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1.
J Ren Nutr ; 29(1): 39-47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30097326

RESUMO

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.


Assuntos
Anemia Ferropriva/epidemiologia , Cardiomegalia/epidemiologia , Falência Renal Crônica/epidemiologia , Idoso , Comorbidade , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Prevalência
2.
Am J Nephrol ; 47(5): 325-332, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29779028

RESUMO

BACKGROUND: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). METHODS: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. RESULTS: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. CONCLUSION: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal/fisiologia , Hiperparatireoidismo Secundário/prevenção & controle , Insuficiência Renal Crônica/dietoterapia , Animais , Modelos Animais de Doenças , Progressão da Doença , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Masculino , Hormônio Paratireóideo/sangue , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Ratos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Resultado do Tratamento
3.
Semin Dial ; 31(5): 519-527, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29738093

RESUMO

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.


Assuntos
Injúria Renal Aguda/epidemiologia , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Doenças Cardiovasculares/etiologia , Estado Terminal/mortalidade , Estado Terminal/terapia , Humanos , Incidência , Insuficiência Renal Crônica/etiologia , Fatores de Risco
4.
Clin Exp Nephrol ; 22(5): 985-1045, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30039479

RESUMO

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention is necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.


Assuntos
Injúria Renal Aguda/terapia , Diálise Renal , Humanos , Japão , Nefrologia , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Substituição Renal
5.
JAMA ; 320(22): 2325-2334, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30535217

RESUMO

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.


Assuntos
Hidroxicolecalciferóis/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Idoso , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Hidroxicolecalciferóis/farmacologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Receptores de Calcitriol/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Método Simples-Cego
6.
Clin Exp Nephrol ; 21(5): 825-834, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27844184

RESUMO

BACKGROUND: Nausea is a major uremic symptom and a frequent indication for starting dialysis. However, preventive medication for uremic nausea has not yet been identified. Vitamin D receptor activators (VDRAs) may prevent uremic nausea via their pleiotropic actions. The objective of this study was to explore whether VDRA administration during the predialysis period is associated with a reduced prevalence of uremic nausea just prior to beginning dialysis. METHODS: A multicenter, retrospective, cross-sectional study was performed to identify a medication to prevent uremic nausea. Patients with stage 5 CKD who were followed-up over 3 months were included. The primary outcomes examined were the prevalence of uremic nausea, congestive heart failure (CHF), and intractable edema at dialysis commencement. The predictor variable was VDRA use during the predialysis period. RESULTS: One thousand five hundred and thirty six patients who had just begun dialysis in nine Japanese facilities between January 2006 and October 2013 were included. Two hundred and thirty (15.0%) patients had commenced dialysis because of uremic nausea, and three hundred and ninety two (25.5%) patients had been using VDRAs before initiating dialysis. Logistic regression analysis showed that, among the medications examined in this study, only VDRA use was independently associated with a lower frequency of uremic nausea (OR 0.512, 95% CI 0.347-0.738, P = 0.0003). On the other hand, CHF and intractable edema were not associated with VDRA administration. CONCLUSION: Use of VDRAs during the predialysis period was the only factor associated with a lower prevalence of uremic nausea, suggesting that VDRAs may prevent uremic nausea in patients with advanced CKD.


Assuntos
Antieméticos/uso terapêutico , Náusea/prevenção & controle , Receptores de Calcitriol/agonistas , Insuficiência Renal Crônica/tratamento farmacológico , Uremia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antieméticos/efeitos adversos , Distribuição de Qui-Quadrado , Estudos Transversais , Edema/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Náusea/diagnóstico , Náusea/epidemiologia , Náusea/metabolismo , Razão de Chances , Prevalência , Receptores de Calcitriol/metabolismo , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Estudos Retrospectivos , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Uremia/diagnóstico , Uremia/epidemiologia , Uremia/metabolismo
7.
Growth Factors ; 34(5-6): 196-202, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28095739

RESUMO

The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220+ CD21/CD35+ CD1d+ CD43- marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c+ CD45R/B220+ CD11b- CD8α- were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23-Klotho signaling could play a biological or immunological role in the spleen.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glucuronidase/metabolismo , Baço/metabolismo , Animais , Linfócitos B/metabolismo , Células Dendríticas/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/genética , Proteínas Klotho , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Baço/citologia
8.
Clin Nephrol ; 80(1): 47-52, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23557791

RESUMO

AIMS: Both steroid pulse (SP) monotherapy and the combination of tonsillectomy and SP therapy (TSP) are effective for achieving clinical remission (CR), defined as negative hematuria and proteinuria, in patients with IgA nephropathy (IgAN). The role of tonsillectomy in the treatment of IgAN has been analyzed only from the aspect of CR or renal survival after TSP treatment, so there is no evidence of its effect on the relapse after CR. METHODS: We retrospectively investigated relapse (re-appearance of urinary abnormalities) from CR after TSP or SP monotherapy in 62 IgAN patients (mean follow-up, 70.1 ± 35.3 months). The SP therapy comprised 0.5 g methylprednisolone administered intravenously on 3 consecutive days followed by oral prednisolone (30 mg/day) on 4 consecutive days, with the course repeated 3 times. Oral prednisolone (30 mg/day) was then given on alternative days and gradually tapered and finished over 1 year. Tonsillectomy was performed either before or within 6 months of starting SP therapy. RESULTS: At baseline, the mean age was 34.6 years, the mean serum creatinine (Cr) level was 0.9 mg/dl, and the mean level of proteinuria was 876 mg/day. There were no differences between the TSP group (41 patients) and SP monotherapy group (21 patients). In total, 24 of the TSP and 10 of the SP patients achieved CR. Of the 34 patients who achieved CR, 13 relapsed after TSP or SP monotherapy. Using Kaplan-Meier analysis, tonsillectomy was associated with a lower incidence of relapse from CR after treatment (p = 0.045). Multivariate Cox regression analysis revealed that tonsillectomy reduced the rate of from CR after SP therapy. CONCLUSION: Tonsillectomy was associated with a reduction in the relapse rate from CR after SP therapy in IgAN patients.


Assuntos
Anti-Inflamatórios/administração & dosagem , Glomerulonefrite por IGA/terapia , Metilprednisolona/administração & dosagem , Tonsilectomia , Adulto , Anti-Inflamatórios/uso terapêutico , Terapia Combinada , Creatinina/sangue , Feminino , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/urina , Humanos , Estimativa de Kaplan-Meier , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Prednisolona/administração & dosagem , Modelos de Riscos Proporcionais , Proteinúria/urina , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Adulto Jovem
9.
Ann Intensive Care ; 13(1): 42, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37184598

RESUMO

BACKGROUND: Patients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF. METHODS: This prospective observational study was conducted in seven university-affiliated ICUs. For urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma IL-6 measurements, samples were collected at initiation, 24 h, 48 h after, and CVVHDF discontinuation in adult patients with severe AKI. The outcomes were deaths during CVVHDF and CVVHDF dependence. RESULTS: A total number of 133 patients were included. Twenty-eight patients died without CVVHDF discontinuation (CVVHDF nonsurvivors). Urinary NGAL and plasma IL-6 at the CVVHDF initiation were significantly higher in CVVHDF nonsurvivors than in survivors. Among 105 CVVHDF survivors, 70 patients were free from renal replacement therapy (RRT) or death in the next 7 days after discontinuation (success group), whereas 35 patients died or needed RRT again (failure group). Urinary NGAL at CVVHDF discontinuation was significantly lower in the success group (93.8 ng/ml vs. 999 ng/ml, p < 0.01), whereas no significant difference was observed in plasma IL-6 between the groups. Temporal elevations of urinary NGAL levels during the first 48 h since CVVHDF initiation were observed in CVVHDF nonsurvivors and those who failed in CVVHDF discontinuation. CONCLUSIONS: Urinary NGAL at CVVHDF initiation and discontinuation was associated with mortality and RRT dependence, respectively. The serial changes of urinary NGAL might also help predict the prognosis of patients with AKI on CVVHDF.

10.
Nephrol Dial Transplant ; 27(3): 1050-4, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21771755

RESUMO

BACKGROUND: Increased blood levels of fibroblast growth factor-23 (FGF-23) are associated with increased mortality. We evaluated the effect of combined therapy with lanthanum carbonate (LaC), a new phosphate binder and calcium carbonate (CaC) on serum levels of phosphate and FGF-23. METHODS: This was a single-arm, open-label, multicenter study. Hemodialysis patients with a serum phosphate level >6.0 mg/dL despite CaC therapy were also given LaC for 16 weeks at a dose up to 2250 mg/day. CaC was given at a fixed dose throughout the 16-week period. RESULTS: Of 42 patients enrolled, 36 completed the 16-week study. The serum phosphate level showed a significant decrease from 6.9 ± 1.4 mg/dL at week 0 to 5.5 + 1.2 mg/dL at week 16 (-20.0%, P < 0.05). The median FGF-23 level showed a significant decrease from 8250 ng/L at week 0 to 5000 ng/L at week 16 (-39.2%, P < 0.05). In contrast, corrected serum calcium and the serum parathyroid hormone level showed no significant changes. A significant positive correlation (r = 0.442, P = 0.007) was demonstrated between the percent reduction of serum FGF-23 and that of serum phosphate. CONCLUSION: Both serum phosphate and FGF-23 levels were significantly decreased by treatment with LaC plus CaC.


Assuntos
Carbonato de Cálcio/uso terapêutico , Cálcio/sangue , Fatores de Crescimento de Fibroblastos/sangue , Hiperfosfatemia/sangue , Hiperfosfatemia/tratamento farmacológico , Lantânio/uso terapêutico , Fosfatos/sangue , Adulto , Idoso , Antiácidos/uso terapêutico , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Falência Renal Crônica , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Diálise Renal , Resultado do Tratamento , Adulto Jovem
11.
Clin Exp Nephrol ; 16(5): 672-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22926697

RESUMO

Acute kidney injury (AKI) is characterized by a rapid decrease in kidney function and increased serum creatinine. The term acute renal failure (ARF) has been applied to such clinical manifestations. Despite several advances in the treatment of ARF, such as pharmacologic treatment and renal replacement therapy (RRT), the mortality rate among patients with ARF has changed little over the past four decades. It is widely recognized that ARF is associated with significantly increased morbidity and mortality especially in critically ill patients with ARF requiring RRT. Therefore, in order to improve outcomes in ARF patients, a new concept of AKI has been proposed. Recently the paradigm shift from ARF to AKI has been received by the research and clinical communities. In this review we will discuss the therapeutic strategies for AKI and focus on its management with an emphasis on RRT.


Assuntos
Injúria Renal Aguda/terapia , Creatinina/urina , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , Proteínas de Fase Aguda , Fator Natriurético Atrial/uso terapêutico , Biomarcadores/sangue , Dopamina/uso terapêutico , Taxa de Filtração Glomerular , Humanos , Lipocalina-2 , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Terapia de Substituição Renal/métodos
12.
Clin Calcium ; 22(10): 1557-66, 2012 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-23023637

RESUMO

Hyperphosphatemia is the most common complication among patients with chronic kidney disease. Large scale observational studies have identified hyperphosphatemia as an independent risk factor for cardiovascular disease and mortality in hemodialysis patients. The combination therapy of dietary phosphate restriction and phosphate removal with dialysis treatment is still not enough to achieve the serum phosphate within the target. Thererfore, phosphate binders is necessary for many dialyzed patients with hyperphosphatemia. In this article, we will review the detail and development of phosphate binders and recommendation for clinical practice in hyperphosphatemia.


Assuntos
Hiperfosfatemia/terapia , Fosfatos/metabolismo , Insuficiência Renal Crônica/terapia , Quelantes/uso terapêutico , Humanos , Hiperfosfatemia/complicações , Rim/metabolismo , Rim/fisiopatologia , Fosfatos/análise , Fosfatos/química , Diálise Renal
13.
Sci Rep ; 11(1): 4600, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633262

RESUMO

The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m2. The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.


Assuntos
Equilíbrio Ácido-Base , Falência Renal Crônica/diagnóstico , Desequilíbrio Ácido-Base/diagnóstico , Idoso , Bicarbonatos/sangue , Cloretos/sangue , Estudos Transversais , Reações Falso-Negativas , Feminino , Humanos , Falência Renal Crônica/metabolismo , Contagem de Leucócitos , Masculino , Sensibilidade e Especificidade
14.
Am J Physiol Renal Physiol ; 299(5): F1212-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20739393

RESUMO

Fibroblast growth factor 23 (FGF23), which is primarily produced by osteocytes in bone, regulates renal phosphate excretion and 1α,25-dihydroxyvitamin D [1,25(OH)(2)D(3)] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating serum FGF23, but the direct effect on circulating FGF23 levels in renal insufficiency is still unclear. To identify the major regulator of FGF23 synthesis in renal insufficiency, we compared the effect of parathyroid hormone (PTH) and 1,25(OH)(2)D(3) on FGF23 synthesis in the calvariae of normal rats with that of uremic rats in vitro. 1,25(OH)(2)D(3) treatment significantly increased the FGF23 concentration in the medium from both groups, but the degree of increase in the uremic group was markedly higher than in the control group. A significant increase in FGF23 mRNA expression occurred as early as 4 h after treatment and reached the maximum within 8 h in the uremic group, whereas in the normal group a significant increase in FGF23 mRNA expression was observed only at 8 h. In addition, the expression of vitamin D receptor (VDR) mRNA in the calvariae of uremic rats was markedly higher than in normal rats. However, in neither group did PTH treatment affect the medium FGF23 concentration or the FGF23 mRNA levels. These results suggest that FGF23 synthesis in bone is regulated by 1,25(OH)(2)D(3) directly, not by PTH, and that increased VDR mRNA expression induced the relatively swift and strong response in the uremic group.


Assuntos
Osso e Ossos/metabolismo , Calcitriol/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Fatores de Crescimento de Fibroblastos/biossíntese , Hormônio Paratireóideo/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/genética , Falência Renal Crônica/metabolismo , Masculino , Nefrectomia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Crânio/efeitos dos fármacos , Crânio/metabolismo , Uremia/metabolismo
15.
Ren Fail ; 32(2): 214-23, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20199184

RESUMO

BACKGROUND: Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown. METHODS: We produced a rat model for vascular calcification with hyperphosphatasemia and hyperparathyroidism, performing a 5/6 nephrectomy and providing a high-phosphorus, low-calcium diet for eight weeks. We examined mRNA obtained from the calcified aortae using microarray analysis, and searched for alterations in gene expression specifically in the calcified lesions. RESULTS: Medial calcification was demonstrated in the abdominal aorta of 12 out of 42 hyperparathyroidism rats. In the aortae of hyperparathyroid rats with vascular calcification, the genes for heparan sulfate proteoglycans, including perlecan, were found to be down-regulated using microarray analysis and real time PCR. Immunohistochemistry also demonstrated reduced production of perlecan in the aortae of hyperparathyroid rats. DISCUSSION: Perlecan is a major component of the vascular wall basement membrane and may play a role in protecting vascular smooth muscle cells from inflammatory cells and various toxins. It has also been reported that heparan sulfate chains may inhibit osteogenesis. Our findings indicate that perlecan may protect vascular smooth muscle cells from various factors that promote vascular calcification. CONCLUSIONS: It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification.


Assuntos
Aorta Abdominal/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Hiperparatireoidismo Secundário/metabolismo , Animais , Aorta Abdominal/patologia , Biomarcadores/sangue , Calcinose/metabolismo , Calcinose/patologia , Técnicas de Cultura de Células , Dieta , Modelos Animais de Doenças , Proteoglicanas de Heparan Sulfato/genética , Hiperparatireoidismo Secundário/patologia , Hiperfosfatemia/metabolismo , Hiperfosfatemia/patologia , Imuno-Histoquímica , Masculino , Análise em Microsséries , Músculo Liso Vascular/citologia , Nefrectomia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
17.
Clin Calcium ; 20(7): 1096-102, 2010 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-20585189

RESUMO

Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate-binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Nefropatias/complicações , Lantânio/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Doença Crônica , Desenho de Fármacos , Lantânio/efeitos adversos , Lantânio/farmacologia , Diálise Renal/efeitos adversos , Risco
18.
Immun Inflamm Dis ; 8(2): 228-235, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32180373

RESUMO

INTRODUCTION: We previously reported that fibroblast growth factor 23 (FGF23)-klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23-klotho signaling pathway in immune cells may occur in these patients. METHODS: We analyzed the number of klotho-positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme-linked immunosorbent assay. RESULTS: The number of klotho-positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients. CONCLUSIONS: We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti-inflammatory and immunosuppressive factor.


Assuntos
Proteína ADAM17/sangue , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/sangue , Leucócitos Mononucleares/metabolismo , Insuficiência Renal Crônica/genética , Proteína ADAM17/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Linhagem Celular , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/genética , Humanos , Hospedeiro Imunocomprometido , Proteínas Klotho , Masculino , Camundongos , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Uremia/sangue , Uremia/genética
19.
Int J Clin Pharm ; 42(2): 635-641, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32026357

RESUMO

Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients with chronic kidney disease is correlated with cardiovascular disease and mortality. Objective This study was performed to determine whether short- and long-acting erythropoiesis-stimulating agents are correlated with the pre-haemodialysis haemoglobin level in patients with chronic kidney disease. Setting This study was conducted at the Blood Purification Center in Wakayama Medical University. Method We enrolled 364 patients undergoing initiation of haemodialysis from January 2009 to June 2015 and analysed them for > 3 months prior to the initiation of haemodialysis. In total, 168 patients were included in the final analysis based on the inclusion and exclusion criteria. Main outcome measures The correlation of the haemoglobin level at the initiation of haemodialysis with various factors according to the type of erythropoiesis-stimulating agent used. Results The median haemoglobin level was 8.8 g/dL, and long-acting erythropoiesis-stimulating agents were used by 69.6% of the patients. Long-acting erythropoiesis-stimulating agents were used significantly more often in patients with high than low haemoglobin levels. The haemoglobin levels at the initiation of haemodialysis and 1 month prior tended to be significantly higher in patients taking long-than short-acting erythropoiesis-stimulating agents. The serum levels of iron and albumin and the use of long-acting erythropoiesis-stimulating agents were independently correlated with the haemoglobin level at the initiation of haemodialysis in the multivariate regression analysis. In addition, the left ventricular mass index was significantly correlated with the haemoglobin level at the initiation of haemodialysis. Conclusion Long-acting erythropoiesis-stimulating agents were correlated with higher haemoglobin levels and may be more useful for patients with a low left ventricular mass index at the initiation of haemodialysis.


Assuntos
Eritropoese/efeitos dos fármacos , Hematínicos/uso terapêutico , Hemoglobinas/metabolismo , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Eritropoese/fisiologia , Feminino , Hematínicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/tendências , Estudos Retrospectivos
20.
Hemodial Int ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33090624

RESUMO

INTRODUCTION: Risks of mortality and cardiovascular disease (CVD) are significantly higher in hemodialysis (HD) patients than in the general population, where dyslipidemia is an established risk factor for CVD and mortality. There is no clear conclusion, however, whether dyslipidemia is a significant risk factor for CVD and mortality in HD patients. Similarly, the association between the polyunsaturated fatty acids (PUFAs) and the mortality is not clear in HD patients. METHODS: We retrospectively investigated mortality and CVD events in 420 HD patients. We classified patients into high- and low-lipid groups depending on their lipid levels. Survival rates were calculated using the Kaplan-Meier analysis and evaluated by the log-rank test. The risk estimates were computed using a multivariate Cox proportional hazard analysis. FINDINGS: During their follow-up (June 2011 to June 2016), 151 patients died (37 of CVD), and 112 patients experienced new CVD events. On Kaplan-Meier analysis, the number of all-cause deaths and CVD events were significantly higher in the low HDL-cholesterol group (P < 0.01, log-rank test). Similarly, the number of all-cause deaths was significantly higher in the high eicosapentaenoic acid/arachidonic acid ratio group (P < 0.01, log-rank test). Multivariate Cox proportional analysis showed that HDL-cholesterol was a significant prognostic indicator for new onset of CVD events (low: 0, high: 1, hazard ratio 0.66, 95% confidence interval 0.44-0.97; P = 0.04). DISCUSSION: In HD patients, LDL-cholesterol and non-HDL-cholesterol levels are not associated with mortality or CVD events. The HDL-cholesterol level, however, is an independent predictor of new CVD events even in HD patients.

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