Pub Date : 2024-10-17DOI: 10.1186/s12882-024-03814-5
Na Li, Jianrong Wu, Jing Chen, Yajing Cui, Yunjie Teng, Xiaoping Yang
Background: The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China.
Methods: A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60-90 ml·min-1·(1.73 m2)-1. The relationship between changes in SUA levels and the eGFR was assessed.
Results: (1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min-1·(1.73 m2)-1, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001).
Conclusion: In people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR.
{"title":"Association between serum uric acid variability and mild eGFR decline in Chinese adults: a retrospective cohort study.","authors":"Na Li, Jianrong Wu, Jing Chen, Yajing Cui, Yunjie Teng, Xiaoping Yang","doi":"10.1186/s12882-024-03814-5","DOIUrl":"https://doi.org/10.1186/s12882-024-03814-5","url":null,"abstract":"<p><strong>Background: </strong>The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China.</p><p><strong>Methods: </strong>A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60-90 ml·min<sup>-1</sup>·(1.73 m<sup>2</sup>)<sup>-1</sup>. The relationship between changes in SUA levels and the eGFR was assessed.</p><p><strong>Results: </strong>(1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min<sup>-1</sup>·(1.73 m<sup>2</sup>)<sup>-1</sup>, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001).</p><p><strong>Conclusion: </strong>In people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1186/s12882-024-03823-4
Shuoyan An, Zixiang Ye, Wuqiang Che, Yanxiang Gao, Jingyi Ren, Jiahui Li, Jingang Zheng
Background: Stress Hyperglycemia Ratio (SHR) reflects the acute blood glucose variation in critically ill conditions. However, its prognostic value in chronic kidney disease (CKD) remains understudied. This study aimed to investigate the association between SHR and one-year mortality in CKD patients hospitalized in the Intensive Care Unit (ICU).
Methods: Patients with diagnosis of CKD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled. Incidence of all-cause mortality within one-year follow-up was used as the primary endpoint.
Results: 1825 CKD patients were included in the study. A "U-shaped" relationship between SHR and one-year mortality as identified using multivariate restricted cubic spline (RCS) analysis. Then study population were categorized into three groups: Group 1 (SHR < 0.70), Group 2 (0.70 ≤ SHR ≤ 0.95) and Group 3 (SHR > 0.95). Group 2 showed significantly better one-year outcomes compared to the other two groups (p = 0.0031). This survival benefit persisted across subgroup analyses stratified by age, sex, CKD stage, anemia and various clinical conditions.
Conclusion: SHR proved to be a meaningful biomarker for predicting one-year mortality in ICU-admitted CKD patients, with a "U-shaped" correlation. The identification of the optimal SHR range (0.70-0.95) provided clinicians with a valuable tool for detecting high-risk populations.
{"title":"Predictive value of stress hyperglycemia ratio on one-year mortality in chronic kidney disease patients admitted to intensive care unit.","authors":"Shuoyan An, Zixiang Ye, Wuqiang Che, Yanxiang Gao, Jingyi Ren, Jiahui Li, Jingang Zheng","doi":"10.1186/s12882-024-03823-4","DOIUrl":"https://doi.org/10.1186/s12882-024-03823-4","url":null,"abstract":"<p><strong>Background: </strong>Stress Hyperglycemia Ratio (SHR) reflects the acute blood glucose variation in critically ill conditions. However, its prognostic value in chronic kidney disease (CKD) remains understudied. This study aimed to investigate the association between SHR and one-year mortality in CKD patients hospitalized in the Intensive Care Unit (ICU).</p><p><strong>Methods: </strong>Patients with diagnosis of CKD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled. Incidence of all-cause mortality within one-year follow-up was used as the primary endpoint.</p><p><strong>Results: </strong>1825 CKD patients were included in the study. A \"U-shaped\" relationship between SHR and one-year mortality as identified using multivariate restricted cubic spline (RCS) analysis. Then study population were categorized into three groups: Group 1 (SHR < 0.70), Group 2 (0.70 ≤ SHR ≤ 0.95) and Group 3 (SHR > 0.95). Group 2 showed significantly better one-year outcomes compared to the other two groups (p = 0.0031). This survival benefit persisted across subgroup analyses stratified by age, sex, CKD stage, anemia and various clinical conditions.</p><p><strong>Conclusion: </strong>SHR proved to be a meaningful biomarker for predicting one-year mortality in ICU-admitted CKD patients, with a \"U-shaped\" correlation. The identification of the optimal SHR range (0.70-0.95) provided clinicians with a valuable tool for detecting high-risk populations.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The prevalence of possible sarcopenia is notably high among maintenance hemodialysis (MHD) patients. Possible sarcopenia, defined as a decrease in muscle strength and/or somatic function, is an early and reversible condition between non-sarcopenic and sarcopenia, and early recognition and intervention for possible sarcopenia is important for preventing adverse outcomes and improving the quality of life of these patients. This study aimed to establish a simple and effective model for screening and identifying MHD patients at high risk of possible sarcopenia by using 50 kHz-Whole Body Phase Angle (PhA), with a specific focus on gender differences.
Methods: This prospective cross-sectional study was conducted from September to December 2023 at the Wenjiang Hemodialysis Center in the Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China. A total of 244 MHD patients, including 130 males and 114 females, were enrolled. Data were collected prospectively, including demographic information and physical measurements. All participants provided informed consent before enrollment. Measurements were taken post-dialysis to ensure consistency. The whole-body phase angle was measured using the InBody S10 device, grip strength was measured using an electronic grip strength tester, and physical function was assessed by the Short Physical Performance Battery (SPPB). The Skeletal Muscle Index (SMI) was also calculated.
Results: A total of 244 patients receiving hemodialysis were enrolled in this study. Among these, 109 patients were categorized as non-sarcopenic, 111 as having possible sarcopenia, and 24 as sarcopenic. The prevalence of sarcopenia among MHD patients is 9.8%, while the prevalence of possible sarcopenia is 45.5%. The receiver operating characteristic (ROC) curve analysis showed that for male patients, the AUC of PhA for predicting possible sarcopenia was 0.798, with a sensitivity of 80.36%, specificity of 69.70%, and a cutoff value of 6.20°. For female patients, the AUC of PhA was 0.701, with a sensitivity of 70.91% and specificity of 62.79%, and a cutoff value of 5.70°.
Conclusions: PhA may be a useful and simple predictor of the risk of possible sarcopenia in MHD patients, and more research is needed to further promote the use of PhA in possible sarcopenia.
{"title":"Bioelectrical impedance analysis-derived phase angle predicts possible Sarcopenia in patients on maintenance hemodialysis: a retrospective study.","authors":"Ying Zeng, Yang Chen, Yujie Yang, Ying Qiu, Ping Fu, Huaihong Yuan","doi":"10.1186/s12882-024-03787-5","DOIUrl":"https://doi.org/10.1186/s12882-024-03787-5","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of possible sarcopenia is notably high among maintenance hemodialysis (MHD) patients. Possible sarcopenia, defined as a decrease in muscle strength and/or somatic function, is an early and reversible condition between non-sarcopenic and sarcopenia, and early recognition and intervention for possible sarcopenia is important for preventing adverse outcomes and improving the quality of life of these patients. This study aimed to establish a simple and effective model for screening and identifying MHD patients at high risk of possible sarcopenia by using 50 kHz-Whole Body Phase Angle (PhA), with a specific focus on gender differences.</p><p><strong>Methods: </strong>This prospective cross-sectional study was conducted from September to December 2023 at the Wenjiang Hemodialysis Center in the Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China. A total of 244 MHD patients, including 130 males and 114 females, were enrolled. Data were collected prospectively, including demographic information and physical measurements. All participants provided informed consent before enrollment. Measurements were taken post-dialysis to ensure consistency. The whole-body phase angle was measured using the InBody S10 device, grip strength was measured using an electronic grip strength tester, and physical function was assessed by the Short Physical Performance Battery (SPPB). The Skeletal Muscle Index (SMI) was also calculated.</p><p><strong>Results: </strong>A total of 244 patients receiving hemodialysis were enrolled in this study. Among these, 109 patients were categorized as non-sarcopenic, 111 as having possible sarcopenia, and 24 as sarcopenic. The prevalence of sarcopenia among MHD patients is 9.8%, while the prevalence of possible sarcopenia is 45.5%. The receiver operating characteristic (ROC) curve analysis showed that for male patients, the AUC of PhA for predicting possible sarcopenia was 0.798, with a sensitivity of 80.36%, specificity of 69.70%, and a cutoff value of 6.20°. For female patients, the AUC of PhA was 0.701, with a sensitivity of 70.91% and specificity of 62.79%, and a cutoff value of 5.70°.</p><p><strong>Conclusions: </strong>PhA may be a useful and simple predictor of the risk of possible sarcopenia in MHD patients, and more research is needed to further promote the use of PhA in possible sarcopenia.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function.
Methods: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models.
Results: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables.
Conclusions: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.
{"title":"Associations between leisure time, non-leisure time physical activity, and kidney function in Japanese adults: a cross-sectional study.","authors":"Ippei Chiba, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Sayuri Tokioka, Tomohiro Nakamura, Satoshi Nagaie, Soichi Ogishima, Taku Obara, Toshimi Sato, Nobuo Fuse, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa","doi":"10.1186/s12882-024-03813-6","DOIUrl":"10.1186/s12882-024-03813-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function.</p><p><strong>Methods: </strong>This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m<sup>2</sup>) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models.</p><p><strong>Results: </strong>The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m<sup>2</sup>. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables.</p><p><strong>Conclusions: </strong>We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1186/s12882-024-03793-7
Tu T Tran, Giae Yun, Sejoong Kim
Acute kidney injury (AKI) presents a significant clinical challenge due to its rapid progression to kidney failure, resulting in serious complications such as electrolyte imbalances, fluid overload, and the potential need for renal replacement therapy. Early detection and prediction of AKI can improve patient outcomes through timely interventions. This review was conducted as a narrative literature review, aiming to explore state-of-the-art models for early detection and prediction of AKI. We conducted a comprehensive review of findings from various studies, highlighting their strengths, limitations, and practical considerations for implementation in healthcare settings. We highlight the potential benefits and challenges of their integration into routine clinical care and emphasize the importance of establishing robust early-detection systems before the introduction of artificial intelligence (AI)-assisted prediction models. Advances in AI for AKI detection and prediction are examined, addressing their clinical applicability, challenges, and opportunities for routine implementation.
急性肾损伤(AKI)是一项重大的临床挑战,因为它会迅速发展为肾衰竭,导致电解质失衡、体液超负荷等严重并发症,并可能需要进行肾脏替代治疗。早期发现和预测 AKI 可通过及时干预改善患者预后。本综述以叙述性文献综述的形式进行,旨在探索早期检测和预测 AKI 的最先进模型。我们对各种研究结果进行了全面回顾,强调了它们的优势、局限性以及在医疗机构实施时的实际考虑因素。我们强调了将其纳入常规临床护理的潜在益处和挑战,并强调了在引入人工智能(AI)辅助预测模型之前建立强大的早期检测系统的重要性。我们研究了人工智能在 AKI 检测和预测方面的进展,探讨了其临床适用性、挑战以及常规实施的机遇。
{"title":"Artificial intelligence and predictive models for early detection of acute kidney injury: transforming clinical practice.","authors":"Tu T Tran, Giae Yun, Sejoong Kim","doi":"10.1186/s12882-024-03793-7","DOIUrl":"https://doi.org/10.1186/s12882-024-03793-7","url":null,"abstract":"<p><p>Acute kidney injury (AKI) presents a significant clinical challenge due to its rapid progression to kidney failure, resulting in serious complications such as electrolyte imbalances, fluid overload, and the potential need for renal replacement therapy. Early detection and prediction of AKI can improve patient outcomes through timely interventions. This review was conducted as a narrative literature review, aiming to explore state-of-the-art models for early detection and prediction of AKI. We conducted a comprehensive review of findings from various studies, highlighting their strengths, limitations, and practical considerations for implementation in healthcare settings. We highlight the potential benefits and challenges of their integration into routine clinical care and emphasize the importance of establishing robust early-detection systems before the introduction of artificial intelligence (AI)-assisted prediction models. Advances in AI for AKI detection and prediction are examined, addressing their clinical applicability, challenges, and opportunities for routine implementation.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1186/s12882-024-03794-6
Ali AlSahow, Anas AlYousef, Nasser AlSabti, Bassam AlHelal, Heba AlRajab, Ahmed AlQallaf, Yousif Bahbahani, Abdulrahman AlKandari, Ahmad Mazroue, Noha Dewidar, Gamal Nessim, Ahmad Atef Mekky, Mohamed Sherif, Hesham Zamel, Ahmed Abdalla, Rajeev Kumar
Introduction: Kuwait has a large expatriate community who experience both restricted access to public health services and lower income than Kuwaiti citizens. Given these conditions, we examined differences in characteristics and management of chronic kidney disease (CKD) between Kuwaitis and expatriates.
Methods: Clinical and laboratory data for adult CKD Stages 3-5 not on dialysis (CKD 3-5 ND) patients with native kidneys attending nephrology clinics in all Ministry of Health hospitals collected from January 1, 2022, to December 31, 2022. Cohort was then divided into Kuwaiti patients and expatriates patients for comparison.
Results: We collected data from 2,610 patients (eGFR: 30.8 ml/min/1.73m2; age: 62.6 years; males: 56.7%; Kuwaitis: 62.1%). Kuwaitis were older (63.94 vs. 60.3 years, p < 0.001), with lower mean eGFR (30.4 vs. 31.5 ml/min/1.73m2, p = 0.052) than non-Kuwaitis, however, Kuwaitis had lower mean blood pressure (137.2/76.5 vs. 139.1/78.9 mmHg, p = 0.006), lower HbA1c in diabetics (7.59 vs. 7.82%, p = 0.010), and better lipid profile despite higher body mass indexes (29.6 vs. 28.9 kg/m2, p = 0.002). Both groups had high diabetes mellitus and hypertension rates. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were used in only 22.6% and renin-angiotensin-aldosterone system inhibitors (RAASi) in only 46.2%.
Conclusion: CKD 3-5 ND is caused by diabetes mellitus in 56.6% of cases, and the majority have hypertension. In our study, non-Kuwaitis had higher eGFR; however, restricted public healthcare access and lower income can lead to an unhealthy diet and suboptimal care, which may cause higher blood pressure, higher HbA1c, and a higher dyslipidemia rate. RAASi and SGLT2i utilization must increase to combat CKD, and antihypertensive selection must improve.
{"title":"Chronic kidney disease in Kuwait: a multicenter study of two cohorts with different levels of access to public healthcare.","authors":"Ali AlSahow, Anas AlYousef, Nasser AlSabti, Bassam AlHelal, Heba AlRajab, Ahmed AlQallaf, Yousif Bahbahani, Abdulrahman AlKandari, Ahmad Mazroue, Noha Dewidar, Gamal Nessim, Ahmad Atef Mekky, Mohamed Sherif, Hesham Zamel, Ahmed Abdalla, Rajeev Kumar","doi":"10.1186/s12882-024-03794-6","DOIUrl":"https://doi.org/10.1186/s12882-024-03794-6","url":null,"abstract":"<p><strong>Introduction: </strong>Kuwait has a large expatriate community who experience both restricted access to public health services and lower income than Kuwaiti citizens. Given these conditions, we examined differences in characteristics and management of chronic kidney disease (CKD) between Kuwaitis and expatriates.</p><p><strong>Methods: </strong>Clinical and laboratory data for adult CKD Stages 3-5 not on dialysis (CKD 3-5 ND) patients with native kidneys attending nephrology clinics in all Ministry of Health hospitals collected from January 1, 2022, to December 31, 2022. Cohort was then divided into Kuwaiti patients and expatriates patients for comparison.</p><p><strong>Results: </strong>We collected data from 2,610 patients (eGFR: 30.8 ml/min/1.73m<sup>2</sup>; age: 62.6 years; males: 56.7%; Kuwaitis: 62.1%). Kuwaitis were older (63.94 vs. 60.3 years, p < 0.001), with lower mean eGFR (30.4 vs. 31.5 ml/min/1.73m<sup>2</sup>, p = 0.052) than non-Kuwaitis, however, Kuwaitis had lower mean blood pressure (137.2/76.5 vs. 139.1/78.9 mmHg, p = 0.006), lower HbA1c in diabetics (7.59 vs. 7.82%, p = 0.010), and better lipid profile despite higher body mass indexes (29.6 vs. 28.9 kg/m<sup>2</sup>, p = 0.002). Both groups had high diabetes mellitus and hypertension rates. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were used in only 22.6% and renin-angiotensin-aldosterone system inhibitors (RAASi) in only 46.2%.</p><p><strong>Conclusion: </strong>CKD 3-5 ND is caused by diabetes mellitus in 56.6% of cases, and the majority have hypertension. In our study, non-Kuwaitis had higher eGFR; however, restricted public healthcare access and lower income can lead to an unhealthy diet and suboptimal care, which may cause higher blood pressure, higher HbA1c, and a higher dyslipidemia rate. RAASi and SGLT2i utilization must increase to combat CKD, and antihypertensive selection must improve.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1186/s12882-024-03803-8
Hyeon Tae Yang, Tae In Park, Yong-Jin Kim, Mee-Seon Kim, Sun-Hee Park, Jeong-Hoon Lim, Yoo Na Kang, DongJa Kim, Man-Hoon Han
Background: Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions.
Methods: Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification.
Results: Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy.
Conclusion: Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association.
背景:免疫球蛋白 A 肾病(IgAN)是全球最主要的原发性肾小球肾炎,其病程和预后一直是积极研究的重点。虽然血管病变与 IgAN 相关,但目前的组织病理学分级系统在预测患者预后时并未考虑肾内血管病变。因此,这项于2016年10月至2021年12月在庆北国立大学医院进行的回顾性研究旨在通过比较有无肾内血管病变患者的临床数据,阐明肾内血管病变在IgAN中的重要性:收集了2016年10月至2021年6月期间在庆北国立大学医院(韩国大邱)经活检确诊的原发性IgAN患者的数据,并审查了他们的病历。两名肾病病理学家(Y. J. K. 和 M. S. K.)使用光学显微镜对这 138 例病例的所有切片进行了独立病理审查。本研究中的血管病变包括纤维内膜增厚、动脉壁增厚和动脉透明变性。所有病例均根据 IgA 肾病牛津分类法(2016 年)和哈斯分类法进行了复查:结果:在138名患者中,88人至少有一处肾内血管病变。动脉壁增厚患者的估计肾小球滤过率(eGFR)降低,血清肌酐水平和尿蛋白肌酐比值升高,肾小球全面硬化的比例增加,活检时组织学上间质纤维化和肾小管萎缩的等级升高:结论:IgAN患者的动脉管壁增厚与eGFR降低和肾小球全面硬化有关。结论:IgAN 患者的动脉壁增厚与 eGFR 降低和肾小球全面硬化有关,而且 eGFR 降低和肾小球全面硬化与终末期肾病的进展相关。虽然血管病变与终末期肾病之间的直接相关性尚不完全清楚,但观察到动脉壁增厚与血管病变之间有轻微的相关性(对数秩检验,p = 0.06)。这项研究表明,血管病变在 IgAN 的预后中具有潜在的重要性,因此需要利用更大规模的队列研究来进一步调查,以建立更明确的关联。
{"title":"Significance of intrarenal vascular lesions in Ig A nephropathy prognosis.","authors":"Hyeon Tae Yang, Tae In Park, Yong-Jin Kim, Mee-Seon Kim, Sun-Hee Park, Jeong-Hoon Lim, Yoo Na Kang, DongJa Kim, Man-Hoon Han","doi":"10.1186/s12882-024-03803-8","DOIUrl":"https://doi.org/10.1186/s12882-024-03803-8","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions.</p><p><strong>Methods: </strong>Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification.</p><p><strong>Results: </strong>Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy.</p><p><strong>Conclusion: </strong>Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1186/s12882-024-03819-0
Henry H L Wu, Malcolm Possell, Long The Nguyen, Wenbo Peng, Carol A Pollock, Sonia Saad
Background: There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this.
Methods: Individuals aged 18-75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography-mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10-25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups.
Results: 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols.
Conclusions: We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression.
{"title":"Evaluation of urinary volatile organic compounds as a novel metabolomic biomarker to assess chronic kidney disease progression.","authors":"Henry H L Wu, Malcolm Possell, Long The Nguyen, Wenbo Peng, Carol A Pollock, Sonia Saad","doi":"10.1186/s12882-024-03819-0","DOIUrl":"https://doi.org/10.1186/s12882-024-03819-0","url":null,"abstract":"<p><strong>Background: </strong>There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this.</p><p><strong>Methods: </strong>Individuals aged 18-75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography-mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10-25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups.</p><p><strong>Results: </strong>64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols.</p><p><strong>Conclusions: </strong>We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s12882-024-03799-1
Helena Rydell, Mårten Segelmark, Naomi Clyne
Background: In-center hemodialysis (IHD) is the most common dialysis modality. Assisted peritoneal dialysis (assPD) is an option for frail and/or incapacitated patients. Both modalities can be used to alleviate uremic symptoms towards the end of life. There are few studies comparing these modalities. The primary aim is to compare hospital admissions between assPD and IHD. The secondary aim is to compare continuation of the dialysis modality and patient survival.
Methods: Patients > 65 years, registered in the Swedish Renal Registry (SRR) and starting dialysis 2010-2017 were eligible for inclusion. Patients starting on assPD were matched with patients starting on IHD according to sex, Charlson Index, age and date for start of dialysis. Data were collected from SRR and other registries.
Results: During the first year, patients on assPD and IHD had in median one (IQR 0-5.0; 0-4.0) hospitalization (p = 0.412). There was no significant difference after two years, in the annual number of days admitted to hospital, in hospitalizations with cardiovascular or infectious disease diagnoses or continuation of the dialysis modality, respectively. However, patients on assPD had a worse median survival (1.1 years IQR 0.6-2.1; IHD 3.1 years IQR 0.2-5.8; p < 0.001).
Conclusion: In this study patients starting assPD, often as a palliative treatment, showed no difference compared to IHD concerning the number of hospitalizations, number of days in hospital/year or continuation of the dialysis modality. Patients on assPD had a worse survival, which is likely due to residual confounding. Without that, patients on assPD would probably have lower number of hospitalizations. Despite limitations due to the retrospective observational design of the study, the results indicate that assPD is a feasible alternative to IHD when self-care dialysis is not possible and/or IHD too arduous.
{"title":"Assisted peritoneal dialysis compared to in-centre hemodialysis - an observational study of outcomes from the Swedish Renal Registry.","authors":"Helena Rydell, Mårten Segelmark, Naomi Clyne","doi":"10.1186/s12882-024-03799-1","DOIUrl":"https://doi.org/10.1186/s12882-024-03799-1","url":null,"abstract":"<p><strong>Background: </strong>In-center hemodialysis (IHD) is the most common dialysis modality. Assisted peritoneal dialysis (assPD) is an option for frail and/or incapacitated patients. Both modalities can be used to alleviate uremic symptoms towards the end of life. There are few studies comparing these modalities. The primary aim is to compare hospital admissions between assPD and IHD. The secondary aim is to compare continuation of the dialysis modality and patient survival.</p><p><strong>Methods: </strong>Patients > 65 years, registered in the Swedish Renal Registry (SRR) and starting dialysis 2010-2017 were eligible for inclusion. Patients starting on assPD were matched with patients starting on IHD according to sex, Charlson Index, age and date for start of dialysis. Data were collected from SRR and other registries.</p><p><strong>Results: </strong>During the first year, patients on assPD and IHD had in median one (IQR 0-5.0; 0-4.0) hospitalization (p = 0.412). There was no significant difference after two years, in the annual number of days admitted to hospital, in hospitalizations with cardiovascular or infectious disease diagnoses or continuation of the dialysis modality, respectively. However, patients on assPD had a worse median survival (1.1 years IQR 0.6-2.1; IHD 3.1 years IQR 0.2-5.8; p < 0.001).</p><p><strong>Conclusion: </strong>In this study patients starting assPD, often as a palliative treatment, showed no difference compared to IHD concerning the number of hospitalizations, number of days in hospital/year or continuation of the dialysis modality. Patients on assPD had a worse survival, which is likely due to residual confounding. Without that, patients on assPD would probably have lower number of hospitalizations. Despite limitations due to the retrospective observational design of the study, the results indicate that assPD is a feasible alternative to IHD when self-care dialysis is not possible and/or IHD too arduous.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s12882-024-03790-w
Robert H Spencer, Patrick K Noonan, Thomas Marbury, Frédérique Menzaghi
Background: Difelikefalin is a selective kappa opioid receptor agonist that is approved for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis (HD). In this study, we assessed the pharmacokinetics (PK) of intravenous (IV) difelikefalin in healthy subjects, in non-dialysis-dependent (NDD) subjects with varying stages of kidney disease, and in subjects with end-stage renal disease (ESRD) undergoing HD.
Methods: The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects. Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Results: Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure. NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects). Clearance of difelikefalin correspondingly decreased with increasing renal impairment. In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3. Safety findings for all subjects were consistent with the known profile of IV difelikefalin.
Conclusions: IV difelikefalin was well tolerated. Similar exposure was observed in NDD subjects with mild renal impairment compared with healthy subjects with normal renal function, with reduced clearance and higher exposure in NDD subjects with moderate or severe renal impairment. Dose proportionality was demonstrated in subjects with ESRD undergoing HD administered IV difelikefalin 3 times per week following dialysis and was shown to be mostly cleared by dialysis.
Trial registration: Single-dose study: NA; multiple-dose study: ClinicalTrials.gov registration number NCT02229929, first registration 03/09/2014.
{"title":"Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus.","authors":"Robert H Spencer, Patrick K Noonan, Thomas Marbury, Frédérique Menzaghi","doi":"10.1186/s12882-024-03790-w","DOIUrl":"https://doi.org/10.1186/s12882-024-03790-w","url":null,"abstract":"<p><strong>Background: </strong>Difelikefalin is a selective kappa opioid receptor agonist that is approved for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis (HD). In this study, we assessed the pharmacokinetics (PK) of intravenous (IV) difelikefalin in healthy subjects, in non-dialysis-dependent (NDD) subjects with varying stages of kidney disease, and in subjects with end-stage renal disease (ESRD) undergoing HD.</p><p><strong>Methods: </strong>The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects. Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).</p><p><strong>Results: </strong>Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure. NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects). Clearance of difelikefalin correspondingly decreased with increasing renal impairment. In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3. Safety findings for all subjects were consistent with the known profile of IV difelikefalin.</p><p><strong>Conclusions: </strong>IV difelikefalin was well tolerated. Similar exposure was observed in NDD subjects with mild renal impairment compared with healthy subjects with normal renal function, with reduced clearance and higher exposure in NDD subjects with moderate or severe renal impairment. Dose proportionality was demonstrated in subjects with ESRD undergoing HD administered IV difelikefalin 3 times per week following dialysis and was shown to be mostly cleared by dialysis.</p><p><strong>Trial registration: </strong>Single-dose study: NA; multiple-dose study: ClinicalTrials.gov registration number NCT02229929, first registration 03/09/2014.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}