Kidney & blood pressure research最新文献

Introduction: Long-term sodium balance studies show that sodium can be temporarily stored and released in tissues, mediated by circaseptan rhythms of aldosterone and cortisol. This complicates the reliability of a single 24-h urine collection to estimate individual sodium intake. We investigated whether repeated timed urine collection with and without correction for plasma aldosterone is a more accurate alternative for estimating daily sodium intake.

Methods: We conducted a post hoc analysis of a metabolic ward study in which 16 healthy male adults consumed a diet with a fixed sodium content (50 or 200 mmol/day) for 7 days. Each day, urine was collected in 4 intervals (7:00-13:00 h, 13:00-19:00 h, 19:00-23:00 h, and 23:00-07:00 h). Plasma aldosterone was measured at 6:30 h, 12:30 h, and 18:30 h. Sodium intakes were estimated by various formulas using 3 timed urines of day 5-7.

Results: During a 200-mmol daily sodium intake, sodium intake estimates based on three repeated timed urine samples and the Toft equation differed 10 [IQR: 3-14], 8 [6-19], 36 [16-49], and 20 [10-43] mmol from the actual intake for intervals 7:00-13:00 h, 13:00-19:00 h, 19:00-23:00 h, 23:00-7:00 h, respectively. These measurements did not significantly differ from a single 24-h urine (20 [12-55] mmol). During a 50-mmol daily sodium intake, repeated timed urine collection performed worse than a single 24-h urine collection. On both diets, correction for plasma aldosterone increased accuracy and sodium intake estimates were significantly more accurate than a single 24-h urine.

Conclusion: In a controlled environment, repeated timed urine collection corrected for plasma aldosterone is more accurate than a single 24-h urine collection.

Introduction: Liddle syndrome is an autosomal dominant monogenic disease that mainly manifests as early-onset hypertension, hypokalaemia and metabolic alkalosis, as well as hyporeninaemia and hypoaldosteronism. The aetiology of Liddle syndrome is missense or frameshift mutations in the SCNN1A, SCNN1B, or SCNN1G genes, which encode for the epithelial sodium channel subunits. Among these, mutations in the SCNN1A gene are very rare.

Case presentation: A Liddle syndrome case caused by a SCNN1A mutation was reported from China. A 59-year-old proband had a 21-year history of chronic hypertension. His blood pressure was poorly controlled with various antihypertensive drugs, and hypokalaemia was found 8 years ago with no definite cause. At this visit, the patient presented with excessive renal potassium excretion and decreased renin activity in the postural stimulation test; however, his aldosterone level was normal. Subsequent genetic testing identified a missense mutation in SCNN1A (c.1475G>A), which encodes for a protein with an altered amino acid at position 492 (p.Arg492Gln). The pedigree investigation found that the older brother and son of the proband also have the same mutation. The patient's serum potassium returned to normal, and blood pressure control was significantly improved after being treated with triamterene.

Conclusion: A middle-aged patient with Liddle syndrome was diagnosed. A new point mutation in the SCNN1A gene was detected in this patient, and the pathogenicity of this mutation was predicted using AlphaFold software, expanding the genetic mutation spectrum of Liddle syndrome. Genetic testing should be improved to exclude monogenic hypertension in patients with hypertension complicated with hypokalaemia.

Background: N-glycosylation is one of the most common posttranslational modifications in humans, and these alterations are associated with kidney diseases.

Methods: A novel technological approach, single-cell N-acetyllactosamine sequencing (scLacNAc-seq), was applied to simultaneously detect N-glycosylation expression and the transcriptome at single-cell resolution in three human kidney tissues from zero-time biopsy. Cell clusters, glycation abundance in each cell cluster, functional enrichment analysis, cell-cell crosstalk, and pseudotime analysis were applied.

Results: Using scLacNAc-seq, 24,247 cells and 22 cell clusters were identified, and N-glycan abundance in each cell was obtained. Transcriptome analysis revealed a close connection between capillary endothelial cells (CapECs) and parietal epithelial cells (PECs). PECs and CapECs communicate with each other through several pairs of ligand receptors (e.g., TGFB1-EGFR, GRN-EGFR, TIMP1-FGFR2, VEGFB-FLT1, ANGPT2-TEK, and GRN-TNFRSF1A). Finally, a regulatory network of cell-cell crosstalk between PECs and CapECs was constructed, which is involved in cell development.

Conclusions: We here, for the first time, constructed the glycosylation profile of 22 cell clusters in the human kidney from zero-time biopsy. Moreover, cell-cell communication between PECs and CapECs through the ligand-receptor system may play a crucial regulatory role in cell proliferation.

Introduction: Diabetic kidney disease (DKD) affects 30-40% of patients with diabetes. The prevalence of nondiabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus (T2D) in Egypt is unknown. This study aimed to assess the prevalence of NDKD in patients with T2D in Egypt.

Methods: In this cross-sectional study, we searched the data of patients with T2D who underwent a native kidney biopsy between January 2010 and December 2020 in a kidney pathology laboratory in Egypt.

Results: Of 12,006 patients who underwent kidney biopsy, 677 patients had T2D. NDKD was found in 285 patients (42.7%), DKD in 220 patients (33%), and mixed DKD and NDKD in 162 patients (24.3%). The total prevalence of NDKD was 67% in patients with T2D in our study group. Membranous nephropathy was the most common histopathological disease in patients with NDKD (20.6%) followed by acute tubular injury (ATI) (19.2%) and focal segmental glomerulosclerosis (15.2%). The presence of ATI in a kidney biopsy was associated with a significantly higher mean serum creatine level (p < 0.001). Minimal change disease was associated with a significantly higher proteinuria level (p < 0.001). In binary logistic regression analysis, combining NDKD and mixed groups, the duration of diabetes was a negative predictor of NDKD, with a longer duration decreasing the likelihood of NDKD.

Conclusion: NDKD is prevalent among patients with T2D who underwent a kidney biopsy. Kidney biopsy remains the gold standard for diagnosing NDKD in patients with T2D.

Introduction: Sepsis and septic shock are significant contributors to the development of acute kidney injury (AKI) in critically ill patients. This study aimed to elucidate the role and mechanism of microRNA-223-3p in sepsis-associated AKI (SA-AKI).

Methods: Bioinformatics methods were used to analyze the expression of microRNA-223-3p in sepsis patients, its correlation with inflammatory cytokines, and to predict the binding site of microRNA-223-3p with SGK1. The binding relationship between microRNA-223-3p and SGK1 was validated using a dual-luciferase reporter gene assay. The expression of microRNA-223-3p was assayed using qPCR in patient serum or lipopolysaccharide (LPS)-treated HK-2 cells. Cell apoptosis; expression of Bax, Bcl-2, cleaved caspase-3; and levels of TNF-α, IL-1β, and IL-6 were measured using TUNEL assay, Western blot (WB), and ELISA, respectively. SGK1 expression of HK-2 cells with different treatments was detected using qPCR and WB.

Results: The expression of microRNA-223-3p was found to be upregulated in sepsis patients and HK-2 cells treated with LPS. Furthermore, microRNA-223-3p promoted apoptosis and inflammation in LPS-induced HK-2 cells. This promotion was mediated by the negative regulation of SGK1 by microRNA-223-3p.

Conclusion: The microRNA-223-3p was found to regulate SGK1 and promote apoptosis and inflammation in LPS-induced HK-2 cells. Our study has elucidated the mechanism of microRNA-223-3p in SA-AKI, providing a potential target for sepsis treatment.

Introduction: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1-2.

Methods: We enrolled adult patients with CKD stages 1-2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality.

Results: Among 99,266 patients with CKD stages 1-2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia were associated with a higher risk of all-cause mortality (hazard ratio: 1.28, 95% CI: 1.16-1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1-2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (p = 0.048).

Conclusions: Hyperphosphatemia was not rare in patients with CKD stages 1-2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease with a prevalence of 1:400 to 1:1,000 in Caucasians. It is caused by mutations in the PKD1 gene located on chromosome 16p13.3 (in about 85% cases) as well as in the PKD2 gene on chromosome 4q13-23. In the Polish population, the disease is associated with PKD1 mutations in 84% of the ADPKD-affected families. PKD1 and PKD2 genes encode the proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The presence of kidney cysts is a characteristic feature in the ADPKD patients. But in the ADPKD patients, cardiovascular abnormalities, such as hypertension (HT) with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, higher left ventricular mass (LVM), intracranial (ICAN) and extracranial aneurysms, and cardiac valve defects, are significantly more common than in the general population.

Summary: According to the literature data, both higher LVM and vascular dysfunction already occur in children and young adults with normal renal function and without HT. Moreover, biventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima-media thickness, and impaired coronary flow velocity reserve are present even in young patients with ADPKD who have normal HT and well-preserved renal function. In patients with ADPKD, hypertension has some specific features; in the youngest age group of children, the prevalence of hypertension is greater if their parents suffer from hypertension; in normotensive young ADPKD-diagnosed individuals, ambulant SBP and DBP values were significantly higher than in age- and gender-matched controls; hypertension appears at least 10 years earlier than spontaneous HT in general population. In adults, HT is often diagnosed before any substantial reduction in the GFR, and a lower nocturnal dip in BP in comparison to hypertensives in the general population. PKD1 and PKD2 gene products (PC1 and PC2 proteins) have been shown to assemble at the plasma membrane and to regulate calcium (Ca2+) entry. A defect in Ca2+ binding mediated by mutations in polycystin proteins is a hypothetical factor contributing to left ventricular mass increase. Altered intracellular Ca2+ handling contributes importantly to impaired contractility associated with heart failure. Impairment of intracellular Ca2+ homeostasis and mitochondrial function has been implicated in the development of LVH.

Key messages: It can be assumed that the cause of LVH in ADPKD patients is the natural course of this disease with developing HT and deteriorating kidney function, which may be influenced by the presence of PKD1- and PKD2-mutated gene products: PC1 and PC2 proteins.

Introduction: Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and a high mortality rate. Therefore, it is essential to understand the role and mechanism of key genes in RCC development and progression. This study aimed to analyze the role of zinc fingers and homeoboxes 2 (ZHX2) in RCC and the underlying mechanism.

Methods: RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein expression was analyzed by Western blotting assay and immunohistochemistry assay. Cell viability was evaluated using CCK-8 assay, and cell proliferation was assessed by EdU assay. The rate of cell apoptosis was quantified by flow cytometry. Transwell assays were conducted to analyze cell migration and invasion. The sphere formation assay was performed to assess the formation of microspheres. Additionally, m6A RNA immunoprecipitation assay and RNA immunoprecipitation assay were utilized to investigate the relationship between ZHX2 and two proteins, methyltransferase like 3 (METTL3) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The stability of ZHX2 mRNA was analyzed through the Actinomycin D assay. Furthermore, a xenograft mouse model assay was conducted to analyze the effect of ZHX2 overexpression and METTL3 silencing on RCC cell tumor properties in vivo.

Results: ZHX2 expression was upregulated in both RCC tissues and cells when compared with healthy renal tissues and human renal cortex proximal convoluted tubule epithelial cells. Depletion of ZHX2 inhibited RCC cell proliferation, migration, invasion, and spheroid-forming capacity but promoted cell apoptosis. Moreover, it was found that METTL3-mediated m6A methylation of ZHX2 and IGF2BP1 also stabilized ZHX2 through m6A methylation modification. Furthermore, ZHX2 overexpression showed a potential for attenuating the effects induced by METTL3 silencing and counteracted the inhibitory effect of METTL3 depletion on tumor formation in vivo.

Conclusion: METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

Introduction: A comprehensive pathophysiological mechanism to explain the relationship between high-salt intake and hypertension remains undefined. Evidence suggests that chloride, as the accompanying anion of sodium in dietary salt, is necessary to develop hypertension. We evaluated whether reducing dietary Cl- while keeping a standard Na+ intake modified blood pressure, cardiac hypertrophy, renal function, and vascular contractility after angiotensin II (AngII) infusion.

Methods: C56BL/6J mice fed with standard Cl- diet or a low-Cl- diet (equimolar substitution of Cl- by a mixture of Na+ salts, both diets with standard Na+ content) received AngII (infusion of 1.5 mg/kg/day) or vehicle for 14 days. We measured systolic blood pressure (SBP), glomerular filtration rate (GFR), natriuretic response to acute saline load, and contractility of aortic rings from mice infused with vehicle and AngII, in standard and low-Cl- diet.

Results: The mice fed the standard diet presented increased SBP and cardiac hypertrophy after AngII infusion. In contrast, low-Cl- diet prevented the increase of SBP and cardiac hypertrophy. AngII-infused mice fed a standard diet presented hampered natriuretic response to saline load, meanwhile the low-Cl- diet preserved natriuretic response in AngII-infused mice, without change in GFR. Aortic rings from mice fed with standard diet or low-Cl- diet and infused with AngII presented a similar contractile response.

Conclusion: We conclude that the reduction in dietary Cl- as the accompanying anion of sodium in salt is protective from AngII pro-hypertensive actions due to a beneficial effect on kidney function and preserved natriuresis.