Kidney & blood pressure research最新文献

Background: Membranous nephropathy constitutes a significant proportion of cases leading to end-stage renal disease. In such instances, the accurate distinction between primary and secondary forms is crucial for proper treatment. Consequently, we systematically examined the link between genetically predicted membranous nephropathy and various diseases.

Methods: The phenome-wide association approach assessed the links between genetically predicted membranous nephropathy and 2,408 diseases. Two-sample Mendelian randomization was then employed to explore causal relationships using methods like inverse variance weighting, MR-Egger, weighted median, and others. A replication analysis was conducted to confirm these associations. Gene enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to explore potential pathogenic mechanisms.

Results: A statistically significant association was noted between genetically predicted Graves' disease, thyrotoxicosis, and thyrotoxicosis with diffuse goiter and an elevated risk of membranous nephropathy. Subsequent replication analysis for Graves' disease demonstrated consistent results. Functional analysis suggests that Graves' disease may affect membranous nephropathy by influencing pathophysiological mechanisms and pathways related to the proliferation and differentiation of lymphocytes and leukocytes, adhesion between leukocytes, and cells, differentiation of CD4+ αβ T cells, and differentiation of Th1 and Th2 cells.

Conclusions: Our study indicates that genetically predicted thyrotoxicosis, thyrotoxicosis with diffuse goiter, and Graves' disease are correlated with an increased likelihood of membranous nephropathy. Graves' disease may affect membranous nephropathy development by influencing leukocyte proliferation and differentiation. Additional research is warranted to validate these findings and ascertain their relevance in clinical management.

Aim The epithelial sodium channel expressed in renal collecting duct epithelia plays a key role in regulating sodium balance. ENaC is regulated by the ubiquitin ligase Nedd4-2, which binds to ⍺ENaC and causes its retrieval, under low energy conditions due to the activation of AMP activated protein kinase (AMPK). Acute kidney injury (AKI) after ischemia reperfusion (I/R) disrupts sodium balance. In this study, we examined the impact of acute renal I/R on renal Na+ handling, ENaC subunits expression in renal membranes and the potential role of AMPK-Nedd4-2 pathway in this process. Methods: Adult Sprague-Dawley rats were randomized into two groups; ischemia/reperfusion (I/R) group, in which both renal arteries were occluded for 30 minutes, and sham group. Data was collected forty-eight hours post I/R. To confirm acute kidney injury, tubular damage and serum creatinine levels were assessed. Serum Na+ concentration and urinary sodium excretion rate were measured. Renal gene expression of α, β and γ-ENaC subunits was studied using RT-PCR with hydroxymethylbilane synthase (HMBS) as a house-keeping gene. Protein expression of α, β and γ-ENaC in renal homogenates and membrane fractions and protein expression of Nedd4-2, phospho-Nedd4-2, AMPK, and p-AMPK in renal homogenates were assessed by Western blot. Results were expressed as mean ±SEM. Control groups were compared to I/R groups using student t test and p<0.05 was set as significant. Results: Acute kidney injury after I/R was confirmed by revealing a significant tubular cell damage and the rise in serum creatinine levels (1.66± 0.14 in I/R vs. 0.64±0.09 in sham group, p<0.001). Serum Na+ concentration and Na+ excretion rate were not altered after I/R. Gene expression of ENaC subunits was not affected by I/R, however protein expression of α-ENaC was decreased in renal membranes (0.03±0.003 in I/R vs. 0.05±0.01 in sham group, p<0.05), with no change in β or γ expression. There were increases in the expressions of Nedd4-2 (0.27±0.04 vs. 0.09±0.03, p<0.05), p-Nedd4-2 (0.15±0.04 vs. 0.04±0.01, p<0.05), AMPK (0.09±0.01 vs. 0.03±0.02, p<0.05) and p-AMPK (1.05±0.2 vs. 0.6±0, p<0.05) indicating the activation of AMPK-Nedd4-2 pathway. Conclusions Ischemia reperfusion caused renal injury, however, did not affect renal sodium handling. A decrease in membrane expression of α-ENaC was detected without a change in total α-ENaC suggesting ENaC trafficking into the cell. This occurred with the concomitant activation of AMPK-Nedd4-2 pathway, which is known to cause retrieval of ENaC and decrease its membrane expression.

Anticoagulant-related nephropathy (ARN) is a serious and often underdiagnosed complication of anticoagulant therapy, particularly associated with vitamin K antagonists, such as warfarin, and more recently, with direct oral anticoagulants (DOACs), including dabigatran, rivaroxaban, edoxaban, and apixaban. ARN is characterized by acute kidney injury (AKI), macroscopic hematuria, glomerular hemorrhage, and red blood cell casts in the kidney tubules. While traditionally considered rare, increasing evidence suggests ARN is more prevalent than previously thought, particularly among patients with pre-existing chronic kidney disease (CKD). Studies show that the condition often leads to poor kidney outcomes, with more than 50% of affected patients failing to recover baseline kidney function after one year. Mortality is also significantly higher among non-recovering patients, with some studies reporting a one-year mortality rate of up to 39%. Despite various treatment approaches, ranging from withdrawal of anticoagulation to supportive therapy and corticosteroids, no definitive treatment exists. This review discusses the epidemiology, pathogenesis, diagnosis, and treatment of ARN.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, affecting 1 in 400 to 1,000 people worldwide. These significant care requirements reflect the importance of early diagnosis and prevention for affected patients and the need for evidence-based guidelines for treatment protocols and best practice measures. The 2025 KDIGO guidelines build on earlier frameworks such as the 2019 International consensus statement on the diagnosis and management of ADPKD in children and young people to improve screening, monitoring, and treatment methodology for pediatric ADPKD patients. Young and adolescent patients face unique challenges to care from detection of asymptomatic disease progression to early-onset hypertension, alongside stress faced by caregivers and families. This executive summary synthesizes the updated 2025 KDIGO recommendations and supporting evidence to outline new advancements and provide a practical approach for pediatric nephrologists to support improved treatment and transition into adulthood.

Introduction: Multidisciplinary education has been shown to slow the progression of chronic kidney disease (CKD) and reduce cardiovascular (CV) risk, although its effects depend partly on patient characteristics. The aim of this study was to assess how patients categorized on the basis of estimated glomerular filtration rate (eGFR) responded to multidisciplinary education in terms of cardiorenal outcomes.

Methods: In this retrospective cohort study, we included 447 CKD patients who received multidisciplinary education between January 1, 2013, and December 31, 2020, at Nara Prefecture General Medical Center. Exposure was four categories according to eGFR slopes before and after multidisciplinary education. The primary outcomes were renal events defined as the composite of dialysis initiation, transplantation, and 30% eGFR decline, and CV events defined as the composite of heart failure requiring hospitalization, coronary or leg revascularization, cardiac sudden death, and stroke.

Results: Multidisciplinary education decreased the median eGFR slope from -5.00 to -0.65 mL/min/1.73 m2/year. In fully adjusted models, the hazard ratios (95% confidence intervals) for total renal events relative to slow-slow eGFR decline were 1.02 (0.50-2.06) for fast-slow decline, 5.30 (2.82-9.97) for slow-fast decline, and 7.53 (4.02-14.1) for fast-fast decline. Only fast-fast eGFR decline was associated with a high risk of CV events. Subgroup analyses showed similar trends. Fast decline after education was independently associated with increased proteinuria and decreased hemoglobin levels.

Conclusions: Fast eGFR decline after but not before multidisciplinary education was significantly associated with renal and CV events in CKD patients. Attention should be paid to CKD patients with limited benefit from multidisciplinary education.

Introduction: Chronic kidney disease (CKD) is a major global health challenge contributing to substantial morbidity, mortality, and healthcare burden. This study analyzed global, regional, and national trends in CKD due to type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), hypertension, and glomerulonephritis from 1990 to 2021, with projections to 2045.

Methods: This population-based study used data from the Global Burden of Disease (GBD) 2021 across 204 countries and territories. The CKD burden by etiology was evaluated using prevalence, incidence, deaths, disability-adjusted life years (DALYs), and corresponding age-standardized rates (ASPR, ASIR, ASMR, ASDR). Temporal trends were assessed using regression and age-period-cohort models, and health inequalities were analyzed across regions and sociodemographic levels.

Results: In 2021, global CKD prevalence reached 673.7 million cases, primarily driven by T2DM and hypertension. T2DM had the highest ASPR (1,259.63) and ASIR (23.07). From 1990 to 2021, ASPRs for CKD from T1DM and glomerulonephritis initially rose but recently declined (T1DM, annual percent change [APC]: -2.51% from 2019 to 2021; glomerulonephritis, APC: -0.53% from 2015 to 2019). However, ASIRs for all four etiologies continued to increase. In 2021, CKD caused 1.53 million deaths, with T2DM contributing most to deaths and DALYs, having the highest ASMR (5.72) and ASDR (131.08). While ASMR increased for all CKD types, the ASDR for T1DM-related CKD initially declined but has risen since 2012, whereas ASDRs for CKD due to T2DM, hypertension, and glomerulonephritis have continuously increased. Middle-social development index (SDI) region saw the largest increases in CKD prevalence and incidence due to T2DM, primarily driven by population growth (69.93% of prevalence rise) and aging (50.05% of deaths, 48.16% of DALYs). While epidemiological changes reduced prevalence by 11.10%, they contributed 23.13% to the incidence increase. High-SDI regions had the fastest growth in ASMR and ASDR. South Asia led in prevalence growth, while East Asia experienced the highest incidence increases, mainly due to aging, highlighting significant regional disparities in CKD drivers. Inequality analysis indicated that wealthier countries had better outcomes for T2DM- and hypertension-related CKD, whereas poorer countries appeared to fare better for T1DM- and glomerulonephritis-related CKD. Projections to 2045 suggest continued increases in CKD from T2DM and hypertension, with potential declines in T1DM- and glomerulonephritis-related CKD.

Conclusion: The global CKD burden has markedly increased from 1990 to 2021, primarily due to T2DM and hypertension. Regional disparities highlight the necessity for targeted public health interventions.

Introduction: Difelikefalin (DFK) is approved to treat chronic kidney disease-associated pruritus (CKD-aP) in adults undergoing maintenance hemodialysis. The influence of concomitant opioid use on DFK treatment outcomes remains uncertain.

Methods: Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105. Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP. We report key endpoints from the primary studies, including reduction in itch intensity (Worst Itching Intensity Numerical Rating Scale [WI-NRS]), and improvements in itch-related quality of life (QoL; 5-D itch and Skindex-10), according to concomitant opioid use (+O or -O).

Results: In KALM-1/KALM-2, 24.2% of participants on DFK and 30.4% on PBO were taking concomitant opioids. Regardless of opioid use, a greater estimated percentage of those receiving DFK achieved ≥3- or ≥4-point clinically relevant reductions in itch intensity (WI-NRS; p < 0.05), or complete response (≥80% weekly mean WI-NRS scores of 0 or 1) by week 12, versus PBO. Greater improvements in itch-related QoL were also reached with DFK, versus PBO, irrespective of concomitant opioid use. With either treatment, nonfatal serious TEAEs were more common among concomitant opioid users (DFK+O: 44.7% vs. DFK-O: 19.0%; PBO+O: 38.0% vs. PBO-O: 15.9%), as were severe TEAEs. In Study 3105, 31% were taking concomitant opioids.

Conclusion: DFK reduced itch intensity and improved QoL, regardless of concomitant opioid use. Similar concomitant opioid-dependent safety findings were observed. With or without concomitant opioid use, DFK demonstrated considerable efficacy that improved QoL. Increased TEAEs with concomitant opioid use with either treatment suggests careful medication management is advisable.

Introduction: Polycystic kidney disease (PKD) is a genetic disorder characterized by renal enlargement due to cyst formation. Besides cystic complications, patients with autosomal dominant PKD (ADPKD) can develop vascular abnormalities. We investigated the impact of ADPKD on aortic morphometry and function in female and male PKD rats.

Methods: Thoracic aortic rings were obtained from six-month-old female (n = 10; 307 ± 4 g) and male (n = 10; 470 ± 24 g) PKD/Mhm (Cy/+) rats, as well as age-matched control female (n = 9; 312 ± 6 g) and control male (+/+) (n = 13; 460 ± 14 g) rats. Vascular function was evaluated ex vivo using organ baths. Biomarkers of renal function were evaluated, and histology was performed.

Results: PKD female and PKD male rats showed elevated serum creatinine levels compared to their respective controls (PKD female: 50.0 ± 1.7 μmol/L vs. control female: 43.9 ± 2.1 μmol/L; PKD male: 178.7 ± 21.0 μmol/L vs. control male: 40.4 ± 1.3 μmol/L, p < 0.05), and these levels were found to be higher in the PKD males than in the PKD females (p < 0.0001). Endothelial dysfunction, characterized by reduced maximum relaxation to acetylcholine, was observed in the PKD males compared to control males (55 ± 2% vs. 77 ± 1%, p < 0.05). Additionally, contractile responses to phenylephrine and high potassium were decreased in PKD male compared to control male. Morphometric analysis revealed increased wall thickness, wall cross-sectional area normalized to body weight, and wall:lumen area ratio in PKD male aortas compared to control male. Additionally, PKD male showed increased cleaved poly(ADP-ribose) polymerase-1 immunoreactivity compared to control males. All these parameters were unchanged in PKD females compared to control females.

Conclusion: Six-month-old male rats with PKD, but not females, display endothelial dysfunction, impaired smooth muscle contraction/relaxation, pathological changes in aortic morphometry, and increased apoptosis, providing a model for studying vascular complications in ADPKD.

Introduction: Sarcopenia is a common comorbidity in end-stage renal disease (ESRD) and is associated with increased risk of adverse clinical outcomes. The genetic mechanisms underlying sarcopenia in ESRD remain largely unclear. This study employed multi-omics bioinformatics approaches to elucidate potential genetic determinants.

Methods: Gene expression datasets GSE1428 and GSE142153 were retrieved from the Gene Expression Omnibus database to identify shared differentially expressed genes. Machine learning approaches were applied to pinpoint hub genes, followed by Mendelian randomization (MR) analyses to assess their associations with ESRD. Candidate therapeutic agents were subsequently predicted based on these hub genes.

Results: ADAM7 emerged as the principal hub gene, with MR analyses suggesting a protective role against ESRD and sarcopenia. Predicted therapeutics included arbutin, metribolone, and phenethyl isothiocyanate. Molecular docking studies revealed favorable interactions, with binding free energies consistently below 5.0 kcal/mol between ADAM7 and these compounds.

Conclusion: Our findings identify ADAM7 as a potential biomarker and therapeutic target for ESRD-associated sarcopenia, offering insights for future intervention strategies.

Introduction: Maintaining fluid balance is one of the major challenges of the dialysis therapy. It includes, in particular, the management of "dry body mass." We postulated that simple measurement of subscapular skinfold thickness before and after hemodialysis could help monitor hydration status in chronic dialysis patients. The aim of the study was to compare the conventional methods of monitoring hydration status during hemodialysis with an assessment of skinfold thickness.

Methods: A total of 50 participants (21 F, 29 M; age 60 ± 15 years) were enrolled. Directly before the hemodialysis session, the following parameters were measured: body composition with bioimpedance spectroscopy, skinfold thickness in subscapular area with standardized caliper and blood tests - blood count, urea, n-terminal pro-B-type natriuretic peptide (nt-proBNP), and pro-adrenomedullin. The procedures were repeated at the end of three consecutive hemodialysis sessions.

Results: The mean change of skinfold thickness in subscapular area before and after hemodialysis session was -2.2 ± 1.6 mm. A significant correlation was found between the change of extracellular water volume and skinfold thickness before and after hemodialysis (r = 0.33; p = 0.02) and between the change of total water volume and body mass before and after hemodialysis (r = 0.49; p < 0.01). There was also a positive correlation between the change of skinfold thickness and systolic blood pressure before and after a hemodialysis session (R = 0.36; p = 0.01). Dialysis vintage correlated significantly with the changes of plasma nt-proBNP level during hemodialysis (r = 0.40; p = 0.02). Multivariate analysis revealed that baseline body mass, BMI, changes of systolic blood pressure determined the variability of skinfold thickness during hemodialysis. Receiver operating curve analysis revealed that BIA spectrometry was more sensitive and specific than the skinfold thickness assessment for the assessment of hydration condition.

Conclusion: The simple measurements of skinfold in subscapular area may approximate changes of hydration status but are inferior to BIA spectroscopy. Further research is needed to confirm the utility of this method in monitoring blood pressure control in dialysis patients.