Kidney & blood pressure research最新文献

Introduction: Previous studies have found a relative risk of 1.6-2 for renal function deterioration with serum uric acid level increment. However, the association between the baseline urinary uric acid (UUA) level and renal function decline remains unclear, and we aimed to assess this association.

Methods: In this retrospective cohort-controlled study, we included patients who met the following inclusion criteria: age >18 years, the presence of at least one UUA level in their electronic medical records (EMR), and two eGFR values. The exclusion criteria were chronic dialysis treatment before the baseline eGFR or any history of kidney transplantation. The EMR of the patients have been retrospectively screened between December 31, 2001, and January 31, 2022. The study group consisted of patients with UUA levels of ≥750 mg/day. In the control group, we included patients whose every UUA level was <750 mg/day. The primary endpoint was a composite of eGFR decline of ≥50%, eGFR <15 mL/min, dialysis initiation, or death. Secondary endpoints were as follows: eGFR decline of ≥50%, the latest eGFR <15 mL/min, or death. The endpoints were compared between the groups by Cox proportional hazards model analysis.

Results: We included 480 patients in the study group and 2,998 in the control group. The primary endpoint was observed in 30.95% and 16.25% of participants in the control and study groups, respectively; however, after it was compared between the two groups using the Cox model, there was no significant difference (HR: 1.20, 95% CI: 0.96-1.51, p = 0.11). Similarly, no significant differences in the rates of secondary endpoints between the two groups were observed, except the difference between the eGFR declines >50% which was significant, as was observed by the Cox model (HR: 2.22, 95% CI: 1.47-3.37, p < 0.001).

Conclusion: There was no significant difference in the rate of the composite endpoint between the study and control groups. Kidney function deterioration (as measured by eGFR decline of ≥50%) was significantly higher among patients with baseline hyperuricosuria (UUA ≥750 mg/day) than in those with normal uricosuria, as was observed by the Cox model. Further prospective studies are needed to clarify the role of uricosuria in renal function deterioration.

Introduction: Limited studies have explored the link between sleep duration and chronic kidney disease (CKD). However, the longitudinal alteration of sleep duration over time, known as sleep duration trajectories, has not been well explored. This gap results in an unclear understanding of the relationship between sleep duration trajectories and the risk of developing CKD, which is addressed in this study.

Methods: Based on longitudinal data from the China Health and Retirement Longitudinal Study (2011, 2013, and 2015 waves), a group-based trajectory model was used to identify distinct patterns of sleep duration. A Cox proportional hazards model was employed to assess the hazard ratios associated with each trajectory in relation to CKD onset (2018 and 2020 waves). Additionally, interaction analysis was conducted to examine potential individual-level modifiers of the relationship between sleep duration trajectories and CKD onset. Three different sensitivity analyses were performed to ensure the robustness of the findings.

Results: A total of 11,059 individuals were included in this survey with three distinct sleep duration trajectories identified: Group 1 (mean sleep duration: 3.56 ± 1.32), Group 2 (mean sleep duration: 5.83 ± 1.36), and Group 3 (mean sleep duration: 7.70 ± 1.17). Group 1 showed the highest risk of developing CKD, with an incidence of 10.54 cases per 1,000 person-years (95% confidence interval 8.77-12.68). Relative to group 1, group 3 was significantly associated with a reduced risk of CKD (hazard ratio 0.55, 95% confidence interval 0.44-0.70). A notable decrease in CKD risk was observed across all subgroups, and no significant interaction effects were found between covariates and the association between sleep duration trajectory and CKD.

Conclusion: Among middle-aged and elderly adults, persistent long sleep duration was associated with a lower risk of CKD. Maintaining adequate and stable sleep duration may be beneficial for CKD risk management in this population. However, further evidence is required to inform definitive public health recommendations.

Objectives: Depression and cognitive decline are common and frequently co-occur among older adults with hypertension, but their symptom-level relationships are poorly understood. This study explored interrelationship between depressive symptoms and cognitive function as well as their associations with quality of life (QoL) in a national hypertension sample from China.

Methods: Depression, cognitive function, and global QoL were assessed utilizing Chinese versions of the 10-item Center for Epidemiological Studies Short Depression Scale (CESD-10), Mini-Mental State Examination, and World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. We identified central symptoms and bridge symptoms based on centrality strength and bridge strength indexes, while symptoms having links to QoL were analyzed via flow network analysis.

Results: The study included 4,683 older adults. The prevalence of depression (CESD-10 total score ≥10) and cognitive impairment (MMSE total score <24) were 28.5% (95% CI = 27.2-29.8%) and 19.9% (95% CI = 18.8-21.1%), respectively. "Feeling blue/depressed" (CESD3) and "language" (Lan) were emerged as the most influential symptoms within the network model. "Naming" and "Language" were identified as most important bridge symptoms. Finally, "sleep disturbances" (CESD10) and "hopelessness" (CESD5) exhibited the strongest negative association with QoL.

Conclusions: Targeting central and bridge symptoms (e.g., depressed emotions, language, and naming ability) may provide pathways for addressing both depression and cognitive decline among older adults with hypertension. Moreover, improving sleep quality and alleviating hopelessness could help increase QoL in this population.

Introduction: Atheroembolic kidney disease (AEKD) is an under-recognized cause of kidney failure, secondary to the obstruction of the renal artery and/or its branches due to the rupture of an unstable atherosclerotic plaque in patients treated with surgical and invasive cardiovascular procedures. The embolization of cholesterol crystals in the renal artery activates the complement and triggers an inflammatory reaction. Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by the hyperactivation of the alternative complement pathway, leading to a prothrombotic and proinflammatory state on the endothelial surface. AEKD and aHUS could share the involvement of the complement in their pathophysiological mechanism and the former could lead to the latter.

Case presentation: A 72-year-old man was referred to our clinic because of a rapid worsening of renal function after 9 months from an endovascular aortic repair (EVAR). After 4 months from the intervention, his renal function worsened, he developed hypereosinophilia and skin lesions; the renal ultrasound showed increased resistance indexes, strongly suggestive of atheroembolic kidney disease. Successively, we observed thrombocytopenia, anemia, increased LDH, low plasmatic haptoglobin, schistocytes in blood smear, and normal ADAMTS13. We promptly diagnosed an atypical hemolytic uremic syndrome and started ravulizumab.

Conclusion: To our knowledge, this is the first case of aHUS secondary to a subacute AEKD. Further studies are necessary to fill the gap in the knowledge of the precise mechanism leading to aHUS secondary to AEKD and to confirm that they are two sides of the same coin.

Introduction: Milan hypertensive strain (MHS) of rat represents as one of the ideal rat models to study the genetic form of hypertension associated with aberrant renal salt reabsorption. In contrast to Milan normotensive strain (MNS), MHS rats possess missense mutations in three adducin genes and develop hypertension at 3 months old due to upregulation of sodium-chloride cotransporter (NCC). At prehypertensive stage (23-25 days old), MHS rats show enhanced protein abundance of Na+-K+-2Cl- cotransporter (NKCC2) but retain blood pressure comparable to MNS probably through enhanced GFR and reduced NCC and α-subunit of epithelial sodium channel (ENaC) expressed in distal convoluted tubule (DCT) and collecting duct (CD).

Methods: In the present study, mRNA and protein expressions of ion transporters in thick ascending limb of Henle's loop (TAL) of young MHS rats were investigated.

Results: Protein abundance of core-glycosylated form of renal outer medullary potassium (ROMK) channel in inner stripe of outer medulla (ISOM) is remarkably increased in MHS rats at prehypertensive stage. Furthermore, basolaterally expressed Na+-K+-ATPase and Barttin were upregulated.

Discussion/conclusion: These results may indicate that in TAL of MHS rats at this age, both total NKCC2 and core-glycosylated ROMK are upregulated in tandem potentially to balance the luminal potassium concentration. On the basolateral side, upregulation of Na+-K+-ATPase and CLC-Ka/b may energize the excretion of sodium and chloride out from the cells. These data may suggest the interplay of apical and basolateral ion transporters in TAL for the modulation of TAL function in favor of enhancing the transepithelial sodium reabsorption, although this seems compensated by NCC and ENaC expressed at the downstream nephron segments in young MHS rats.

Introduction: Urolithiasis is characterized by a high morbidity and recurrence rate, primarily attributed to metabolic disorders. The identification of more metabolic biomarkers would provide valuable insights into the etiology of stone formation and the assessment of disease risk. The present study aimed to seek potential organic acid (OA) biomarkers from morning urine samples and explore new methods based on machine learning (ML) for metabolic risk prediction of urolithiasis.

Methods: Morning urine samples were collected from 117 healthy controls and 156 urolithiasis patients. Gas chromatography-mass spectrometry was used to obtain metabolic profiles. Principal component analysis and ML were carried out to screen robust markers and establish a prediction evaluation model.

Results: There were 25 differential metabolites identified, such as palmitic acid, l-pyroglutamic acid, glyoxylate, and ketoglutarate, mainly involving arginine and proline metabolism, fatty acid degradation, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylic acid metabolism. The urinary OA markers significantly improved the performance of the ML model. The sensitivity and specificity were up to 87.50% and 84.38%, respectively. The area under the receiver operating characteristic curve (AUC) was significantly improved (AUC = 0.9248).

Conclusion: The results suggest that OA profiles in morning urine can improve the accuracy of predicting urolithiasis risk and possibly help understand the involvement of metabolic perturbations in metabolic pathways of stone formation and to provide new insights.

Introduction: Interstitial cells are crucial to the development of kidney structure and function, although the mechanism underlying their role in it remains unclear to date. Our previous study identified cell clusters in human fetal kidney tissue, and we further analyzed the interstitial cell cluster within this context.

Methods: We extracted the barcoded cDNA from tissue samples and prepared spatial transcriptome libraries. Sequencing data were quality-checked, normalized, and clusters were identified using Seurat. Single-cell and spatial data were integrated using multimodal intersection analysis, and cell types were deconvoluted. DEGs in interstitial cells were identified and functionally annotated using DAVID. CellPhoneDB was used to predict ligand-receptor interactions between cell types.

Results: The results of the present study revealed that this cluster of interstitial cells appeared to be scattered in the junction between the cortical and medullary regions. The subsequent Kyoto Encyclopedia of Genes and Genome pathway analysis revealed that the differentially expressed genes (DEGs) in this cluster of interstitial cells were involved in the WNT signaling pathway. The Gene Ontology (GO) analysis revealed that these DEGs were involved in multiple pathways associated with kidney development, with six of the genes (NKD2, TCF21, WNT5A, WNT4, MDK, and SFRP1) associated with kidney development exhibiting significant upregulation. Accordingly, it was inferred that these interstitial cells might be involved in regulating epithelial cell differentiation, ureteral bud development, and morphogenesis. The subsequent cell-cell communication analysis revealed that the cellular crosstalk was primarily regulated mainly by ligand-receptor pairs. Additionally, 17 genes reported to be associated with kidney disease were focused on, and these genes were found to be predominantly expressed in a single-cell type.

Conclusion: In summary, the present study revealed the characteristics of a previously identified cluster of interstitial cells in the kidney tissue, thereby providing fresh insights into the process of kidney development.

Background: Acute kidney injury (AKI) is a serious condition in clinical medicine that significantly increases morbidity and mortality, particularly in critically ill patients. Rapid and accurate identification of the underlying causes of AKI are crucial for determining appropriate therapeutic management and potentially saving the patient's life. Although endocrine emergencies are a less common cause of AKI in critically ill patients, recognizing when they occur is vital to comprehensive care.

Summary: AKI can impair the endocrine system and result in critical conditions for patients, particularly in cases of sepsis. In addition, several factors can contribute to severe conditions associated with AKI, including thyrotoxicosis, adrenal crisis, severe hypothyroidism, complications related to diabetes mellitus, panhypopituitarism, diabetes insipidus with acute hypernatremia, severe hypercalcemia, neuroendocrine tumors, and ovarian hyperstimulation syndrome.

Key message: The early recognition of endocrine emergencies and the impact of AKI on the endocrine system in critically ill patients are essential to intensive and comprehensive care.

Background: Intradialytic hypotension (IDH) occurs suddenly and without warning, although it is generally reversible. While ultrafiltration rate, cardiac function, and vascular resistance have been widely studied, more attention should be given to venous blood return to the heart in relation to blood stagnation. Both existing literature and clinical observations suggest that as a hemodialysis session progresses, the vascular bed of the liver expands, reducing venous return to the heart. This decrease in cardiac output may further increase hepatic blood volume, potentially playing a central role in the development of IDH.

Summary: This review explores the role of reduced venous return to the heart, caused by liver blood stagnation, as a key contributor to IDH.

Key messages: We tentatively name this pathophysiological mechanism "liver circulation jam." The clinical significance of this concept requires validation through future research.

Introduction: MicroRNAs have been increasingly recognized for their roles in cardiovascular diseases. Among these microRNAs, miR-214 was reported to be involved in hypertension. However, the role of endothelial miR-214 in hypertension is still unknown. The aim of this study was to determine the role of cell-specific miR-214 on regulating blood pressure, as well as the potential mechanisms.

Methods: We detected the levels of miR-214 in hypertensive mice and cultured mouse aortic endothelial cells (MAECs). In addition, mouse miR-214 inhibitor, miR-214 mimics, vascular endothelial cell-specific miR-214-deficient mice, smooth muscle cell-specific miR-214-deficient mice, renal proximal tubule cell-deficient mice, and various cellular and molecular techniques were employed to define the role of miR-214 in Ang II-induced hypertension.

Results: In mice and MAECs, Ang II significantly enhanced miR-214 levels, and anti-miR-214 markedly attenuated Ang II hypertension in line with enhanced eNOS/p-eNOS in aorta. Then, we generated vascular endothelial cell-specific miR-214 knockout mice and found an antihypertensive phenotype in endothelial miR-214 conditional knockout mice after Ang II treatment. In normotensive animals and MAECs, exogenous miR-214 administration reduced eNOS expression at protein and mRNA levels; in contrast, anti-miR-214 played an opposite role in regulating eNOS. By luciferase assay, our results confirmed that eNOS was a direct target gene for miR-214 in endothelial cells. However, smooth muscle cell-specific or renal tubular cell-specific deletion of miR-214 did not alter Ang II-induced hypertension.

Conclusion: Our findings suggested that endothelial miR-214 promoted Ang II hypertension by targeting eNOS in mice, which increased the understanding on the pathogenic mechanism of hypertension.