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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.

3.
BMC Nephrol ; 22(1): 240, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193064

RESUMO

BACKGROUND: Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood. METHODS: Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation. RESULTS: We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584-2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400-2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358). CONCLUSION: Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.

4.
J Infect Chemother ; 27(10): 1471-1476, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34183236

RESUMO

INTRODUCTION: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown. METHODS: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period. RESULTS: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001). CONCLUSION: Early L-AMB administration at septic shock onset may be associated with early shock cessation.


Assuntos
Choque Séptico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Humanos , Choque Séptico/tratamento farmacológico
5.
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.

6.
Intern Med ; 60(14): 2255-2260, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33612667

RESUMO

A 48-year-old woman presented with a fever, microscopic hematuria, proteinuria, and rapid deterioration of the renal function. Pulmonary alveolar hemorrhaging and a high level of anti-glomerular basement membrane (GBM) antibodies (700 IU/mL) were observed. Based on her medical history and positive findings of serum lupus anticoagulant, anti-phospholipid antibody syndrome (APS) was suspected. A renal biopsy revealed cellular crescentic glomerulonephritis with thrombosis, suggesting anti-GBM disease with catastrophic APS. The patient was treated with pulse steroid therapy, plasma exchange, hemodialysis, and intravenous cyclophosphamide pulse therapy. To our knowledge, this is the first report of a patient with anti-GBM disease and APS.


Assuntos
Doença Antimembrana Basal Glomerular , Síndrome Antifosfolipídica , Glomerulonefrite Membranoproliferativa , Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos , Feminino , Hemorragia/etiologia , Humanos , Pessoa de Meia-Idade , Troca Plasmática
8.
Clin Exp Nephrol ; 25(3): 279-287, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33179180

RESUMO

BACKGROUND: Liposomal amphotericin B (L-AMB), a broad-spectrum antifungicidal drug, is often used to treat fungal infections. However, clinical evidence of its use in patients with renal dysfunction, especially those receiving renal replacement therapy (RRT), is limited. Therefore, we evaluated the usage and occurrence of adverse reactions during L-AMB therapy in patients undergoing RRT. METHODS: Using claims data and laboratory data, we retrospectively evaluated patients who were administered L-AMB. The presence of comorbidities, mortality rate, treatment with L-AMB and other anti-infective agents, and the incidence of adverse reactions were compared between patients receiving RRT, including continuous renal replacement therapy (CRRT) and maintenance hemodialysis (HD), and those that did not receive RRT. RESULTS: In total, 900 cases met the eligibility criteria: 24, 19, and 842 cases in the maintenance HD, CRRT, and non-RRT groups, respectively. Of the patients administered L-AMB, mortality at discharge was higher for those undergoing either CRRT (15/19; 79%) or maintenance HD (16/24; 67%) than for those not receiving RRT (353/842; 42%). After propensity score matching, the average daily and cumulative dose, treatment duration, and dosing interval for L-AMB were not significantly different between patients receiving and not receiving RRT. L-AMB was used as the first-line antifungal agent for patients undergoing CRRT in most cases (12/19; 63%). Although the number of subjects was limited, the incidence of adverse events did not markedly differ among the groups. CONCLUSION: L-AMB may be used for patients undergoing maintenance HD or CRRT without any dosing, duration, or interval adjustments.

9.
Sci Rep ; 10(1): 15033, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929112

RESUMO

Liposomal amphotericin B (L-AMB) is a broad-spectrum antifungal drug that is used to treat fungal infections. However, clinical evidence of its use in patients with renal failure is limited. Here, we aimed to identify factors associated with acute kidney injury (AKI) in patients administered L-AMB. We retrospectively utilized a combination of Diagnosis Procedure Combination data and laboratory data obtained from hospitals throughout Japan between April 2008 and January 2018. In total, 507 patients administered L-AMB were identified. After L-AMB treatment initiation, AKI, which was defined as a ≥ 1.5-fold increase within 7 days or ≥ 0.3 mg/dL increase within 2 days in serum creatinine according to the KDIGO criteria, was recognized in 37% of the total patients (189/507). The stages of AKI were stage 1 in 20%, stage 2 in 11%, and stage 3 in 7%. Five factors were associated with AKI of all stages: prior treatment with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers or carbapenem; concomitant administration of catecholamines or immunosuppressants; and ≥ 3.52 mg/kg/day of L-AMB dosing. Serum potassium < 3.5 mEq/L before L-AMB therapy was associated with severe AKI of stage 2 and 3. Altogether, these factors should be carefully considered to reduce the occurrence of AKI in patients administered L-AMB.


Assuntos
Injúria Renal Aguda/etiologia , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Micoses/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Carbapenêmicos/administração & dosagem , Catecolaminas/administração & dosagem , Creatinina/sangue , Análise Fatorial , Feminino , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Imunossupressores/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Micoses/complicações
10.
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
11.
CEN Case Rep ; 9(4): 375-379, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32506365

RESUMO

Bartter syndrome and Gitelman syndrome (GS) are autosomal recessive disorders usually caused by homozygous or compound heterozygous mutations in causative genes. In some patients, these two syndromes cannot be discriminated based on clinical features or mutation type; thus, a single disease concept, salt-losing tubulopathies (SLTs), has been used instead. Despite the existence of several SLT causative genes, cases of digenic heterozygous mutations in two different genes are extremely rare. Here, we report the case of a 36-year-old woman with renal insufficiency and hypokalemia caused by an SLT. To evaluate the SLT phenotype, we performed next-generation sequencing (NGS) with a gene panel including SLC12A3, SLC12A1, CLCNKB, and CLCNKA as well as laboratory examinations and diuretic loading tests. The results of the diuretic loading tests were consistent with a GS phenotype, while the NGS results showed that the patient had heterozygous mutations in SLC12A1 and CLCNKB. Both genes have been associated with BS, suggesting that the SLT was caused by digenic heterozygous mutations in two different genes. To date, only a few SLT cases caused by digenic heterozygous mutations in two different genes have been reported. The digenic SLT phenotype in the patient was presumably accelerated by moderate renal insufficiency.

12.
Med Mycol ; 58(7): 958-964, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32060526

RESUMO

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.


Assuntos
Antígenos de Fungos/sangue , Líquido da Lavagem Broncoalveolar/microbiologia , Técnicas e Procedimentos Diagnósticos , Diagnóstico Precoce , Mucormicose/sangue , Mucormicose/diagnóstico , Rhizopus/isolamento & purificação , Animais , Humanos , Camundongos
14.
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
15.
Int J Artif Organs ; 43(3): 150-156, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31623507

RESUMO

INTRODUCTION: Hemodialysis patients with atrial fibrillation are at high risk for stroke. Intravenous recombinant tissue plasminogen activator is considered for acute ischemic stroke. However, recombinant tissue plasminogen activator therapy is contraindicated for some hemodialysis patients with atrial fibrillation. These patients and those who have received recombinant tissue plasminogen activator therapy without blood flow recovery are candidates for endovascular therapy. METHODS AND RESULTS: Three hemodialysis patients with atrial fibrillation received endovascular therapy for acute cerebral infarction. Cerebrovascular incident occurred during or after hemodialysis in two of these patients. All three patients achieved successful recanalization after endovascular therapy. CONCLUSION: In this series, endovascular therapy showed good results without complications. More cases should be investigated to obtain more evidence of successful endovascular therapy for hemodialysis patients.


Assuntos
Fibrilação Atrial/complicações , Procedimentos Endovasculares/métodos , Falência Renal Crônica , Diálise Renal , Acidente Vascular Cerebral , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Terapia Trombolítica/métodos , Resultado do Tratamento
16.
PLoS One ; 14(10): e0224111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31639169

RESUMO

The effect of statin on hemodialysis patients is controversial. Although previous large-scale studies did not clarify its effect in this population, recent studies suggest that statins could be useful in reducing the risk of cardiovascular events and all-cause mortality in specific groups of patients undergoing hemodialysis. The aforementioned large-scale studies included a small percentage of Asians, and few studies have investigated the effects of statins in Asians undergoing hemodialysis. Thus, we investigated the benefits of statins in patients undergoing maintenance hemodialysis at a single center in Japan. We obtained demographic, clinical, and hemodialysis data of all patients who underwent maintenance hemodialysis at the Nagasaki Renal Center between July 2011 and June 2012. Patients were followed-up until June 2018. We studied 339 patients, of which 51 (15.0%) were prescribed pitavastatin. The mean observation period was 4.1±2.3 years, 43% were women, and the median hemodialysis vintage at baseline was 4.7 years. During the follow-up, 198 patients (58%) died, of which 22 (43%) were prescribed pitavastatin and 176 (61%) were not prescribed any statins. After propensity score matching based on age, sex, dialysis vintage, dialysis time, diabetes mellitus, ischemic heart disease, dry weight, left ventricular ejection fraction, and serum albumin, an intergroup comparison between those who received statins and those who did not (44 patients in each group) showed significant differences in survival rate based on the log-rank test (P<0.05). Although the causes of death did not differ significantly between groups, deaths due to cardiovascular events, infections, and cancer were fewer in the group prescribed statins. Our results suggest that statins may reduce mortality in Japanese patients undergoing maintenance hemodialysis. Although potential residual confounders exist, statins may have an influence on the reduction in the incidence of cardiovascular events, infections, and cancer. Nevertheless, further studies are required to prove this hypothesis.


Assuntos
Insuficiência Cardíaca/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Falência Renal Crônica/terapia , Neoplasias/mortalidade , Diálise Renal/efeitos adversos , Idoso , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Masculino , Neoplasias/etiologia , Neoplasias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Int J Mol Sci ; 20(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382656

RESUMO

Chronic kidney disease (CKD) is characterized by kidney damage with proteinuria, hematuria, and progressive loss of kidney function. The final stage of CKD is known as end-stage renal disease, which usually indicates that approximately 90% of normal renal function is lost, and necessitates renal replacement therapy for survival. The most widespread renal replacement therapy is dialysis, which includes peritoneal dialysis (PD) and hemodialysis (HD). However, despite the development of novel medical instruments and agents, both dialysis procedures have complications and disadvantages, such as cardiovascular disease due to excessive blood fluid and infections caused by impaired immunity. Periodontal disease is chronic inflammation induced by various pathogens and its frequency and severity in patients undergoing dialysis are higher compared to those in healthy individuals. Therefore, several investigators have paid special attention to the impact of periodontal disease on inflammation-, nutrient-, and bone metabolism-related markers; the immune system; and complications in patients undergoing dialysis. Furthermore, the influence of diabetes on the prevalence and severity of manifestations of periodontal disease, and the properties of saliva in HD patients with periodontitis have been reported. Conversely, there are few reviews discussing periodontal disease in patients with dialysis. In this review, we discuss the available studies and review the pathological roles and clinical significance of periodontal disease in patients receiving PD or HD. In addition, this review underlines the importance of oral health and adequate periodontal treatment to maintain quality of life and prolong survival in these patients.


Assuntos
Falência Renal Crônica/epidemiologia , Doenças Periodontais/epidemiologia , Diálise Peritoneal/efeitos adversos , Diálise Renal/efeitos adversos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/microbiologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/imunologia , Falência Renal Crônica/microbiologia , Saúde Bucal , Doenças Periodontais/complicações , Doenças Periodontais/imunologia , Doenças Periodontais/microbiologia , Qualidade de Vida
18.
Int J Mol Sci ; 20(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336777

RESUMO

Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.


Assuntos
Transplante de Rim/efeitos adversos , Doenças Periodontais/etiologia , Insuficiência Renal Crônica/complicações , Biomarcadores , Comorbidade , Suscetibilidade a Doenças , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Transplante de Rim/métodos , Estresse Oxidativo , Doenças Periodontais/metabolismo , Doenças Periodontais/patologia , Insuficiência Renal Crônica/terapia
19.
Sci Rep ; 9(1): 9331, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249356

RESUMO

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF) can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Micafungina/farmacologia , Fibrose Peritoneal/complicações , Peritonite/complicações , Peritonite/microbiologia , Animais , Biomarcadores , Citocinas , Modelos Animais de Doenças , Histocitoquímica , Humanos , Camundongos , Fibrose Peritoneal/patologia , Peritonite/tratamento farmacológico , Peritonite/patologia , Prognóstico , Resultado do Tratamento
20.
BMC Nephrol ; 20(1): 210, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174486

RESUMO

BACKGROUND: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient's prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. METHODS: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. RESULTS: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005) had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001). CONCLUSIONS: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient's calcium level.


Assuntos
Cálcio/sangue , Hemorragia Cerebral , Falência Renal Crônica , Diálise Renal , Estudos de Casos e Controles , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal/efeitos adversos , Diálise Renal/métodos
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