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BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.
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Corticoesteroides/administración & dosificación , Nefrosis Lipoidea/tratamiento farmacológico , Tacrolimus/administración & dosificación , Adolescente , Adulto , Anciano , Esquema de Medicación , Humanos , Inmunosupresores/uso terapéutico , Cumplimiento de la Medicación , Persona de Mediana Edad , Seguridad del Paciente , Prednisolona/uso terapéutico , Recurrencia , Inducción de Remisión , República de Corea , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). METHODS: From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < - 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. RESULTS: Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27-48) and 38 (27-50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0-3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982-0.991] and HR = 0.988 [0.983-0.993], respectively; all p < 0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57-3.13], HR = 2.03 [1.44-2.86], respectively; all p < 0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). CONCLUSIONS: Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.
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Creatinina/sangre , Cistatina C/sangre , Tasa de Filtración Glomerular , Fallo Renal Crónico , Insuficiencia Renal Crónica , Progresión de la Enfermedad , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Pronóstico , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Poor vessel quality and limited life expectancy in the elderly may make arteriovenous fistula (AVF) less ideal than arteriovenous graft (AVG) or catheter for vascular access (VA) in hemodialysis (HD). METHODS: A total of 946 adult incident HD patients from clinical research center registry for end-stage renal disease prospective cohort in South Korea were analyzed for outcomes with AVF and AVG. RESULTS: Overall, AVF was associated with better patient survival only in male (p < 0.001) and diabetic (p = 0.004) patients, although it was superior to AVG in access patency, regardless of diabetes mellitus status and gender. AVG (vs. AVF; hazard ratio (HR) 2.282; 95% CI 1.071-4.861; p = 0.032) was associated with poor patient survival. In elderly patients (≥65 years), AVF was associated with survival benefit only in male (p < 0.001) and diabetic (p = 0.04) patients, and with better access patency only in female (p = 0.05) and diabetic (p = 0.04) patients. AVG (vs. AVF; HR 3.158; 95% CI 1.080-9.238; p = 0.036) was associated with poor patient survival. In septuagenarian patients, AVF was associated only with survival benefit (p = 0.01) and there was no advantage in access patency (p = 0.12). However, AVF was superior to AVG in both access patency (p = 0.001) and patient survival (p = 0.03) even with propensity matching. CONCLUSION: AVF is the more desirable VA and its survival benefits warrant its consideration in septuagenarian patients although a prolonged life expectancy is essential to realize the potential benefits of AVF.
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Derivación Arteriovenosa Quirúrgica/estadística & datos numéricos , Fallo Renal Crónico/terapia , Diálisis Renal , Injerto Vascular/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Implantación de Prótesis Vascular , Complicaciones de la Diabetes/complicaciones , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea , Factores Sexuales , Tasa de Supervivencia , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND/AIMS: ß2-Microglobulin (ß2-M) is a surrogate marker of middle-molecule uremic toxins and is associated with mortality in chronic hemodialysis patients. However, the impact of serum ß2-M levels on mortality in peritoneal dialysis (PD) patients is uncertain. The purpose of this study was to examine the association of serum ß2-M levels with all-cause mortality in PD patients. METHODS: A total of 771 PD patients were selected from the Clinical Research Center registry for end-stage renal disease cohort in Korea. Patients were categorized into 3 groups by tertiles of serum ß2-M levels. The primary outcome was all-cause mortality. RESULTS: The median value of serum ß2-M was 23.6 mg/l (interquartile range 14.8-33.4 mg/l), and the median follow-up period was 39 months. The Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of serum ß2-M in PD patients (p=0.03, log-rank). Multivariate Cox proportional analysis showed that the hazards ratio for all-cause mortality was 1.02 (95% CI 1.01-1.04, p=0.006) per 1 mg/l increase in ß2-M after adjustment for multiple confounding factors that relate to malnutrition and inflammation marker. However, serum ß2-M was not associated with all-cause mortality after adjustment for residual renal clearance. CONCLUSIONS: These results are supportive of the potential role of the serum ß2-M level as a predictor of mortality in PD patients.
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Fallo Renal Crónico/terapia , Mortalidad , Diálisis Peritoneal , Sistema de Registros , Microglobulina beta-2/sangre , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , República de CoreaRESUMEN
In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Δ1.2 ± 2.9 mL/min/1.73 m(2), P=0.027) and urine volume (-Δ363.6 ± 543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Δ0.5 ± 2.7 mL/min/1.73 m(2), P=0.266; -Δ108.6 ± 543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, ß2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549].
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Soluciones para Diálisis/uso terapéutico , Glucanos/uso terapéutico , Glucosa/uso terapéutico , Fallo Renal Crónico/terapia , Adulto , Anciano , Antígeno Ca-125/análisis , Creatinina/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Icodextrina , Interleucina-6/análisis , Riñón/fisiopatología , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Diálisis Peritoneal , Diálisis Peritoneal Ambulatoria Continua , Urea/orinaRESUMEN
BACKGROUND: The relationship between glycated haemoglobin and the incidence of end-stage renal disease (ESRD) in patients with diabetes remains uncertain, especially in those with decreased glomerular filtration rate (GFR). The aim of this study was to assess the appropriate HbA(1c) level for diabetics for minimizing the incidence of ESRD and all-cause mortality. METHODS: A cohort of patients aged 25 years or older who had been treated for diabetes was generated from the Seoul National University Bundang Hospital database using diagnosis code and prescribed medication during 2004. The 4474 patients were classified into three groups according to the baseline HbA(1c) in 2004 (HbA(1c) < 6.50%, 6.50-7.49% and ≥ 7.50%; termed groups 1, 2 and 3, respectively). The outcomes were extracted from the database of Statistics Korea for mortality and registry in the Korean Society of Nephrology for ESRD incidence. RESULTS: Ninety patients developed ESRD during 5.29 ± 1.22 years of mean follow-up period. Group 1 patients showed the lowest incidence of ESRD (P = 0.003). Compared with this group, the adjusted hazard ratio of ESRD was 2.915 and 4.219 in groups 2 and 3, respectively. The incidence of ESRD increased in patients with HbA(1c) ≥ 6.50% compared with the patients with HbA(1c) < 6.50%, regardless of GFR. However, HbA(1c) < 6.50% showed no benefit on ESRD development in patients older than 80 years and in patients with diabetic duration > 10 years. All-cause mortality was not associated with the level of HbA(1c). CONCLUSIONS: HbA(1c) < 6.50% was associated with reduced development of ESRD in all patients and later stages of chronic kidney disease.
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Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/fisiopatología , Hemoglobina Glucada/metabolismo , Fallo Renal Crónico/etiología , Fallo Renal Crónico/metabolismo , Adulto , Anciano , Creatinina/metabolismo , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Incidencia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/metabolismo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Many studies have compared patient survival outcome between hemodialysis (HD) and peritoneal dialysis (PD); however, time-varying risks of dialysis modality have been rarely investigated. This study aimed to investigate dialysis modality switch and its association with the survival outcome in the Korean population. METHODS: Data from the Korean Society of Nephrology were used. A total of 21,840 incident dialysis patients who started dialysis in or after 2000 were analyzed. For the survival analysis, both proportional and non-proportional hazard assumptions were applied. For the modality switch, time-varying covariate Cox regression was applied. RESULTS: During the median follow-up of 8 years, PD group showed increased adjusted hazard ratio (HR) of 1.248 (95% CI 1.071-1.454, p = 0.004) for mortality. Interaction of PD status with female sex was significant with an HR of 1.080 (95% CI 1.000-1.165, p = 0.050). Dialysis modality switch was associated with increased HR of 1.094 (95% CI 1.015-1.180, p = 0.019), albeit switch from PD to HD did not show significant HR until 6 years. Interestingly, time-varying risk analysis showed a decreased HR of PD after 10 years in the non-switcher group, which was consistent in patients with high traditional risk factors (with diabetes, elderly). CONCLUSIONS: PD was associated with increased HR of mortality in the first 8 years, then it was associated with decreased HR of mortality after 10 years. Dialysis modality switch was associated with increased mortality risk, but switch from PD to HD within 6 years did not show significant hazard of mortality.
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Fallo Renal Crónico , Diálisis Peritoneal , Anciano , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , República de Corea , Factores de RiesgoRESUMEN
BACKGROUND: While the final goal of renal replacement therapy is to achieve normal social adaptation and employment, many studies to date have focused on the analysis of complications and causes of death. In contrast, the analysis of dialysis patients with normal job employment and exhibiting a good medical status can be important for clinical treatment policy. This study assessed various clinical parameters according to rehabilitation and employment status to elucidate characteristics correlated with better rehabilitation status among hemodialysis patients. METHODS: A total of 29,865 hemodialysis patients who were registered with rehabilitation status information in the Korean Society of Nephrology end-stage renal disease registration program from January 2017 to April 2019 were included and divided into five groups according to their rehabilitation status. RESULTS: About half (47%) of enrolled patients belonged to the "independent but without a job" group and 21% of patients belonged to the "employed with a full-time job" group. Analysis revealed significantly younger mean age, longer mean hemodialysis duration, a higher proportion of male sex, and a lower proportion of diabetic nephropathy cases in the full-time job group than in the other hemodialysis patient groups. Also, hemoglobin, albumin, and phosphorus levels were higher but the urea reduction ratio was lower in the full-time job group. CONCLUSION: A better rehabilitation and employment state of hemodialysis patients was associated with younger age, male sex, and underlying chronic glomerulonephritis. Patients with full-time jobs generally have better laboratory data but lower dialysis efficacy.
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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.
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Fístula Arteriovenosa/cirugía , Derivación Arteriovenosa Quirúrgica/mortalidad , Grado de Desobstrucción Vascular/fisiología , Anciano de 80 o más Años , Fístula Arteriovenosa/mortalidad , Femenino , Humanos , Masculino , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The End-stage Renal Disease Registry Committee of the Korean Society of Nephrology collects data on the dialysis therapy in Korea through an internet-based registry program and reports it annually. In this article, the method and clinical implications of the mortality hazard ratio analyses of various clinical parameters in the 2017 registry report have been described, with the inclusion of data on four additional parameters. The mortality risk based on clinical parameters was analyzed only for hemodialysis patients. The number of registered patients with laboratory data was 13,943 (8,446 male and 5,497 female patients), and death was reported in 3,139 patients. Analysis of the effects of various clinical parameters on mortality was performed using non-linear Cox proportional hazard model with the R statistics program. For all clinical parameters, univariate and adjusted multivariate hazard ratio analyses were performed. Analysis of the mortality hazard ratio showed that low body mass index, low hemoglobin, low serum albumin, low serum phosphorus, and low urea reduction ratio were associated with a significantly increased mortality risk, whereas paradoxically high serum creatinine levels were associated with low mortality risk.
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BACKGROUND: Unlike patterns observed in the general population, obesity is associated with better survival among hemodialysis patients, which could be explained by reverse causation or illness-related weight loss. However, the time-varying effect of body mass index (BMI) on hemodialysis survival has not been investigated. Therefore, this study investigated the time-varying effect of BMI on mortality after starting hemodialysis. METHODS: In the present study, we examined Korean Society of Nephrology data from 16,069 adult patients who started hemodialysis during or after the year 2000. Complete survival data were obtained from Statistics Korea. Survival analysis was performed using Cox regression and a non-proportional hazard fractional polynomial model. RESULTS: During the median follow-up of 8.6 years, 9,272 patients (57.7%) died. Compared to individuals with normal BMI (18.5-24.9 kg/m2), the underweight group (< 18.5 kg/m2) had a higer mortality hazard ratio (HR, 1.292; 95% confidence interval [CI], 1.203-1.387; P < 0.001) and the overweight group (25.0-29.9 kg/m2) had a lower mortality HR (0.904; 95% CI, 0.829-0.985; P = 0.022). The underweight group had increasing HRs during the first 3 to 7 years after starting hemodialysis, which varied according to age group. The young obese group (< 40 years old) had a U-shaped temporal trend in their mortality HRs, which reflected increased mortality after 7 years. CONCLUSION: The obese hemodialysis group had better survival during the early post-dialysis period, although the beneficial effect of obesity disappeared 7 years after starting hemodialysis. The young obese group also had an increased mortality HR after 7 years.
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INTRODUCTION: Previous studies have revealed that vascular access resistance is constant during hemodialysis, but differs according to vascular access type. It is possible that intra-access flow volume (Qac) variation during hemodialysis may also differ according to vascular access type. We conducted this study to investigate whether there are differences in Qac according to vascular access type during hemodialysis. METHODS: A total of 58 lower-arm arteriovenous fistula, 14 lower-arm arteriovenous graft, 27 upper-arm arteriovenous fistula, and 45 upper-arm arteriovenous graft cases were studied. Three consecutive Qac values (at 30, 120, and 240 min after the start of hemodialysis) were measured in each patient by the ultrasound dilution technique. Variations in Qac over time were analyzed using repeated measures analysis of variance and multivariate regression analyses, to assess the impact of different factors on Qac variation. RESULTS: The repeated measures analysis of variance revealed that a significant interaction exists between time and vascular access type (p < 0.001). This suggests that vascular access type affects Qac change (%) variation over time during hemodialysis. In a multivariate analysis, mean arterial pressure change during hemodialysis (p = 0.009), access type (p < 0.001), and access location (p < 0.001) were independent variables causing Qac change variation. CONCLUSION: This study showed that there is a significant difference in Qac variation according to vascular access type during hemodialysis and that arteriovenous graft (vs arteriovenous fistula) and the lower-arm location (vs upper arm) were associated with a decrease in Qac during hemodialysis. This suggests that consideration of vascular access type is required to minimize Qac variation during hemodialysis.
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Derivación Arteriovenosa Quirúrgica/métodos , Implantación de Prótesis Vascular/métodos , Diálisis Renal , Extremidad Superior/irrigación sanguínea , Adulto , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Velocidad del Flujo Sanguíneo , Implantación de Prótesis Vascular/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Flujo Sanguíneo Regional , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
The prevalence rate and the incidence rate of hemodialysis and functioning kidney transplant recipients have continuously increased; on the contrary, those of peritoneal dialysis have continuously decreased since 2006. Dialysis patients have been getting older and have been maintained on dialysis longer. Diabetic nephropathy was the leading cause of end stage renal disease. The type of hemodialysis vascular access has been stable during the last 5 years (arteriovenous fistulas 76%, arteriovenous grafts 16%, central venous catheters 8% at 2016). Peritoneal dialysis catheter was mostly inserted surgically (67%), and swan neck straight tip peritoneal dialysis catheter was the most commonly used (48%). Vascular access was managed by radiologists and surgeons, and the management was fragmented among them in the past. However, since the nephrologists became interested in and knowledgeable about the vascular access, they began to play roles in vascular access management. Vascular access has been mostly created by vascular surgeons (≈60%); tunneled central venous hemodialysis catheter insertion and endovascular intervention such as percutaneous transluminal angioplasty (PTA) and thrombectomy have been mostly performed by radiologists (≈70%). Tunneled hemodialysis catheter insertion and endovascular intervention by nephrologists have slowly but consistently increased. Recently, the number of central venous hemodialysis catheter insertion has decreased, and tunneled hemodialysis catheter has been inserted more than non-tunneled hemodialysis catheter, indicating that vascular access has been created timely and the vascular access team has been educated about and following international guidelines.
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Derivación Arteriovenosa Quirúrgica/tendencias , Implantación de Prótesis Vascular/tendencias , Cateterismo Venoso Central/tendencias , Enfermedades Renales/terapia , Evaluación de Procesos y Resultados en Atención de Salud/tendencias , Diálisis Peritoneal/tendencias , Pautas de la Práctica en Medicina/tendencias , Diálisis Renal/tendencias , Anciano , Angioplastia/tendencias , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Obstrucción del Catéter , Cateterismo Venoso Central/efectos adversos , Femenino , Oclusión de Injerto Vascular/epidemiología , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/cirugía , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Nefrólogos/tendencias , Radiólogos/tendencias , República de Corea/epidemiología , Cirujanos/tendencias , Trombectomía/tendencias , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-ß1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-ß1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-ß1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI.
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Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , NADPH Oxidasa 4/metabolismo , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Lesión Renal Aguda/fisiopatología , Animales , Apoptosis/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Pruebas de Función Renal , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , NADPH Oxidasa 4/antagonistas & inhibidores , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Pirazoles/farmacología , Pirazolonas , Piridinas/farmacología , Piridonas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Diabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Dialysis patients with diabetes mellitus (DM) have more complications and shorter survival duration than non-DM dialysis patients, requiring more clinical attention and difficult management. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an on-line registry program and analyzed the characteristics of patients. A survey of dialysis patients in 2016 showed that 50.2% of new dialysis patients had DM nephropathy as the cause of end-stage renal disease. The proportion of patients receiving hemodialysis (HD) for more than 5 years was 38% in DM patients and 51% in non-DM patients. The mean pulse pressure in DM HD patients was 71.5 mmHg, compared with 62.6 mmHg in non-DM patients. The proportion of DM patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of non-DM patients (73% vs. 78%). Mean serum creatinine of DM and non-DM dialysis patients was 8.4 mg/dL and 9.5 mg/dL respectively. As vascular access of the DM HD patients was poor, the dialysis adequacy of DM patients was slightly lower than that of non-DM patients. The 5-year survival rate for DM HD patients was 53.9%, which was much lower than that of chronic glomerulonephritis patients (78.2%). The proportion of patients with a full-time job was 17% for DM patients and 28% for non-DM patients.
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PURPOSE: Sevelamer, a noncalcium phosphate binder, has been shown to attenuate the progression of vascular calcification and improve survival in patients with chronic kidney disease undergoing dialysis compared with calcium-based binders. Using real-world data from a cohort study and the Health Insurance Review and Assessment Service database, we conducted a cost-effectiveness analysis comparing sevelamer with calcium acetate in dialysis patients from the perspective of the National Health Insurance Service in South Korea. METHODS: Data (demographic, diagnostic, laboratory, and survival) from 4674 patients undergoing dialysis enrolled in a multicenter prospective cohort study conducted in South Korea between September 2008 and December 2012 were linked to phosphate binder use, hospitalization, and cost data available from the Health Insurance Review and Assessment Service database. After propensity score matching, a dataset comprising comparable patients treated with either sevelamer (n = 501) or calcium acetate (n = 501) was used in the cost-effectiveness analysis. A Markov model was used to estimate costs, life years, quality-adjusted life years (QALYs), and cost-effectiveness over each patient's lifetime. Forty-month treatment-specific overall survival (OS) data available from the dataset were extrapolated to lifetime survival with the use of regression analysis. FINDINGS: Patients had a mean age of 56.3 years and were treated with dialysis for a mean duration of 67.6 months. Compared with calcium acetate, sevelamer was associated with an incremental cost of South Korean Won (â©) 12,246,911 ($10,819) and a gain of 1.758 life years and 1.108 QALYs per patient. This outcome yielded incremental cost-effectiveness ratios of â©6,966,350 ($6154) and â©11,057,699 ($9768) per life year and QALY gained, respectively. Conclusions regarding sevelamer's cost-effectiveness were insensitive to alternative assumptions in time horizon, discount rate, hospitalization rate, costs, and health utility estimates, and they remained consistent in 100% of the model iterations, considering a willingness-to-pay threshold of â©31,894,720 ($28,176) per QALY gained. IMPLICATIONS: This analysis of real-world data found that sevelamer's higher cost relative to calcium acetate was adequately offset by improved survival among patients undergoing dialysis in South Korea. As such, sevelamer offers good value for money, representing a cost-effective alternative to calcium-based binders.
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Acetatos/economía , Quelantes/economía , Diálisis Renal/economía , Insuficiencia Renal Crónica/economía , Sevelamer/economía , Acetatos/uso terapéutico , Adulto , Anciano , Pueblo Asiatico , Compuestos de Calcio/economía , Compuestos de Calcio/uso terapéutico , Quelantes/uso terapéutico , Análisis Costo-Beneficio , Femenino , Hospitalización/economía , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Programas Nacionales de Salud , Estudios Prospectivos , Años de Vida Ajustados por Calidad de Vida , Análisis de Regresión , Insuficiencia Renal Crónica/terapia , República de Corea , Sevelamer/uso terapéuticoRESUMEN
PURPOSE: The exchange from a non-tunneled hemodialysis catheter to a tunneled one over a guidewire using a previous venotomy has been reported to be safe. However, some concerns that it may increase infection risk prevent its clinical application. This approach seems particularly useful for acute kidney injury patients requiring initial renal replacement therapy, in whom we frequently worry about the choice of non-tunneled versus tunneled catheters. MATERIALS AND METHODS: From March 2012 to February 2016, 88 cases to receive the over-the-guidewire exchange method from a non-tunneled to a tunneled catheter and 521 cases to receive de novo tunneled catheter placement from the hemodialysis vascular access cohort were compared retrospectively. RESULTS: The immediate complication, later catheter dysfunction requiring replacement, and infection rates were comparable between the two groups. Newly placed tunneled catheter survival in the over-the-guidewire exchange group was comparable with survival in the de novo tunneled catheter group (p = 0.24). In addition, when we compared the same two methods among only intensive care unit patients; they remained similar (p = 0.19). CONCLUSION: An exchange with the over-the-guidewire method from a non-tunneled to a tunneled catheter was comparable to a de novo catheter placement technique. Therefore, this method should be viewed more favorably and should especially be considered for acute kidney injury patients.
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Lesión Renal Aguda/terapia , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Remoción de Dispositivos/métodos , Diálisis Renal , Grado de Desobstrucción Vascular , Lesión Renal Aguda/diagnóstico , Anciano , Obstrucción del Catéter/etiología , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Toma de Decisiones Clínicas , Remoción de Dispositivos/efectos adversos , Diseño de Equipo , Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
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.
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BACKGROUND: It is thought that hyperuricemia might lower the risk of mortality among hemodialysis patients, unlike in the general population, but the evidence is controversial. The aim of the current study was to evaluate the impact of serum uric acid level on the long-term clinical outcomes of hemodialysis patients in Korea. METHODS: Retrospective analysis was performed on data from the End-Stage Renal Disease Registry of the Korean Society of Nephrology. This included data for 7,333 patients (mean age, 61 ± 14 years; 61% male) who received hemodialysis from January 2001 through April 2015. Initial laboratory data were used in the analysis. RESULTS: The mean serum uric acid level in this study was 7.1 ± 1.7 mg/dL. Body mass index, normalized protein catabolic rate, albumin, and cholesterol were positively correlated with serum uric acid level after controlling for age and sex. After controlling for demographic data, comorbidities, and residual renal function, a higher uric acid level was independently associated with a significantly lower all-cause mortality (hazard ratio [HR], 0.90 per 1 mg/dL increase in uric acid level; 95% confidence interval [CI], 0.83-0.97; P = 0.008), but not cardiovascular mortality (HR, 0.90; 95% CI, 0.80-1.01; P = 0.078). Comparing uric acid levels in the highest and lowest quintiles, the HR for all-cause mortality was 0.65 (95% CI, 0.42-0.99; P = 0.046). CONCLUSION: Hyperuricemia was strongly associated with a lower risk of all-cause mortality, but there seems to be no significant association between serum uric acid level and cardiovascular mortality among Korean hemodialysis patients with end-stage renal disease.
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INTRODUCTION: To increase the rate of arteriovenous fistula (AVF) use, assisted procedures for immature AVF have been strenuously performed. However, this is controversial in that an AVF matured by these assisted procedures may require more frequent intervention to maintain its patency, and have decreased long-term patency. METHODS: Eighty four AVFs that were matured with assisted maturation procedures and 266 AVFs that matured spontaneously without intervention, created between November 2009 and March 2013 from the hemodialysis (HD) vascular access (VA) cohort, were compared retrospectively and we also investigated the factors that may influence AVF long-term patency. Median follow-up was 26.8 months (interquartile range, 6.6-45.0 months). FINDINGS: Access survival did not differ between AVFs matured by assisted procedures and spontaneously mature AVFs (P = 0.29). In multivariate Cox regression analysis of AVF survival, age (HR, 1.029; 95% CI, 1.004-1.056; P = 0.024), maturation without assisted procedures 4-6 weeks after AVF creation (HR, 0.233; 95% CI, 0.107-0.506; P < 0.001), and AVF thrombosis (HR, 26.511; 95% CI, 10.986-63.978; P < 0.001) were significantly associated with AVF survival. Performance of assisted procedures to induce AVF maturation did not influence AVF survival (HR, 0.437; 95% CI, 0.191-1.002; P = 0.05). DISCUSSION: Our results support that idea that assisted maturation procedures can ensure the success of immature AVF without compromising long-term patency. These procedures can be considered more positively for increasing AVF use for VA placement in HD patients.