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1.
Yeungnam Univ J Med ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045804

RESUMO

Donepezil is a cholinesterase inhibitor used extensively to treat Alzheimer's disease. The increased cholinergic activity is associated with adverse effects, therefore gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are common. Hypokalemia is a rare adverse event that occurs in less than 1% of donepezil-treated patients. Although hypokalemia of mild and moderate grade does not present serious signs and symptoms, severe hypokalemia often results in prolonged hospitalization and mortality. Herein, we report a case of hypokalemia developed after the initiation of donepezil therapy for cognitive impairment.

2.
Korean J Intern Med ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32942841

RESUMO

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

3.
J Clin Med ; 9(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806730

RESUMO

Approximately 5% of patients with IgA nephropathy (IgAN) exhibit mild mesangial lesions with acute onset nephrotic syndrome and diffuse foot process effacement representative of minimal change disease (MCD). It is not clear whether these unusual cases of IgAN with MCD (IgAN-MCD) are variant types of IgAN or coincidental deposition of IgA in patients with MCD. In a retrospective multicenter cohort study of 18 hospitals in Korea, we analyzed 46 patients with IgAN-MCD. Patients with endocapillary proliferation, segmental sclerosis, and crescent were excluded, and the clinical features and prognosis of IgAN-MCD were compared with those of pure MCD. In addition, we performed galactose-deficient IgA1 (KM55) staining to characterize IgAN-MCD. Among the 21,697 patients with glomerulonephritis enrolled in the database, 46 patients (0.21%) were diagnosed with IgAN-MCD, and 1610 patients (7.4%) with pure MCD. The 46 patients with IgAN-MCD accounted for 0.6% of primary IgAN patients (n = 7584). There was no difference in prognosis between patients with IgAN-MCD and those with only MCD. IgA and KM55 showed double positivity in all patients with IgAN-MCD (n = 4) or primary IgAN (n = 5) under double immunofluorescent staining. However, in four patients with lupus nephritis, mesangial IgA was deposited, but galactose-deficient-IgA1 (Gd-IgA1) was not. These findings suggest that IgAN-MCD is a dual glomerulopathy in which MCD was superimposed on possibly indolent IgAN. We confirmed by KM55 staining that IgAN-MCD is true IgAN, enabling better characterizations of the disease. Furthermore, IgAN-MCD shows a good prognosis when treated according to the usual MCD treatment modality.

4.
Acta Pharmacol Sin ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555441

RESUMO

Reducing immunosuppressant-related complications using conventional drugs is an efficient therapeutic strategy. L-carnitine (LC) has been shown to protect against various types of renal injury. In this study, we investigated the renoprotective effects of LC in a rat model of chronic tacrolimus (TAC) nephropathy. SD rats were injected with TAC (1.5 mg · kg-1 · d-1, sc) for 4 weeks. Renoprotective effects of LC were assessed in terms of renal function, histopathology, oxidative stress, expression of inflammatory and fibrotic cytokines, programmed cell death (pyroptosis, apoptosis, and autophagy), mitochondrial function, and PI3K/AKT/PTEN signaling. Chronic TAC nephropathy was characterized by severe renal dysfunction and typical histological features of chronic nephropathy. At a molecular level, TAC markedly increased the expression of inflammatory and fibrotic cytokines in the kidney, induced oxidative stress, and led to mitochondrial dysfunction and programmed cell death through activation of PI3K/AKT and inhibition of PTEN. Coadministration of LC (200 mg · kg-1 · d-1, ip) caused a prominent improvement in renal function and ameliorated histological changes of kidneys in TAC-treated rats. Furthermore, LC exerted anti-inflammatory and antioxidant effects, prevented mitochondrial dysfunction, and modulated the expression of a series of apoptosis- and autophagy-controlling genes to promote cell survival. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TAC (50 µg/mL) in vitro, which induced production of intracellular reactive oxygen species and expression of an array of genes controlling programmed cell death (pyroptosis, apoptosis, and autophagy) through interfering with PI3K/AKT/PTEN signaling. The harmful responses of HK-2 cells to TAC were significantly attenuated by cotreatment with LC and the PI3K inhibitor LY294002 (25 µM). In conclusion, LC treatment protects against chronic TAC nephropathy through interfering the PI3K/AKT/PTEN signaling.

5.
Hemodial Int ; 24(3): 309-316, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32372545

RESUMO

INTRODUCTION: Arteriovenous fistula (AVF) is historically known to be the ideal option for vascular access (VA) for hemodialysis compared with arteriovenous graft (AVG). However, this approach has been recently questioned in the aging population because of their poor vessel quality and multiple comorbidities. METHODS: Data from a total of 2200 patients from the VA category of The Catholic Medical Center nephrology registry from March 2009 to February 2017 were analyzed. We compared VA patency and patient survival between two groups, AVF and AVG, according to age. FINDINGS: Compared with the AVG group, survival benefit in the AVF group continued even in patients ≥80 years. In the whole population, all the primary patency (PP), primary-assisted patency (PAP), and secondary patency (SP) measures were superior in the AVF group. With regard to subgroups, PP was comparable between the two groups in patients ≥65 years, whereas PAP and SP were superior in the AVF group even in septuagenarian patients who are from 70 to 79 years old. In patients ≥80 years, all the patency measures were comparable between the two groups. When the separate comparison of lower-arm AVF (or upper-arm AVF) and AVG, lower-arm AVF failed to demonstrate its superiority in any kind of patency in septuagenarian patients compared with AVG, whereas upper-arm AVF demonstrated its superiority in PAP and SP in septuagenarian patients. However, even upper-arm AVF failed to demonstrate its superiority in any kind of patency in patients ≥80 years. DISCUSSION: Arteriovenous fistula if using upper-arm vessel showed the superior VA patency up to septuagenarian patients, whereas, in HD patients ≥80 years, AVF and AVG were comparable in VA patency.

6.
Korean J Intern Med ; 35(1): 25-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31935318

RESUMO

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

7.
Sci Rep ; 9(1): 17679, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776362

RESUMO

Adequate fluid management plays an important role in decreasing cardiovascular risk in peritoneal dialysis (PD) patients. We evaluated whether strict volume control monitored by bioimpedance spectroscopy (BIS) affects cardiac function in PD patients. This study is a secondary analysis of a multicentre, prospective, randomized, controlled trial. Fluid overload was assessed by the average overhydration/extracellular water (OH/ECW) at baseline, 6 months and 12 months. Patients were categorized as time-averaged overhydrated (TA-OH/ECW ≥15%) or normohydrated (TA-OH/ECW <15%), and echocardiographic parameters were compared between groups. Among a total of 151 patients, 120 patients exhibited time-averaged normohydration. Time-averaged overhydrated patients had a significantly higher left atrial (LA) diameter and E/e' ratio and a lower left ventricular (LV) ejection fraction at 12 months than time-averaged normohydrated patients. LA diameter, end-systolic volume and end-diastolic volume were decreased at 12 months compared to baseline in time-averaged normohydrated patients only. TA-OH/ECW was independently associated with ejection fraction at 12 months (ß = -0.190; p = 0.010). TA-OH/ECW, but not OH/ECW at 12 months, was an independent risk factor for LV dysfunction (odds ratio 4.020 [95% confidence interval 1.285-12.573]). Overhydration status based on repeated BIS measurements is an independent predictor of LV systolic function in PD patients.


Assuntos
Doenças Cardiovasculares/etiologia , Espectroscopia Dielétrica/métodos , Testes de Função Cardíaca/métodos , Diálise Peritoneal/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estado de Hidratação do Organismo , Estudos Prospectivos , Desequilíbrio Hidroeletrolítico
8.
Kidney Res Clin Pract ; 38(4): 509-516, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31640307

RESUMO

Background: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades. Methods: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969-1998, 1999-2006, 2007-2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy. Results: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999-2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48). Conclusion: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.

9.
Kidney Blood Press Res ; 44(5): 1101-1114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31533093

RESUMO

BACKGROUND: Diet modification, especially a decrease in salt intake, might be an important non-pharmacological strategy to improve chronic kidney disease (CKD) prognosis. OBJECTIVES: We conducted a prospective cohort study to investigate whether an intensive low-salt diet education program effectively attenuated the rate of renal function decline in hypertensive patients with CKD. METHODS: This cohort study recruited 171 participants from a previous open-labelled, case-controlled, randomized clinical trial that originally consisted of 245 hypertensive CKD patients who were assigned to two groups, intensive low-salt diet or conventional education. We evaluated the renal outcomes, which included the rate of change in estimated glomerular filtration rate (eGFR) per year, the increase in serum creatinine ≥50%, the decrease in eGFR ≥30%, and the percent change in albuminuria throughout the entire study period. RESULTS: The baseline characteristics of the cohort participants between the two groups were similar at the time of trial phase randomization. During the whole study period, the rate of renal function decline was significantly faster in the conventional group (0.11 ± 4.63 vs. -1.53 ± 3.04 mL/min/1.73 m2/year, p = 0.01). The percent of incremental change in serum creatinine ≥50% was 1.1% in the intensive group and 8.2% in the conventional group (p = 0.025), and the percent of decremental change in eGFR ≥30% was 3.3% in the intensive group and 11.1% in the conventional group (p= 0.048). With logistic regression analysis adjusted for related factors, we found that the conventional group showed a higher risk for deterioration in serum creatinine and eGFR during the entire study period. Especially, we found that the intensive education program preserved eGFR in participants with one, several, or all of the following characteristics at the time of randomization: older age, female, obese, had higher protein intake, higher amounts of albuminuria, higher salt intake. CONCLUSION: This cohort study demonstrated that an intensive low-salt diet education program attenuated the rate of renal function decline in hypertensive CKD patients independent of its effect on lowering salt intake or albuminuria during the 36 months of follow-up.


Assuntos
Dieta Hipossódica/métodos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipertensão/terapia , Insuficiência Renal Crônica/terapia , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/patologia
10.
Korean J Intern Med ; 34(5): 1091-1099, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408925

RESUMO

BACKGROUND/AIMS: Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN. METHODS: The outcomes of 135 patients with histologically proven MN were analyzed. 'Older' was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients. RESULTS: The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients. CONCLUSION: Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids.


Assuntos
Corticosteroides/uso terapêutico , Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Corticosteroides/efeitos adversos , Adulto , Fatores Etários , Idoso , Doenças Transmissíveis/etiologia , Ciclosporina/efeitos adversos , Progressão da Doença , Feminino , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Terapia de Substituição Renal , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul , Fatores de Tempo , Resultado do Tratamento
11.
Cell Death Dis ; 10(3): 219, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833548

RESUMO

Recent studies have demonstrated that chronic inflammation-induced lymphangiogenesis plays a crucial role in the progression of various renal diseases, including diabetic nephropathy. SAR131675 is a selective vascular endothelial cell growth factor receptor-3 (VEGFR-3)-tyrosine kinase inhibitor that acts as a ligand for VEGF-C and VEGF-D to inhibit lymphangiogenesis. In this study, we evaluated the effect of SAR131675 on renal lymphangiogenesis in a mouse model of type 2 diabetes. Male C57BLKS/J db/m and db/db mice were fed either a regular chow diet or a diet containing SAR131675 for 12 weeks from 8 weeks of age. In addition, we studied palmitate-induced lymphangiogenesis in human kidney-2 (HK2) cells and RAW264.7 monocytes/macrophages, which play a major role in lymphangiogenesis in the kidneys. SAR131475 ameliorated dyslipidemia, albuminuria, and lipid accumulation in the kidneys of db/db mice, with no significant changes in glucose and creatinine levels and body weight. Diabetes-induced systemic inflammation as evidenced by increased systemic monocyte chemoattractant protein-1 and tumor necrosis factor-α level was decreased by SAR131475. SAR131475 ameliorated the accumulation of triglycerides and free fatty acids and reduced inflammation in relation to decreased chemokine expression and pro-inflammatory M1 macrophage infiltration in the kidneys. Downregulation of VEGF-C and VEGFR-3 by SAR131475 inhibited lymphatic growth as demonstrated by decreased expression of LYVE-1 and podoplanin that was further accompanied by reduced tubulointerstitial fibrosis, and inflammation in relation to improvement in oxidative stress and apoptosis. Treatment with SAR131475 improved palmitate-induced increase in the expression of VEGF-C, VEGFR-3, and LYVE-1, along with improvement in cytosolic and mitochondrial oxidative stress in RAW264.7 and HK2 cells. Moreover, the enhanced expression of M1 phenotypes in RAW264.7 cells under palmitate stress was reduced by SAR131475 treatment. The results suggest that modulation of lymphatic proliferation in the kidneys is a new treatment approach for type 2 diabetic nephropathy and that SAR131675 is a promising therapy to ameliorate renal damage by reducing lipotoxicity-induced lymphangiogenesis.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Naftiridinas/farmacologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/patologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Linfangiogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naftiridinas/uso terapêutico , Células RAW 264.7 , Triglicerídeos/metabolismo
12.
Sci Rep ; 9(1): 1994, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760777

RESUMO

Lymphangiogenesis occurs in response to renal injury and is correlated with interstitial fibrosis. Diabetes- and high-fat diet (HFD)-induced intrarenal lipotoxicity and their relationships with lymphangiogenesis are not established. We used PPARα agonist, fenofibrate, to unravel the linkage between lipotoxicity and lymphangiogenesis. Eight-week-old male C57BLKS/J db/db mice and HFD Spontaneously hypertensive rats (SHRs) were fed fenofibrate for 12 weeks. HK-2 and RAW264.7 cells were used to investigate their lymphangiogenic capacity in relation to lipotoxicity. Fenofibrate improved intrarenal lipotoxicity by increasing expression of PPARα and phosphorylation of AMPK. Lymphatic proliferation was attenuated; expression of lymphatic endothelial hyaluronan receptor-1 (LYVE-1), podoplanin, vascular endothelial growth factor-C (VEGF-C), and vascular endothelial growth factor receptor-3 (VEGFR-3) was decreased. In parallel, extent of tubulointerstitial fibrosis, apoptosis and inflammatory cell infiltration was reduced. In HK2 cells, palmitate- and high glucose-induced over expression of lymphatic makers was diminished by fenofibrate via activation of PPARα-AMPK-pACC signaling. Enhanced expression of M1 phenotype in RAW264.7 cells correlated with increased lymphatic growth. A causal relationship between lipotoxicity and lymphatic proliferation with a cellular link to macrophage activation can be speculated; pro-inflammatory M1 type macrophage is involved in the development of lymphangiogenesis through stimulation of VEGF-C and by its transdifferentiation into lymphatic endothelial cells.


Assuntos
Lesão Renal Aguda/patologia , Nefropatias Diabéticas/patologia , Dieta Hiperlipídica/efeitos adversos , Fenofibrato/farmacologia , Linfangiogênese/fisiologia , Linfócitos/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus/patologia , Fibrose/patologia , Rim/patologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , PPAR alfa/agonistas , Fosforilação , Células RAW 264.7 , Ratos , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
BMC Nephrol ; 20(1): 39, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717699

RESUMO

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.


Assuntos
Lesão Renal Aguda/patologia , Função Retardada do Enxerto/etiologia , Seleção do Doador/normas , Transplante de Rim , Doadores de Tecidos , Transplantados , Transplantes/patologia , Lesão Renal Aguda/fisiopatologia , Adulto , Idoso , Cadáver , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/fisiopatologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Transplantes/fisiopatologia , Resultado do Tratamento
14.
J Vasc Access ; 20(4): 397-403, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30444167

RESUMO

PURPOSE: To assess the causes of immature hemodialysis arteriovenous fistula and the outcome of endovascular salvage. METHODS: The outcome of 207 endovascular salvage procedures in 139 patients after the first successful cannulation was analyzed retrospectively from January 2011 to December 2017 in the Catholic University of Korea, Seoul St. Mary's Hospital. RESULTS: Of the 139 patients aged 62 ± 13 years, 45% were women, 59% had diabetes, and 71% were maintained on hemodialysis using central venous catheters. Mean interval between arteriovenous fistula creation and referral to angiography was 87 ± 63 days. While inflow stenosis (54.4%) was the most common cause of immature forearm fistulas (n = 76), both inflow (38.6%) and mixed stenosis (35.1%) were the main causes of immature upper arm fistulas (n = 63). Endovascular salvage procedures included percutaneous transluminal angioplasty (n = 174) and accessory vein obliteration (n = 30). The overall technical and clinical success rates were 97% and 93.4%, respectively. Mean interval between endovascular procedure and the first successful cannulation of the fistula was 28 ± 35 days. At 3, 6, and 12 months following the first successful cannulation, the primary patency rates were 81%, 69.5%, and 57.6%, respectively, and the secondary patency rates were 97.2%, 96%, and 94.8%, respectively. Mixed stenosis was the only determinant of secondary patency rate of immature arteriovenous fistula (hazard ratio = 6.334, confidence interval = 1.364-29.423, p = 0.018), and patients with mixed stenosis had poorer access outcomes (p = 0.016). CONCLUSION: Immature arteriovenous fistulas can be successfully salvaged by aggressive and timely endovascular intervention. Mixed stenosis is associated with poor access outcomes.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Procedimentos Endovasculares , Oclusão de Enxerto Vascular/cirurgia , Diálise Renal , Terapia de Salvação/métodos , Idoso , Cateterismo , Procedimentos Endovasculares/efeitos adversos , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Terapia de Salvação/efeitos adversos , Seul , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
15.
Korean J Intern Med ; 34(5): 1078-1090, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29432674

RESUMO

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor ß1 [TGF-ß1] and TGF-ß inducible gene-h3 [ßig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-ß1/Smad2/3, ßig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSION: SK protects against TAC-induced renal injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Tacrolimo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
Nutrients ; 10(11)2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30424556

RESUMO

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2'-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.


Assuntos
Angiotensina II/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Resveratrol/farmacologia , Albuminúria , Angiotensina I/metabolismo , Animais , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Fibrose , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Angiotensina/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/prevenção & controle , Superóxido Dismutase/metabolismo
17.
PLoS One ; 13(10): e0205011, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30289927

RESUMO

BACKGROUND: We investigated whether the Kidney Donor Profile Index (KDPI) system is useful in predicting clinical outcomes in deceased donor kidney transplantation (DDKT). METHODS: Four hundred sixty-nine kidney transplant recipients (KTRs) receiving kidneys from 359 deceased donors were included in this study, which involved three transplant centers. KTRs were divided into high and low KDPI KTR groups based on the median KDPI score of 67%. We compared clinical outcomes between the high KDPI and low KDPI groups. RESULTS: There were no significant differences in the incidence of delayed graft function and acute rejection between high and low KDPI KTR groups. In comparison with histologic findings in allograft tissues obtained within three months from KT, the proportion of glomerulosclerosis was significantly higher in the high KDPI KTR group than in the low KDPI KTR group. With Kaplan-Meier analysis, the graft survival rate was significantly lower in the high KDPI KTR group than in the low KDPI KTR group (Log rank, P = 0.017), and multivariate analysis also demonstrated that a high KDPI score was a significant risk factor for death censored allograft failure (HR 2.62, 95% CI, 1.29-5.33, P = 0.008). CONCLUSION: The KDPI scoring system is useful in predicting allograft outcomes in a Korean DDKT cohort.


Assuntos
Morte , Doadores de Tecidos/estatística & dados numéricos , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
18.
Kidney Res Clin Pract ; 37(3): 266-276, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30254851

RESUMO

Background: We investigated the associations between mineral metabolism parameters and mortality to identify optimal targets in Korean hemodialysis patients. Methods: Among hemodialysis patients registered in the end-stage renal disease registry of the Korean Society of Nephrology between March 2012 and June 2017, those with serum calcium, phosphorus, and intact parathyroid hormone (iPTH) measured at enrollment were included. Association of serum levels of calcium, phosphorus, and iPTH with all-cause mortality was analyzed. Results: Among 21,433 enrolled patients, 3,135 (14.6%) died during 24.8 ± 14.5 months of follow-up. After multivariable adjustment, patients in the first quintile of corrected calcium were associated with lower mortality (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.71-0.99; P = 0.003), while those in the fifth quintile were associated with higher mortality (HR, 1.39; 95% CI, 1.20-1.61; P < 0.001) compared with those in the third quintile. For phosphorus, only the lowest quintile was significantly associated with increased mortality (HR, 1.24; 95% CI, 1.08-1.43; P = 0.003). The lowest (HR, 1.18; 95% CI, 1.02-1.36; P = 0.026) and highest quintiles of iPTH (HR, 1.24; 95% CI, 1.05-1.46; P = 0.013) were associated with increased mortality. For target counts achieved according to the Kidney Disease Outcomes Quality Initiative guideline, patients who did not achieve any mineral parameter targets hadhigher mortality than those who achieved all three targets (HR, 1.37; 95% CI, 1.12-1.67; P = 0.003). Conclusion: In Korean hemodialysis patients, high serum calcium, low phosphorus, and high and low iPTH levels were associated with increased all-cause mortality.

19.
PLoS One ; 13(8): e0202676, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30148871

RESUMO

BACKGROUND: Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear. METHOD: This observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0-4 months, 0-26 months, and 0-38 months. The renal outcome was defined as a decline in eGFR ≥ 40% during the entire study period. RESULT: The albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR ≥ 40% was increased by 1.690-folds [95% CI 1.110-2.572, P = 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR ≥ 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients. CONCLUSION: The time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR ≥ 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome.


Assuntos
Albuminúria/diagnóstico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Albuminúria/complicações , Área Sob a Curva , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Olmesartana Medoxomila/uso terapêutico , Curva ROC , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Fatores de Risco
20.
Kidney Res Clin Pract ; 37(2): 157-166, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29971211

RESUMO

Background: The aim of this study is to narrow the gap between global guidelines and local practices, we recently established domestic recommendations by adapting the international guidelines for management of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients on maintenance hemodialysis (MHD). This study was undertaken to determine whether application of this guideline adaptation was associated with improved serum mineral profiles in patients with CKD-MBD. Methods: A total of 355 patients on MHD were enrolled from seven dialysis units. After adhering to our strategy for one year, serum phosphorus, calcium, intact parathyroid hormone (iPTH), and alkaline phosphatase (AP) levels were compared with the baseline. The endpoint was improvement in the proportion of patients with serum mineral levels at target recommendations. Results: The median serum phosphorus level and proportion of patients with serum phosphorus within the target range were not changed. Although the median serum calcium level was significantly increased, the proportion of patients with serum calcium within the target range was not significantly affected. The proportion of patients with serum iPTH at the target level was not altered, although the median serum iPTH was significantly decreased. However, both median serum AP and the proportion of patients with serum AP at the target level (70.4% vs. 89.6%, P < 0.001) were improved. Conclusion: In our patients with MHD, serum mineral profiles were altered and the serum AP level stabilized after implementing our recommendations. Long-term follow-up evaluations are necessary to determine whether uremic bone disease and cardiovascular calcifications are affected by these recommendations.

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