Kidney & blood pressure research最新文献

Introduction: Cognitive impairment (CI) is common in patients with end-stage renal disease, but the mechanism of uremia-associated CI is poorly recognized.

Methods: In this study, we constructed uremic rat models, treated with high-level phosphate (Pi) and the vascular calcification (VC) inhibitor, sodium thiosulphate (STP). We assessed the spatial learning and memory by the Morris Water Maze test, detected the VC by histological staining, and monitored the osteogenic factors alkaline phosphatase (ALP) and Runx2 expressions in Uremia + Pi and Uremia + Pi + STP rats through qPCR, Western blotting analysis, and immunohistochemistry analysis. Moreover, we examined the calcium content and the ALP and Runx2 expressions in vascular smooth muscle cells (VSMCs) treated with Pi and STP.

Results: The results showed that both the learning and memory abilities and the spatial exploration ability of the rats in the Uremia + Pi group were significantly decreased with enhanced expressions of ALP and Runx2, calcium content, and ALP activity; however, STP supplementation significantly alleviated the spatial learning and memory damage, reduced the ALP and Runx2 expressions, calcium content, and ALP activity. Moreover, Pi treatment significantly increased the calcium and malondialdehyde content in VSMCs, as well as ALP and Runx2 expressions. STP addition reversed these changes, indicating that a high phosphate level induced VC development.

Conclusion: Taken together, these results indicated that elevated serum phosphate might promote VC in uremic rats by activating the expressions of ALP and Runx2, thereby causing damage to the kidneys and uremia-associated complications such as CI. Therefore, this study improved the understanding to possible pathogenic mechanisms of uremia-induced CI, and will be beneficial to optimize the prevention and treatment strategy for CI in uremic patients.

Background: Pheochromocytomas and paragangliomas are rare chromaffin cell-derived tumors characterized by catecholamine-secreting activity. Pheochromocytomas account for 1.7% of pediatric hypertension cases. Surgical resection, the definitive pheochromocytoma treatment, carries risks of hemodynamic instability and cardiovascular complications. Nevertheless, mortality rates decreased significantly in the latter half of the 20th century due to effective perioperative blood pressure (BP) management. The literature on BP management tailored to pediatric pheochromocytoma is limited, while the sustained hypertension rate in this population is high (up to 90%) and related to a high risk of intraoperative complications. In this narrative review, we provide up-to-date recommendations regarding BP management to minimize perioperative comorbidities in children with pheochromocytoma.

Summary: Antihypertensive agents, primarily alpha (α)-blockers, should be promptly administered for suspected pheochromocytoma. Beta (β)-blockers may be introduced thereafter to counteract reflex tachycardia. The patient must be salt- and water-replete preoperation. Intraoperatively, stable hemodynamics should be ensured during anesthesia and surgery, and short-acting intravenous medications and resuscitation fluid should be supplied. Postoperatively, patients should be admitted to the pediatric intensive care unit for close monitoring for at least 24-48 h. Genetic testing is recommended for all pheochromocytoma patients. Identifying underlying mutations, like in succinate dehydrogenase subunit B, which is linked to a higher risk of multifocality and metastasis, is imperative for tailoring treatment strategies and prognostication.

Key messages: Achieving optimal outcomes in pediatric pheochromocytoma relies on preoperative BP optimization with appropriate antihypertensive agents, intraoperative hemodynamic stability, and postoperative routine long-term follow-up to monitor for complications, recurrence, and metastasis. Future research should prioritize well-designed prospective multicenter studies with adequate sample sizes and, where feasible, randomized controlled trials with standardized protocols and appropriate endpoints. These studies should focus on the efficacy and safety of preoperative nonselective versus selective α-blockers, whether as monotherapy or combined with other medications (e.g., calcium channel blockers and/or β-blockers), or treatment without preoperative anti-hypertensives.

Background: Renal fibrosis is a key driver of chronic kidney disease, often leading to end-stage renal disease (ESRD). Secreted phosphoprotein 1 (Spp1) is implicated in fibrotic processes, but its specific role in renal fibrosis, particularly associated with hydronephrosis, remains underexplored. This study investigates Spp1's involvement using transcriptomic analysis, machine learning, and clinical data integration.

Methods: Renal tissues from sham-operated mice with unilateral ureteral obstruction for 7 days were analyzed via transcriptome sequencing to identify differentially expressed genes (DEGs). Hub genes were identified through Weighted Gene Co-Expression Network Analysis and pathway enrichment. LASSO regression pinpointed potential biomarkers, with Spp1 validated in mouse and human samples through RT-PCR and immunohistochemistry. Clinical correlations were drawn from hydronephrosis patient data.

Results: Transcriptomic analysis revealed 5,219 DEGs, highlighting key pathways including IL-17, TNF, and PI3K/AKT. Spp1 emerged as a significant biomarker, strongly associated with tubular injury and fibrosis markers such as neutrophil gelatinase-associated lipocalin. Logistic regression and receiver operating characteristic (ROC) analysis confirmed Spp1 and urinary transferrin (U-TRF) as predictors of severe hydronephrosis, with high diagnostic accuracy (area under the ROC curve: 0.898 for Spp1; 0.938 for U-TRF).

Conclusions: Spp1 is a critical mediator in renal fibrosis and a promising biomarker for assessing hydronephrosis severity. Its diagnostic value, particularly when combined with U-TRF, underscores the need for further research into Spp1-targeted therapies in renal fibrosis.

Introduction: Acute kidney injury (AKI) is a prevalent issue in intensive care units (ICUs). There is a paucity of data regarding the use of blood gas and electrolyte measurements in predicting the risk of significant endpoints (kidney replacement therapy [KRT], death) in emerging, yet undiagnosed AKI.

Methods: Retrospective, observational, single-center study. The study documented 4 admission electrolytes (serum sodium, potassium, ionized calcium, and phosphate) and 3 admission blood gas variables (arterial pH, actual bicarbonate, pCO₂). The endpoints of the study were the need for KRT and death in the ICU.

Results: A total of 213 patients were included in the study. The ICU mortality rate was 31%, and 22.5% of all subjects required at least one individual KRT session. There were significant differences in admission serum sodium and phosphate levels between survivors and non-survivors (both lower in survivors), and in arterial pH and actual bicarbonate levels (both higher in survivors). The majority of all tested variables were identified as independent predictors of either the need for KRT or ICU death.

Conclusions: Integrating admission electrolytes and blood gas variables may potentially aid in identifying subsets of AKI patients at risk of death.

Introduction: Chronic kidney disease (CKD) is associated with elevated mortality risk. The study aimed to investigate the extent to which multiple risk factors controlled could attenuate CKD-related excess mortality.

Methods: The study included 2,394 CKD patients and 15,962 non-CKD individuals from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Seven modifiable risk factors included blood pressure, body mass index, hemoglobin A1c, non-high-density lipoprotein cholesterol, smoking, physical activity, and diet. CKD patients were categorized by the number of controlled risk factors. Cox models were used to estimate associations between risk factors controlled and risks of all-cause and cause-specific mortality.

Results: Among CKD patients, each additional risk factor control was significantly associated with a 19% lower risk of all-cause mortality (HR [hazard ratio]: 0.81; 95% CI [confidence interval]: 0.71-0.93), with the optimal control of 6-7 risk factors associated with a 59% lower risk of all-cause mortality (HR: 0.41; 95% CI: 0.19-0.90). Furthermore, compared with non-CKD individuals (death rate per 1,000 person-years: 2.69 [95% CI: 1.77-4.09]), CKD patients with 6-7 risk factors controlled had no significantly different risks of all-cause mortality (absolute rate difference per 1,000 person-years: 0.79 [95% CI: -2.65, 6.63]; HR: 1.29 [95% CI: 0.62-2.66]), cardiovascular disease mortality (absolute rate difference: 0.27 [95% CI: -0.80, 3.00]; HR: 1.51 [95% CI: 0.43-5.34]), and cancer mortality (absolute rate difference: 0.27 [95% CI: -0.80, 3.00]; HR: 1.06 [95% CI: 0.28-3.96]).

Conclusions: Multiple risk factors controlled were associated with reduced CKD-related excess mortality. Optimal control of 6-7 factors was associated with the elimination of increased mortality risks relative to non-CKD individuals. These findings highlight the need for integrated management strategies targeting biological and lifestyle risk factors in CKD populations.

Introduction: This study aimed to investigate the potential association between the fatty liver index (FLI), metabolic dysfunction-associated steatotic liver disease (MASLD), and the risk of kidney stones using large-scale population-based data.

Methods: This study employed a cross-sectional design, utilizing data from the 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) database. A total of 24,342 participants were enrolled in the study, and fatty liver status was assessed by calculating the FLI. MASLD was diagnosed by FLI in conjunction with cardiometabolic criteria. Data on the history of kidney stones were obtained by self-report. We employed logistic regression models to analyze the association between FLI, MASLD, and kidney stone risk and constructed multivariable adjustment models to control for potential confounders. Furthermore, we used restricted cubic spline curve models to investigate the dose-response relationship between FLI and kidney stone risk and conducted subgroup and interaction analyses.

Results: The study's results indicate a strong correlation between increasing FLI quartiles and a notable rise in the prevalence of kidney stones. Specifically, the risk of developing kidney stones was 1.68 times higher among participants in the highest FLI quartile compared to those in the lowest. Furthermore, patients with MASLD exhibited a 1.35-fold increased risk of developing kidney stones compared to those with non-MASLD. Subgroup analyses demonstrated that the correlation between MASLD and kidney stone risk was consistent across multiple subgroups. However, a significant interaction was observed in the subgroups of smoking status, physical activity level, and hypertension (interaction p < 0.05). The restricted cubic spline analysis did not yield a statistically significant nonlinear association between FLI and kidney stone risk. However, the study did identify inflection point values for FLI.

Conclusion: This study demonstrated an association between FLI and MASLD and the risk of kidney stones. This suggests that these conditions may be pivotal risk factors for kidney stones. Further investigation is required to elucidate these associations' underlying mechanisms and develop efficacious interventions to reduce the risk of kidney stones. Also, formulating personalized prevention and treatment strategies for different population subgroups is paramount.

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide. The management of DKD relies on controlling glycemia and blood pressure levels, as well as reducing proteinuria. While the traditional renin-angiotensin-aldosterone system inhibitors (RAASi) and the recently approved type 2 Na+/glucose co-transporter inhibitors (SGLT2i) have significantly improved patient outcomes, residual risks remain unaddressed.

Summary: This review explores (1) the mechanisms of action of finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (ns-MRA), (2) the evidence of finerenone-induced kidney protection in clinical trials, and (3) the comparative advantages over conventional MRAs. The potential synergy between finerenone and SGLT2i is also addressed, alongside research perspectives and practical considerations for implementation in clinical practice.

Key messages: Finerenone has emerged as a breakthrough therapy in the management of DKD, demonstrating robust nephro- and cardio-protective effects.

Introduction: Regular physical activity is beneficial for health but is often reduced in patients receiving maintenance hemodialysis treatment. Irisin is a muscle-secreted hormone that reportedly improves metabolism and slows down the progression of some chronic diseases. In this study, we aimed to investigate the relationship between physical activity capacity and serum irisin levels in hemodialysis patients.

Methods: Our study included 252 patients undergoing hemodialysis at Xuanwu Hospital Capital Medical University. Enzyme-linked immunosorbent assay was used to measure blood irisin levels. Body composition was analyzed by bioelectrical impedance analysis. The International Physical Activity Questionnaire (IPAQ) was used to score physical activity ability.

Results: Bivariate correlation analysis showed a positive correlation between IPAQ scores and ln irisin (the natural logarithm of irisin; r = 0.326, p < 0.001). Independent determinants of IPAQ scores were ln irisin, age, fasting glucose, and carbon dioxide combining power.

Conclusion: Our findings provide the first clinical evidence that serum irisin levels are positively correlated with physical activity capacity in hemodialysis patients.

Introduction: Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear.

Methods: The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic curve analysis. The correlation of serum PAF with blood pressure was assessed using Spearman analysis.

Results: Both systolic blood pressure and diastolic blood pressure were significantly higher in HDCP patients, as well as the serum levels of TNF-α and IL-1β at diagnosis/enrollment, while serum levels of IL-10 showed the opposite trend. Serum PAF levels were significantly higher in patients with HDCP compared to normal pregnant women. Furthermore, serum PAF levels were higher in HDCP patients with mild preeclampsia compared to those with gestational hypertension and even more elevated in HDCP patients with severe preeclampsia at the early pregnancy stage and at diagnosis. In HDCP patients, increased serum PAF levels at early pregnancy and at diagnosis were associated with poor outcomes. Additionally, serum PAF levels could predict the occurrence of HDCP and poor outcomes.

Conclusion: Serum PAF from HDCP patients at both the early pregnancy and diagnosis stages could effectively predict the occurrence and outcome of HDCP.

Introduction: Gout, characterized by hyperuricemia and urate crystal deposition, is associated with systemic inflammatory complications, including kidney injury. This study aimed to investigate the role of serum nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome and associated cytokines (IL-1β and IL-18) in gout-related kidney injury (GRI).

Methods: A total of 279 gout patients (96 with renal injury and 183 without renal injury) and 100 healthy controls were included. Serum NLRP3, IL-1β, and IL-18 were measured and compared using an enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was carried out to evaluate the diagnostic values of individual or combinational biomarkers. Spearman's correlation analysis was employed to analyze correlations between NLRP3, IL-1β, and IL-18 and renal function indicators or serum uric acid.

Results: Serum levels of NLRP3, IL-1β, and IL-18 were significantly higher in gout patients compared to healthy controls (p < 0.001, gout group with kidney injury [GKI]: n = 96, gout group without kidney injury [GNKI]: n = 183, controls: n = 100), with elevated levels observed in GKI patients compared to GNKI (p < 0.001). Correlations between these markers were confirmed among all gout patients (n = 279), including serum NLRP3 with IL-1β (r = 0.34, p < 0.001) and NLRP3 with IL-18 (r = 0.47, p < 0.001). ROC analysis revealed that the combined model of NLRP3, IL-1β, and IL-18 showed improved diagnostic accuracy for GRI, with an AUC of 0.85 (95% CI: 0.81-0.89, p < 0.001). In GKI patients (n = 96), serum NLRP3, IL-1β, and IL-18 were inversely correlated with eGFR (NLRP3: r = -0.43, p < 0.01). Additionally, serum IL-18 positively correlated with serum uric acid levels (r = 0.27, p = 0.009).

Conclusion: These findings highlight the potential of serum NLRP3, IL-1β, and IL-18 as diagnostic markers and therapeutic targets in GRI, providing insights into early intervention and improved clinical outcomes in gout patients with renal complications.