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1.
J Clin Med ; 13(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38541842

ABSTRACT

(1) Background: The relationship between nonalcoholic fatty liver disease (NAFLD) and incident chronic kidney disease (CKD) is unclear, and long-term follow-up data are limited. Therefore, this study aimed to evaluate whether NAFLD, as assessed by the fatty liver index (FLI), could predict the development of CKD in a community-based Korean cohort over 16 years. (2) Methods: Among the 10,030 total participants, 7778 patients without CKD were selected from the Korean Genome and Epidemiology Study (KoGES). The FLI grade ranged from 0 to 100 and was divided into three groups: low (FLI, <30), intermediate (FLI, 30-59), and high (FLI, ≥60). An estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or the development of proteinuria was considered to indicate incident CKD. (3) Results: During the 16-year follow-up period, 919 individuals (11.8%) developed CKD. The HRs of incident CKD in the intermediate FLI group (30-59) and high FLI group (≥60) increased compared with the reference low FLI group (<30) after adjusting for potentially confounding variables. NAFLD, as assessed by the FLI, was an independent risk factor for CKD. (4) Conclusions: Our findings suggest that the FLI, a simple surrogate biomarker of fatty liver disease, may be used to identify people at high risk of incident CKD in clinical practice.

2.
Kidney Res Clin Pract ; 42(6): 751-761, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37098669

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) should be educated about their condition so that they can initiate dialysis at the optimal time and make an informed choice between dialysis modalities. Shared decision-making (SDM) empowers patients to select their own treatment and improves patient outcomes. This study aimed to evaluate whether SDM affects the choice of renal replacement therapy among CKD patients. METHODS: This is a multicenter, open-label, randomized, pragmatic clinical trial. A total of 1,194 participants with CKD who are considering renal replacement therapy were enrolled. The participants will be randomized into three groups in a 1:1:1 ratio: the conventional group, extensive informed decision-making group, and SDM group. Participants will be educated twice at months 0 and 2. Videos and leaflets will be provided to all patients. Patients in the conventional group will receive 5 minutes of education at each visit. The extensive informed decision-making group will receive more informed and detailed education using intensive learning materials for 10 minutes each visit. Patients in the SDM group will be educated for 10 minutes each visit according to illness perception and item-based analysis. The primary endpoint is the ratio of hemodialysis to peritoneal dialysis and kidney transplantation among the groups. Secondary outcomes include unplanned dialysis, economic efficiency, patient satisfaction, patient evaluation of the process, and patient adherence. DISCUSSION: The SDM-ART is an ongoing clinical study to investigate the effect of SDM on the choice of renal replacement therapy in patients with CKD.

3.
Kidney Res Clin Pract ; 42(2): 262-271, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36328988

ABSTRACT

BACKGROUND: T50 is a novel serum-based marker that assesses the propensity for calcification in serum. A shorter T50 indicates a greater propensity to calcify and has been associated with cardiovascular disease and mortality among patients with chronic kidney disease. The factors associated with T50 and the correlation between T50 and bone mineral density (BMD) are unknown in hemodialysis (HD) patients. METHODS: This cross-sectional study included 184 patients undergoing HD. Individuals were grouped into tertiles of T50 to compare the demographic and disease indicators of the tertiles. Linear regression was used to evaluate the association between T50 and hip and spinal BMD in a multivariate model. RESULTS: Mineral and inflammatory parameters, including serum phosphate (r = -0.156, p = 0.04), albumin (r = 0.289, p < 0.001), and high-sensitivity C-reactive protein (r = -0.224, p = 0.003) levels, were associated with T50. We found a weak association between T50 and BMD in the total hip area in the unadjusted model (ß = 0.030, p = 0.04) but did not find a statistically significant association with the total hip (ß = 0.017, p = 0.12), femoral neck (ß = -0.001, p = 0.96), or spinal BMD (ß = 0.019, p = 0.33) in multivariable-adjusted models. CONCLUSION: T50 was moderately associated with mineral and inflammatory parameters but did not conclusively establish an association with BMD in HD patients. Broad-scale future studies should determine whether T50 can provide insights into BMD beyond traditional risk factors in this population.

4.
Front Med (Lausanne) ; 9: 862023, 2022.
Article in English | MEDLINE | ID: mdl-35572997

ABSTRACT

Objective: Among the various risk factors associated with contrast-induced acute kidney injury (CI-AKI), the importance of osmolality and viscosity is emerging among the characteristics of contrast media (CM) itself. High osmolality CM (HOCM) is deprecated and low osmotic pressure (LOCM) and iso-osmotic pressure (IOCM) are mainly used in clinical situations where the results of studies on their effect on the development of CI-AKI are contradictory. We evaluated the association between the type of CM and the risk of CI-AKI. Materials and Methods: A retrospective observational cohort study to analyze the effect of the type of CM on the development of CI-AKI. Using propensity score (PS) matching, 2,263 LOCM and IOCM groups were paired for analysis from 5,267 patients and fulfilled the inclusion criteria among 12,742 patients who underwent CAG between 1 January 2007, and 31 December 2016. LOCM included iopromide and iopamidol, IOCM was iodixanol. CI-AKI, which was the primary endpoint, was defined based on the Kidney Disease Improving Global Outcomes criteria within 48 h after exposure to the CM. A multivariable logistic regression analysis was used in the unmatched and matched cohorts, respectively. In addition, a stratified model on clinically important variables, including a high Mehran score (≥ 6), was also used in the matched cohort. Results: LOCM users showed an increased incidence of CI-AKI (11.7% vs. 9.3%; p = 0.006), but it lost statistical significance after PS matching (9.9% vs. 9.5%, p = 0.725). In multivariable analyses, the adjusted odds ratio for CI-AKI in the LOCM group were 1.059 [95% confidence interval (CI) = 0.875-1.282; p = 0.555] in unmatched cohort and 0.987 (95% CI = 0.803-1.214; p = 0.901) in matched cohort. These results were also consistent with the high-risk (high Mehran score) group. Conclusions: Although the role of CM types in the development of CI-AKI has been debated, our observation shows that the selection between LOCM and IOCM during CAG has no influence on the incidence of CI-AKI.

6.
Kidney Res Clin Pract ; 41(2): 175-187, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34974651

ABSTRACT

BACKGROUND: Shared decision-making is a two-way symmetrical communication process in which clinicians and patients work together to achieve the best outcome. This study aimed to develop self-assessment items as a decision aid for choosing a dialysis modality in patients with chronic kidney disease (CKD) and to assess the construct validity of the newly developed items. METHODS: Five focus group interviews were performed to extract specific self-assessment items regarding patient values in choosing a dialysis modality. After survey items were refined, a survey of 330 patients, consisting of 152 hemodialysis (HD) and 178 peritoneal dialysis (PD) patients, was performed to validate the self-assessment items. RESULTS: The self-assessment for the decision aid was refined to 35 items. The structure of the final items appeared to have three dimensions of factors; health, lifestyle, and dialysis environment. The health factor consisted of 12 subscales (α = 0.724), the lifestyle factor contained 11 subscales (α = 0.624), and the dialysis environment factor was represented by 12 subscales (α = 0.694). A structural equation model analysis showed that the relationship between the decision aid factors (health, lifestyle, and dialysis environment), patients' CKD perception, and cognition of shared decision-making differed between HD patients and PD patients. CONCLUSION: We developed and validated self-assessment items as part of a decision aid to help patients with CKD. This attempt may assist CKD patients in making informed and shared decisions closely aligned with their values when considering dialysis modality.

7.
Clin Nephrol ; 97(2): 78-85, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34423775

ABSTRACT

Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.


Subject(s)
Kidney Failure, Chronic , Renal Dialysis , Hospitalization , Humans , Iron , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Longitudinal Studies , Prospective Studies
8.
BMC Nephrol ; 22(1): 391, 2021 11 25.
Article in English | MEDLINE | ID: mdl-34823497

ABSTRACT

BACKGROUND: Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups. CONCLUSION: This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia. TRIAL REGISTRATION: The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.


Subject(s)
Anemia/drug therapy , Epoetin Alfa/therapeutic use , Hematinics/therapeutic use , Adult , Aged , Anemia/etiology , Double-Blind Method , Epoetin Alfa/adverse effects , Female , Hematinics/adverse effects , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Renal Dialysis , Treatment Outcome
9.
Exp Clin Transplant ; 19(7): 736-738, 2021 07.
Article in English | MEDLINE | ID: mdl-34325625

ABSTRACT

Posttransplant diabetes mellitus, presenile deafness, and myopathy are not commonly accompanied symptoms after kidney transplant. We report the case of a 48-year-old woman with diabetes mellitus, sensorineural hearing loss, and severe myopathy without neuropathy after deceased donor kidney transplant. ShehadamitochondrialDNApointmutation at position 3243 (A>G), and mitochondrial diseases such as maternally inherited diabetes deafness or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodeswere suspected.Diabetes andother symptoms following kidney transplant can often be overlooked as complications of immunosuppressants taken after kidney transplant. However, in patients without a known cause of their symptoms, appropriate examinations and consultation for other diseases, including genetic diseases, should be considered.


Subject(s)
Deafness , Diabetes Mellitus, Type 2 , Diabetes Mellitus , Hearing Loss, Sensorineural , Kidney Transplantation , Muscular Diseases , DNA, Mitochondrial/genetics , Deafness/complications , Deafness/genetics , Diabetes Mellitus/genetics , Diabetes Mellitus, Type 2/complications , Female , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/surgery , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Middle Aged , Muscular Diseases/complications , Treatment Outcome
10.
Sci Rep ; 11(1): 6691, 2021 03 23.
Article in English | MEDLINE | ID: mdl-33758303

ABSTRACT

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1 < 60.0 kg). Secondary outcomes were not significantly different between aspirin users and non-users. It needs to be individualized of prescribing low-dose aspirin for the prevention of cardiovascular events in patients with chronic kidney disease, particularly patients with low bodyweight (< 60 kg).


Subject(s)
Aspirin/administration & dosage , Aspirin/adverse effects , Body Weight , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Glomerular Filtration Rate , Humans , Kidney Function Tests , Prognosis , Proportional Hazards Models , Renal Insufficiency, Chronic/diagnosis , Risk Assessment
11.
Kidney Res Clin Pract ; 40(1): 109-119, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33706479

ABSTRACT

BACKGROUND: The soluble forms of suppression of tumorigenicity-2 (ST2) and galectin-3 have been proposed as novel biomarkers for cardiac fibrosis and heart failure, as well as predictors of cardiovascular events and mortality. However, there are limited data on the association between soluble ST2 and galectin-3 and clinical outcomes in patients with kidney failure on replacement therapy. To determine this, we examined the associations between soluble ST2 and galectin-3 and all-cause mortality and cardiovascular events in patients on hemodialysis. METHODS: This study included maintenance hemodialysis patients (over 18 years old) who consented to preserve their serum in the Biobank at our institution between March 2014 and March 2015. We used Cox proportional hazards regression analysis to evaluate the associations between soluble ST2, galectin-3 levels, and clinical outcomes. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease, and patients were followed for both outcomes until March 2018. RESULTS: A total of 296 patients were analyzed in this study. The mean age was 57 ± 13 years, and 53.0% were male. Serum concentration of soluble ST2 was significantly associated with higher mortality, after adjustment for confounding factors, but was not associated with cardiovascular disease. Serum galectin-3 level was not independently associated with either outcome after adjustment. CONCLUSION: Elevated soluble ST2 is independently associated with an increased risk of mortality, but not with cardiovascular disease, in patients on hemodialysis. Elevated galectin-3 was not associated with mortality or cardiovascular disease.

12.
Am J Nephrol ; 52(2): 119-130, 2021.
Article in English | MEDLINE | ID: mdl-33725696

ABSTRACT

BACKGROUND: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. METHODS: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. RESULTS: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, ß-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. CONCLUSIONS: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.


Subject(s)
Disease Progression , Galectins/blood , Interleukin-1 Receptor-Like 1 Protein/blood , Renal Insufficiency, Chronic/blood , Aged , Biomarkers/blood , Blood Proteins , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Creatinine/blood , Creatinine/urine , Female , Glomerular Filtration Rate , Heart Failure/blood , Humans , Male , Middle Aged , Proportional Hazards Models , Proteinuria/urine , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Risk Factors
13.
Electrolyte Blood Press ; 19(2): 56-60, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35003287

ABSTRACT

Adipsia is a rare disorder that occurs due to damage to the osmoreceptor and not feeling thirst despite hyperosmolality. Adipsic hypernatremia can occur when there is damage to the anterior communicating artery that supplies blood to osmoreceptors, and the level of arginine vasopressin secretion varies widely. A 37-year-old woman, suffering from severe headache, was consulted to the nephrology department for hypernatremia and polyuria after clipping of a ruptured aneurysm in the anterior communicating artery. Despite her hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. She was diagnosed adipsic hypernatremia by evaluating the osmoregulatory and baroregulatory function tests. Because adipsic hypernatremia is caused by not enough drinking water even for hyperosmolality due to the lack of thirst stimulus, the strategies of treatment are that setting the target body weight when serum osmolality is normal and have the patient drink water until patient reach the target body weight. Adipsic hypernatremia should be considered to be a rare complication of subarachnoid hemorrhage associated with an anterior communicating artery aneurysm.

14.
J Vasc Access ; 22(2): 218-224, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32588721

ABSTRACT

BACKGROUND: Regular monitoring of vascular access in patients on maintenance hemodialysis is important to detect early vascular access complications. We compared vascular access blood flow determined by blood temperature monitor and Doppler ultrasonography to evaluate the usefulness of blood temperature monitor. METHODS: In total, 70 patients on maintenance hemodialysis were enrolled from three dialysis centers. Vascular access blood flow was measured thrice at 6-month intervals using Doppler ultrasonography to determine arterial inflow (Q-DUa), venous outflow (Q-DUv), and flow between punctures (Q-DUb) using BTM® (Q-BTM). Twister® was placed between the hemodialysis needle and blood lines, allowing simple reversal of flow without stopping the hemodialysis pump. RESULTS: In total, 203 measurements were recorded, with median values (interquartile range) for Q-BTM, Q-DUa, Q-DUv, and Q-DUb of 1139.0 (868.0-1588.0) mL/min, 960.3 (658.7-1380.4) mL/min, 946.0 (552.0-1515.0) mL/min, and 1067.7 (544.8-1635.0) mL/min, respectively. For all measurements, the mean intraclass correlation coefficients were 0.52 (95% confidence interval, 0.36-0.64) for Q-DUa; 0.37 (95% confidence interval, 0.15-0.53) for Q-DUv; and 0.45 (95% confidence interval, 0.26-0.59) for Q-DUb. Analysis of a receiver operating characteristics curve yielded a cut-off of 627 mL/min for Q-BTM to predict stenosis. CONCLUSION: In patients on maintenance hemodialysis, blood flow measured by blood temperature monitor moderately correlated with Doppler blood flow. It was more related to arterial inflow than venous outflow or flow between punctures. The blood temperature monitor method was not inferior to Doppler ultrasonography. Therefore, blood temperature monitor could be recommended for routine vascular access monitoring because it can be done quickly without interrupting dialysis.


Subject(s)
Arteriovenous Shunt, Surgical , Body Temperature , Renal Dialysis , Thermography/instrumentation , Ultrasonography, Doppler , Vascular Patency , Aged , Blood Flow Velocity , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Regional Blood Flow , Republic of Korea , Treatment Outcome
15.
PLoS One ; 15(6): e0235077, 2020.
Article in English | MEDLINE | ID: mdl-32569271

ABSTRACT

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.


Subject(s)
Phosphates/blood , Proteinuria/blood , Renal Insufficiency, Chronic/blood , Cohort Studies , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Glomerular Filtration Rate , Glucuronidase/blood , Humans , Kidney Tubules/metabolism , Kidney Tubules/pathology , Klotho Proteins , Male , Middle Aged , Regression Analysis , Renal Insufficiency, Chronic/physiopathology , Republic of Korea , Treatment Outcome
16.
Int J Mol Sci ; 21(10)2020 May 17.
Article in English | MEDLINE | ID: mdl-32429518

ABSTRACT

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.


Subject(s)
Adaptor Proteins, Signal Transducing/blood , Adipokines/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Renal Insufficiency, Chronic/metabolism , Vascular Calcification/metabolism , Wnt Signaling Pathway/genetics , rho-Associated Kinases/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adenine/toxicity , Adipokines/genetics , Animals , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Disease Models, Animal , Gene Expression Profiling , Humans , JNK Mitogen-Activated Protein Kinases/genetics , Male , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Osteogenesis/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Rats , Rats, Sprague-Dawley , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/genetics , Vascular Calcification/chemically induced , Vascular Calcification/genetics , Wnt Signaling Pathway/drug effects , rho-Associated Kinases/genetics
17.
Trials ; 20(1): 651, 2019 Nov 28.
Article in English | MEDLINE | ID: mdl-31779697

ABSTRACT

BACKGROUND: Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared from Actinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck's Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated. DISCUSSION: The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis. TRIAL REGISTRATION: Clinical Trials.gov, NCT03576235. Registered on 4 July 2018.


Subject(s)
Actinidia , Plant Extracts/therapeutic use , Pruritus/drug therapy , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Actinidia/chemistry , Adult , Aged , Double-Blind Method , Humans , Middle Aged , Plant Extracts/adverse effects
18.
J Clin Med ; 8(5)2019 May 14.
Article in English | MEDLINE | ID: mdl-31091750

ABSTRACT

Background: Aspirin is often prescribed empirically to improve the patency of hemodialysis (HD) vascular access. Therefore, this study aimed to investigate the impact of aspirin on the survival of vascular access in incident HD patients with arteriovenous fistula (AVF) or arteriovenous graft (AVG). Methods: A prospective cohort of 881 incident HD patients was enrolled between 2009 and 2014. The primary outcome was defined as the first AVF/AVG intervention or salvage procedure, including percutaneous transluminal angioplasty or surgery for vascular access failure. Cox analyses were performed to determine the association between aspirin usage and the occurrence of the primary outcome. Results: The mean age of the patient group was 57.9 ± 13.4, and 63.8% of the patients were male. Aspirin was prescribed in 241 (27.4%) patients, and the median follow-up duration was 30 months. During follow-up, 180 (20.4%) patients experienced the primary outcome event. Univariate analysis showed that age, gender, presence of diabetes mellitus (DM), preexisting peripheral arterial disease, and the type of vascular access used (AVG versus AVF) were significantly associated with the development of the primary outcome. However, aspirin usage from the baseline was not significantly associated with primary outcome events (hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.84-1.60; p = 0.378). Multivariate analysis showed that gender, the presence of DM, and the type of vascular access were still significantly associated with the occurrence of the primary outcome. Moreover, we did not observe the protective effect of taking aspirin on primary vascular access failure, even in subgroup analyses stratified according to gender, the presence of DM, and the type of vascular access. Conclusion: Physicians should carefully consider when they prescribe aspirin for the prevention of primary vascular access failure in Korean incident HD patients. In addition, larger prospective interventional studies are needed to elucidate the effect of aspirin on vascular access failure.

19.
Sci Rep ; 9(1): 4777, 2019 03 18.
Article in English | MEDLINE | ID: mdl-30886220

ABSTRACT

Procalcitonin (PCT) is a useful marker for the diagnosis of systemic inflammatory response syndrome. In addition, PCT is affected by renal function. However, few studies have investigated the relationship between PCT and the development of acute kidney injury (AKI). Hence, we investigated whether serum PCT levels at the time of admission were associated with the development of AKI and clinical outcomes. A total of 790 patients in whom PCT was measured on admission to the intensive care unit (ICU) were analyzed retrospectively. We attempted to investigate whether serum PCT levels measured at the time of admission could be used as a risk factor for the development of AKI in septic and nonseptic patients or as a risk factor for all-cause mortality, and diagnostic usefulness of PCT was further assessed. Serum PCT levels were significantly higher in patients with AKI than in those without AKI (P < 0.001). After multivariable adjustment for clinical factors, laboratory findings, and comorbidities, PCT as a continuous variable showed a significant association with AKI (OR 1.006, 95% CI [1.000-1.011]; P = 0.035). However, PCT was not effective in predicting mortality. The cut-off value of PCT for the prediction of AKI incidence was calculated to be 0.315 ng/ml, with sensitivity and specificity of 60.9% and 56.9%, respectively. The odds ratios (ORs) from an equation adjusted for optimum thresholds of PCT levels for developing AKI with and without sepsis were 2.422 (1.222-4.802, P = 0.011) and 1.798 (1.101-2.937, P = 0.019), respectively. However, there were no absolute differences between the pre- and posttest probabilities after including the PCT value for AKI development. This study suggests that the PCT value was higher in AKI patients than in non-AKI patients, but PCT measurement at the time of admission did not improve the prediction model for AKI.


Subject(s)
Acute Kidney Injury/blood , Procalcitonin/blood , Acute Kidney Injury/diagnosis , Adult , Aged , Biomarkers/blood , Critical Illness , Female , Humans , Male , Middle Aged
20.
Korean J Intern Med ; 34(4): 858-866, 2019 Jul.
Article in English | MEDLINE | ID: mdl-29172403

ABSTRACT

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT00860431). METHODS: A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes. RESULTS: The mean level of serum renalase was 75.8 ± 34.8 µg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10- µg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD. CONCLUSION: Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.


Subject(s)
Kidney Failure, Chronic/blood , Monoamine Oxidase/blood , Renal Insufficiency, Chronic/blood , Adult , Aged , Biomarkers/blood , Cause of Death , Disease Progression , Female , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Male , Middle Aged , Predictive Value of Tests , Prognosis , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Up-Regulation
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