Kidney & blood pressure research最新文献

Introduction: Difelikefalin (DFK) is approved to treat chronic kidney disease-associated pruritus (CKD-aP) in adults undergoing maintenance hemodialysis (HD). 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, non-fatal 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.

Background: 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 GSE142135 were retrieved from the Gene Expression Omnibus (GEO) database to identify shared differentially expressed genes (DEGs). Machine learning approaches were applied to pinpoint hub genes, followed by Mendelian Randomization (MR) analyses to validate 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: We previously reported the efficacy and safety of low-dose (12.5 mg/day) spironolactone for chronic kidney disease (CKD) with diabetes. Few studies have examined the characteristics of patients who may have reduced urinary albumin-creatinine ratio (UACR) on mineralocorticoid receptor antagonists. In this study, we aimed to identify the clinical characteristics of patients prone to benefit from UACR reduction with low-dose spironolactone.

Methods: This was a post-hoc analysis of a previous trial and included 55 patients assigned to the spironolactone group. Univariate regression analysis was performed to determine the association between the change in UACR after 24 weeks of low-dose spironolactone administration and baseline exploratory parameters. Multiple regression analysis was conducted on the associated parameters, and regression models were created for analysis. A similar analysis was performed for changes in serum potassium levels and estimated glomerular filtration rate (eGFR) after 24 weeks of spironolactone administration.

Results: In the univariate analysis, baseline UACR, triglyceride levels, and eGFR were associated with changes in UACR. The regression coefficient estimates were significant for baseline UACR, triglyceride levels, and eGFR (p = 0.002, 0.017, and 0.003, respectively). The reduction in UACR was greater with higher baseline UACR and triglyceride levels, and lower baseline eGFRs. The increase in serum potassium levels due to low-dose spironolactone administration showed a negative correlation with baseline serum potassium levels and no correlation with baseline eGFR, suggesting its safety.

Conclusions: It may not be too late to start treatment with low-dose spironolactone, even in patients with relatively advanced CKD with diabetes.

: Background: Kidney transplantation (KT) offers substantial improvements in both survival and quality of life compared to dialysis in patients with end-stage kidney disease. However, the success of KT is critically dependent on effective immunosuppression. There has been improvement in short-term graft survival outcomes, but chronic rejection and cumulative drug toxicities continue to present significant challenges. Regarding immunosuppression monitoring strategies, calcineurin inhibitor trough concentrations is a standard practice, but for the mycophenolate mofetil (MMF), fixed dosing remains widespread despite considerable evidence supporting for dose optimization based on mycophenolic acid (MPA) area under the curve (AUC) monitoring. To elucidate current immunosuppressive practices and mycophenolate dosing strategies, we conducted a survey of multiple transplant centers in India, Australia, and New Zealand.

Methods: An internet-based questionnaire was sent via professional societies and direct correspondence to practitioners across Australia, New Zealand and India.

Results: We received responses from 142 centers across the three regions. Most respondents (90%) reported use of antibody induction therapy in standard risk recipients. Maintenance immunosuppression overwhelmingly involved "triple therapy" with tacrolimus (98%), mycophenolate (78% as mycophenolate mofetil), long-term corticosteroid continuation (96%). Overall, 78% reported never using MPA concentrations to guide management, though with geographic differences: 90% of respondents from India reported never measuring MPA, compared to only 32% from Australia and New Zealand (p<0.001). Major reasons for not measuring MPA given were difficulty in attaining MPA concentrations (56%), cost (33%), and uncertainty around techniques to assess exposure and concentration targets (36%). Only a minority (11%) of respondents questioned the clinical value of monitoring in clinical care.

Conclusion: Across distinct geographic regions, immunosuppression regimen including tacrolimus, MMF and long-term corticosteroids in standard risk kidney transplant recipients was homogenous. MPA concentration measurement to guide therapy is rarely used in India, though not uncommon across Australia and New Zealand at least in specific circumstances. Overcoming practical barriers and ensuring accessible clinical guidance may provide opportunities to improve the uptake of MPA monitoring.

Objective: Managing blood pressure in patients with chronic kidney disease (CKD) complicated by resistant hypertension (RH) presents significant challenges. The clinical utility of pharmacogenomics (PGx) in this high-risk patient population requires investigation. This study aimed to assess the impact of PGx-guided precision therapy on blood pressure control, medication optimization, and safety in CKD patients with RH.

Methods: A single-center prospective cohort study was conducted utilizing the "Yidu Cloud" big data platform from Xinjiang Uygur Autonomous Region People's Hospital. Sixty-five CKD patients with RH were enrolled and randomized into either an empirical medication control group (Empirical group, n=22) or a PGx-guided group (PGx group, n=43). The PGx group received individualized treatment based on gene testing for 21 antihypertensive drugs, while the Empirical group received conventional treatment. The primary outcome was the BP target achievement rate (systolic BP <140 mmHg, diastolic BP <90 mmHg) at 24 months. Secondary outcomes included medication optimization, adverse events, and changes in kidney function. adverse eventadverse events.

Results: The PGx group exhibited significant improvements early in the intervention, achieving a higher systolic BP target rate at 0.5 months compared to the Empirical group (20.93% vs 0%, P=0.021). At 3 months, the diastolic BP target achievement rate increased significantly in the PGx group (72.09% vs 27.27%, P=0.001), maintaining an advantage through the 24-month endpoint (systolic BP target rate 44.18% vs 13.63%, P=0.014). Medication optimization in the PGx group showed a 46.5% reduction in patients requiring 4-5 drug combinations from baseline, compared to 31.8% in the Empirical group, along with a 41% reduction in overall adverse event risk (34.88% vs 59.09%, P=0.016). Genetic testing revealed high sensitivity to ARB drugs (candesartan 86.05%, telmisartan 79.07%, irbesartan 76.74%) and CCB drugs (amlodipine, nitrendipine, felodipine all 81.40%), with ACEI drugs generally showing poor efficacy. Additionally, the decline in eGFR at 24 months was significantly lower in the PGx group compared to the Empirical group (8.82% vs 30.00%, P<0.001), suggesting a protective effect on kidney function.

Conclusion: PGx-guided precision therapy facilitates rapid BP control, reduces polypharmacy and adverse events, and delays kidney function decline in CKD patients with RH. This study, the first PGx clinical trial targeting a multi-ethnic population in Northwest China, offers valuable insights into personalized treatment approaches for CKD with RH in East Asia.

Background Maintaining fluid balance is one of 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. Aim of the study The aim of the study was to compare the conventional methods of monitoring hydration status during hemodialysis with an assessment of skin fold thickness. Materials and Methods 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 (pro-ADM). 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. Conclusions 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.

Background: Primary aldosteronism (PA) is the predominant cause of secondary hypertension, leading to cardiovascular and renal damage. However, current epidemiology findings on the association between PA and estimated glomerular filtration rate (eGFR) remain inconsistent.

Methods: A 1:1 gender- and age-matched case-control study was conducted among participants with PA, essential hypertension (EH), and normotension, with 204 participants in each group. Multiple linear regression was used to explore the correlations of PA with eGFR. Subgroup analyses were conducted to examine variations in the PA-eGFR association. Mediation analysis was performed to explore the role of inflammatory markers in this relationship.

Results: Compared to the EH group, the PA group showed no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), or eGFR, but exhibited significantly higher levels of plasma aldosterone concentration (PAC) and aldosterone-to-renin ratio (ARR), along with lower plasma renin concentration (PRC) levels. PA was associated with a decline in eGFR after adjusted potential confounders. When stratified the PA patients into three groups according to the levels of PAC, PRC and ARR, patients in the highest PAC groups, the lowest PRC group, and the highest ARR group had much lower eGFR compared to the EH group. The inverse associations mentioned above remained significant even further adjusted for SBP or DBP, respectively. Age (β = -0.422, [95% CI: -1.28, -0.606], P<0.001), PRA (β = -0.225, [95% CI: -0.035, -0.006], P=0.005), and uric acid (UA) (β = -0.285, [95% CI: -0.035, -0.006], P<0.001) were inversely associated with eGFR (P < 0.05) in PA patients. lymphocyte-to-monocyte ratio (LMR) attributed a proportion of 7.62% for the total effect.

Conclusion: Our study indicates that PA is associated with lower eGFR independent of blood pressure, and the adverse effects might be greater than negative controls or EH patients. Inflammation could be a potential mediator of this detrimental effect. In PA, elevated uric acid may promote crystal formation and glomerular obstruction, contributing to renal dysfunction.

Introduction: Alpha-blockers are considered an additional option when the major antihypertensive drug classes are insufficient in reducing blood pressure. While the impact of alpha-blockers on blood pressure control seems comparable, data evaluating their effects on renal outcomes are lacking. This systematic review and meta-analysis assess the impact on renal function from a medium to long-term perspective.

Methods: A search and analysis according to the PRISMA statement across Medline, the Web of Science, and ScienceDirect was conducted, covering articles in English on adult populations without time restrictions to December 14, 2023, including all types of studies with a minimum follow-up of 12 weeks.

Results: Seventeen studies were included in the review, encompassing a total of 26,170 patients treated with alpha-blockers. Most studies were performed in the 20th century and often lacked an adequate number of participants and sufficient follow-up duration. Bayesian meta-analysis showed neutral effects of alpha-blockers on eGFR and serum creatinine, comparable with those of other antihypertensive agents. Compared with baseline, the data suggests an overall small but clinically unimportant increase in creatinine clearance in patients treated with alpha-blockers (95% credible interval: 1.61 to 9.97 ml/min/1.73 m2).

Conclusion: A significant dearth of evidence concerning the long-term impact of alpha-blockers on renal function was revealed. The available evidence suggests that alpha-blockers have a neutral or non-inferior effect on renal function in comparison with other antihypertensive agents. Further research is needed to evaluate the role of alpha-blockers and their impact on preserving renal function.

Background: Urinary acidification is a crucial aspect of kidney tubular function that helps maintain the body's acid-base balance. The primary component of net acid excretion is ammonium (NH4+), which is formed when hydrogen ions (H+) secreted from the tubule combine with the major urinary buffer, ammonia (NH3). Consequently, both H+ and NH3 influence urine NH4+ excretion. While urine NH4+ is the standard measure of renal acid excretion, urine pH is also valuable for assessing urinary acidification, as it reflects the extent of H+ secretion from the collecting duct. Urine pH can be accurately measured using a pH meter, and urine NH4+ can be quantified through an enzymatic method adapted from plasma ammonia assays.

Summary: A low urinary NH4+ excretion < 40 mmol/day is a hallmark of renal tubular acidosis (RTA) and is essential for excluding non-renal causes of hyperchloremic metabolic acidosis. Urine pH is valuable in the differential diagnosis of RTA; Type 1 distal RTA is characterized by a urine pH > 5.3, while Type 4 RTA is characterized by a urine pH < 5.3. In Type 2 proximal RTA, urine pH is variable and depends on the serum HCO3- level. Low urine NH4+ levels in patients with chronic kidney disease (CKD) may indicate that acid is retained in the kidneys, leading to tubulointerstitial inflammation and fibrosis. A post-hoc analysis of the AASK trial found that low urinary NH4+ excretion < 20 mmol/day was associated with end-stage kidney disease (ESKD) even before metabolic acidosis developed. In the NephroTest cohort, lower tertile urinary NH4+ excretion was linked to ESKD during a median follow-up of 4.3 years. Typically, CKD patients exhibit acidic urine pH, indicative of renal acid retention. A Japanese observational study found that lower urine pH was associated with the incidence of CKD. When urine pH was considered alongside urine NH4+, the prognostic value for CKD progression was significantly enhanced.

Key messages: Urine pH serves as a valuable tool for the differential diagnosis of RTA, but direct measurement of urine NH4+ is essential. In CKD, low urine NH4+ levels may indicate a diminished capacity for acid excretion causing systemic acid retention, which can contribute to the progression of CKD. Additionally, the low urine pH observed in CKD reflects renal acid retention and may be associated with both incident and prevalent CKD. The integration of urine pH and NH4+ measurements would enhance the predictability of CKD progression.

Introduction: Given the increased incidence of renal anemia and cognitive dysfunction in patients with chronic kidney disease (CKD), the association between hemoglobin levels and cognitive function in these patients remains elucidated. An optimal level of hemoglobin for the best cognitive performance in CKD has yet to be determined.

Methods: A retrospective cross-sectional study was conducted using data from 2011-2014 of the National Health and Nutrition Examination Survey (NHANES). Enrolled subjects for analysis were divided into the CKD and the non-CKD groups. The Animal Fluency Test (AF), Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease Word Learning Test (CERAD-WL) and Word List Recall Test (CERAD-DR) were used to evaluate cognitive performances. We quantified the association between hemoglobin levels and cognitive function in patients with CKD and non-CKD subjects by using the logistic regression analysis. Plotted curves and inflection points were calculated by a recursive algorithm.

Results: The ratio of cognitive impairment was higher in the CKD group than in the non-CKD group. Hemoglobin levels were correlated with CERAD-DR and DSST in patients with CKD. For non-CKD subjects, the hemoglobin level was not correlated with any test results. The potential range of the hemoglobin level was 11.0 - 12.7 mg/dL for keeping better cognitive performance of patients with CKD.

Conclusion: Hemoglobin levels are associated with cognitive performance in patients with CKD. The treatment of renal anemia would be meaningful to reduce cognitive impairment in CKD.