RESUMO
BACKGROUND: This study aims to compare patency rates of the 0- and 30-s (sec) balloon dilation time in hemodialysis (HD) patients with restenosis after percutaneous transluminal angioplasty (PTA). METHODS: The patients who underwent PTA within 6 months for failed arteriovenous fistula at the forearm were randomly assigned the 0-s or 30-s dilation time group. Effect of dilation time on the 3- and 6-month patency rates after PTA was examined. RESULTS: Fifty patients were enrolled in this study. The 3-month patency rate in the 30-s dilation group was better than that in the 0-s dilation group (P = 0.0050), while the 6-month patency rates did not show a significant difference between the two groups (P = 0.28). Cox's proportional hazard model revealed that 30-s of inflation time (hazard ratio 0.027; P = 0.0072), diameter of the proximal (hazard ratio 0.32; P = 0.031), and dilation pressure (hazard ratio 0.63; P = 0.014) were associated with better 3-month patency. Dilation pressure between previous and present PTA did not differ in the 0-s (P = 0.15) and 30-s dilation groups (P = 0.16). The 6-month patency rate of the present PTA in the 30-s dilation group was higher than that of the previous PTA (P = 0.015). The visual analog scale did not differ between the two groups (P = 0.51). CONCLUSION: The presenting data suggest that 30-s dilation potentially results in a better 3-month patency rate than 0-s dilation in HD patients with restenosis after PTA.
Assuntos
Angioplastia com Balão , Derivação Arteriovenosa Cirúrgica , Oclusão de Enxerto Vascular , Diálise Renal , Grau de Desobstrução Vascular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Fatores de Tempo , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/terapia , Modelos de Riscos Proporcionais , Resultado do Tratamento , Recidiva , Adulto , Antebraço/irrigação sanguíneaRESUMO
BACKGROUND: The effect of dialytic modality at the start of renal replacement therapy on prognosis is controversial. METHODS: This multicenter, prospective cohort study included patients undergoing incident hemodialysis (HD) (n = 646) and peritoneal dialysis (PD) (n = 72). We excluded patients who lacked complete data for 3 months. One-to-one propensity score (PS) matching was performed before between-group comparison of survival rates (Kaplan-Meier method and log-rank test) and identification of factors affecting prognosis (Cox proportional-hazards regression analysis). RESULTS: We enrolled 621 and 71 patients undergoing HD and PD, respectively (overall mean ± standard deviation age: 74 ± 13 years); 20% had cardiovascular disease (CVD). The median follow-up period was 41 (interquartile range 24-66) months. Following PS matching, we analyzed 65 patients undergoing HD and PD each. The 5-year overall survival rates did not differ between the groups (P = 0.97). The PD group exhibited a better CVD-related survival rate (P = 0.03). PD yielded adjusted hazard ratios for all-cause and CVD-related mortality of 0.99 (95% confidence interval [CI] 0.49-1.99, P = 0.97) and 3.92 (95% CI 1.05-14.7, P = 0.04), respectively. Age (P < 0.001) and the use of a central venous catheter (CVC) at dialytic initiation (P = 0.02) were independent risks for all-cause mortality; whereas, only the use of a CVC (P = 0.01) was an independent risk for CVD-related mortality. CONCLUSION: Although no differences were observed in overall survival, CVD-related survival may be better with dialytic initiation with PD than with HD.
Assuntos
Doenças Cardiovasculares , Falência Renal Crônica , Diálise Peritoneal , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diálise Renal , Taxa de Sobrevida , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologia , Estudos Prospectivos , Pontuação de Propensão , Estimativa de Kaplan-Meier , Diálise Peritoneal/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Risco , Estudos RetrospectivosRESUMO
The transcription factors hypoxia-inducible factor-1α and -2α (HIF-1α/2α) are the major regulators of the cellular response to hypoxia and play a key role in renal fibrosis associated with acute and chronic kidney disease. Jumonji domain-containing 1a (JMJD1A), a histone H3 lysine 9 (H3K9) demethylase, is reported to be an important target gene of HIF-α. However, whether JMJD1A and H3K9 methylation status play a role in renal fibrosis is unclear. Here, we investigated the involvement of HIF-α, JMJD1A, and monomethylated/dimethylated H3K9 (H3K9me1/H3K9me2) levels in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Intraperitoneal administration of FG4592, an inhibitor of HIF-α prolyl hydroxylase, which controls HIF-α protein stability, significantly attenuated renal fibrosis on days 3 and 7 following UUO. FG4592 concomitantly increased JMJD1A expression, decreased H3K9me1/me2 levels, reduced profibrotic gene expression, and increased erythropoietin expression in renal tissues of UUO mice. The beneficial effects of FG4592 on renal fibrosis were inhibited by the administration of JMJD1A-specific siRNA to mice immediately following UUO. Incubation of normal rat kidney-49F and/or -52E cells with transforming growth factor-ß1 (TGF-ß1) in vitro resulted in upregulated expression of α-smooth muscle actin and H3K9me1/me2, and these effects were inhibited by cotreatment with FG4592. In contrast, FG4592 treatment further enhanced the TGF-ß1-stimulated upregulation of JMJD1A but had no effect on TGF-ß1-stimulated expression of the H3K9 methyltransferase euchromatic histone-lysine N-methyltransferase 2. Collectively, these findings establish a crucial role for the HIF-α1/2-JMJD1A-H3K9me1/me2 regulatory axis in the therapeutic effect of FG4592 in renal fibrosis.NEW & NOTEWORTHY Using a mouse model of renal fibrosis and transforming growth factor-ß1-stimulated rat cell lines, we show that treatment with FG4592, an inhibitor of hypoxia-inducible factor-1α and -2α (HIF-1α/2α) prolyl hydroxylase decreases renal fibrosis and concomitantly reduces methylated lysine 9 of histone H3 (H3K9) levels via upregulation of Jumonji domain-containing 1a (JMJD1A). The results identify a novel role for the HIF-1α/2α-JMJD1A-H3K9 regulatory axis in suppressing renal fibrosis.
Assuntos
Eritropoetina , Nefropatias , Inibidores de Prolil-Hidrolase , Obstrução Ureteral , Ratos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Inibidores de Prolil-Hidrolase/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Histonas/metabolismo , Lisina/metabolismo , RNA Interferente Pequeno , Actinas/metabolismo , Fibrose , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológico , Nefropatias/complicações , Hipóxia/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Eritropoetina/metabolismoRESUMO
BACKGROUND: The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in this study, we investigate whether high NT-proBNP levels are associated with future stroke events in this population. METHODS: This was a multicenter prospective observational study with post hoc analysis. Baseline NT-proBNP levels were measured at the first HD session of the week and classified into tertiles (first tertile: < 2255 pg/mL; second tertile: ≥ 2255 and < 5657 pg/mL; third tertile: ≥ 5657 pg/mL). Overall hospitalization-free survival rates were compared using the Kaplan-Meier method. The association between NT-proBNP level and hospitalization for stroke was assessed using the multivariate Cox proportional hazards models. RESULTS: During a 5-year follow-up of 1,229 patients, 103 (8.4%) were hospitalized and 23 (1.9%) died from stroke. The hospitalization-free survival rate for ischemic stroke was lowest in the third tertile (P < 0.01). The crude hazard ratio (HR) of hospitalization was higher in the third tertile compared with the first tertile for both ischemic stroke (HR: 3.92; 95% confidence interval [CI] 2.08-7.37; P < 0.01) and hemorrhagic stroke (HR: 3.75; 95% CI 1.35-10.43; P = 0.01). On multivariate Cox hazard analysis, the adjusted HRs for ischemic stroke were higher in the third tertile. The hospitalization-free survival rates for hemorrhagic stroke and the adjusted HRs did not differ significantly. CONCLUSIONS: Elevated NT-proBNP level was associated with hospitalization for ischemic stroke, suggesting that NT-proBNP level is a valid biomarker for predicting hospitalization for ischemic stroke in HD outpatients.
Assuntos
Insuficiência Cardíaca , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Humanos , Japão/epidemiologia , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Diálise Renal , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: A few previous clinical studies have shown that chloride (Cl) contributes to the progression and development of hypertension or proteinuria. Therefore, we aimed to determine whether hyperchloremia is associated with hypertension or proteinuria in patients with chronic kidney disease (CKD) and to define the relationships between the reduction in serum Cl concentration associated with CKD treatment and improvements in hypertension and/or proteinuria. METHODS: We performed a retrospective observational study of new or referred patients with CKD who had hyperchloremia, moderate proteinuria, renal dysfunction, and hypertension. Patients taking medication for metabolic acidosis or with a history of dialysis were excluded. The participants' systolic and diastolic blood pressure (BP), serum sodium (Na) and Cl concentrations, and urinary protein (UP) concentration were measured at baseline and after 1 month of CKD treatment. RESULTS: Fifty-one patients with CKD were included in the study. Their serum Cl concentration independently correlated with sBP and UP at baseline (P = 0.022 and P = 0.033, respectively). After 1 month's CKD treatment, their serum Na and Cl concentrations, sBP, and UP were significantly lower. The change in sBP during the month (ΔsBP) correlated with the change in serum Cl (ΔCl) (P = 0.012) but not with the change in serum Na. Multivariate analysis showed that ΔsBP was independently associated with ΔCl (P = 0.029). CONCLUSIONS: Hyperchloremia is an independent predictor of hypertension and proteinuria for patients with CKD.
Assuntos
Hipertensão , Insuficiência Renal Crônica , Desequilíbrio Hidroeletrolítico , Pressão Sanguínea , Humanos , Proteinúria/complicações , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnósticoRESUMO
AIM: The effect of convection volume (CV) in patients on pre-dilution online haemodiafiltration (Pre-OL-HDF) was evaluated. METHODS: We conducted a retrospective, cross-sectional study in 126 patients on Pre-OL-HDF. Dialysis conditions, laboratory data, and same day post-dialysis body composition measurements using bioimpedance spectroscopy were assessed. Patients were divided into two groups according to their CV: ≥ median value and < median value. Linear regression analyses for reduction ratios (RRs) of ß2-microglobulin and α1-microglobulin, and body composition, were conducted. RESULTS: Age, dialysis vintage, and CVs of the study patients were 64 ± 12 years, 81 (48-154) months, and 43.2 (38.5-55.9) L/session, respectively. The higher CV (≥ 43 L/session) group (n = 66) had significantly higher RRs of ß2-microglobulin and α1-microglobulin, lean tissue index, body cell mass index, total body water (TBW), extracellular water (ECW), and intracellular water (ICW) compared with the lower CV (< 43 L/session) group (n = 60, p < .01). Serum albumin and fat tissue index were not significantly different between the groups. CV/ECW, CV/TBW, and CV/ICW but not un-adjusted CV, were significant determinants for ß2-microglobulin and α1-microglobulin RRs (p < .05). Lean tissue and body cell mass indexes, but not the fat tissue index, showed significant associations with CV, and RRs of ß2-microglobulin and α1-microglobulin (p < kb.05). CONCLUSIONS: Among patients on Pre-OL-HDF, higher values in the lean tissue index and body cell mass index were observed in those with higher CV versus lower CV, and CV adjusted to body water may be useful to prescribe individualized conditions for Pre-OL-HDF.
Assuntos
Hemodiafiltração , Idoso , Composição Corporal , Convecção , Estudos Transversais , Hemodiafiltração/efeitos adversos , Hemodiafiltração/métodos , Humanos , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos , ÁguaRESUMO
The ischemia-reperfusion injury (IRI) of rat kidneys is used as a model of acute kidney injury. Salt-sensitive hypertension occurs in rats after IRI, and the distal nephrons play important roles in the development of this condition. We investigated the role of the mineralocorticoid receptor (MR) in the progression of IRI-induced salt-sensitive hypertension in rats. Fourteen days after right-side nephrectomy, IRI was induced by clamping the left renal artery, with sham surgery performed as a control. IRI rats were provided with normal water or water with 1.0% NaCl (IRI/NaCl), or they were implanted with an osmotic mini-pump to infuse vehicle or aldosterone (IRI/Aldo). Esaxerenone, a non-steroidal MR blocker (MRB), was administered to IRI/NaCl and IRI/Aldo rats for 6 weeks. MR expression increased by day 7 post-IRI. Blood pressure and urinary protein excretion increased in IRI/NaCl and IRI/Aldo rats over the 6-week period, but these effects were negated by MRB administration. The MRB attenuated the expression of the gamma-epithelial sodium channel (ENaC) and renal damage. The ENaC inhibitor, amiloride, ameliorated hypertension and renal damage in IRI/NaCl and IRI/Aldo rats. Our findings thus showed that MR upregulation may play a pivotal role in ENaC-mediated sodium uptake in rats after IRI, resulting in the development of salt-sensitive hypertension in response to salt overload or the activation of the renin-angiotensin-aldosterone system.
Assuntos
Hipertensão , Traumatismo por Reperfusão , Aldosterona/metabolismo , Animais , Pressão Sanguínea , Hipertensão/metabolismo , Rim/metabolismo , Ratos , Receptores de Mineralocorticoides/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/metabolismo , Regulação para Cima , Água/metabolismoRESUMO
Klotho is an antiaging protein reported to suppress transforming growth factor-ß1 (TGF-ß1) signaling. Aging kidneys are characterized by interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress. TGF-ß1 signaling is involved in these processes. In this study, we investigated whether klotho overexpression improves these features in the kidneys of aging mice and examined the inhibitory effect of klotho on signaling molecules related to transforming growth of TGF-ß1. Klotho transgenic (KLTG) and wild-type (WT) mice were used, and 8-wk-old and 24-mo-old mice were defined as young and aging, respectively. We found that klotho expression was decreased in aging WT mice, but it was maintained in aging KLTG mice. Klotho overexpression improved the survival of 24-mo-old mice. Although the serum Ca2+ level was significantly lower in aging KLTG mice than in aging WT mice, the serum phosphate level did not differ between these mice. Klotho overexpression attenuated the increases in blood pressure, serum blood urea nitrogen level, and serum creatinine level in aging mice. Interstitial fibrosis, accumulation of cell cycle-arrested cells, and oxidative stress did not differ between young KLTG and WT mice, but they were significantly suppressed in aging KLTG mice compared with aging WT mice. Furthermore, the expression of TGF-ß1-related signaling molecules was increased in aging WT mice, whereas it was inhibited in aging KLTG mice. These data suggest that klotho overexpression protects against kidney aging along with suppression of TGF-ß1 signaling pathways.NEW & NOTEWORTHY Klotho is considered as an antiaging protein, and its overexpression may be a candidate therapy for protection against kidney damage with advanced aging. Although multiple factors are involved in the aging process, we showed that klotho overexpression inhibited interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress in the kidneys of aging mice, suppressing transforming growth factor-ß1-related signaling pathways. The present data showed that klotho overexpression protects against age-associated kidney damage.
Assuntos
Envelhecimento/efeitos dos fármacos , Fibrose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Camundongos Transgênicos , Substâncias Protetoras/farmacologia , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed. METHODS: This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5 years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models. RESULTS: During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1 year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1 year were 4550 and 5467 ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805 ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters. CONCLUSION: NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients.
Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Renal/sangue , Insuficiência Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Diálise Renal , Insuficiência Renal/terapiaRESUMO
AIM: Assess the association and predictive value of geriatric nutritional risk index (GNRI), body composition, and bone mineral density (BMD) in haemodialysis (HD) patients. METHODS: Laboratory data, body composition parameters measured via body composition monitor, and radius, lumbar spine, femoral neck BMD measured using dual energy X-ray absorptiometry were assessed in all subjects on HD or online haemodiafiltration (HDF) at baseline. Regression analysis for GNRI, Cox proportional hazard analyses and comparison of multiple receiver operating characteristic (ROC) curves were performed. RESULTS: Among all 264 patients, age was 65 ± 12 years and dialysis vintage was 79 (39-144) months. GNRI tertile (T)1, T2, and T3 were 88 (85-91), 94 (93-95), and 98 (97-101), respectively. Patients in GNRI T1 had lower fat tissue index (FTI), lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD, but higher overhydration/extracellular fluid than patients in GNRI T2 or T3 (P < .05). GNRI was significantly associated with FTI, lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD (P < .01). GNRI was a significant predictor of 2-year all-cause mortality (HR 0.92, P < .05). Area under the ROC curve for all-cause mortality using traditional risk factors (age, sex, diabetes mellitus, cardiovascular disease, use of vasopressors for dialysis-related hypotension, and C-reactive protein) was 0.67 and changed by adding GNRI (0.78, P < .05), FTI (0.75), or femoral neck BMD (0.66), respectively. CONCLUSION: Associations between GNRI, body composition, and BMD were confirmed in HD patients. Combining GNRI with traditional risk factors improved mortality prediction in HD patients.
Assuntos
Composição Corporal , Densidade Óssea , Avaliação Geriátrica , Avaliação Nutricional , Diálise Renal , Idoso , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de RiscoRESUMO
OBJECTIVE: A high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients. METHODS: We studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston's CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted. RESULTS: The median (interquartile range) age and duration of dialysis of the participants were 67 (60-75) years and 73 (37-138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05). CONCLUSION: We have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Ferro/sangue , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Calcificação Vascular/epidemiologia , Idoso , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Feminino , Ferritinas/sangue , Ferritinas/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Diálise Renal/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Transferrina/análise , Transferrina/metabolismo , Calcificação Vascular/sangue , Calcificação Vascular/etiologia , Calcificação Vascular/patologiaRESUMO
Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD.
Assuntos
Injúria Renal Aguda/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Traumatismo por Reperfusão/terapia , Animais , Células Cultivadas , Humanos , Injeções Intra-Arteriais/métodos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Albuminuria and estimated glomerular filtration rate (eGFR) are clinically measured to evaluate the severity of chronic kidney disease (CKD). The aim of our study was to clarify the association between clinical parameters, including albuminuria and eGFR, and the risk of incident CKD in a nondiabetic population with normal range of albuminuria and eGFR. METHODS: A 10-year follow-up, retrospective cohort study involving 317 Japanese men (mean age, 42 years) with eGFR ≥ 90 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) < 30 mg/gCr was performed. Participants were free of diabetes mellitus. Multivariate logistic regression approaches were used to assess independent predictors of the incidence of CKD. RESULTS: Twenty-nine (9%) participants developed CKD (eGFR < 60 mL/min/1.73 m2 and/or UACR ≥ 30 mg/gCr) through 10 years of follow-up. At the baseline examination, age, blood pressure, UACR, and eGFR were higher in participants who developed CKD than in those without CKD. After adjustment for confounders, high-normal albuminuria (P < 0.001) and hypertension (P = 0.045) were associated with an increased incidence of CKD. From receiver-operating characteristic curves, UACR ≥ 7.0 mg/gCr was defined as high-normal albuminuria. Logistic regression analysis also showed that, in addition to presence of hypertension, UACR ≥ 7.0 mg/gCr was identified as an independent risk of incident CKD within 10 years after adjustment for age, body mass index, smoking status, and dyslipidemia [UACR: odds ratio (OR) 17.36 (95% CI 6.16-48.93, P < 0.001)]. CONCLUSION: High-normal albuminuria and hypertension are associated with incident CKD in a nondiabetic population with normal-range UACR and eGFR.
Assuntos
Albuminúria/urina , Taxa de Filtração Glomerular , Hipertensão/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Creatinina/urina , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Renal function declines with aging and is pathologically characterized by chronic inflammation and fibrosis. Renal senescence is induced not only by aging but also by various stimuli, including ischemia reperfusion injury. Recently, the accumulation of p16INK4a-positive cells in the kidney has been considered a molecular feature of renal senescence, with the p16INK4a gene reportedly regulated by mixed-lineage leukemia 1 (MLL1)/WD-40 repeat protein 5 (WDR5)-mediated histone 3 lysine 4 trimethylation (H3K4me3). Here, we determined whether inhibition of MLL1/WDR5 activity attenuates renal senescence, inflammation, and fibrosis in mice with ischemia reperfusion injury and in cultured rat renal fibroblasts. MM-102 or OICR-9429, both MLL1/WDR5 protein-protein interaction inhibitors, and small interfering RNA (siRNA) for MLL1 or WDR5 suppressed the expression of p16INK4a in mice with ischemia reperfusion injury, accompanied by downregulation of H3K4me3 expression. MM-102 attenuated renal fibrosis and inflammation in the kidney of mice with ischemia reperfusion injury. Moreover, in vitro study showed that transforming growth factor-ß1 induced the expression of MLL1, WDR5, H3K4me3, and p16INK4a. Finally, chromatin immunoprecipitation identified the p16INK4a promoter at an H3K4me3 site in renal fibroblasts. Thus, our findings show that H3K4me3 inhibition ameliorates ischemia reperfusion-induced renal senescence along with fibrosis and inflammation.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Compostos de Bifenilo/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Fibroblastos/efeitos dos fármacos , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Proteína de Leucina Linfoide-Mieloide/antagonistas & inibidores , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Compostos de Bifenilo/farmacologia , Linhagem Celular , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Di-Hidropiridinas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteína de Leucina Linfoide-Mieloide/metabolismo , Ratos , Insuficiência Renal/prevenção & controle , Traumatismo por Reperfusão/complicaçõesRESUMO
Objective: This study evaluated associations of serum matrix Gla protein (MGP), plasma vitamin K1, and plasma vitamin K2 with coronary artery calcium score (CACS) and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods: Subjects comprised 112 MHD patients aged 30-60 years and 40 age-matched healthy subjects. Total MGP, vitamin K1, vitamin K2, and lipid profile were examined in all subjects; other clinical data, medication use, and CACS were assessed only in MHD patients. Determinants of MGP in all subjects were identified by regression analysis. Factors associated with CACS and CVD in MHD patients were identified by regression analysis and logistic analysis, respectively. Results: Lower plasma levels of vitamin K1 corrected for triglycerides [0.39 (0.24-0.70) vs. 0.77 (0.48-1.34) ng/mg, p < 0.001], higher frequency of plasma vitamin K2 ≤ 0.05 ng/ml (p = 0.23), and higher serum total MGP (288.4 ± 44.2 vs. 159.7 ± 40.6 ng/ml, p < 0.0001) were observed in MHD patients than in healthy controls. Total MGP level was significantly associated with levels of vitamin K1 corrected for triglycerides (p <0 .001) and vitamin K2 ≤ 0.05 ng/ml (p < 0.05) in all subjects. Total MGP level was significantly associated with presence of CVD (p <0 .05), but not CACS, in MHD patients. Conclusion: The end-stage renal disease on hemodialysis is a deficiency state of vitamin K. Total MGP was significantly higher in MHD patients compared to healthy subjects and total MGP was associated with the presence of CVD, but not CACS, in MHD patients.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Calcificação Vascular/epidemiologia , Vitamina K/sangue , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Calcificação Vascular/sangue , Calcificação Vascular/etiologia , Proteína de Matriz GlaRESUMO
Recently, in addition to epithelial sodium channel alpha-subunit (αENaC), the thiazide-sensitive sodium-chloride cotransporter (NCC) and pendrin, also known as sodium-independent chloride/iodide transporter, were reported to be activated by aldosterone. Here, we investigated whether chloride (Cl-) is responsible for hypertension, inflammation, and renal damage in aldosterone-infused rats. Following left nephrectomy, 8-wk-old male Sprague-Dawley rats were allocated into four groups: 1) drinking 1.0% sodium chloride solution with aldosterone infusion (Aldo/NaCl rats); 2) drinking 1.44% sodium bicarbonate solution with aldosterone infusion (Aldo/NaHCO3 rats); 3) drinking distilled water with aldosterone infusion (Aldo/water rats); and 4) drinking distilled water without aldosterone infusion (sham rats). Additionally, heminephrectomized rats with aldosterone infusion were fed a 0.26% NaCl diet (control); 8.0% NaCl diet (high-Na/high-Cl); or a 4.0% NaCl 6.67% sodium citrate diet (high-Na/half-Cl). Last, Aldo/NaCl rats were treated with or without hydrochlorothiazide. Blood pressure in the Aldo/NaCl rats was significantly higher than in the Aldo/NaHCO3 rats, which was associated with the increased expression of NCC. Expression of markers of inflammation (CD3, CD68, interleukin-17A) and fibrosis (α-smooth muscle actin, collagen 1) were also increased in Aldo/NaCl rats. Similarly, aldosterone-infused rats fed a high-Na/half-Cl diet had lower blood pressure than those fed a high-Na/high-Cl diet, with a reduction of phosphorylated NCC, but not αENaC and pendrin. NCC inhibition with hydrochlorothiazide attenuated interleukin-17A protein expression along with the phosphorylation of NCC in Aldo/NaCl rats. These findings suggest that NCC-mediated Cl- uptake plays important roles in the development of aldosterone-induced hypertension and renal injury.
Assuntos
Aldosterona , Pressão Sanguínea , Cloretos/metabolismo , Hipertensão/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Canais Epiteliais de Sódio/metabolismo , Fibrose , Hidroclorotiazida/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nefropatias/prevenção & controle , Masculino , Nefrectomia , Fosforilação , Ratos Sprague-Dawley , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/metabolismo , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta , Citrato de Sódio , Membro 3 da Família 12 de Carreador de Soluto/efeitos dos fármacos , Membro 3 da Família 12 de Carreador de Soluto/metabolismoRESUMO
Multicentric Castleman disease (MCD) is a rare systemic lymphoproliferative disorder and is infrequently associated with renal complications that include amyloid A (AA) amyloidosis. Although it has been reported that patients with MCD and amyloidosis usually have a poor prognosis, recently, tocilizumab, a humanized anti-interleukin-6 receptor antibody, has emerged as an effective and specific treatment for AA amyloidosis secondary to chronic inflammatory disorders. Here we report a case of an MCD patient with secondary AA renal amyloidosis who was successfully treated with tocilizumab. The patient was initially referred to nephrology specialists because of a decline in renal function and proteinuria. Percutaneous renal biopsy revealed the presence of Congo red-positive amorphous depositions and AA protein-positive areas in glomeruli, vessel walls, and interstitium, confirming a diagnosis of renal AA amyloidosis secondary to MCD. At 1 year after starting tocilizumab treatment, a second renal biopsy showed the clearance of amyloid deposits in the interstitium. These observations suggest that tocilizumab may be an effective therapy for AA amyloidosis secondary to MCD.â©.
Assuntos
Amiloidose/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperplasia do Linfonodo Gigante/complicações , Rim/patologia , Amiloidose/etiologia , Amiloidose/metabolismo , Amiloidose/patologia , Biópsia , Hiperplasia do Linfonodo Gigante/diagnóstico , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Amiloide A Sérica/metabolismoRESUMO
BACKGROUND: The definition of sepsis was updated to sepsis-3 in February 2016. Currently, direct hemoperfusion therapy using the polymyxin B-immobilized fiber cartridge (PMX-DHP) is widely performed to treat sepsis and septic shock. However, the prognostic factors of PMX-DHPs in patients with sepsis using the new definition are unclear. We retrospectively assessed prognostic factors in patients who had received PMX-DHP therapy for sepsis and septic shock. METHODS: We included 71 patients with severe infection who underwent PMX-DHP treatment from January 2006 to August 2015 in this study. Participants were re-evaluated according to the criteria of sepsis-3. The patients were divided into two groups based on having survived (n = 59) or not survived (n = 12) for 28 days after PMX-DHP treatment. Clinical data before and after PMX-DHP treatment were compared between the two groups. RESULTS: Non-survivors showed a lower Glasgow Coma Scale (GCS) score before PMX-DHP treatment compared with 28-day survivors [12 (6-14) vs 14 (12-15), P < 0.01]. Furthermore, pH after the first PMX-DHP session was significantly lower in non-survivors than in survivors (7.28 ± 0.23 vs 7.39 ± 0.06, P = 0.03). Multivariate logistic regression analysis showed that only lower pH after the first PMX-DHP session was a predictor of 28-day mortality independent of age, sex, GCS score, and mean arterial pressure (odds ratio per pH of 0.01, 0.93; 95% confidence interval, 0.83-0.99; P = 0.02). CONCLUSION: The pH after the first PMX-DHP session is an independent risk factor for mortality in patients receiving PMX-DHP for sepsis and septic shock.
Assuntos
Hemoperfusão , Polimixina B , Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/terapia , Choque Séptico/terapiaRESUMO
BACKGROUND: High-normal albuminuria is an important risk factor for incident chronic kidney disease in diabetic populations, in contrast to an uncertain association in nondiabetic populations. This study aimed to reveal the relationship between high-normal albuminuria and incident chronic kidney disease in a Japanese nondiabetic population. METHODS: A 10-year follow-up retrospective cohort study was performed involving 1378 Japanese men (mean age 44 ± 5.3 years) without chronic kidney disease and diabetes mellitus. Chronic kidney disease was diagnosed as either estimated glomerular filtration rate < 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: At baseline, age, estimated glomerular filtration rate, and the presence of hematuria, hypertension, and dyslipidemia were independently associated with the albumin-to-creatinine ratio. Among the 1378 participants, 185 (13.4%) fulfilled diagnostic criteria for chronic kidney disease over the 10-year follow-up period. Median annual estimated glomerular filtration rate decline showed a deterioration with increasing quartiles of baseline albumin-to-creatinine ratio (P = 0.004). Participants who had a baseline albumin-to-creatinine ratio in the highest quartile (5.9-28.9 mg/g) were more likely to develop micro- or macroalbuminuria (odds ratio: 16.23, 95% confidence interval 6.56-54.03), chronic kidney disease (odds ratio: 2.48, 95% confidence interval 1.64-3.82), and hypertension (odds ratio 2.06, 95% confidence interval 1.30-3.31), but not diabetes mellitus compared with those who had an albumin-to-creatinine ratio in the lowest quartile (1.3-3.6 mg/g) after adjustment for potential confounders. CONCLUSIONS: High-normal albuminuria was associated with incident chronic kidney disease in this Japanese nondiabetic male population.
Assuntos
Albuminúria/complicações , Insuficiência Renal Crônica/complicações , Adulto , Albuminúria/epidemiologia , Creatinina , Taxa de Filtração Glomerular , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIM: Many studies have validated Agatston's coronary artery calcification score (CACS) for assessing vascular calcification (VC) in chronic kidney disease (CKD) patients. This study aimed to evaluate the CACS and common iliac artery calcification score (IACS) and to examine the variables related to each score. METHODS: The subjects were 145 non-dialysis CKD patients. The CACS and IACS were determined using the same thoracicoabdominal multi-detector computed tomography. Multiple regression analyses were performed to assess the factors associated with the CACS or IACS. The associations between progression to renal replacement therapy (RRT) and the CACS or IACS were studied using Cox hazards models. RESULTS: The subjects' median age, estimated glomerular filtration rate (eGFR), and follow-up period were 72 (62-78) years, 32 (18-50) mL/min/1.73m2 , and 864 (550-1425) days, respectively. Age, diabetes, the serum phosphate level, and the eGFR were found to be significant factors of the CACS [ß (95% CI): 0.38 (0.02-0.04), P < 0.0001, 0.28 (0.19-0.50), P < 0.0001, 0.16 (0.03-0.45), P < 0.05 and -0.15 (-0.02-0.00), P < 0.05, respectively]. Age and diabetes were shown to be significant factors of the IACS [ß (95% CI): 0.53 (0.04-0.06), P < 0.0001, and 0.18 (0.07-0.40), P < 0.01, respectively]. Progression to RRT occurred in 31 patients and was significantly associated with the CACS (hazard ratio: 1.01, P < 0.01), urinary protein level and eGFR, but not the IACS. CONCLUSION: Chronic kidney disease related risk factors for VC, such as the eGFR and hyperphosphataemia, are significantly associated with a high CACS, but not a high IACS, and the CACS is a significant predictor of progression to RRT.