Kidney & blood pressure research最新文献

Introduction: Urine proteomics plays an important role in the screening of biomarkers for infant diseases. However, there is no unified standard for the selection of urine samples for urine proteomics. It is also unclear whether there are differences in proteomics between whole urine and urine supernatant. Therefore, the urine of preterm infants was used as the research sample to explore the differences in protein profiles between the whole urine and urine supernatant of preterm infants by proteomics.

Methods: Urine samples were collected from five preterm infants with a gestational age of <28 weeks at their corrected gestational age of 37 weeks. Each preterm urine was divided into whole urine and supernatant. Urine protein was extracted and analyzed by liquid chromatography-tandem mass spectrometry.

Results: The two groups of urine samples did not show significant clustering in the principal component analysis. A total of 2,607 proteins were detected in the two groups of urine samples, of which 82 proteins were unique to whole urine samples and 56 proteins were unique to urine supernatant samples. The molecular functions, the main biological processes, and subcellular localization of the differential proteins were analyzed. In other neonatal-related diseases, there was no significant difference in protein enrichment between whole urine and urine supernatant.

Conclusions: This study analyzed the differences between whole urine and urine supernatant in urine proteomics of preterm infants. In neonatal-related diseases, there is no significant difference in urinary protein biomarkers between whole urine and urine supernatant.

Background: Inflammatory rheumatic diseases regularly require the use of disease-modifying antirheumatic drugs (DMARDs). The use of DMARDs in patients with end-stage chronic kidney disease (CKD stage 5D) is particularly challenging due to the lack of systematic studies available for this patient population. This narrative review aimed to address the aspect of DMARD therapy in CKD 5D.

Summary: The current article is a narrative review. References were sourced from the following databases: PubMed, Web of Science, Cochrane Library, and Scopus. The search period spanned from 1975 to 2024. There is a notable lack of systematic data on this topic. The available literature was reviewed to provide insights, despite the limited availability of comprehensive studies. Individuals with terminal kidney disease can presumably be safely treated with leflunomide, mycophenolic acid, sulfasalazine, azathioprine, belimumab, and anti-CD20. For all other substances, there are either significant restrictions, insufficient data, or inadequate experience.

Key messages: Some conventional and biologic DMARDs are available for the management of inflammatory rheumatic diseases in CKD stage 5D. It is essential to consider the limitations on kidney function, as they can significantly affect the pharmacokinetics of medications. Consequently, slightly more frequent checkups are recommended when using the defined preparations.

Introduction: End-stage kidney disease patients on maintenance hemodialysis (HD) are prone to increase cardiovascular and non-cardiovascular mortality at long and short interdialytic intervals of an intermittent thrice-weekly schedule. Variations in fluid and electrolyte status during and in dialysis-free periods may predispose patients to sudden cardiac death (SCD). We studied SCD in HD in relation to the interdialytic interval in patients on a twice-weekly HD schedule.

Methods: An ambispective cohort study was done and data of HD patients on a twice-weekly schedule were collected from January 2009 to December 2017. The primary outcome was cardiovascular mortality and the secondary outcome was an estimate of the standard mortality ratio (SMR) at each 12-h period interval of the HD schedule. Deaths were categorized as SCD, non-SCD, and non-cardiac death as per standard definitions.

Results: Of 413 participants, 289 died. The rate of cardiovascular death accounted for 121 (42%), and non-cardiac death was 168 (58.1%). SCD was the most common cardiovascular event, accounting for 83 (28.7%) of overall mortality. SCD is more likely to occur in the first 12 h after dialysis following the 3-day-long interdialytic interval (SMR: 1.68) and in the 12 h before the next dialysis session after a short interval (SMR: 1.39).

Conclusion: Occurrence of SCD was higher at two different time points, i.e., 12-h period from the starting with the dialysis procedure and 12-h period before the start of the next session of HD at the end of a short interval.

Background: Patients diagnosed with chronic kidney disease (CKD) are at a higher risk of encephalopathy, a condition exacerbated by the presence of various chronic diseases. Hypertension is a significant risk factor for brain damage in the general population but is limitedly discussed in patients with CKD. Brain magnetic resonance imaging (MRI) is an excellent tool for evaluating cerebral white matter lesions. Most previous studies showed the association between hypertension and cerebral white matter lesions in the general population but were less focused on CKD patients. Therefore, the present study aims to investigate the effect of hypertension on the cerebral white matter lesions of brain MRI in patients with CKD.

Methods: In this retrospective study, we enrolled 1,749 CKD patients who underwent brain MRIs to evaluate their brain lesions in Kaohsiung Medical University Hospital. The cerebral white matter hyperintensities (WMHs) on MRI were evaluated according to the Fazekas scale, including separate periventricular and deep white matter lesions from grade 0 to grade 3. The multivariable ordinal regression model was analyzed to determine the independent association between hypertension or blood pressure and cerebral WMHs with adjustment of controlling age, sex, education, comorbidities (hyperlipidemia, cerebrovascular disease, chronic heart failure), laboratory data (hemoglobin, albumin, triglyceride, estimated glomerular filtration rate).

Results: Hypertension was associated with the Fazekas scale of periventricular lesions in multivariable-adjusted ordinal regression analysis (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.15-2.30) after full adjustment. However, the hypertension comorbidities did not associate with the Fazekas scale of deep white matter lesions in the fully adjusted model (OR 1.24, 95% CI [0.89-1.75]). A positive association between blood pressure (per 10 mm Hg increase) and the Fazekas scale was mainly on diastolic blood pressure rather than systolic blood pressure.

Conclusions: In CKD patients, hypertension was associated with brain white matter damage; in particular, Fazekas scale of periventricular lesions. Further study is needed to evaluate adequate blood pressure control to decrease the risk of brain damage in CKD patients.

Introduction: CFHR5 nephropathy is considered a subtype of C3 glomerulopathy. It was originally described in Greek Cypriot families and it is characterized by the time with the development of microscopic hematuria and proteinuria associated with a fast progression toward ESKD, especially in men. These symptoms present an autosomal dominant inheritance pattern and are associated with the exon 2 to 3 duplication of the CFHR5 gene.

Case presentation: Here, we describe a novel clinical phenotype associated with a variant of the CFHR5. The affected subjects present the clinical features of autosomal dominant tubulo-interstitial kidney disease. They present with CKD of unknown origin with no hematuria nor proteinuria. Like the classical CFHR5 nephropathy, males have a worse prognosis than females, with a fast progression toward ESKD in the second-third decade of life. Kidney pathology shows severe tubular atrophy and interstitial fibrosis and infiltrate. Arteries involvement is characterized by thickening of the intima layer, while no major alterations are described at the glomerular level. Electron microscopy confirms no interstitial or glomerular filtration barrier alterations.

Conclusion: The exact mechanism behind this phenomenon remains unclear; we hope that our case will encourage further investigation.

Introduction: Chronic kidney disease worsens the prognosis of cardiovascular disease (CVD) and vice versa. This study aimed to evaluate the mortality of patients with a high CVD burden and unplanned start of maintenance hemodialysis (HD).

Methods: A retrospective study was performed at a tertiary cardiological hospital in São Paulo, Brazil. Hospitalized patients ≥18 years old were identified by the public chronic kidney replacement therapy regulatory system between January 1, 2014, and December 31, 2018. In-hospital and post-discharge mortality, along with associated risk factors, were assessed. Death information up to December 31, 2022, was obtained from the state of São Paulo mortality database.

Results: A total of 302 patients with unplanned start of HD were included. The mean age was 65 ± 13 years old; 68% were male. The heart conditions were as follows: 60% chronic heart failure, 27% coronary artery disease, 13% arrhythmia, and 7% valve disease. Comorbidities included: 93% hypertension, 62% diabetes, 31% dyslipidemia, and 27% known CKD. The mortality rate (deaths per 100 patient-years) was 71.4 between 0 and 3 months, 23.0 between 3 and 12 months, and 39.5 over the entire 0 to 12 months period. The factors independently associated with in-hospital death were age, heart valve disease, chronic obstructive pulmonary disease, positive serology for hepatitis B, and need for HD catheter replacement. The factors associated with post-discharge death (mean ± SD follow-up: 6.4 ± 1.4 years) were age, presence of two or more heart diseases, and HD catheter-related infection.

Conclusion: Patients with a high burden of cardiovascular morbidity and an unplanned start of HD exhibit elevated mortality rates. Some factors independently related to poorer outcomes, such as HD catheter-related complications, could potentially be mitigated through adequate pre-dialysis care.

Introduction: Shikonin is the major bioactive compound abundant in Lithospermum erythrorhizon and possesses diverse pharmacological properties. This study aimed to examine shikonin roles in experimental renal ischemia/reperfusion (I/R) injury.

Methods: Renal tissues and blood were collected from experimental renal I/R injury models. Kidney functions, structural injuries, and cellular death were assessed. Markers of endoplasmic reticulum (ER) stress were evaluated by RT-qPCR and Western blotting. The effect of shikonin on Sirt1/Nrf2/HO-1 signaling was detected by Western blotting and immunofluorescence staining. HK-2 cells that underwent hypoxia/reoxygenation (H/R) process were used to perform CCK-8 and flow cytometry.

Results: For in vivo analysis, renal dysfunctions and tissue structural damage induced by I/R were relieved by shikonin. Additionally, shikonin alleviated ER stress-induced apoptosis in I/R mice. For in vitro analysis, shikonin inhibited ER stress-stimulated apoptosis of H/R cells. Mechanistically, shikonin activated Sirt1/Nrf2/HO-1 signaling post-I/R, and inhibition of Sirt1 limited shikonin-mediated protection against ER stress-stimulated apoptosis in both animal and cellular models.

Conclusion: By activating Sirt1/Nrf2/HO-1 signaling, shikonin inhibits apoptosis caused by ER stress and relieves renal I/R injury.

Background: The Wilms' tumor suppressor gene (WT1) is a critical regulator in kidney development and disease pathogenesis. With the identification of at least 36 isoforms in mammals, each potentially playing distinct roles, WT1's complexity is becoming increasingly apparent. The -KTS and +KTS isoforms, in particular, have been implicated in DNA and RNA regulation, respectively. This review consolidates recent insights into WT1's multifaceted role in renal morphogenesis and its implications in kidney diseases.

Summary: Our review highlights WT1's expression during embryonic kidney development and its maintenance in postnatal kidney function. We discuss the association of WT1 mutations with genetic nephropathies like Denys-Drash and Frasier syndromes, emphasizing its genetic significance. Additionally, we explore the implications of WT1 expression alterations in glomerular diseases, such as IgA nephropathy and lupus nephritis, where its role extends beyond a mere biomarker to a potential therapeutic target.

Key messages: The WT1 gene and its protein products are central to understanding kidney morphogenesis and the molecular basis of renal disorders. As our understanding of WT1's regulatory mechanisms expands, so does the potential for developing targeted therapies for kidney diseases. This review calls for further research to elucidate the precise functions of WT1 isoforms and to explore the upstream regulators of WT1 that could offer novel treatment strategies for kidney pathologies. The significance of WT1 in intricate signaling pathways governing kidney health and disease is underscored, highlighting the need for continued investigation into this pivotal gene.

Introduction: An autosomal recessive hereditary disorder of the glyoxylate metabolism, primary hyperoxaluria (PH), causes an excess of oxalate to be formed in the body. Three genes have so far been found to cause the three forms of PH (I, II, and III). Overall, 10% of PH patients are type III and are caused by a mutation in the HOGA1 gene. Pathogenic variants responsible for the disease have been identified in several populations. In the present study, we are going to genetically analyze 14 Iranian patients who are suspicious of being affected with PH III.

Methods: We studied 14 patients from 11 unrelated Iranian families with a clinical diagnosis of hyperoxaluria disease. The kidney stone was detected in all patients. All of them had high levels of creatinine and oxalate in their urine. Sanger sequencing of the HOGA1 gene was performed in all 14 patients. Next-generation sequencing has also been performed on 1 patient who did not have any causative variants in the HOGA1 gene.

Results: We identified one homozygous likely pathogenic missense variant in the HOGA1 (c.266G>A).

Conclusion: This is the first report of analyzing the HOGA1 gene in Iranian patients suspicious of being affected with hyperoxaluria type III, which can expand our knowledge about this gene and its mutations.

Background: Fabry disease (FD) is an X-linked genetic condition caused by variants in the GLA gene, leading to a deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and the accumulation of complex glycosphingolipids such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3). The systemic disorder primarily affects the cardiovascular, renal, and nervous systems, resulting in decreased life expectancy. The timing of treatment initiation and optimal dosing play crucial roles in improving outcomes and quality of life in Fabry patients. Available FD treatments include enzyme replacement therapy with agalsidase alfa, aglasidase beta, and pegunigalsidase alfa, as well as oral chaperone therapy with migalastat, which can all stabilize or reduce the disease burden.

Summary: This review focuses exclusively on newly available drugs and future therapeutic approaches for treating FD, including migalastat, pegunigalsidase alfa, substrate reduction therapy (SRT), and gene therapy. Migalastat provides benefits such as oral administration and non-immunogenicity; however, it is only appropriate for patients with "amenable" GLA variants. The recently approved pegunigalsidase alfa is a pegylated form of α-Gal A manufactured in plant cell cultures, with apparent reduced immune response and prolonged circulating half-life. SRT (venglustat, lucerastat) reduces Gb3 synthesis, helping to normalize metabolic processes while offering certain advantages such as oral administration, non-immunogenic properties, and the possible crossing of the blood-brain barrier. Clinical trials in human and animal model studies are currently investigating ex vivo and in vivo gene therapy techniques, showing positive early outcomes.

Key messages: The ongoing development of novel treatments for FD suggests that patients will soon have access to a wider array of therapies, enabling more individualized care approaches. Although a definitive FD cure has not been achieved and the expense of combining therapies remains challenging, new therapeutic options such as gene and mRNA-based treatments show promise, though more research is needed.