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1.
BMC Nephrol ; 25(1): 168, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760707

ABSTRACT

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.


Subject(s)
Kidney Failure, Chronic , Natriuretic Peptide, Brain , Peptide Fragments , Peritoneal Dialysis , Peritonitis , Humans , Natriuretic Peptide, Brain/blood , Male , Female , Peritoneal Dialysis/adverse effects , Peptide Fragments/blood , Middle Aged , Peritonitis/etiology , Peritonitis/blood , Retrospective Studies , Risk Factors , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Treatment Failure , Aged , Adult , Biomarkers/blood
4.
Sci Rep ; 14(1): 11323, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760468

ABSTRACT

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.


Subject(s)
Cardiovascular Diseases , Heart Disease Risk Factors , Interleukin-16 , Renal Dialysis , Humans , Male , Female , Middle Aged , Interleukin-16/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Aged , Oxalates/blood , Biomarkers/blood , Cohort Studies , Adult , Risk Factors , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality
6.
PeerJ ; 12: e17266, 2024.
Article in English | MEDLINE | ID: mdl-38650643

ABSTRACT

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.


Subject(s)
Glomerulonephritis, IGA , Uric Acid , Humans , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/pathology , Male , Female , Uric Acid/blood , Retrospective Studies , Adult , Prognosis , Hyperuricemia/blood , Middle Aged , Disease Progression , Risk Factors , Kidney Failure, Chronic/blood
7.
Iran J Kidney Dis ; 18(2): 118-123, 2024 03.
Article in English | MEDLINE | ID: mdl-38660699

ABSTRACT

INTRODUCTION: Peritoneal dialysis (PD) is an effective treatment  modality for advanced kidney failure, offering patients a significant  degree of independence. However, the long-term use of PD is  limited due to the degeneration of the peritoneal membrane,  resulting in reduced dialysis adequacy. Evaluating the peritoneal  membrane condition in patients with advanced kidney failure  who are undergoing PD is challenging with existing methods.  Therefore, this study aimed to investigate the correlation between  8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal  solution of patients undergoing PD and various factors, such  as peritoneal equilibration test (PET), dialysis adequacy (Kt/V),  underlying diseases, serum ferritin, and albumin levels. 8OHDG  is a sensitive marker of oxidative stress caused by DNA damage. METHODS: A total of 56 patients were included in this cross-sectional  study. Five milliliters of PD fluid were collected from the patients,  and 8-OHdG levels were measured using ELISA method. Then, they  were compared with PET, Kt/V, albumin, and ferritin markers in  the patients' files, and the results were analyzed by statistical tests. RESULTS: The study examined the correlation between 8OHDG  and other markers. It was found that this index had significant  associations with PET and underlying HTN (P < .05), whereas no  significant associations were identified with the other markers. CONCLUSION: The results of the present study demonstrate that  the level of 8OHDG, as one of the oxidative stress markers, could  be used to evaluate the function of the peritoneum in patients  undergoing PD. DOI: 10.52547/ijkd.7654.


Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Oxidative Stress , Peritoneal Dialysis , Female , Humans , Male , 8-Hydroxy-2'-Deoxyguanosine/analysis , Biomarkers/blood , Biomarkers/metabolism , Cross-Sectional Studies , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Deoxyguanosine/blood , Ferritins/blood , Ferritins/analysis , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Peritoneal Dialysis/adverse effects , Peritoneum/chemistry , Peritoneum/metabolism , Peritoneum/pathology , Serum Albumin/analysis , Serum Albumin/metabolism
9.
Perit Dial Int ; 44(3): 194-202, 2024 May.
Article in English | MEDLINE | ID: mdl-38449341

ABSTRACT

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD). METHODS: Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality. RESULTS: A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively. CONCLUSION: High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.


Subject(s)
Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Fibroblast Growth Factors/blood , Male , Female , Middle Aged , Prospective Studies , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/blood , Adult , Proportional Hazards Models , Cohort Studies , Kaplan-Meier Estimate , Risk Assessment , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Enzyme-Linked Immunosorbent Assay
10.
Am Heart J ; 271: 38-47, 2024 May.
Article in English | MEDLINE | ID: mdl-38401646

ABSTRACT

BACKGROUND: Circulating concentrations of vascular endothelial growth factor (VEGF) family members may be abnormally elevated in type 2 diabetes (T2D). The roles of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFLT-1), and VEGF-A in cardio-renal complications of T2D are not established. METHOD: The 2602 individuals with diabetic kidney disease (DKD) from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial were randomized to receive canagliflozin or placebo and followed for incident cardio-renal outcomes. PlGF, sFLT-1, and VEGF-A were measured at baseline, year 1, and year 3. Primary outcome was a composite of end-stage kidney disease, doubling of the serum creatinine, or renal/cardiovascular death. Cox proportional hazard regression was used to investigate the association between biomarkers with adverse clinical events. RESULTS: At baseline, individuals with higher PlGF levels had more prevalent cardiovascular disease compared to those with lower values. Treatment with canagliflozin did not meaningfully change PlGF, sFLT-1, and VEGF-A concentrations at years 1 and 3. In a multivariable model, 1 unit increases in baseline log PlGF (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.23, 2.54, P-value = .002), sFLT-1 (HR: 3.34, [95% CI: 1.71, 6.52], P-value < .001), and PlGF/sFLT-1 ratio (HR: 4.83, [95% CI: 0.86, 27.01], P-value = .07) were associated with primary composite outcome, while 1 unit increase in log VEGF-A did not increase the risk of primary outcome (HR: 0.96 [95% CI: 0.81, 1.07]). Change by 1 year of each biomarker was also assessed: HR (95% CI) of primary composite outcome was 2.45 (1.70, 3.54) for 1 unit increase in 1-year concentration of log PlGF, 4.19 (2.18, 8.03) for 1 unit increase in 1-year concentration of log sFLT-1, and 21.08 (3.79, 117.4) for 1 unit increase in 1-year concentration of log PlGF/sFLT-1. Increase in 1-year concentrations of log VEGF-A was not associated with primary composite outcome (HR: 1.08, [95% CI: 0.93, 1.24], P-value = .30). CONCLUSIONS: People with T2D and DKD with elevated levels of PlGF, sFLT-1, and PlGF/sFLT-1 ratio were at a higher risk for cardiorenal events. Canagliflozin did not meaningfully decrease concentrations of PlGF, sFLT-1, and VEGF-A. CLINICAL TRIAL: CREDENCE, https://clinicaltrials.gov/ct2/show/NCT02065791.


Subject(s)
Biomarkers , Canagliflozin , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Placenta Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1 , Aged , Female , Humans , Male , Middle Aged , Biomarkers/blood , Canagliflozin/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Diabetic Nephropathies/epidemiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/blood , Placenta Growth Factor/blood , Risk Factors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-1/blood
11.
BMC Pulm Med ; 24(1): 78, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38341544

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is a complication of chronic kidney disease (CKD) that contributes to mortality. Sclerostin, a SOST gene product that reduces osteoblastic bone formation by inhibiting Wnt/ß-catenin signaling, is involved in arterial stiffness and CKD-bone mineral disease, but scanty evidence to PH. This study explored the relationship between sclerostin and PH in CKD 5, pre-dialysis end-stage kidney disease (ESKD) patients. METHODS: This cross-sectional prospective observational cohort study included 44 pre-dialysis ESKD patients between May 2011 and May 2015. Circulating sclerostin levels were measured using an enzyme-linked immunosorbent assay. PH was defined as an estimated pulmonary artery systolic pressure > 35 mmHg on echocardiography. RESULTS: Patients with higher sclerostin levels ≥ 218.18pmol/L had echocardiographic structural cardiac abnormalities, especially PH (P < 0.01). On multivariate logistic analysis, sclerostin over 218.19pmol/L was significantly associated with PH (odds ratio [OR], 41.14; 95% confidence interval [CI], 4.53-373.89, P < 0.01), but multivariate Cox regression analysis showed the systemic vascular calcification score over 1 point (Hazard ratio [HR] 11.49 95% CI 2.48-53.14, P = 0.002) and PH ([HR] 5.47, 95% CI 1.30-23.06, P = 0.02) were risk factors for all-cause mortality in pre-dialysis ESKD patients. CONCLUSIONS: Serum sclerostin and PH have a positive correlation in predialysis ESKD patients. The higher systemic vascular calcification score and PH have an association to increase all-cause mortality in pre-dialysis ESKD patients.


Subject(s)
Adaptor Proteins, Signal Transducing , Hypertension, Pulmonary , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Vascular Calcification , Humans , Bone Morphogenetic Proteins , Cross-Sectional Studies , Dialysis/adverse effects , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/complications , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Prospective Studies , Renal Dialysis/adverse effects , Adaptor Proteins, Signal Transducing/blood
12.
Am J Hematol ; 99(6): 1168-1169, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38174980

ABSTRACT

A puzzling case of thrombocytopenia and giant unusual platelets in blood smear reveals a past diagnosis of Alport syndrome in 44-year-old woman with end-stage renal disease and abnormal CBC values.


Subject(s)
Blood Platelets , Nephritis, Hereditary , Thrombocytopenia , Humans , Nephritis, Hereditary/complications , Nephritis, Hereditary/diagnosis , Female , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology , Thrombocytopenia/blood , Adult , Blood Platelets/pathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications
13.
Clin Chem Lab Med ; 62(6): 1118-1125, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38253354

ABSTRACT

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.


Subject(s)
Creatinine , Renal Dialysis , Saliva , Sweat , Urea , Humans , Urea/analysis , Urea/blood , Saliva/chemistry , Creatinine/blood , Creatinine/analysis , Sweat/chemistry , Female , Male , Cohort Studies , Middle Aged , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Adult , Biomarkers/analysis , Biomarkers/blood
14.
Clin Exp Nephrol ; 28(5): 457-464, 2024 May.
Article in English | MEDLINE | ID: mdl-38238500

ABSTRACT

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.


Subject(s)
Biomarkers , Hospitalization , Kidney Failure, Chronic , Myocardial Ischemia , Natriuretic Peptide, Brain , Peptide Fragments , Renal Dialysis , Humans , Male , Natriuretic Peptide, Brain/blood , Biomarkers/blood , Peptide Fragments/blood , Myocardial Ischemia/blood , Myocardial Ischemia/epidemiology , Myocardial Ischemia/diagnosis , Middle Aged , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Heart Failure/blood , Heart Failure/therapy , Heart Failure/epidemiology , Prognosis , Incidence , Stroke/blood , Stroke/epidemiology , Predictive Value of Tests , ROC Curve , Proportional Hazards Models , Japan/epidemiology
15.
Ren Fail ; 45(1): 2211157, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37293774

ABSTRACT

The role of facility-level serum potassium (sK+) variability (FL-SPV) in dialysis patients has not been extensively studied. This study aimed to evaluate the association between FL-SPV and clinical outcomes in hemodialysis patients using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5. FL-SPV was defined as the standard deviation (SD) of baseline sK+ of all patients in each dialysis center. The mean and SD values of FL-SPV of all participants were calculated, and patients were divided into the high FL-SPV (>the mean value) and low FL-SPV (≤the mean value) groups. Totally, 1339 patients were included, with a mean FL-SPV of 0.800 mmol/L. Twenty-three centers with 656 patients were in the low FL-SPV group, and 22 centers with 683 patients were in the high FL-SPV group. Multivariate logistic regression analysis showed that liver cirrhosis (OR = 4.682, 95% CI: 1.246-17.593), baseline sK+ (<3.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 2.394, 95% CI: 1.095-5.234; ≥5.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 1.451, 95% CI: 1.087-1.939), dialysis <3 times/week (OR = 1.472, 95% CI: 1.073-2.020), facility patients' number (OR = 1.088, 95% CI: 1.058-1.119), serum HCO3- level (OR = 0.952, 95% CI: 0.921-0.984), dialysis vintage (OR = 0.919, 95% CI: 0.888-0.950), other cardiovascular disease (OR = 0.508, 95% CI: 0.369-0.700), and using high-flux dialyzer (OR = 0.425, 95% CI: 0.250-0.724) were independently associated with high FL-SPV (all p < .05). After adjusting potential confounders, high FL-SPV was an independent risk factor for all-cause death (HR = 1.420, 95% CI: 1.044-1.933) and cardiovascular death (HR = 1.827, 95% CI: 1.188-2.810). Enhancing the management of sK+ of hemodialysis patients and reducing FL-SPV may improve patient survival.


Subject(s)
Kidney Failure, Chronic , Renal Dialysis , Humans , East Asian People , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Potassium/blood , Prospective Studies , Renal Dialysis/methods , Renal Dialysis/mortality
16.
Clin Ther ; 45(7): 633-642, 2023 07.
Article in English | MEDLINE | ID: mdl-37385905

ABSTRACT

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.


Subject(s)
Hyperkalemia , Kidney Failure, Chronic , Renal Dialysis , Adult , Humans , Middle Aged , China , East Asian People , Hyperkalemia/blood , Hyperkalemia/drug therapy , Hyperkalemia/etiology , Potassium/blood , Renal Insufficiency/blood , Renal Insufficiency/complications , Renal Insufficiency/therapy , Double-Blind Method , Aged , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy
17.
Dis Markers ; 2022: 4428484, 2022.
Article in English | MEDLINE | ID: mdl-35756496

ABSTRACT

Objective: To assess the prognostic value of serum interleukin-6 (IL-6), nuclear factor-κB (NF-κB), and monocyte chemoattractant protein 1(MCP-1) assay in patients with diabetic nephropathy. Methods: From May 2019 to March 2020, 104 patients with diabetic nephropathy treated in our institution assessed for eligibility were recruited and assigned at a ratio of 1 : 1 to either the observation group ([urinary albumin excretion rate (UAER)] of 30 mg-300 mg/24 h) or the research group ([UAER] >300 mg/24 h). IL-6, MCP-1, renal function indices, and NF-κB levels were determined, and their correlation with DN was analyzed. Logistic regression was used to analyze the influencing factors of end-stage renal disease in patients with diabetic nephropathy. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to analyze the predictive value of combined detection of IL-6, MCP-1, and NF-κB in the prognosis of patients with diabetic nephropathy. Results: The eligible patients with UAER of 30 mg-300 mg/24 h were associated with significantly higher levels of IL-6, MCP-1, NF-κB, blood urea nitrogen (BUN), and serum creatinine (Scr) versus those with UAER >300 mg/24 h (P < 0.05). During the follow-up, a total of 38 patients progressed to end-stage renal diseases. Eligible patients with end-stage renal diseases showed significantly higher serum IL-6, MCP-1, and NF-κB levels versus those without end-stage renal diseases (P < 0.05). Serum IL-6, MCP-1, and NF-κB are independent risk factors for the occurrence of end-stage renal disease in patients with diabetic nephropathy. The AUCs of IL-6, MCP-1, and NF-κB for predicting the prognosis of patients with diabetic nephropathy were 0.562, 0.634, and 0.647, respectively, and the AUC of the three combined detection for predicting the prognosis of patients with diabetic nephropathy was 0.889. Conclusion: Serum IL-6, NF-κB, and MCP-1 levels are closely related to renal injury and poor prognosis in patients with diabetic nephropathy, and the combined assay is valuable for assessing patients' condition and prognosis.


Subject(s)
Chemokine CCL2 , Diabetes Mellitus , Diabetic Nephropathies , Interleukin-6 , NF-kappa B , Chemokine CCL2/blood , Diabetes Mellitus/blood , Diabetic Nephropathies/blood , Humans , Interleukin-6/blood , Kidney Failure, Chronic/blood , NF-kappa B/blood , Prognosis
18.
BMC Nephrol ; 23(1): 156, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35459121

ABSTRACT

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. METHODS: Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. RESULTS: Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value(R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex (R = 0.550, P = 0.015), adjusting for age, sex and CHD (R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb (R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) (R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca (R = 0.644, P < 0.001), Ca and ACR (R = 0.534, P = 0.013) in Spearman coefficient analysis. CONCLUSION: There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.


Subject(s)
Aorta, Thoracic , Aortic Diseases , Calcinosis , Kidney Failure, Chronic , Lipocalin-2 , Aorta, Thoracic/diagnostic imaging , Aortic Diseases/blood , Aortic Diseases/complications , Aortic Diseases/pathology , Biomarkers , Calcinosis/blood , Calcinosis/complications , Cross-Sectional Studies , Diabetes Complications , Diabetes Mellitus , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Lipocalin-2/blood , Renal Dialysis
19.
Clin Nephrol ; 98(1): 1-9, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35445659

ABSTRACT

OBJECTIVES: Osteocalcin, an osteoblast-derived hormone, is associated with the development of osteoporosis and arteriosclerosis in the general population. However, its role on the pathogenesis of osteoporosis and vascular calcification in patients with chronic kidney disease (CKD) is unclear. Here, we investigated the connection between osteocalcin, bone mineral density (BMD), and abdominal aortic calcification (AAC) in CKD patients. MATERIALS AND METHODS: In total, 95 patients with stage 2 to stage 5 CKD were enrolled. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. BMD was determined by dual-energy X-ray absorptiometry, and AAC scores were generated from lateral lumbar radiograph findings. RESULTS: 95 patients were assigned into normal bone density (30.5%, n = 29), osteopenia (45.3%, n = 43), and osteoporosis (24.2%, n = 23) groups. The osteoporosis group was characterized by older age, higher female-to-male ratio, phosphorous levels, calcification scores, osteocalcin levels, and intact parathyroid hormone (PTH) levels, while with lower hemoglobin levels as compared to normal and osteopenia groups. Multivariate multinominal regression analysis showed age, female sex, intact PTH, and serum osteocalcin level were independent determinants of osteoporosis severity in CKD patients. Furthermore, serum osteocalcin level is positively correlated to intact PTH in multivariate linear regression model, indicating that osteocalcin might be a bone turnover marker in patients with CKD. Multivariate stepwise linear regression analysis revealed that age, diabetes mellitus, poorer renal function, rather than osteocalcin, have independent associations with AAC score. CONCLUSION: Elevated serum osteocalcin levels could be considered as a marker of osteoporosis rather than that of vascular calcification in patients with CKD.


Subject(s)
Osteocalcin , Osteoporosis , Renal Insufficiency, Chronic , Absorptiometry, Photon , Biomarkers/blood , Bone Density , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/etiology , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Male , Osteocalcin/blood , Osteoporosis/blood , Osteoporosis/diagnostic imaging , Osteoporosis/etiology , Parathyroid Hormone , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Vascular Calcification/blood , Vascular Calcification/etiology
20.
Nephrol Dial Transplant ; 37(10): 1951-1961, 2022 09 22.
Article in English | MEDLINE | ID: mdl-35234930

ABSTRACT

BACKGROUND: Chronic kidney disease is an important contributor to morbidity and mortality. 3-methylhistidine (3-MH) is the by-product of actin and myosin degradation reflecting skeletal muscle turnover. Markedly elevated 3-MH levels have been documented in uraemic patients, but the interpretation of high 3-MH concentration in maintenance haemodialysis (MHD) patients remains unclear. Indeed, it is not known whether elevated serum 3-MH levels are a marker of excessive muscle catabolism or a better lean tissue mass. Here, we evaluated the association between serum 3-MH levels and clinical outcomes in these patients. METHODS: Serum 3-MH concentration was measured by reverse-phase liquid chromatography/tandem mass spectrometry in a cohort of MHD patients. We analysed the relationships between various clinical/laboratory indices, lean tissue mass measured by bioimpedance spectroscopy, mortality and cardiovascular (CV) events. RESULTS: Serum 3-MH concentration was positively correlated with serum albumin, normalized protein catabolic rate (nPCR), simplified creatinine index (SCI) and lean tissue mass. Of 291 MHD patients, during a mean follow-up of 847 days, 91 patients died and 101 patients experienced a CV event. Survival was significantly better in patients with high 3-MH concentrations (P = .002). A higher level of 3-MH was also associated with a lower CV mortality and lower incidence of CV events (P = .015 and P < .001, respectively). Low serum 3-MH levels remained significantly associated with CV events but not with mortality after adjustment for demographic, metabolic and CV risk factors. CONCLUSION: Elevated serum 3-MH concentration appears to be a marker of better lean tissue mass and nutritional status. Low serum 3-MH is a robust and independent predictor of CV events in the MHD population.


Subject(s)
Actins , Kidney Failure, Chronic , Methylhistidines , Renal Dialysis , Actins/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Creatinine , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/therapy , Methylhistidines/blood , Methylhistidines/metabolism , Serum Albumin/analysis , Serum Albumin/metabolism
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