Kidney & blood pressure research最新文献

Introduction: Nutrition and physical activity are two major issues in the management of CKD patients who are often older, have comorbidities and are prone to malnutrition and physical inactivity, conditions that cause loss of quality of life and increase the risk of death. We performed a multidimensional assessment of nutritional status and of physical performance and activity in CKD patients on conservative therapy in order to assess the prevalence of sedentary behaviour and its relationship with body composition.

Methods: 115 consecutive stable CKD patients aged 45-80 years were included in the study. They had no major skeletal, muscular or neurological disabilities. All patients underwent a multidimensional assessment of body composition, physical activity and exercise capacity.

Results: Sedentary patients, as defined by mean daily METs < 1.5 were older and differed from non-sedentary patients in terms of body composition, exercise capacity and nutrient intake, even after adjusting for age. Average daily METs were positively associated with lean body mass, muscle strength, 6-MWT performance, but negatively associated with fat body mass, body mass index and waist circumference. In addition, a sedentary lifestyle may have negative effects on free fat mass, muscle strength and exercise capacity, and may increase fat body mass. Conversely, s decrease in muscle mass and/or an increase in fat mass may lead to a decrease in physical activity and exercise capacity.

Conclusion: There is a clear association and potential interrelationship between nutritional aspects and exercise capacity in older adults with CKD: they are really the two sides of the same coin.

Introduction: Acute Kidney Injury (AKI) is a prevalent renal disorder. The occurrence of AKI may promote the formation of renal calcium oxalate stones by exerting continuous effects on renal tubular epithelial cells. We aimed to delineate the molecular interplay between AKI and nephrolithiasis.

Methods: A mild (20 min) and severe (30 min) renal ischemia-reperfusion injury model was established in mice. Seven days after injury, calcium oxalate stones were induced using glyoxylate (Gly) to evaluate the impact of AKI on the formation of kidney stones. Transcriptome sequencing was performed on tubular epithelial cells (TECs) to elucidate the relationship between AKI severity and kidney stones. Key transcription factors (TF) regulating differential gene transcription levels were identified using motif analysis, and pioglitazone, ginkgetin, and fludarabine were used for targeted therapy to validate key transcription factors as potential targets for kidney stone treatment.

Results: Severe AKI led to increased deposition of calcium oxalate crystals in renal, impaired kidney function, and upregulation of kidney stone-related gene expression. In contrast, mild AKI was associated with decreased crystal deposition, preserved kidney function, and downregulation of similar gene expression. Transcriptomic analysis revealed that genes associated with inflammation and cell adhesion pathways were significantly upregulated after severe AKI, while genes related to energy metabolism pathways were significantly upregulated after mild AKI. An integrative bioinformatic analysis uncovered a TF regulatory network within TECs, pinpointing that PKNOX1 was involved in the upregulation of inflammation-related genes after severe AKI, and inhibiting PKNOX1 function with Pioglitazone could simultaneously reduce the increase of calcium oxalate crystals after severe AKI in kidney. On the other hand, motif analysis also revealed the protective role of STAT1 in the kidneys after mild AKI, enhancing the function of STAT1 with Ginkgetin could reduce kidney stone formation, while the specific inhibitor of STAT1, Fludarabine, could eliminate the therapeutic effects of mild AKI on kidney stones.

Conclusion: Inadequate repair of tubular epithelial cells after severe AKI increases the risk of kidney stone formation, with the upregulation of inflammation-related genes regulated by PKNOX1 playing a role in this process. Inhibiting PKNOX1 function can reduce kidney stone formation. Conversely, after mild AKI, effective cell repair through upregulation of STAT1 expression can protect TEC function, reduce stone formation, and activating STAT1 function can also achieve the goal of treating kidney stones.

Introduction: Limited information exists regarding the impact of preoperative serum creatinine changes on cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to investigate the development of AKI in patients with a baseline estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 who present with an elevation in preoperative serum creatinine.

Methods: This retrospective cohort study assessed patients who underwent open-heart surgery. Preoperative serum creatinine change was calculated as the ratio of the maximum preoperative serum creatinine value to the baseline creatinine (MCR). Patients were categorized into three groups based on MCR: non-elevation (≤1.0), mild elevation (1.0 to 1.5), and pronounced elevation (≥1.5). Multivariable logistic regression was used to estimate the risk of AKI, severe AKI, and non-recovery from AKI.

Results: There were significant increases in the odds of AKI (adjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.29-1.57; per 0.1 increase in MCR), severe AKI (adjusted OR, 1.28; 95% CI, 1.15-1.41), and AKI non-recovery (adjusted OR, 1.29; 95% CI, 1.16-1.43). Pronounced elevation in preoperative serum creatinine was associated with a higher risk of AKI (adjusted OR, 15.45; 95% CI, 6.63-36.00), severe AKI (adjusted OR, 3.62; 95% CI, 1.20-10.87), and AKI non-recovery (adjusted OR, 4.74; 95% CI, 1.63-13.89) than non-elevation. Mild elevation in preoperative serum creatinine was also significantly associated with AKI (adjusted OR, 3.76; 95% CI, 1.92-7.37).

Conclusions: Elevation in preoperative serum creatinine from baseline was associated with an increased risk of AKI; even mild elevation significantly increased the risk of AKI.

Introduction: Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI.

Methods: An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF-1α, ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting used to measure the phosphorylation of ERK level.

Results: In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of extracellular signal-regulated kinase (ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, Gpx, and ERK phosphorylation (p-ERK). In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and ERK phosphorylation, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, proinflammatory factors levels, oxidative stress response, and p-ERK levels.

Conclusion: FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Background: The potential applications of nanotechnology in the medical field have become increasingly recognized in recent years. Nanocarriers have emerged as a versatile tool, offering a wide range of applications due to their unique properties. In addition to the targeted drugs delivery, nanocarriers have also proven to be extremely effective in imaging and diagnostics. Continuous advances in nanotechnology have paved the way for innovative solutions to complex challenges in human health, shaping the future of nanotechnology and its applications.

Summary: By exploring different types of nanoparticles, this review delves into the different characteristics that can be tailored to enhance their kidney access. Although the structural complexity of the kidney may prevent nanocarriers passage, optimization of nanocarrier characteristics such as shape, size, charge, and surface modifications may overcome these barriers, allowing for targeted delivery. By harnessing the potential of nanoparticles, researchers aim to develop targeted and efficient therapies that can address various kidney-related disorders.

Key messages: This review highlights the promising advancements in nanotechnology and their potential impact on improving the therapeutic outcomes for several kidney diseases.

Introduction: Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China.

Methods: We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022 to January 8, 2023. The non-contrast enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient's clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality.

Results: This study included a total of 858 hemodialysis patients, of which 660 were infected with COVID-19. The mean age was (55.61±14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level and calcium were independent risk factors for disease severity, while platelets, urea nitrogen and creatinine were identified as independent protective factors. Furthermore, total iron- binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p < 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes.

Conclusion: The majority of HD patients are susceptible to COVID-19. Demographic, clinical features and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Background: Chronic kidney disease (CKD) and hypertension are significant global health challenges that often coexist and aggravate each other. Renin-angiotensin system (RAS) inhibitors are important to the management of these conditions; however, their efficacy for advanced CKD remains uncertain.

Summary: Angiotensin receptor-neprilysin inhibitor (ARNI) have superior efficacy for heart failure (HF) management, as evidenced by landmark trials such as the PARADIGM-HF and PARAGON-HF, thus leading to its endorsement by various guidelines. Although direct evidence supporting the renal-protective effects of ARNI is lacking, post hoc analyses have suggested its potential to mitigate the decline of the estimated glomerular filtration rate and renal events, particularly in patients with HF with a relatively preserved ejection fraction. Mechanistically, ARNI augments the glomerular filtration rate by dilating glomerular arterioles, relaxing mesangial cells, and improving renal medullary blood flow, thereby mitigating interstitial fibrosis progression. ARNI also effectively addresses non-dipper hypertension, particularly in salt-sensitive individuals, thereby reducing the cardiovascular risk.

Key messages: Uncertainties regarding the efficacy and safety of ARNI for advanced renal failure (estimated glomerular filtration rate <30 mL/min) exist. Excessive hypotension associated with ARNI use may exacerbate the renal function decline, especially in older patients with comorbid HF with a reduced ejection fraction. Hence, vigilant blood pressure monitoring is essential to optimizing the renal benefits of ARNI and minimizing adverse effects. Evidence supporting the renal benefits of ARNI continues to evolve; therefore, ARNI could mitigate renal dysfunction in select patient populations. Further research should be performed to clarify the efficacy of ARNI for advanced renal failure and refine its therapeutic application for patients with concurrent HF and renal dysfunction.

Introduction: The correlation between hypercholesterolemia and cardiovascular disease in kidney transplant recipients (KTR) remains uncertain. We sought to characterize the association between abnormal cholesterol profiles and cardiovascular morbidity and mortality in this unique population.

Methods: This retrospective cohort study was conducted at a single center and included all adult KTR, transplanted between January 2005 and April 2014. The primary outcome was Major Adverse Cardiovascular Events (MACE) while the secondary outcome was the composite outcome of MACE and all-cause mortality. Exposure to abnormal cholesterol levels was calculated using a time-weighted average (TWA) calculation. MACE and mortality risk were analyzed using a multivariate time varying Cox model.

Results: The final cohort comprised 737 KTR, with a median follow-up of 2920 days. A total of 126 patients (17.1%) experienced MACE. High LDL-C levels and MACE risk were correlated by multivariate analysis (HR 1.008 per mg/dl, 95%CI 1.001 - 1.016), while low HDL-C levels were not significantly associated with MACE (HR 0.992 per mg/dl, 95%CI 0.976 - 1.009). A higher LDL-C/HDL-C ratio was significantly associated with an increased risk of MACE in multivariate analyses (HR 1.502 per unit, 95%CI 1.147-1.968), and also correlated with the composite outcome (HR 1.35 per unit, 95%CI 1.06 - 1.71).

Conclusions: A high LDL-C /HDL-C ratio is predictive of an increased risk of cardiovascular morbidity and mortality in kidney transplant recipients. These findings emphasize the significance of the LDL-C/HDL-C ratio as a valuable marker of cardiovascular risk and support current recommendations to improve hypercholesterolemia in this high-risk group.

Background: Platelets play parts in infection and immune processes. However, the association between platelet count and the risk of peritoneal dialysis-associated peritonitis is unclear.

Methods: This was a retrospective, observational, single-center cohort study. A Cox regression analysis was used to evaluate the independent association of platelet count with the occurrence of first PD-associated peritonitis. Models were adjusted for gender, age, BMI, cardiovascular disease, diabetes mellitus, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, albumin level, potassium level, and anti-platelet medication usage.

Results: A total of 2374 patients were enrolled in this study (59% men; mean age 47.40 ± 12.12). The average platelet count was 229.30±82.12 x 109/L. 467 (20%) patients suffered from PD-associated peritonitis at least once. In the multivariable model, the adjusted hazard ratios (HRs) for quartiles 2, 3 and 4 versus quartile 1 were 1.428 (95% CI 1.060-1.924, P=0.019), 1.663 (95% CI 1.240-2.229, P<0.001) and 1.843 (95% CI 1.363-2.492, P<0.001) with baseline data. A nonlinear relationship between platelet count and first PD-associated peritonitis was observed. Further, the association between platelet and first PD-associated peritonitis was significant in the patients with hypokalemia (P for interaction=0.040).

Conclusion: In PD patients, elevated platelet counts were significantly associated with an increased risk of the first onset of PD-associated peritonitis.

Introduction: Peritoneal Ultrafiltration (PUF) has been proposed as an additional therapeutic option for Refractory Congestive Heart Failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trials data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases (CKD). In this article, we describe a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients.

Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a Phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guidelines-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient's mortality or worsening of the patient's condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months.

Conclusion: The PURE Study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guidelines-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients' condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients.

Clinicaltrials: gov Identifier: NCT03994874.