Renal Failure最新文献

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease globally. Recent research has identified insulin-like growth factor-binding proteins 2 (IGFBP2) and 4 (IGFBP4) as potential biomarkers for DKD. Overactivation of the complement pathway in DKD remains poorly understood.

Methods: Blood samples were collected from patients for proteomic analysis, complemented by both in vitro and in vivo experiments to investigate the roles of IGFBP2, IGFBP4, and the complement pathway in DKD.

Results: Elevated levels of IGFBP2 and IGFBP4 were observed in DKD patients. The levels of IGFBP2 and IGFBP4 increased in DKD mice, accompanied by the activation of the complement pathway, and a deterioration in renal function. High glucose and serum from DKD mice stimulated an increase in the levels of IGFBP2 and IGFBP4 in HK-2 cells. The supernatant from HK-2 cells was used to culture THP-1 cells, resulted in an increase in the M1 type of THP-1 cells, a decrease in the M2 type, and activation of the complement pathway. The supernatant from THP-1 cells affected the growth of primary human renal podocytes. The exogenous addition of IGFBP2 and IGFBP4 proteins to primary human renal podocytes did not affect their growth. However, when human renal podocytes were cultured with the supernatant from THP-1 cells, the growth of the podocytes was affected.

Conclusions: IGFBP2 and IGFBP4 interact to stimulate the activation of the complement pathway in macrophages, which induces podocyte apoptosis and subsequently promotes the development of DKD.

Background: Chronic kidney disease (CKD) is a prevalent chronic, non-communicable disease. The long-term health effects of dietary live microbes, primarily probiotics, on CKD patients remain insufficiently understood. This study aims to investigate the association between dietary intake of live microbes and long-term health outcomes among individuals with CKD.

Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) database, Cox regression analysis assessed the association between medium and high categories dietary live microbe intake and health outcomes (all-cause, cardiovascular disease [CVD], and cancer-related mortality) in CKD patients.

Results: A total of 3,646 CKD patients were enrolled. During the follow-up period, 1,593 all-cause mortality events were recorded, including 478 CVD deaths and 268 cancer deaths. In the fully adjusted model, compared to CKD patients in the lowest quartile (quartile 1) of live microbes intake, those in quartiles 3 and 4 exhibited a 20% and 26% reduced risk of all-cause mortality, with hazard ratios (HR) of 0.80 (95% confidence interval, CI: 0.69, 0.94) and 0.74 (95% CI: 0.62, 0.90), respectively. Additionally, compared to those with low live microbe intake (quartile 1), higher live microbe intake in quartile 4 was associated with a 37% reduction in the risk of CVD mortality for CKD patients, with an HR of 0.63 (95% CI: 0.45, 0.88). Consistent results were observed in subgroup and sensitivity analyses. A significant negative association was observed between live microbe intake and the risk of all-cause mortality as well as CVD mortality in the CKD population, with a p-value for trend < 0.05.

Conclusion: Our study indicated that high dietary live microbe intake could mitigate the risk of all-cause and CVD mortality in CKD patients. These findings support the inclusion of live microbes in dietary recommendations, highlighting their significant roles in CKD.

Background: Vascular calcification is highly prevalent and associated with mortality in hemodialysis patients. However, extreme splanchnic arterial calcification in calciphylaxis with poor prognosis raises questions regarding the reliability of previous vascular calcification scoring methods. Therefore, this study aimed to examine the distribution characteristics of abdominal aortic branch calcification and identify a more reliable predictor of mortality in hemodialysis patients.

Methods: The cohort study included 237 hemodialysis patients. The distribution characteristics of abdominal aortic branch calcification were determined by quantifying the calcification volumes. The primary and secondary outcomes were all-cause mortality and new-onset cardiovascular events, respectively. We compared the prognostic values of abdominal aortic branch calcification and constructed a predictive nomogram model.

Results: The prevalence of abdominal vascular calcification in hemodialysis patients was 95.36%, with the highest prevalence in the abdominal aorta (88.61%) and internal iliac artery (85.65%). During a median follow-up period of 3.92 years, 137 patients died. Internal iliac artery and mesenteric artery calcification showed the greatest predictive values for mortality. Internal iliac artery calcification and serum albumin level were independently associated with mortality in hemodialysis patients (p < .001). The nomogram model constructed with internal iliac artery calcification, serum albumin level, age, and comorbid cardiovascular disease was well discriminative, calibrated, and clinically applicable for predicting 3-year survival.

Conclusion: Abdominal aortic branch calcification, particularly internal iliac artery calcification, is a preferable prognostic predictor than abdominal aorta or coronary artery calcification in hemodialysis patients.

Background: Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population.

Methods: A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels. Patients were categorized into four groups: non-to-mild AoAC/low Alk-P, non-to-mild AoAC/high Alk-P, moderate-to-severe AoAC/low Alk-P, and moderate-to-severe AoAC/high Alk-P. The Cox proportional hazard model and Kaplan-Meier analysis were used to evaluate the risks of major adverse cardiovascular effects (MACEs) and cardiovascular and all-cause mortality after multivariate adjustment.

Results: Among 376 chronic HD patients recruited, 125 (33%) had non-to-mild AoAC/low Alk-P, 76 (20%) had non-to-mild AoAC/high Alk-P, 89 (24%) had moderate-to-severe AoAC/low Alk-P, and 86 (23%) had moderate-to-severe AoAC/high Alk-P. After 3 years of follow-up, patients with coexisting moderate-to-severe AoAC and high Alk-P had a higher risk of MACEs (aHR 1.76; 95% CI 1.06-2.92), and cardiovascular (aHR 2.49; 95% CI 1.21-5.11) and all-cause mortality (aHR 2.67; 95% CI 1.39-5.13) compared to those with non-to-mild AoAC/low Alk-P even after adjustments for significant clinical variables.

Conclusions: In chronic HD patients, moderate to severe AoAC co-existed with high Alk-P levels and enhanced the risk of MACEs and cardiovascular and all-cause mortality. Interventions to attenuate these risk factors simultaneously should be emphasized in this population.

Background: Vascular calcification (VC), especially coronary artery calcification (CAC), serves as a robust predictor of cardiovascular mortality in chronic kidney disease (CKD) patients. Recent studies have revealed that the presence of extra-coronary calcifications (ECCs) contributes to cardiovascular disease (CVD). Elevated myocardial injury markers predict mortality risk in CKD patients and are associated with CVD. Nevertheless, the relationship between VC, including CAC and ECCs, and myocardial injury markers remain unexplored in non-dialysis CKD patients.

Methods: In 278 non-dialysis CKD patients of stage G3 to G5, we assessed calcified scores in CAC (Agatston score) and ECCs including thoracic aortic calcification (TAC), abdominal aortic calcification (AAC), carotid artery calcification, and valvular calcification. We analyzed the relationships between VC and myocardial injury markers of cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB).

Results: A total of 278 non-dialysis CKD patients (median age 52.4 ± 13.2; male 65.1%; diabetes 33.5%) were enrolled. A total of 71.8% (227) of patients had cTnT levels above the upper limit of normal (> 0.014 ng/mL). Moderate to severe (calcified score ≥100 vs. <100), CAC (OR 6.39; 95% CI 1.03-39.61) and TAC (OR 6.16; 95% CI 1.76-21.55) were significantly associated with higher cTnT concentrations after adjustment for confounders. Additionally, male sex and a lower eGFR were also associated with cTnT elevation. However, when we included CAC and TAC in one model, only moderate to severe TAC (OR 4.85; 95% CI 1.38-16.96) was a risk factor for cTnT elevation, but not CAC. Furthermore, patients with severer TAC presented lower diastolic blood pressure (DBP), wider pulse pressure (p < 0.001) and higher prevalence of left ventricular hypertrophy (LVH).

Conclusion: Moderate to severe thoracic aortic calcification (TAC score ≥ 100) is significantly associated with elevated cTnT concentrations in non-dialysis CKD patients of stage G3 to G5. The linkage may result from decreased coronary perfusion and relative myocardial ischemia.

Background: Adjusting dietary potassium intake based on 24-hour urinary potassium excretion is the primary method of preventing hyperkalemia. Currently, there is no accurate and convenient method for calculating maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients. We developed and validated two new models to assess the upper limit of dietary potassium consumption in this high-risk cohort, using the maximum 24-hour urinary potassium excretion as a proxy.

Methods: The data of 145 kidney failure without replacement therapy patients with hyperkalemia was gathered. The prediction models were developed using multilayer perceptron and stepwise multiple linear regression utilizing a stochastic sample of 102 (70%) patients. Within the rest 43 (30%), the performance of various models was independently verified.

Results: The two new models had low bias (-0.02 and -0.57 mmol/24h vs 66.74 and 79.91 mmol/24h, mean absolute error = 5.57 and 5.22 vs 68.95 and 81.37), high accuracy (percentage of calculated values within_±30% of measured values = 83.45% and 84.14% vs 0.00% and 0.00%), high correlation with measured values (Spearman correlation coefficient = 0.72 and 0.72 vs 0.46 and 0.45, intraclass correlation coefficient = 0.67 and 0.70 vs 0.03 and 0.03) and high agreement with 24-hour urine potassium measurements (95% limits of agreement of Bland-Altman plot = 13.70 and 13.20 mmol/24h vs 113.8 and 191.3 mmol/24h).

Conclusion: These new models show high clinical application value for the calculation of maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients with hyperkalemia.

Objective: The innate immune defense plays a pivotal role in protecting the urinary tract from uropathogenic invasion and maintaining immune homeostasis. Dysregulation of the innate immune system can result in recurrent urinary tract infections (RUTI) due to heightened susceptibility to uropathogens. Despite this, predicting the risk of recurrence and the degree of immune compromise in patients who have had one urinary tract infection remains challenging. Also identifying which patients are more susceptible to developing pyelonephritis rather than the more local disease of cystitis is imperfect, although delayed diagnosis of a UTI is a good indicator for developing pyelonephritis. This study aims to assess the potential of urinary Tamm-Horsfall protein (THP) and Pentraxin 3 (PTX3) as predictors of RUTI symptom severity and recurrence, while also evaluating the efficacy of the Chinese herbal formulation Tailin Formula (TLF) as a clinical therapeutic intervention for RUTI.

Methods: A single-center cohort study was conducted involving 142 participants, consisting of 31 healthy individuals (non-RUTI group, n = 31) and 111 patients with RUTI. The RUTI patients were divided into two groups: one group received continuous low-dose antibiotic therapy (CLAT group, n = 55), and the other group received herbal preparations (Tailin formula) (TLF group, n = 56). All patients received consistent lifestyle guidance. Descriptive analysis was performed on the RUTI cohort.

Results: Urinary THP levels were significantly lower in RUTI patients (TLF and CLAT groups) compared to the non-RUTI, whereas PTX3 levels showed a tendency toward elevation. After treatment, urinary THP levels were markedly higher in the TLF group (27.43 ± 7.07) compared to pretreatment levels (10.00 ± 2.79), while levels remained lower in the CLAT group (8.91 ± 2.23) than in the TLF group. Urinary PTX3 levels decreased post-treatment in both groups after treatment than before (CLAT: 0.30 ± 0.13 vs. 1.04 ± 0.38; TLF: 0.29 ± 0.12 vs. 1.15 ± 0.36). Additionally, THP was negatively correlated with renal tubular injury markers NAG/Cr and β2-MG in RUTI patients (r = -0.5041 and -0.6169, respectively), while PTX3 showed a positive correlation with NAG/Cr and β2-MG (r = 0.28 and 0.498, respectively). Notably, as RUTI symptoms improved and recurrence rates decreased, urinary THP levels increased, while PTX3 levels decreased.

Conclusion: This study suggests that urinary THP and PTX3 are likely involved in the pathogenesis of RUTI. These biomarkers may serve as valuable predictors for assessing symptom severity, recurrence risk, and therapeutic efficacy in patients with RUTI at risk of disease progression.

Objective: The mortality rate of patients undergoing maintenance hemodialysis (MHD) remains high. The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel biomarker that reflects inflammation, nutritional and immune status, all merged into one single derived parameter. No study has yet linked the CALLY index to survival in hemodialysis. This study aims to explore the correlation between the CALLY index and mortality in MHD patients, and develop and validate a nomogram to estimate the likelihood of death in this population.

Methods: This retrospective cohort study collected data from 436 patients and they were divided into survival group (n = 335) and non-survival group (n = 101). Multivariate logistic regression analysis was used to screen factors associated with death, and nomograms were developed to estimate the risk of death in MHD patients. The discrimination and calibration of nomograms were validated using the area under the receiver operating characteristic (ROC) curve (AUC) and calibration curve. In the study, stratification analysis and covariate adjustment were conducted to explore the correlation between the CALLY index and the mortality of MHD patients.

Results: In the final model, logistic regression showed that the CALLY index, creatinine, triglycerides, dialysis duration, absolute neutrophil count, blood urea nitrogen, sodium and ferritin were variables associated with mortality in MHD patients. A nomogram was developed to assess the risk of death in MHD patients. The AUC of the model was 0.821 (95% CI: 0.778-0.861). The results of stratified analysis and calibration model showed that the CALLY index was a protective factor for maintaining the mortality of MHD patients.

Conclusions: The CALLY index is closely related to the mortality of MHD patients. A nomogram constructed based on CALLY index can effectively evaluate the mortality risk of MHD patients.