Kidney & blood pressure research最新文献

Introduction: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis.

Methods: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients.

Results: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis.

Conclusion: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Introduction: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN.

Methods: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records.

Results: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001).

Conclusions: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

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.

Introduction: The present study investigated the role of long non-coding RNA (lncRNA) GABPB1-IT1 in ischemia-induced acute kidney injury (AKI).

Methods: The expression of GABPB1-IT1 in the plasma of patients with ischemia-induced AKI and healthy controls was detected by RT-qPCR. GABPB1-IT1 and miR-204-5p were overexpressed in human renal proximal tubular epithelial cells (HRPTEpCs), followed by RT-qPCR to assess the overexpression effect and the regulatory relationship between GABPB1-IT1 and miR-204-5p. Methylation-specific PCR was performed to assess the promoter methylation status of miR-204-5p. Additionally, a cell apoptosis assay was carried out to evaluate the correlation between miR-204-5p and GABPB1-IT1 in the context of hypoxia-induced apoptosis of HRPTEpCs.

Results: GABPB1-IT1 was upregulated in the plasma of patients with ischemia-induced AKI. In HRPTEpCs, hypoxia upregulated the expression of GABPB1-IT1. MiR-204-5p was downregulated in ischemia-induced AKI, and the expression of miR-204-5p was inversely correlated with GABPB1-IT1. In HRPTEpCs, overexpression of GABPB1-IT1 decreased the expression levels of miR-204-5p and increased miR-204-5p gene methylation. In addition, overexpression of GABPB1-IT1 reduced the inhibitory effects of miR-204-5p on the apoptosis of HRPTEpC induced by hypoxia. Furthermore, overexpression of GABPB1-IT1 promoted kidney injury, renal tissue injury scores, and the level of serum creatinine. However, miR-204-5p had the opposite effect.

Conclusion: GABPB1-IT1 was upregulated in ischemia-induced AKI and may induce hypoxia-induced apoptosis of HRPTEpC by methylation of miR-204-5p.

Introduction: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG).

Method: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90 mL/min/1.73 m2, and recruited individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness.

Results: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR, and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73 m2, and 1,423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (β = -25.68 95% CI: -46.42, -7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (β = -3.54 95% CI: -11.88, -0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG.

Conclusion: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration.

Introduction: Accumulating evidence has disclosed that IgA nephropathy (IgAN) could present shortly after the second dose of COVID-19 mRNA vaccine. However, the undying mechanism remains unclear and we aimed to investigate the potential molecular mechanisms.

Methods: We downloaded gene expression datasets of COVID-19 mRNA vaccination (GSE201535) and IgAN (GSE104948). Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify co-expression modules related to the second dose of COVID-19 mRNA vaccination and IgAN. Differentially expressed genes (DEGs) were screened, and a transcription factor (TF)-miRNA regulatory network and protein-drug interaction were constructed for the shared genes.

Results: WGCNA identified one module associated with the second dose of COVID-19 mRNA vaccine and four modules associated with IgAN. Gene ontology (GO) analyses revealed enrichment of cell cycle-related processes for the COVID-19 mRNA vaccine hub genes and immune effector processes for the IgAN hub genes. We identified 74 DEGs for the second dose of COVID-19 mRNA vaccine and 574 DEGs for IgAN. Intersection analysis with COVID-19 vaccine-related genes led to the identification of two shared genes, TOP2A and CEP55. The TF-miRNA network analysis showed that hsa-miR-144 and ATF1 might regulate the shared hub genes.

Conclusions: This study provides insights into the common pathogenesis of COVID-19 mRNA vaccination and IgAN. The identified pivotal genes may offer new directions for further mechanistic studies of IgAN secondary to COVID-19 mRNA vaccination.

Introduction: The correlation between hypercholesterolemia and cardiovascular disease in kidney transplant recipients (KTRs) 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 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 2,920 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 KTRs. 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.

Introduction: The calcineurin inhibitor cyclosporine A (CsA) has been shown to effectively reduce proteinuria. However, its precise mechanism is still not fully understood. Our previous study showed that CsA reduced proteinuria by directly stabilizing the foot process (FP) cytoskeletal structure via cofilin-1, suggesting that synaptopodin, a podocyte-specific actin protein, is not the sole target of CsA in podocytes.

Methods: In this study, we established an adriamycin (ADR)-induced nephropathy rat model and a cultured podocyte injury model. We employed Western blotting and immunofluorescence techniques to assess the expression and distribution of transgelin, Krüppel-like factor-4 (KLF-4), nephrin, and synaptopodin.

Results: We observed a significant increase in proteinuria levels accompanied by loss of normal FP structure in the ADR-induced nephropathy rat model. The levels of the actin cross-linking protein transgelin were increased significantly, while those of the podocyte-specific molecules nephrin and synaptopodin were decreased in vivo. Treatment with CsA effectively reduced proteinuria while restoring FP effacement stability in ADR-induced nephropathy models and restoring the expression of transgelin, nephrin, and synaptopodin both in vivo and in vitro. Furthermore, CsA treatment dose-dependently decreased transgelin levels while significantly increasing KLF-4 expression in injured podocytes. In addition, CsA failed to downregulate transgelin when KLF-4 was specifically knocked down.

Conclusion: Our findings suggest that CsA protects against podocyte injury by downregulating abnormally high levels of transgelin via upregulation of KLF-4 expression.

Introduction: Contrast nephropathy (CN) is characterized by oxidative stress, vasoconstriction, tubular toxicity, and hypoxia of the renal medulla. We aimed to test the therapeutic effects of an α7 nicotinic acetylcholine receptor (nAChR) agonist, GTS-21, in an experimental CN model.

Methods: Male Sprague-Dawley rats (n = 40) were divided into 4 groups: saline-treated control, GTS-21-treated control, contrast, and GTS-21-treated contrast groups. Starting on the 1st day, GTS-21 (4 mg/kg, intraperitoneally) or saline was administered twice a day for 3 days. CN was induced on the second day by intravenous injection of indomethacin (10 mg/kg), l-NAME (10 mg/kg), and a contrast agent with high osmolarity (6 mL/kg; Urografin 76%). At the 72nd hour, blood and kidney samples were obtained for the determination of biochemical, histological, and gene expression parameters.

Results: Compared to those in control rats, the elevated serum BUN level in the contrast group decreased with GTS-21 treatment, while H&E staining and TUNEL assays showed that contrast-induced renal injury was improved by GTS-21. Moreover, GTS-21 treatment in the CN also increased the antioxidant glutathione level. In the contrast group, a significant increase in IL-6 expression and a decrease in TGF-β expression were observed; however, GTS-21 treatment decreased IL-6 expression and increased TGF-β expression.

Conclusion: GTS-21 significantly alleviated renal injury parameters through antioxidant, anti-inflammatory, and antiapoptotic mechanisms in the CN model.