Kidney & blood pressure research最新文献

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.

Introduction: Chronic kidney disease (CKD) is classified according to the estimated glomerular filtration rate (eGFR), but kidney volume (KV) can also provide meaningful information. Very few radiomics (RDX) studies on CKD have utilized computed tomography (CT). This study aimed to determine whether non-enhanced computed tomography (NECT)-based RDX can be useful in evaluation of patients with CKD and to compare it with KV.

Methods: The NECT scans of 64 subjects with impaired kidney function (defined as <60 mL/min/1.73 m2) and 60 controls with normal kidney function were retrospectively analyzed. Kidney segmentations, volume measurements, and RDX features extraction were performed. Machine-learning models using RDX were constructed to classify the kidneys as having structural markers of impaired or normal function.

Results: The median KV in the impaired kidney function group was 114.83 mL vs. 159.43 mL (p < 0.001) in the control group. There was a statistically significant strong positive correlation between KV and eGFR (rs = 0.579, p < 0.001) and a strong negative correlation between KV and serum creatinine level (rs = -0.514, p < 0.001). The KV-based models achieved the best area under the curve (AUC) of 0.746, whereas the RDX-based models achieved the best AUC of 0.878.

Conclusions: RDX can be useful in identifying patients with impaired kidney function on NECT. RDX-based models outperformed KV-based models. RDX has the potential to identify patients with a higher risk of CKD based on imaging, which, as we believe, can indirectly support clinical decision-making.

Introduction: In the past, elevated blood pressure was considered an exclusion criterion for living kidney donation because of concerns about premature kidney failure. Hypertension leads to complement deposits and renal fibrosis in the kidney. Therefore, the aim of this study was to investigate whether increased complement deposits and fibrosis can be observed in grafts of hypertensive compared to normotensive living donors.

Methods: Zero-time renal biopsies from 238 living donors (52 hypertensive) and the corresponding 1-year protocol biopsies were examined for complement deposits of C1q, C3c, and MASP-2. Findings were compared to kidney biopsies from patients with hypertensive nephropathy. Further, renal fibrosis was visualized by Sirius red staining, scored semiquantitatively, and compared to biopsies from deceased donors and kidneys with hypertensive nephropathy. Additionally, zero-time biopsies from hypertensive (n = 6) and normotensive (n = 5) living donors were analyzed for expression of fibrosis-associated genes by multiplex mRNA analysis and compared to zero-time biopsies (n = 6) from deceased donors.

Results: In all zero-time biopsies from living donors, complement deposits were minimal for C1q, C3c, and MASP-2 compared to samples with hypertensive nephropathy, regardless of whether the donor was hypertensive or normotensive. In 1-year protocol biopsies, complement deposits were unchanged, while renal fibrosis was slightly but not significantly increased in hypertensive compared to normotensive living donors. Gene expression data showed that the 11 zero-time biopsies from hypertensive and normotensive living donors clustered together and were clearly separated from the deceased donor biopsies.

Conclusion: The use of kidneys from hypertensive living donors appears to have no or little effect on renal complement deposits and fibrosis 1 year after transplantation.

Introduction: Fibroblast growth factor 23 (FGF23) has emerged as an important endocrine regulator of renal phosphate and vitamin D metabolism and as a factor implicated in pathophysiological processes in further organs, including the heart. In myocardial infarction, elevations of plasma FGF23 can be observed that may be related to left ventricular hypertrophy or fibrosis. A critical event in the development of myocardial infarction and thrombosis is platelet aggregation due to thromboxane A2 (TxA2) formation. We studied whether TxA2 is a regulator of FGF23.

Methods: Experiments were performed in rat UMR-106 osteoblast-like cells and differentiated mouse MC3T3-E1 cells upon exposure to TxA2, pharmacological manipulation of TxA2 signaling, or co-incubation with platelets isolated from healthy volunteers. Fgf23 transcripts were analyzed by qRT-PCR and FGF23 protein by enzyme-linked immunosorbent assay.

Results: As a result, TxA2 or stable TxA2 receptor agonists I-BOP or U46619 significantly suppressed Fgf23 gene expression, an effect abrogated by TxA2 receptor antagonist SQ29548. TxA2 signaling also down-regulated FGF23 protein concentration in the cell culture supernatant. Co-incubation of UMR-106 cells with freshly isolated human thrombocytes activated by thrombin, but not with non-activated platelets or thrombin alone, significantly lowered Fgf23 gene expression in UMR-106 cells.

Conclusion: Taken together, TxA2 signaling suppresses FGF23 production in UMR-106 and MC3T3-E1 bone cells. TxA2-dependent regulation of FGF23 synthesis may be particularly relevant for common diseases associated with enhanced platelet aggregation.

Objective: The objective was to explore bone metabolism in chronic kidney disease (CKD) and its correlation with nutritional indicators and to identify risk factors for abdominal aortic calcification (AAC).

Methods: This cross-sectional study enrolled 148 adults (>18 years) with CKD stages 3-5 (stage 3: n = 13, stage 4: n = 15, stage 5: n = 120 including dialysis and non-dialysis patients) between May 2018 and May 2021. Participants met strict criteria: confirmed CKD diagnosis per Kidney Disease Outcomes Quality Initiative guidelines, stable nutritional status without malabsorption disorders, and no vitamin K antagonist use. Exclusion criteria included acute kidney injury, transplant recipients, malignancies, and thyroid/parathyroid disorders. Using convenience sampling, we assessed correlations between nutritional/mineral markers via Pearson's analysis and identified intima-media thickness (IMT)/AAC risk factors through binary logistic regression.

Results: Positive correlations were observed between serum calcium and 25-hydroxyvitamin D (25-[OH]D), haemoglobin, albumin (Alb), prealbumin (PAlb) and serum magnesium. Negative correlations were found with blood urea nitrogen (BUN), serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum phosphorus, and intact parathyroid hormone (iPTH). Serum phosphorus was positively correlated with BUN, SCr, uric acid, cystatin C (CysC), calcium-phosphate product (Ca × P), iPTH, PAlb, and serum magnesium and negatively correlated with eGFR and 25-(OH)D. Parathyroid hormone levels were positively correlated with BUN, SCr, CysC, Ca × P, Alb, and PAlb and negatively correlated with eGFR and 25-(OH)D. Logistic regression identified age, sex, and diabetes as independent risk factors for IMT, and age, dialysis vintage, and low Alb as risk factors for AAC. Significant differences in AAC were found for sex, dialysis vintage, cholesterol, high-density lipoprotein, and serum calcium levels.

Conclusion: Calcium-phosphorus metabolism plays a role in vascular calcification in CKD, with age, diabetes, dialysis vintage, lipid levels, and low Alb levels contributing to this process.