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INTRODUCTION: The relationship between fat mass and osteoporosis, sarcopenia and osteosarcopenia is complex. While higher fat mass generally has a negative impact on bone and muscle health in the general population, the impact in peritoneal dialysis (PD) patients is less well understood. METHODS: In this study of 359 PD patients, sarcopenia was identified using appendicular skeletal muscle per square meter (ASM/m²), with cut-off values of <7.0 kg/m² for men and <5.5 kg/m² for women. Fat tissue index (FTI) and lean tissue index (LTI) were determined using body composition monitoring, with the lowest tertile classified as low FTI and low LTI. Bone mineral density (BMD) was measured, with a T-score below -2.5 indicating osteoporosis. RESULTS: The prevalence of osteoporosis, sarcopenia, and osteosarcopenia was 25%, 32%, and 15%, respectively. Notably, 60% of osteoporotic patients had sarcopenia, and about 45% of sarcopenic patients had osteoporosis. Patients with osteoporosis were older and had significantly lower LTI (15.3 vs. 12.7 kg/m², p<0.001) and ASM (7.3 vs. 5.8 kg/m2, p<0.001). Osteoporotic patients also had lower FTI, but this was more pronounced in men than in women. Patients with both sarcopenia and osteoporosis had the lowest LTI and FTI compared to those with only one or neither condition. Low FTI was a significant determinant for osteoporosis (OR, 2.34; 95% CI, 1.43-3.85; P = 0.001), sarcopenia (OR, 2.91; 95% CI, 1.82-4.64; P < 0.001), and osteosarcopenia (OR, 2.34; 95% CI, 1.30-4.24; P = 0.005) in univariate analysis, and these associations remained significant after adjustment for age and body mass index. CONCLUSION: Osteoporosis and sarcopenia are common and interrelated in PD patients. Low fat mass, but not normal/high fat mass, was significantly associated with these conditions, suggesting the importance of maintaining adequate fat mass in PD patients.
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Interleukin (IL)-17-secreting invariant natural killer T (NKT) cells are involved in several inflammatory diseases. However, their role in lupus nephritis (LN) has not been fully characterized. Samples from patients with LN or glomerulonephritis and healthy controls were obtained, and elevated IL-17+ NKT cell numbers and IL-17 expression were observed in blood cells and kidneys, respectively, in patients with LN. Comparison of a mouse model of experimental autoimmune LN with the parental strain (NKT-deficient B6.CD1d-/- mice) revealed improved proteinuria, disease severity, and histopathology and decreased levels of chemokine (C-X-C motif) ligand 16 and T cell receptor-α variable 14 expression. Spleens and kidneys of B6.CD1d-/- mice also showed downregulation of inflammatory markers and IL-17. In coculture with renal mesangial and NKT cells, inflammatory markers and IL-17 were upregulated following α-galactosylceramide treatment and downregulated after treatment with IL-17-blocking antibodies. This was most prominent with killer cell lectin-like receptor subfamily B member 1 C (NK1.1)- NKT cells. Thus, IL-17 is upregulated in LN. Activation of NKT cells regulates IL-17-related immune responses systemically and in the kidneys, primarily via NK1.1- NKT cells. IL-17-secreting NK1.1- NKT cells could serve as diagnostic and therapeutic targets for LN.NEW & NOTEWORTHY This study makes a significant contribution to the literature because our results indicate that IL-17 is upregulated in lupus nephritis and that natural killer T (NKT) cells are involved in its pathogenesis. Activation of NKT cells regulates IL-17-related immune responses, both systemically and in the kidney, and this mainly involves NK1.1- NKT cells. Furthermore, IL-17-secreting NK1.1- NKT cells could serve as a diagnostic and therapeutic target for lupus nephritis.
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Interleucina-17/metabolismo , Riñón/metabolismo , Nefritis Lúpica/metabolismo , Activación de Linfocitos , Células T Asesinas Naturales/metabolismo , Animales , Estudios de Casos y Controles , Comunicación Celular , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Humanos , Riñón/inmunología , Riñón/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Células T Asesinas Naturales/inmunología , Fenotipo , Índice de Severidad de la Enfermedad , Células Th17/inmunología , Células Th17/metabolismo , Regulación hacia ArribaRESUMEN
We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-ß1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1ß) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-ß1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-ß1/Smad pathway.
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Lesión Renal Aguda/patología , Insuficiencia Renal Crónica/metabolismo , Proteína smad7/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Animales , Fibrosis/patología , Humanos , Riñón/metabolismo , Ratones Endogámicos C57BL , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Acute kidney injury (AKI) is a very common complication with high morbidity and mortality rates and no fundamental treatment. In this study, we investigated whether the hepatocyte growth factor (HGF)/cMet pathway is associated with the development of AKI and how the administration of a cMet agonistic antibody (Ab) affects an AKI model. In the analysis using human blood samples, cMet and HGF levels were found to be significantly increased in the AKI group, regardless of underlying renal function. The administration of a cMet agonistic Ab improved the functional and histological changes after bilateral ischaemia-reperfusion injury. TUNEL-positive cells and Bax/Bcl-2 ratio were also reduced by cMet agonistic Ab treatment. In addition, cMet agonistic Ab treatment significantly increased the levels of PI3K, Akt and mTOR. Furthermore, after 24 hours of hypoxia induction in human proximal tubular epithelial cells, treatment with the cMet agonistic Ab also showed dose-dependent antiapoptotic effects similar to those of the recombinant HGF treatment. Even when the HGF axis was blocked with a HGF-blocking Ab, the cMet agonistic Ab showed an independent dose-dependent antiapoptotic effect. In conclusion, cMet expression is associated with the occurrence of AKI. cMet agonistic Ab treatment attenuates the severity of AKI through the PI3K/Akt/mTOR pathway and improves apoptosis. cMet agonistic Ab may have important significance for the treatment of AKI.
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Lesión Renal Aguda/metabolismo , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Anciano , Animales , Ciclo Celular/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/etiología , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below-median (Group 2) and above-median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary-cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)-α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria (P < .001). During the follow-up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr < 300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF-α treatment, the proliferation of mesangial cells and increased interleukin-8 and intercellular adhesion molecule-1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.
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Glomerulonefritis por IGA/orina , Proteínas Proto-Oncogénicas c-met/orina , Adulto , Biomarcadores/orina , Creatinina/orina , Femenino , Glomerulonefritis por IGA/complicaciones , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Pronóstico , Proteinuria/complicaciones , Inducción de RemisiónRESUMEN
Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share risk factors, and recent meta-analysis confirmed that NAFLD is an independent risk factor for incident CKD.1 Genetic variants associated with NAFLD, such as patatin-like phospholipase domain-containing-3 (PNPLA3) rs7384092 and transmembrane 6 superfamily member 2 (TM6SF2) rs5854292,2 have been reported to be associated with renal function in NAFLD subjects.
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Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Aciltransferasas/genética , Biopsia , Predisposición Genética a la Enfermedad , Humanos , Lipasa/genética , Hígado , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo de Nucleótido Simple , Insuficiencia Renal Crónica/genéticaRESUMEN
BACKGROUNDS: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). METHODS: The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. DISCUSSION: Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. TRIAL REGISTRATION: NCT03929887 .
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Bancos de Muestras Biológicas , Bases de Datos Factuales , Glomerulonefritis/patología , Fallo Renal Crónico/patología , Riñón/patología , Glomerulonefritis/genética , Glomerulonefritis/metabolismo , Glomerulonefritis/terapia , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Evaluación del Resultado de la Atención al Paciente , Terapia de Reemplazo Renal , República de CoreaRESUMEN
Periostin plays a crucial role in fibrosis, and acute kidney injury results in a high risk of progression to chronic kidney disease. Therefore, we hypothesized that periostin was involved in the progression of acute kidney injury to kidney fibrosis. Unilateral ischemia-reperfusion injury (UIRI) was induced in 7- to 8-wk-old male wild-type and periostin-null mice, and the animals were observed for 6 wk. In vitro, human kidney-2 cells and primary-cultured human tubular epithelial cells were incubated under hypoxic conditions (5% O2, 5% CO2, and 90% N2) for 5 days. The cells were also cultured with recombinant periostin (rPeriostin) and a p38 mitogen-activated protein kinase (MAPK) inhibitor in a hypoxic incubator. At 6 wk after UIRI, interstitial fibrosis/tubular atrophy was significantly alleviated in periostin-null mice compared with wild-type controls. In addition, periostin-null mice had attenuated expression of fibrosis/apoptosis markers and phosphorylated-p38 MAPK compared with wild-type controls. In vitro, hypoxic injury increased the expression of fibrosis markers, periostin, and phosphorylated-p38 MAPK, which was comparable to or substantially greater than their expression levels following treatment with recombinant transforming growth factor-ß1 under normoxic conditions. Furthermore, rPeriostin treatment under hypoxic conditions enhanced fibrosis/apoptosis markers and phosphorylated-p38 MAPK. In contrast, p38 MAPK inhibition ameliorated hypoxia-induced fibrosis, and the addition of the p38 MAPK inhibitor to rPeriostin significantly ameliorated the changes induced by rPeriostin. In conclusion, periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against chronic kidney disease progression.
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Lesión Renal Aguda/metabolismo , Moléculas de Adhesión Celular/metabolismo , Riñón/metabolismo , Transducción de Señal/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Animales , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/farmacología , Línea Celular , Fibrosis/genética , Fibrosis/metabolismo , Fibrosis/patología , Humanos , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Ratones , Ratones Noqueados , Fosforilación/efectos de los fármacos , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is an important cause of acute kidney injury and often a potentially reversible disease. However, the role of steroids in ATIN remains controversial and the underlying mechanisms remain unresolved. METHODS: A total of 113 adult patients with biopsy-proven ATIN were recruited from three tertiary referral centers. Of 102 patients with idiopathic or drug-induced ATIN, outcomes such as renal recovery, end-stage renal disease, and all-cause mortality were compared between the steroid-treated and non-treated groups. Plasma and urine inflammatory cytokine levels at the time of biopsy were analyzed in patients (n = 33) using a bead-based multiplex assay and compared with those of healthy individuals (n = 40). RESULTS: Steroids were used in 92 (81.4%) of the total patients and in 82 (80.3%) patients with idiopathic or drug-induced ATIN. The rate of renal recovery and the risks of end-stage renal disease and mortality were not different between the steroid-treated and non-treated groups. Despite using a propensity score matching method (n = 20 in each group), none of the outcomes were different between the two groups. Several cytokines, such as monocyte chemotactic protein-1, interferon-α, and interleukin-6 and interleukin-8 levels, were markedly elevated in plasma and urine of patients compared with those in healthy individuals. However, cytokines related to Th2 response, such as IL-10, IL-33, were not different between the two groups. CONCLUSIONS: Steroid use does not affect the overall outcome of ATIN. Based on the fact that targeting therapy should be investigated to improve outcomes, the present cytokine results will be helpful for developing a novel therapy for ATIN.
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Citocinas/metabolismo , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nefritis Intersticial/diagnóstico , Esteroides/uso terapéuticoRESUMEN
OBJECTIVES: Long-term risk of a major adverse cardiovascular events in ICU survivors who underwent acute renal replacement therapy requires further investigation. DESIGN: Nationwide population-based study using the claims database of Korea. SETTING: Index admission cases of ICU survivors in government-designated tertiary hospitals PATIENTS:: The study group consisted of ICU survivors who underwent acute renal replacement therapy, and the control group consisted of those without acute renal replacement therapy. Patients were excluded if they 1) were under age 20, 2) expired within 30 days after discharge, 3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5) had a history of major adverse cardiovascular event, or 6) had a major adverse cardiovascular event-related cardio/cerebrovascular diseases. The outcomes of the patients who received continuous renal replacement therapy were compared with those of patients who received only intermittent renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information regarding patient characteristics and treatment modalities was collected and adjusted. The main outcome was major adverse cardiovascular event, including acute myocardial infarction, revascularization, and acute ischemic stroke. Patient mortality and progression to end-stage renal disease were also evaluated. We included 12,380 acute renal replacement therapy patients and 382,018 patients in the control group. Among the study group, 6,891 patients were included in the continuous renal replacement therapy group, and 5,034 in the intermittent renal replacement therapy group. The risks of major adverse cardiovascular event (adjusted hazard ratio, 1.463 [1.323-1.619]; p < 0.001), all-cause mortality (adjusted hazard ratio, 1.323 [1.256-1.393]; p < 0.001), and end-stage renal disease (adjusted hazard ratio, 18.110 [15.779-20.786]; p < 0.001) were higher in the acute renal replacement therapy patients than the control group. When we compared the continuous renal replacement therapy patients with the intermittent renal replacement therapy patients, the risk of major adverse cardiovascular event was comparable (adjusted hazard ratio, 1.049 [0.888-1.239]; p = 0.575). CONCLUSIONS: Clinicians should note the increased risk of a long-term major adverse cardiovascular event in acute renal replacement therapy patients and consider appropriate risk factor management. Significant difference in the risk of postdischarge major adverse cardiovascular event was not identified between continuous renal replacement therapy and intermittent renal replacement therapy.
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Lesión Renal Aguda/mortalidad , Enfermedades Cardiovasculares/mortalidad , Enfermedad Crítica/mortalidad , Terapia de Reemplazo Renal/estadística & datos numéricos , Sobrevivientes/estadística & datos numéricos , Lesión Renal Aguda/cirugía , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Alta del Paciente/estadística & datos numéricos , República de CoreaRESUMEN
OBJECTIVES: Severe acute kidney injury requiring continuous renal replacement therapy is associated with a high risk of early mortality. Our objectives were to identify a cohort of early survivors and to follow their renal progress and long-term mortality. DESIGN: Multicenter, observational, retrospective cohort study. SETTING: ICUs in tertiary academic hospitals in Korea. PATIENTS: From 2009 to 2013, we identified 1,764 severe acute kidney injury patients who were started on continuous renal replacement therapy at four hospitals. Of these, we identified 331 survivors for whom we could identify renal function at baseline and at 3 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 331 patients were separated into two groups based on their renal function at 3 months after the start of continuous renal replacement therapy. Those who displayed significant deterioration in renal function compared to baseline, defined as greater than or equal to 50% increase in serum creatinine or greater than or equal to 35% decrease in the estimated glomerular filtration rate, or those who continued to receive renal replacement therapy were designated as a "3-month chronic kidney disease progression" group. Those with a return to baseline, less than 50% increase in serum creatinine or less than 35% decrease in the estimated glomerular filtration rate, were designated as a "3-month chronic kidney disease nonprogression" group. The acute kidney injury patients requiring continuous renal replacement therapy showed a higher risk of progression to end-stage renal disease compared to that of stage 3 chronic kidney disease patients who did not undergo an acute kidney injury episode, even if the acute kidney injury was recovered at 3 months after continuous renal replacement therapy initiation. Furthermore, "3-month chronic kidney disease progression" was associated with a high risk of progression to end-stage renal disease and long-term mortality over a median follow-up period of 12.7 (3.8-33.2) and 20.4 (7.5-39.7) months, respectively. Older age, higher baseline serum creatinine levels, and higher blood urea nitrogen concentrations at continuous renal replacement therapy initiation, and lower 24-hour urine output after continuous renal replacement therapy initiation are associated with an increased risk of "3-month chronic kidney disease progression." CONCLUSIONS: Renal functional assessment at 3 months after continuous renal replacement therapy initiation can be useful in predicting progression to end-stage renal disease and long-term mortality. Furthermore, continuous close monitoring and management of acute kidney injury patients requiring continuous renal replacement therapy are required, even in those with recovered renal function.
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Lesión Renal Aguda/epidemiología , Progresión de la Enfermedad , Fallo Renal Crónico/mortalidad , Insuficiencia Renal Crónica/terapia , Terapia de Reemplazo Renal , Factores de Edad , Anciano , Nitrógeno de la Urea Sanguínea , Estudios de Casos y Controles , Estudios de Cohortes , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Oliguria/epidemiología , Insuficiencia Renal Crónica/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Periostin is responsible for tissue regeneration, fibrosis, and wound healing via its interaction with integrin. Recently, the role of periostin has been shown to contribute to fibrosis in chronic kidney disease. We investigated the role of periostin and the effect of periostin blockade in renal fibrogenesis. METHODS: We investigated the function of periostin in vivo in wild-type and periostin-null mice (Postn-KO) in a unilateral ureteral obstruction (UUO) model. For the in vitro experiments, primary cultured inner medullary collecting duct cells from the wild-type and Postn-KO mice were used. RESULTS: Periostin expression was strongly induced by UUO in the wild-type mice. UUO induced renal fibrosis and morphological changes in the obstructed kidney of wild-type mice, whereas global knockout of periostin reduced fibrosis induced by UUO and improved kidney structure. Fibrosis- and inflammation-related mRNA were significantly induced in the wild-type mice and were decreased in the Postn-KO mice. Additionally, α-smooth muscle actin expression was increased following the administration of recombinant periostin in vitro. The effect of periostin blockade was examined using 2 methods. The integrin blockade peptide decreased fibrosis-related gene expression in in vitro experiments. Anti-periostin polyclonal antibody attenuated renal fibrosis induced by UUO through changes in transforming growth factor-ß signaling and the inflammatory and apoptotic pathways. CONCLUSION: Periostin is a marker of renal fibrosis and may augment the progression of fibrogenesis as an extracellular matrix protein. Periostin blockade effectively attenuated renal fibrogenesis. Thus, periostin inhibition may be a therapeutic strategy for the amelioration of renal disease progression.
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Moléculas de Adhesión Celular/metabolismo , Nefroesclerosis/etiología , Animales , Biomarcadores/metabolismo , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/genética , Células Cultivadas , Citocinas/metabolismo , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/patología , Humanos , Inflamación/metabolismo , Integrinas/antagonistas & inhibidores , Integrinas/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Nefroesclerosis/metabolismo , Oligopéptidos , Factor de Crecimiento Transformador beta , Obstrucción UreteralRESUMEN
Blood pressure (BP) control is considered the most important treatment for preventing chronic kidney disease (CKD) progression and associated cardiovascular complications. However, clinic BP is insufficient to diagnose hypertension (HT) and to monitor overall BP control because it does not correlate well with ambulatory blood pressure monitoring (ABPM). We enrolled 387 hypertensive CKD patients (stages G1-G4, 58.4% male with median age 61 years) from 3 hospitals in Korea. HT of clinic BP and ABPM was classified as ≥ 140/90 and ≥ 130/80 mmHg, respectively. Clinic BP control rate was 60.2%. The median 24-hour systolic blood pressures (SBPs) of CKD G3b and CKD G4 were significantly higher than those of CKD G1-2 and CKD G3a. However, the median 24-hour SBPs were not different between CKD G1-2 and CKD G3a or between CKD G3b and CKD G4. Of all patients, 5.7%, 38.0%. 42.3%, and 14.0% were extreme-dippers, dippers, non-dippers, and reverse-dippers, respectively. Non-/reverse-dippers independently correlated with higher Ca × P product, higher intact parathyroid hormone (iPTH), and lower albumin. Normal BP was 33.3%, and sustained, masked, and white-coat HT were 29.7%, 26.9%, and 10.1%, respectively. White-coat HT independently correlated with age ≥ 61 years and masked HT independently correlated with CKD G3b/G4. In conclusion, ABPM revealed a high prevalence of non-/reverse-dippers and sustained/masked HT in Korean CKD patients. Clinicians should try to obtain a CKD patient's ABPM, especially among those who are older or who have advanced CKD as well as those with abnormal Ca × P product, iPTH, and albumin.
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Presión Sanguínea/fisiología , Insuficiencia Renal Crónica/patología , Adulto , Anciano , Pueblo Asiatico , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Tasa de Filtración Glomerular , Hospitales , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Hormona Paratiroidea/análisis , Insuficiencia Renal Crónica/complicaciones , República de Corea , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). METHODS: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). RESULTS: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. CONCLUSION: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.
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Moléculas de Adhesión Celular/orina , Glomerulonefritis por IGA/orina , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Moléculas de Adhesión Celular/sangre , Línea Celular , Femenino , Fibrosis , Glomerulonefritis por IGA/sangre , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/patología , Humanos , Riñón/patología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Fallo Renal Crónico/orina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Continuous renal replacement therapy (CRRT) is essential in the management of critically ill patients with acute kidney injury (AKI). However, the optimal timing for initiating CRRT remains controversial, especially in elderly patients. Therefore, we investigated the outcomes of early CRRT initiation in elderly patients with AKI. METHODS: A total of 607 patients ≥65 years of age who started CRRT due to AKI between August 2009 and December 2013 were prospectively enrolled. They were divided into two groups based on the median 6-hour urine output immediately before CRRT initiation. Propensity score matching was used to compare the overall survival rate, CRRT duration, and hospitalization duration. RESULTS: The median age of both groups was 73.0 years, and 60 % of the patients were male. The most common cause of AKI was sepsis. In the early CRRT group, the mean arterial pressure was higher, but the prothrombin time and total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were lower. The overall cumulative survival rate was higher in the early CRRT group (log-rank P < 0.01). Late CRRT initiation was associated with a higher mortality rate than early initiation after adjusting for age, sex, the Charlson comorbidity index, systolic arterial pressure, prothrombin time, the total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels, cumulative fluid balance and diuretic use (hazard ratio, 1.35; 95 % confidence interval 1.06, 1.71, P = 0.02). Following propensity score matching, patient survival was significantly better in the early CRRT group than in the late CRRT group (P < 0.01). The total duration of hospitalization from the start of CRRT was shorter among the survivors when CRRT was started earlier (26.7 versus 39.1 days, P = 0.04). CONCLUSION: A better prognosis can be expected if CRRT is applied early in the course of AKI in critically ill, elderly patients.
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Lesión Renal Aguda/terapia , Enfermedad Crítica/mortalidad , Terapia de Reemplazo Renal/métodos , Factores de Tiempo , APACHE , Lesión Renal Aguda/epidemiología , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Estudios de Cohortes , Enfermedad Crítica/epidemiología , Femenino , Humanos , Masculino , Pronóstico , Puntaje de Propensión , Estudios Prospectivos , Análisis de Regresión , Terapia de Reemplazo Renal/normas , República de Corea/epidemiología , Análisis de SupervivenciaRESUMEN
AIM: In the general population, proteinuria is associated with progression to kidney failure, cardiovascular disease, and mortality. Here, we analyzed the effects of proteinuria on outcomes in kidney transplant recipients. METHODS: We performed a retrospective, multi-centre cohort study involving 2047 recipients to evaluate the effects of post-transplant proteinuria on adverse cardiovascular events, graft failure, and mortality. Patients were classified into two groups according to their levels of proteinuria: patients without proteinuria (<150 mg/day, n = 1113) and proteinuric patients (≥ 150 mg/day, n = 934). Multivariate Cox hazard model was conducted with using the maximal proteinuria as time-varying covariate. RESULTS: During a median 55.3-month (range, 0.6-167.1) follow-up, there were 50 cases of major adverse cardiac events (cardiac death, nonfatal myocardial infarction, or coronary revascularization), 115 cases of graft failure, and 52 patient deaths. In multivariate Cox regression with time-varying covariate, proteinuric recipients were significantly associated with major adverse cardiac events (hazard ratio [HR] 8.689, 95% confidence interval [CI] 2.929-25.774, P < 0.001) compared to those without proteinuria. Recipients with proteinuria showed significantly higher incidences of acute rejection (23.1% vs. 9.4%, P < 0.001) and graft failure rate (HR 6.910, 95% CI 3.270-14.601, P < 0.001). In addition, mortality rate was also significantly higher in patients with proteinuria (HR 6.815, 95% CI 2.164-21.467, P = 0.001). CONCLUSION: Post-transplant proteinuria correlates with adverse cardiovascular events, graft failure, and mortality. Therefore, proteinuria should be evaluated and managed to improve the outcomes of renal recipients.
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Enfermedades Cardiovasculares/epidemiología , Rechazo de Injerto/epidemiología , Trasplante de Riñón/efectos adversos , Proteinuria/epidemiología , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Distribución de Chi-Cuadrado , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/mortalidad , Humanos , Incidencia , Estimación de Kaplan-Meier , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Proteinuria/diagnóstico , Proteinuria/mortalidad , República de Corea/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Contrast-induced nephropathy (CIN) is an important cause of hospital-acquired acute kidney injury. An accurate understanding of the pathogenesis of CIN is crucial. The aim of this study was to evaluate the clinical role of circulating tumour necrosis factor receptors (cTNFRs) in CIN. METHODS: From May 2013 to February 2014, 262 patients who underwent coronary angiography and/or percutaneous coronary intervention at Seoul National University Boramae Medical Center were enrolled. CIN was defined as either an increase in serum creatinine ≥ 22.1 µmol/L or ≥ 25% within 48 h after the procedure. RESULTS: Diabetes and chronic kidney disease accounted for 27.5% and 17.6% of the patients, respectively, and the mean age was 65 years. All patients received fluid therapy, and 36.3% underwent percutaneous coronary intervention. A total of 4.2% of the patients developed CIN; younger age, underlying diseases (e.g., stroke and chronic kidney disease), the use of N-acetylcysteine, and elevated concentrations of ln(cTNFRs) were associated with development of CIN. Increased values of ln(cTNFR1) (OR 6.32, 95% CI 2.46-16.28, P < 0.001) and ln(cTNFR2) (OR 3.24, 95% CI 1.26-8.31, P = 0.015) were significantly associated with CIN after adjusting for other risk factors, including baseline renal function. Moreover, an increase of cTNFRs levels was independently correlated with the deterioration of renal function. CONCLUSION: Markedly elevated concentrations of circulating TNFRs were correlated with the occurrence of CIN and significantly associated with prolonged renal dysfunction regardless of the development of CIN.
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Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Riñón/efectos de los fármacos , Intervención Coronaria Percutánea/efectos adversos , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Centros Médicos Académicos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Anciano , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Riñón/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Prospectivos , República de Corea , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: Malnutrition, inflammation, and atherosclerosis (MIA) syndrome is associated with a high mortality rate in patients with end-stage renal disease. However, the clinical relevance of MIA syndrome in kidney transplantation (KT) recipients remains unknown. METHODS: We enrolled 1348 adult KT recipients. Recipients were assessed based on serum albumin, cholesterol, or body mass index for the malnutrition factor and C-reactive protein level for the inflammation factor. Any history of cardiovascular (CV), cerebrovascular, or peripheral vascular disease satisfied the atherosclerosis factor. Each MIA factors were assessed by univariate analysis and we calculated an overall risk score by summing up scores for each independent variable. The enrolled patients were divided into 4 groups depending on the MIA score (0, 2-4, 6, 8-10). RESULTS: The patients with higher MIA score showed worse outcome of fatal/non-fatal acute coronary syndrome (ACS) (p < 0.001) and composite outcomes of ACS and all-cause mortality (p < 0.001) than with the lower MIA score. In multivariate analysis, ACS showed significantly higher incidence in the MIA score 8-10 group than in the MIA score 0 group (Hazard ratio 6.12 95 % Confidence interval 1.84-20.32 p = 0.003). CONCLUSIONS: The presence of MIA factors before KT is an independent predictor of post-transplant CV outcomes.
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Síndrome Coronario Agudo/epidemiología , Aterosclerosis/epidemiología , Trastornos Cerebrovasculares/epidemiología , Inflamación/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Desnutrición/epidemiología , Enfermedades Vasculares Periféricas/epidemiología , Síndrome Coronario Agudo/mortalidad , Adulto , Anciano , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Trastornos Cerebrovasculares/mortalidad , Colesterol/metabolismo , Comorbilidad , Femenino , Humanos , Inflamación/metabolismo , Fallo Renal Crónico/epidemiología , Masculino , Desnutrición/metabolismo , Persona de Mediana Edad , Mortalidad , Análisis Multivariante , Enfermedades Vasculares Periféricas/mortalidad , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/metabolismoRESUMEN
Visit-to-visit systolic blood pressure variability (VTV-SBPV) is correlated with cardiovascular complications. However, it still remains unclear whether VTV-SBPV is related to cardiovascular outcomes in patients with peritoneal dialysis (PD), who often manifest hypertension. We, therefore, evaluated the association of VTV-SBPV with all-cause mortality, cardiovascular complications, or the loss of residual renal function (RRF) that is a powerful predictor of mortality and morbidity in PD patients. We retrospectively reviewed the medical records for patients undergoing maintenance PD for at least 12 months at Seoul National University Hospital. The patients were divided into quartiles of VTV-SBPV based on the standard deviation of systolic blood pressure (SBP). We checked the SBP of the patients for up to 2 years after the initiation of PD. Among 216 PD patients, 16 primary outcome events (cardiovascular complications and all-cause mortality) occurred. VTV-SBPV was not associated with primary outcomes. During the follow-up, RRF loss occurred in 46 patients. The hazard ratios (HRs) for the loss of RRF in the 4 quartiles of VTV-SBPV, based on the highest to the lowest variability, were as follows: 6.201 (95% CI: 1.982-19.401, p = 0.002), 2.542 (95% CI: 0.859-7.523, p = 0.092), and 2.133 (95% CI: 0.635-7.165, p = 0.246), respectively. The loss of RRF was more frequently detected in patients with higher VTV-SBPV. VTV-SBPV was indicated as an independent risk factor for the loss of RRF. Therefore, the degree of variations in SBP should be carefully monitored to preserve the RRF of these patients.
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Presión Sanguínea , Pruebas de Función Renal , Diálisis Peritoneal , Sístole , Adulto , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Resultado del TratamientoRESUMEN
The relationship between molybdenum and kidney-related disease outcomes, including hyperuricemia, is not well investigated. This study aims to determine whether molybdenum and its antioxidative property are associated with systemic inflammation and kidney-related disease parameters including hyperuricemia. Urinary molybdenum's epidemiological relationship to hyperuricemia and kidney-disease related outcomes was evaluated in 15,370 adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2016. Individuals' urinary molybdenum levels were corrected to their urinary creatinine concentrations. The association between urinary molybdenum-to-creatinine ratio and kidney-disease related outcomes were assessed by multivariable linear and logistic regression analyses, adjusting for covariates including age, sex, ethnicity, diabetes mellitus, hypertension, body mass index, and estimated glomerular filtration rate. Antimony and tungsten were used as control trace metals. Experimentally, HK-2 cell was used to assess molybdenum's antioxidative properties. HK-2 cells were challenged with H2O2-induced oxidative stress. Oxidative stress was measured using a fluorescent microplate assay for reactive oxygen species (ROS) and antioxidation levels were assessed by measuring the expression of manganese superoxide dismutase. In the adult NHANES population, urinary molybdenum-to-creatinine ratio was significantly associated with decreased serum uric acid (ß, -0.119; 95% CI, -0.148 to -0.090) concentrations, and decreased prevalence of hyperuricemia (OR, 0.73; 95% CI, 0.64-0.83) and gout (OR, 0.71; 95% CI, 0.52-0.94). Higher urinary molybdenum levels were associated with lower levels of systemic oxidative stress (gamma-glutamyltransferase levels; ß, -0.052; 95% CI, -0.067 to -0.037) and inflammation (C-reactive protein levels; ß, -0.184; 95% CI, -0.220 to -0.148). In HK-2 cells under H2O2-induced oxidative stress, molybdenum upregulated manganese superoxide dismutase expression and decreased oxidative stress. Urinary molybdenum levels are associated with decreased prevalence of hyperuricemia and gout in adult population. Molybdenum's antioxidative properties might have acted as an important mechanism for the reduction of systemic inflammation, ROS, and uric acid levels.