Kidney & blood pressure research最新文献

Chronic kidney disease (CKD) presents an extensive healthcare burden globally. Diabetes mellitus (DM) is the most prevalent cause of CKD and end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT). Type II DM remains the most prevalent subtype, as it is closely related to metabolic syndrome, whose prevalence is also rising with a sedentary lifestyle and Western diet. Therefore, understanding the pathophysiology of diabetic kidney disease (DKD), its early recognition and early initiation of the currently available therapy remains an important measure to slow the progression of the disease. Pathophysiology of DKD is a complex process, where all the mechanisms are still being elucidated on preclinical animal and in-vitro models as well as in clinical studies. Changes in glomerular hemodynamics, glomerular and tubular hypertrophy, hyperfiltration, overactivation of the renin-angiotensin-aldosterone system (RAAS), podocyte injury, inflammation, oxidative stress, renal hypoxia, mitochondrial injury, and epigenetic changes are the main mechanisms leading to albuminuria, glomerulosclerosis and fibrosis. In the latter years, the importance of gut microbiota in DKD has also been shown. Understanding the mechanisms behind DKD is important, especially for researching current and possibly future pharmacological treatment of DKD. While angiotensin convertase enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) alongside nonpharmacological measures have been the pillars of DKD treatment and reduction of albuminuria for many decades, novel pharmacological agents are emerging. Starting with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been proven to affect many of the pathophysiological mechanisms, continuing with novel non-steroidal mineralocorticoid receptor antagonists (MRAs), which are a new anti-inflammatory and antifibrotic possibility, and finishing with glucagon-like peptide 1 receptor antagonists (GLP1RA) which have recently joined the therapeutic options for DKD. This comprehensive review focuses on the main pathophysiological mechanisms of DKD and current available pharmacological and non-pharmacological possibilities.

Background: 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.

Method: Thoracic aortic rings were obtained from six-month-old female (n=10; 307±4g) and male (n=10; 470±24g) PKD/Mhm (Cy/+) rats, as well as age-matched control-female (n=9; 312±6g) and control-male (+/+) (n=13; 460±14g) 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±1.7μmol/L vs. control-female: 43.9±2.1μmol/L; PKD-male: 178.7±21.0μmol/L vs. control-male: 40.4±1.3μmol/L, p<0.05), and that in the PKD-males 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: 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.

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.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, with cyst formation and structural kidney changes present during childhood or before birth. The 2025 KDIGO guidelines build on earlier frameworks to improve screening, monitoring, and treatment methodology for pediatric ADPKD patients.

Methods: This executive summary synthesizes the updated 2025 KDIGO recommendations and supporting evidence to outline advancements in diagnosis, blood pressure and proteinuria management, follow-up, and transition planning.

Results: The guidelines introduce more precise definitions of disease subtypes, tighter blood pressure targets, and expanded recommendations for genetic testing, ultrasound screening, and symptom-driven follow-up. KDIGO emphasizes ambulatory blood pressure monitoring from age five, renin-angiotensin system inhibitors as first-line therapy, and structured transition planning during adolescence.

Conclusion: The 2025 KDIGO pediatric ADPKD guidelines provide a practical, family-centered framework for individualized care and improved transition to adult services, promoting early detection, proactive management, and shared decision making to support long-term outcomes.

Background: Complement 3(C3)-dominant Glomerulonephritis (GN) are rare diseases resulting from alternative complement pathway dysregulation, include C3 Glomerulopathy(C3G), paraprotein associated GN and C3 dominant infection-related glomerulonephritis (IRGN). To our knowledge long-term follow-up studies of clinical profile and outcomes of this rare disorder are sparse. We studied kidney histopathology baseline findings, outcomes, treatment, and its complications of C3-dominant GN in our setting.

Objectives: We studied the clinical, pathological profiles and outcomes of patients with C3-dominant GN.

Methods: Design: Single centre, retrospective, case record based observational study.

Participants: Consecutive patients of C3-dominant GN on kidney biopsy from 2013 to 2023.

Measurements: Demography, laboratory and histopathological data, treatment and outcomes were studied.

Results: Of 2175 kidney biopsies, 141(6.48%) showed C3-dominant Glomerulonephritis; 74 (52.5%) C3G, 67(47.5%) IRGN. Median age was 43 years (IQR 29-59.5), males 90 (63.8%). Preceding skin/throat infections were seen in 32/141 (22.7%). At presentation median serum creatinine was 1.7mg/dL (IQR: 1.2-3.6), eGFR <60ml/min/1.73m2 in 91/141 (64.5%), 111/141 (78.7%) had low serum C3 levels. Nephrotic proteinuria was seen in 65/141 (46%), Crescents in 45(31.9%). Remission was partial in 38/141(27%), complete in 45/141(31.9%) and 31/141(22%) progressed to End stage kidney disease (ESKD). On immunosuppression commonest infection was pneumonia in 15/70 (21.4%) and 27/141(19.1%) died at an average follow up of 25.7 months. Diabetes mellitus, percentage sclerosis and presence of crescents predicted development of CKD stage 5.

Conclusion: Over ten years, C3-dominant GN represented 6.48% of kidney biopsies. Nephrotic proteinuria and kidney failure are common at presentation with 58% achieving some remission, 22 % going on to ESKD and mortality of 19%.

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: 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.