Kidney & blood pressure research最新文献

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.

Background: Renal damage in Fabry disease (FD) is a consequence of pathological and progressive glycosphingolipids accumulation, which occurs in different magnitudes among FD phenotypes, but is a constant renal tissue phenomenon in all patients with renal involvement. A significant correlation between plasma Lyso-Gb3 (Gb3 analog) and disease severity has been described but, there is lack of information from clinical studies regarding the correlation between Lyso-Gb3 and renal events in humans and, the few results have certain discrepancies. In clinical practice, it is necessary to have disease-specific biomarkers, non-invasive and useful in diagnosis, prognosis and therapeutic response. Evidence relating to the prognostic value of lyso-GL3 is mixed.

Summary: We reviewed the evidence on renal effect of plasma and/or urinary Lyso-Gb3 in FD patients and the usefulness as a biomarker of diagnostic and therapeutic response. Additionally, the in vitro renal effects of Lyso-Gb3 were reviewed. The literature search was conducted in PubMed, Embase, Scopus, Cochrane, and Google academic. Search terms were (Fabry disease + [Lyso-Gb3 or Lyso-GL3] + ["renal" or "kidney"]).

Inclusion criteria: (i) "in vitro" studies in which a direct effect of Lyso-Gb3 on kidney tissue has been studied, both in animals and/or humans; (ii) retrospective, cross-sectional, or prospective "in vivo" studies in which a correlation between Lyso-Gb3 and renal clinical events or renal function biomarkers has been studied.

Key messages: Ten studies presented evidence of "in vitro" renal damage due to Lyso-Gb3; 4 studies presented correlation between plasma Lyso-Gb3 and renal events in FD patients; and 3 studies reported correlation between urinary Lyso-Gb3 and renal events in FD patients.

Conclusion: The small number of publications and the methodological heterogeneity do not allow a statistical analysis of them. Regarding the "in vivo" and "in vitro" renal effects of Lyso-Gb3 in FD: There is evidence of harmful effects on renal cells in vitro due to Lyso-Gb3 but this evidence is not sufficient to use Lyso-Gb3 (neither plasma nor urinary) as a biomarker for monitoring renal damage in FD patients. Plasma Lyso-Gb3 is a useful biomarker in (i) FD diagnosis and (ii) stratification of phenotype and severity of FD. In FD "classic" patients receiving enzyme replacement therapy (ERT), it is useful to determine plasma Lyso-Gb3 periodically because an inconsistent reduction during ERT may indicate the formation of neutralizing anti-agalsidase antibodies.

Introduction: Patients with chronic kidney disease (CKD) often experience symptoms consistent with orthostatic hypotension (OH); however, not much is known about OH in this population. Therefore, study analyzed OH prevalence and risk according to renal function decline.

Methods: A community-based cohort study was conducted using data from the Korean Genome and Epidemiology Study (KoGES). OH prevalence was assessed at baseline and at a 2-year follow-up across three estimated glomerular filtration rate (eGFR) categories: high (≥90 mL/min/1.73 m2, G1), moderate (60-89 mL/min/1.73 m2, G2), and low (<60 mL/min/1.73 m2, G3).

Results: Among 9,597 participants, baseline OH, 2-year OH, and persistent OH were evaluated within each eGFR group: high (n = 6,743), moderate (n = 2,758), and low (n = 96). The low eGFR group demonstrated the highest prevalence of baseline OH (n = 52, p = 0.024) and 2-year OH (n = 42, p = 0.002). This group also exhibited the largest decline in systolic blood pressure at both baseline and follow-up. In adjusted logistic regression, participants aged <50 years with low eGFR had 3.54-fold higher odds of OH (p = 0.035). Additionally, adherence to a low-sodium diet was associated with increased 2-year OH prevalence across groups (p = 0.001).

Conclusion: The low eGFR group showed a higher baseline and follow-up OH prevalence. A low-sodium diet was also associated with elevated OH risk, underscoring the need for careful dietary management in patients with CKD.

Introduction: Four different antihypertensive drug classes are equivalently recommended in the previous guidelines for first-line treatment of arterial hypertension (HTN). However, it is unclear, whether one of these drugs is more capable than the others to reach blood pressure (BP) control. We sought to compare response rates and BP control in these 4 classes.

Methods: Patients with newly diagnosed mild to moderate HTN on 24-h BP measurements (ABPM) were randomized in a 1:1:1:1 fashion to either perindopril, olmesartan, amlodipine, or hydrochlorothiazide (HCT). ABPM was completed at baseline (BL) and after 4 weeks of half dose (treatment period 1 [TP1]). If BP control was not reached after TP1, drug dose was doubled and another ABPM completed after 4 weeks (treatment period 2 [TP2]). Patients were classified as controlled if 24-h mean BP was <130/80 mm Hg, awake BP <135/85 mm Hg, and night BP <120/70 mm Hg, and as optimal if 24-h mean BP was 115-124/65-74 mm Hg.

Results: 88 patients were randomized: 20 (23%) to perindopril, 23 (26%) to olmesartan, 24 (27%) to amlodipine, and 21 (24%) to HCT. Median 24-h mean BP reduction from BL to TP1 was -11/-6 mm Hg and from TP1 to TP2 -4/-2 mm Hg. The highest BP reduction was reached with olmesartan (-15/-10 mm Hg), particularly for diastolic values, the lowest with HCT (-8/-1 mm Hg). 27% of patients reached systo-diastolic BP control, with the best control rate with perindopril and olmesartan (40 and 39%), the lowest with HCT (5%), and 21%/18% reached an optimal treatment goal for systolic/diastolic 24-h mean values, respectively, after TP1. Three additional participants (4%) reached BP control after TP2.

Conclusion: Initial antihypertensive monotherapy failed in most patients (73% uncontrolled, 21%/18% reached optimal treatment goal at TP1) even in low-risk patients, with efficacy varying by drug class (inhibitors of the renin-angiotensin-aldosterone system best, HCT least). These findings support guideline-recommended combination therapy.

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.

Background: Chronic kidney disease (CKD) affects over 850 million people worldwide and is associated with significant morbidity and mortality. There has been recent expansion in treatment options to reduce CKD progression and cardiovascular risk, and it is essential that this translates into clinical practice.

Summary: The primary objectives of this review were to outline current CKD care models and associated care gaps and review the literature for alternative care models, with a focus on the early detection and management of CKD. Several care models have been proposed to improve CKD management including nurse-led, pharmacy-led, integrated care models and digital interventions, with mixed results.

Key messages: There is a need for ongoing health systems and implementation research to improve translation of evidence into practice in the management of CKD.

Background: Kidney transplantation was an effective method for treating chronic kidney failure via transplanting a healthy kidney from a donor to a patient with the loss of kidney function. However, clinical studies revealed that the posttransplantation status of patients was associated with a substantial aggregation of risk factors contributing to metabolic syndrome.

Summary: This article provided a comprehensive review of the current researches on metabolic syndrome after kidney transplantation, and the latest advances in the interaction between metabolism and immune cells were also covered.

Key messages: Our aim was to identify and intervene high-risk recipients in time and thus improving the prognosis of recipients.