2020. We retrospectively analyzed the frequency of post-renal biopsy complications (hemoglobin decrease of ≥10%, hypotension, blood transfusion, renal artery embolization, nephrectomy and death) and compared their incidence among physicians with varied experience in nephrology. After renal biopsy, a hemoglobin decrease of ≥10%, hypotension and transfusion occurred in 13.1%, 3.8% and 0.8% of patients, respectively. There were no cases of post-biopsy renal artery embolism, nephrectomy, or death. The composite complication rate was 16.0%. The incidence of post-biopsy complications was similar between physicians with ≥3 years and <3 years of clinical nephrology experience (12.5% vs. 16.8%, p = 0.64). Furthermore, the post-biopsy composite complication rates were similar between physicians with ≥6 months and <6 months of clinical nephrology experience (16.3% vs. 15.6%, p > 0.99). Under attending nephrologist supervision, a physician with short clinical nephrology experience can safely perform renal biopsy.

7.
Perit Dial Int ; 41(4): 394-403, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33522431

RESUMO

BACK GROUND: Krüppel-like transcription factor 5 (KLF5) is a transcription factor regulating cell proliferation, angiogenesis and differentiation. It has been recently reported that Am80, a synthetic retinoic acid receptor α-specific agonist, inhibits the expression of KLF5. In the present study, we have examined the expression of KLF5 in fibrotic peritoneum induced by chlorhexidine gluconate (CG) in mouse and evaluated that Am80, as an inhibitor of KLF5, can reduce peritoneal fibrosis. METHODS: Peritoneal fibrosis was induced by intraperitoneal injection of CG into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. Control mice received only a vehicle (0.5% carboxymethylcellulose solution). After 3 weeks of treatment, peritoneal equilibration test (PET) was performed and peritoneal tissues were examined by immunohistochemistry. RESULTS: The expression of KLF5 was less found in the peritoneal tissue of control mice, while KLF5 was expressed in the thickened submesothelial area of CG-injected mice receiving the vehicle. Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening, accompanied with the reduction of type III collagen expression. The numbers of transforming growth factor ß-positive cells, α-smooth muscle actin-positive cells and infiltrating macrophages were significantly decreased in Am80-treated group. PET revealed the increased peritoneal permeability in CG mice, whereas Am80 administration significantly improved the peritoneal high permeability state. CONCLUSIONS: These results indicate the involvement of KLF5 in the progression of experimental peritoneal fibrosis and suggest that Am80 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of KLF5 expression.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Animais , Fibrose , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Endogâmicos ICR , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/prevenção & controle , Peritônio/patologia
8.
Med Sci Monit ; 26: e928236, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347426

RESUMO

BACKGROUND Liver-type fatty acid-binding protein (L-FABP) is a predictive marker for the early detection of acute kidney injury; however, less is known about how useful it is for predicting residual renal function (RRF) decline in patients on peritoneal dialysis (PD). MATERIAL AND METHODS The study subjects were 35 patients on PD who underwent multiple peritoneal equilibration tests (PETs) between October 2011 and October 2019. Urinary L-FABP levels were analyzed with enzyme-linked immunosorbent assay. The relationship between baseline clinical data, including urinary L-FABP levels and the subsequent annual rate of renal Kt/V decline, was investigated. RESULTS The median follow-up duration was 11 months and the rate of renal Kt/V decline was 0.29/y. Compared with outcomes in the group with renal Kt/V preservation, renal Kt/V decline was associated with both high daily levels of urinary protein excretion (0.60 g/d [range, 0.50-0.87] vs. 0.36 g/d [range, 0.19-0.48]; P=0.01) and high daily levels of urinary L-FABP excretion (111.2 mg/d [range, 76.1-188.6] vs. 61.5 mg/d [range, 35.7-96.0]; P=0.002). Multiple logistic regression analysis showed that only high daily levels of urinary L-FABP excretion were independently associated with renal Kt/V decline (odds ratio 1.03, 95% confidence interval 1.00-1.05; P=0.001). Furthermore, higher daily levels of urinary L-FABP excretion were significantly correlated with the higher annual rate of renal Kt/V decline (r=0.71, P<0.001). CONCLUSIONS We demonstrated that daily levels of urinary L-FABP are associated with RRF decline in patients on PD. The results of the present study indicate that assessment of urinary L-FABP levels may help predict RRF decline in patients on PD.


Assuntos
Proteínas de Ligação a Ácido Graxo/urina , Falência Renal Crônica , Diálise Peritoneal/métodos , Biomarcadores/urina , Progressão da Doença , Feminino , Humanos , Rim/fisiopatologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Falência Renal Crônica/urina , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade
9.
Nutrients ; 12(9)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899702

RESUMO

Educational hospitalization of patients with chronic kidney disease (CKD) may slow the progression of renal dysfunction. However, the educational aspect that is more effective has not been identified to date. In this study, patients with CKD were evaluated for gustatory threshold for salty taste and received augmented salt reduction guidance under educational hospitalization at Nagasaki University Hospital from October 2016. In total, 277 eligible patients were enrolled and hospitalized from 2012 to 2019 (mean age of 69.2 years; men comprised 62.1%). We compared 141 patients (Group A) who were educated in the hospital after October 2016 and 136 patients (Group B) who received standard education in the hospital before October 2016. The changes in the estimated glomerular filtration rate (ΔeGFR) after hospitalization and dialysis induction rate within one year after hospitalization were evaluated. The ΔeGFR was significantly improved in Group A compared to Group B (A: 1.05 mL/min/1.73 m2/month, B: 0.55 mL/min/1.73 m2/month; p = 0.02). The dialysis induction rate was significantly lower in Group A than in Group B (A: 8.5%, B: 15.5%; p = 0.001). These trends were also observed by multivariate analyses. In conclusion, educational hospitalization with enhanced salt reduction guidance may reduce the risk of end-stage renal disease.


Assuntos
Dieta Hipossódica/psicologia , Falência Renal Crônica/prevenção & controle , Educação de Pacientes como Assunto/métodos , Insuficiência Renal Crônica/psicologia , Sódio na Dieta/análise , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Hospitalização , Humanos , Falência Renal Crônica/etiologia , Masculino , Análise Multivariada , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Comportamento de Redução do Risco , Limiar Gustativo
10.
Clin Exp Nephrol ; 24(5): 411-419, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31912273

RESUMO

BACKGROUND: Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51-56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI. METHODS: Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q. RESULTS: In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage. CONCLUSION: Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Túbulos Renais Proximais/patologia , Mitocôndrias/metabolismo , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Animais , Antineoplásicos/farmacologia , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Cisplatino/farmacologia , Creatinina/sangue , Humanos , Masculino , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar
11.
Drugs R D ; 17(3): 389-396, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28547536

RESUMO

BACKGROUND AND OBJECTIVE: We compared the hemoglobin-maintaining effects between continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) in patients with chronic kidney disease (CKD) during the 3 months before dialysis initiation. METHODS: This study was conducted with 37 CERA-administered patients and 26 DA-administered patients who had initiated dialysis at a participating facility between January 2012 and December 2014. We investigated clinical laboratory data 3 months before and at dialysis initiation, and compared these data between the CERA and DA groups. RESULTS: No significant differences in hemoglobin level or reticulocyte count were found between the two groups 3 months before dialysis initiation. However, at dialysis initiation, the hemoglobin level (CERA 9.82 ± 1.52 vs. DA 8.79 ± 1.07 g/dL; P = 0.003) and the reticulocyte count (CERA 5.21 ± 2.95 vs. DA 3.15 ± 1.62 × 104/µL; P = 0.004) were significantly higher in the CERA group than in the DA group. Moreover, the extent of changes in the erythropoietin resistance index during the 3 months before dialysis initiation was significantly increased in the DA group compared with the CERA group. CONCLUSIONS: Our results suggest that CERA may be more effective than DA in maintaining hemoglobin levels in patients with CKD during 3 months before dialysis initiation.


Assuntos
Darbepoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Contagem de Reticulócitos , Fatores de Tempo
12.
Med Sci Monit ; 23: 1464-1470, 2017 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-28343234

RESUMO

BACKGROUND Endocan is expressed in vascular endothelial cells, and its expression is enhanced following endothelial injury via inflammatory cytokines. Subsequently, endocan is secreted into the circulation. Thus, serum endocan levels are considered a marker of endothelial injury. However, to the best of our knowledge, no data on the serum endocan levels in peritoneal dialysis (PD) patients are available. MATERIAL AND METHODS This study included 21 PD patients who underwent peritoneal equilibration test (PET) more than once between 2011 and 2015. Serum samples were collected from each patient, and the 24-h urine volume was measured at the time of PET. Serum endocan levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of the first PET, and their relationship with clinical data or the extent of urine volume decline (mL/year) was analyzed retrospectively. RESULTS Serum endocan levels were positively correlated with proteinuria level, serum creatinine level, serum tumor necrosis factor (TNF)-α level, ß2-microglobulin level, and PD drainage volume, but not with urine volume at baseline. The extent of decline in urine volume was significantly associated with serum endocan level, proteinuria level, serum creatinine level, and serum TNF-α level at baseline in a simple linear regression analysis. Moreover, multiple linear regression analysis showed that the serum endocan level and proteinuria level at baseline were independent predictors for the extent of decline in urine volume. CONCLUSIONS The results of this study indicate that serum endocan level and proteinuria level may be useful predictive markers for decreased urine volume in PD patients.


Assuntos
Rim/fisiopatologia , Proteínas de Neoplasias/sangue , Diálise Peritoneal/métodos , Proteinúria/urina , Proteoglicanas/sangue , Adulto , Idoso , Biomarcadores/sangue , Creatina/sangue , Células Endoteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Micção/fisiologia
13.
Intern Med ; 55(13): 1735-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27374673

RESUMO

A 77-year-old man on maintenance dialysis developed hypotension, nausea and abdominal pain one hour after beginning to undergo hemodialysis. Abdominal computed tomography (CT) showed gas shadows in the intrahepatic portal vein and the small intestinal wall, but no signs indicating intestinal necrosis. Three days later, the gas shadows on abdominal CT disappeared by conservative therapy. In cases with both pneumatosis cystoides intestinalis and hepatic portal venous gas, intestinal necrosis should therefore be suspected and surgical therapy should also be considered, particularly in hemodialysis patients with a risk of intestinal ischemia. However, conservative therapy may be an option in cases with no intestinal necrosis.


Assuntos
Tratamento Conservador/métodos , Pneumatose Cistoide Intestinal/terapia , Diálise Renal , Idoso , Humanos , Masculino , Pneumatose Cistoide Intestinal/diagnóstico , Veia Porta/patologia , Tomografia Computadorizada por Raios X
14.
CEN Case Rep ; 4(1): 24-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-28509264

RESUMO

A 75-year-old man was diagnosed with pulmonary nontuberculous mycobacterial (NTM) infection in February 2005 and was treated with rifampicin, ethambutol, and clarithromycin. However, the infection was resistant to treatment, and his chest radiograph showed an abnormality that gradually seemed to aggravate. The patient's sputum was positive for Mycobacteria. Moreover, the patient had dyspnea and an underlying chronic inflammation in the lungs. He visited our hospital because of dyspnea and leg edema in June 2011. Laboratory evaluation on admission revealed proteinuria (6 g/day) and decreased serum total protein (5.8 g/dL) and albumin (1.6 g/dL) levels, indicating nephrotic syndrome. Percutaneous renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) in the acute stage and AA amyloidosis of mild degree. AA amyloidosis was also diagnosed histologically on gastric and colonic biopsy, in addition to renal biopsy. His renal function decreased gradually, and therefore, he underwent hemodialysis therapy in January 2012. However, his gastrointestinal-related symptoms persisted, and his appetite diminished, because of which he had become severely malnourished; he died 8 months later. This is a rare case of a patient with two different renal lesions (MPGN and AA amyloidosis) complicated with NTM. Our case suggests that MPGN and amyloidosis should be considered in elderly patients with nephrotic syndrome onset and chronic inflammation.

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