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1.
Korean J Intern Med ; 35(1): 25-40, 2020 Jan.
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.

2.
Sci Rep ; 9(1): 17679, 2019 Nov 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.

3.
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.

4.
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.

5.
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.

6.
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.

7.
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
8.
Sci Rep ; 9(1): 1994, 2019 Feb 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.

9.
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.

10.
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
11.
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
12.
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
13.
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.

14.
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
15.
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.

16.
Ann Lab Med ; 38(5): 450-457, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29797816

RESUMO

BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. METHODS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. RESULTS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (-) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017-24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R. CONCLUSIONS: Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.


Assuntos
Autoanticorpos/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Transplante de Rim , Receptor Tipo 1 de Angiotensina/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Rim/patologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos , Transplante Homólogo
17.
Kidney Res Clin Pract ; 37(1): 49-58, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29629277

RESUMO

Background: Weight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients. Methods: This study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight. Results: Fifty-eight participants (25.6%) were assigned to group 1 (≥1.5% decrease in body weight after 16 weeks), 32 participants (14.1%) were assigned to group 2 (1.5-0.1% decrease in body weight), and 136 participants (59.9%) were assigned to group 3 (≥ 0.0% increase in body weight). Characteristics at enrollment were not different among the three groups, but mean differences in weight and percent changes in urinary sodium excretion over the period were statistically different (P < 0.001 and P = 0.017). Over the study period, unintentional weight loss independently increased the probability of reduced albuminuria (group 1, relative risk 6.234, 95% confidence interval 1.913-20.315, P = 0.002). Among urinary cytokines, only podocalyxin level decreased significantly in participants who lost weight (P = 0.013). Conclusion: We observed that weight loss had an additive effect on the anti-proteinuric effects of ARBs in nondiabetic hypertensive CKD patients, although it was minimal. An additive effect was shown in both obese and non-obese participants, and its possible mechanism is related to reduction of podocyte damage.

18.
Korean J Intern Med ; 33(5): 961-969, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29551056

RESUMO

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.


Assuntos
Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Falência Renal Crônica , Idoso , Ácidos Aristolóquicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Falência Renal Crônica/induzido quimicamente , Masculino , República da Coreia/epidemiologia
19.
Cell Death Dis ; 9(3): 270, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449563

RESUMO

Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinaseß (CaMKKß)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression. Interestingly, intracellular chelator BAPTA-AM reversed cinacalcet-induced CaMKKß elevation and LKB1 phosphorylation. Cinacalcet reduced albuminuria without influencing either blood glucose or Ca2+ concentration and ameliorated diabetes-induced renal damage, which were related to the increased expression of calcium-sensing receptor and the phosphorylation of CaMKKß-LKB1. Subsequent activation of AMPK was followed by the activation of peroxisome proliferator-activated receptor γ coactivator-1α and phospho-Ser1177eNOS-nitric oxide, resulting in a decrease in apoptosis and oxidative stress as well as an increase in autophagy.Our results suggest that cinacalcet increases intracellular Ca2+ followed by an activation of CaMKKß-LKB1-AMPK signaling in GECs and podocytes in the kidney, which provides a novel therapeutic means for type 2 diabetic nephropathy by modulation of apoptosis and autophagy.

20.
Atherosclerosis ; 270: 123-131, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29407880

RESUMO

BACKGROUND AND AIMS: This study evaluated the effects of resveratrol on arterial aging and the renin-angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs). METHODS: Aging mice were divided into control and resveratrol groups. Histological changes, inflammation, oxidative stress, RAS components, and the expression of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), and anti-oxidative enzymes was measured in thoracic aortas of 24-month-old mice. The effect of resveratrol on fibrosis, cell senescence, and RAS components was also investigated in VSMCs stimulated by angiotensin (Ang) II. RESULTS: Aorta media thickness, inflammation, fibrosis, and oxidative stress were significantly lower in the resveratrol group than in the control group. Resveratrol treatment decreased serum Ang II level and the aortic expression of prorenin receptor (PRR) and angiotensin converting enzyme (ACE), and increased serum Ang-(1-7) level and the expression of ACE2, Ang II type 2 receptor (AT2R), and Mas receptor (MasR). Resveratrol increased the expression of phosphorylated AMPK, SIRT1, PGC-1α, phosphorylated endothelial nitric oxide synthase and superoxide dismutase 1 and 2, and decreased that of NADPH oxidase 2 and 4. In Ang II-stimulated VSMCs, resveratrol treatment markedly decreased the number of senescence associated ß-galactosidase stained cells and pro-fibrotic protein expression and increased the expression of AT2R and MasR. CONCLUSIONS: Resveratrol protects against arterial aging and this effect is associated with reduced activity of the PRR-ACE-Ang II axis and stimulation of the ACE2-Ang-(1-7)-ATR2-MasR axis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Senescência Celular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Resveratrol/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Fatores Etários , Envelhecimento , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Células Cultivadas , Fibrose , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sistema Renina-Angiotensina/genética , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
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