INTRODUCTIONPrimary aldosteronism (PA), a common secondary cause of arterial hypertension, is treated either surgicaly, or pharmacologically with mineralocorticoid receptor antagonists (MRA). These drugs, while effective, can cause allergic reactions and have side-effects, including menstrual cycle disorders in women. Finerenone is a new, highly selective, nonsteroidal MRA with excellent side-effect profile, primarily intended to slow the progression of diabetic kidney disease and improve cardiovascular outcomes in these patients. No data are available data so far on its effect on patients with PA.CASE PRESENTATIONWe present a case of a female patient with confirmed primary aldosteronism, in whom adrenal vein sampling failed twice. The patient developed a skin allergic reaction to spironolactone and experienced prolonged vaginal bleedings with eplerenone, which was attributed to the drug's affinity for progesterone receptors. A trial of finerenone was initiated, resulting in mild increase in plasma renin activity and serum potassium and somewhat control of blood pressure, but far from optimal blood pressure control, normokalemia or unsupression of plasma renin activity.CONCLUSIONThis case highlights the challenges of managing PA and describes an attempt of treatment with finerenone to which this patient unfortunately did not adequately respond.
导言原发性醛固酮增多症（PA）是继发性动脉高血压的常见病因，可通过手术或矿物质皮质激素受体拮抗剂（MRA）进行药物治疗。这些药物虽然有效，但会引起过敏反应和副作用，包括女性月经周期紊乱。非格列酮（Finerenone）是一种新型、高选择性、非甾体类 MRA，具有良好的副作用，主要用于减缓糖尿病肾病的进展和改善这些患者的心血管预后。到目前为止，还没有关于其对 PA 患者影响的数据。病例介绍我们介绍了一例确诊为原发性醛固酮增多症的女性患者，她的肾上腺静脉采样两次失败。患者对螺内酯产生了皮肤过敏反应，使用依普利酮后出现了长时间的阴道出血，其原因是该药物对孕酮受体具有亲和力。患者开始试用非格列酮，结果血浆肾素活性和血清钾轻度升高，血压得到一定控制，但血压控制、正钾血症或血浆肾素活性抑制远未达到最佳状态。
{"title":"A trial of finerenone in a patient with primary aldosteronism.","authors":"Sandra Karanović Štambuk","doi":"10.1159/000541441","DOIUrl":"https://doi.org/10.1159/000541441","url":null,"abstract":"INTRODUCTIONPrimary aldosteronism (PA), a common secondary cause of arterial hypertension, is treated either surgicaly, or pharmacologically with mineralocorticoid receptor antagonists (MRA). These drugs, while effective, can cause allergic reactions and have side-effects, including menstrual cycle disorders in women. Finerenone is a new, highly selective, nonsteroidal MRA with excellent side-effect profile, primarily intended to slow the progression of diabetic kidney disease and improve cardiovascular outcomes in these patients. No data are available data so far on its effect on patients with PA.CASE PRESENTATIONWe present a case of a female patient with confirmed primary aldosteronism, in whom adrenal vein sampling failed twice. The patient developed a skin allergic reaction to spironolactone and experienced prolonged vaginal bleedings with eplerenone, which was attributed to the drug's affinity for progesterone receptors. A trial of finerenone was initiated, resulting in mild increase in plasma renin activity and serum potassium and somewhat control of blood pressure, but far from optimal blood pressure control, normokalemia or unsupression of plasma renin activity.CONCLUSIONThis case highlights the challenges of managing PA and describes an attempt of treatment with finerenone to which this patient unfortunately did not adequately respond.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. Methods: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. Results: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09−1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05–0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. Conclusions: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.
{"title":"In-center Automated Peritoneal Dialysis: Clinical Features, Practice Patterns, and Patient Survival From a 6-year Cohort Study in China","authors":"Shouci Hu, Tong Ren, Bo Yang, Ming-Ming Pei, Xiangfu Gao, Hongtao Yang, Hongbo Chen","doi":"10.1159/000535566","DOIUrl":"https://doi.org/10.1159/000535566","url":null,"abstract":"Introduction: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. Methods: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. Results: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09−1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05–0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. Conclusions: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138591637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Kidney transplantation (KT) has surpassed dialysis as the optimal therapy for end-stage kidney disease. Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods: To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and nonrejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus database. Then, we used weighted gene coexpression network analysis (WGCNA) to analyze the coexpression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. Results: As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. Three key modules had 21 mutual Gene Ontology term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes, Yip1 interacting factor homolog B, membrane trafficking protein, toll like receptor 8, neutrophil cytosolic factor 4, glutathione peroxidase 8, mesenteric estrogen dependent adipogenesis, decorin, serpin family F member 1, integrin subunit beta like 1, SRY-box transcription factor 15, trophinin associated protein, SRY-box transcription factor 1, metallothionein 3, lysosomal protein transmembrane, FERM domain containing kindlin 3, and cathepsin S, had a great diagnostic performance (AUC > 0.7). Conclusion: This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.
{"title":"Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis","authors":"Yifan Zhu, Yuyan Tang, Yinshun Peng, Ping Hu, Weiqian Sun, Meiping Jin, Ping Liu, Jiajun Wu, Haidong He, Xu-dong Xu","doi":"10.1159/000525386","DOIUrl":"https://doi.org/10.1159/000525386","url":null,"abstract":"Introduction: Kidney transplantation (KT) has surpassed dialysis as the optimal therapy for end-stage kidney disease. Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods: To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and nonrejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus database. Then, we used weighted gene coexpression network analysis (WGCNA) to analyze the coexpression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. Results: As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. Three key modules had 21 mutual Gene Ontology term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes, Yip1 interacting factor homolog B, membrane trafficking protein, toll like receptor 8, neutrophil cytosolic factor 4, glutathione peroxidase 8, mesenteric estrogen dependent adipogenesis, decorin, serpin family F member 1, integrin subunit beta like 1, SRY-box transcription factor 15, trophinin associated protein, SRY-box transcription factor 1, metallothionein 3, lysosomal protein transmembrane, FERM domain containing kindlin 3, and cathepsin S, had a great diagnostic performance (AUC > 0.7). Conclusion: This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81601906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Roccatello, R. Fenoglio, V. Oddone, S. Sciascia
Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a cluster of potentially life-threatening disorders, often involving the kidney with a necrotizing crescentic glomerulonephritis with scanty deposition of immunoglobulins and complement. Historically the role of complement has been considered ancillary. Recently, an anti-myeloperoxidase (MPO) AAV model in complement-deficient mice has shown an involvement for the complement cascade in the development of the renal injuries. Further animal studies showing that in contrast to mice deficient for factor B and C5 animals deficient for C4 were susceptible to AAV development by injection of anti-MPO antibodies emphasized the specific involvement of the alternative pathway. Consonantly, the C5a receptor (Cd88) blockade was found to protect mice from MPO-AAV. CCX168, i.e., avacopan, a powerful inhibitor of C5a receptor that can be administered orally, was shown to reduce the proinflammatory effects of C5a and abolish the activation of neutrophils, their migration and adherence to endothelium, and the vascular endothelial cell retraction that increases permeability. Summary: Avacopan was found to be safe in healthy volunteers given a wide range of doses in a phase 1 clinical trial. The phase 2 trial CLEAR assessed the possibility to decrease dose or entirely replace glucocorticosteroids in the standard-of-care therapy of AAV. Avacopan, added to CYC or RTX either in combination with GCs or not, shortened the time to remission in patients with either newly diagnosed or relapsing AAV. The phase 3 ADVOCATE study compared the ability of an avacopan-associated regimen to induce and sustain remission in AAV patients versus a conventional GC-associated scheme. Remission at week 26 was observed in 72.3% of patients given avacopan and in 70.1% of those given prednisone. Sustained remission at week 52 (second primary endpoint) was obtained in 65.7% of patients given avacopan and in 54.9% receiving prednisone. The avacopan-associated regimen was noninferior at week 26 and superior at week 52 in sustaining remission as compared to the GC-based scheme. Key Messages: The results of the ADVOCATE trial opened new prospects for the treatment of AAV and also other immune-mediated diseases with renal involvement. The possible position of avacopan in a routine clinical setting and its possible indications in specific subsets of patients with AAV are extensively discussed.
{"title":"How the Availability of Anti-C5a Agents Could Change the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis","authors":"D. Roccatello, R. Fenoglio, V. Oddone, S. Sciascia","doi":"10.1159/000525357","DOIUrl":"https://doi.org/10.1159/000525357","url":null,"abstract":"Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a cluster of potentially life-threatening disorders, often involving the kidney with a necrotizing crescentic glomerulonephritis with scanty deposition of immunoglobulins and complement. Historically the role of complement has been considered ancillary. Recently, an anti-myeloperoxidase (MPO) AAV model in complement-deficient mice has shown an involvement for the complement cascade in the development of the renal injuries. Further animal studies showing that in contrast to mice deficient for factor B and C5 animals deficient for C4 were susceptible to AAV development by injection of anti-MPO antibodies emphasized the specific involvement of the alternative pathway. Consonantly, the C5a receptor (Cd88) blockade was found to protect mice from MPO-AAV. CCX168, i.e., avacopan, a powerful inhibitor of C5a receptor that can be administered orally, was shown to reduce the proinflammatory effects of C5a and abolish the activation of neutrophils, their migration and adherence to endothelium, and the vascular endothelial cell retraction that increases permeability. Summary: Avacopan was found to be safe in healthy volunteers given a wide range of doses in a phase 1 clinical trial. The phase 2 trial CLEAR assessed the possibility to decrease dose or entirely replace glucocorticosteroids in the standard-of-care therapy of AAV. Avacopan, added to CYC or RTX either in combination with GCs or not, shortened the time to remission in patients with either newly diagnosed or relapsing AAV. The phase 3 ADVOCATE study compared the ability of an avacopan-associated regimen to induce and sustain remission in AAV patients versus a conventional GC-associated scheme. Remission at week 26 was observed in 72.3% of patients given avacopan and in 70.1% of those given prednisone. Sustained remission at week 52 (second primary endpoint) was obtained in 65.7% of patients given avacopan and in 54.9% receiving prednisone. The avacopan-associated regimen was noninferior at week 26 and superior at week 52 in sustaining remission as compared to the GC-based scheme. Key Messages: The results of the ADVOCATE trial opened new prospects for the treatment of AAV and also other immune-mediated diseases with renal involvement. The possible position of avacopan in a routine clinical setting and its possible indications in specific subsets of patients with AAV are extensively discussed.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79206289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Hernandez-Arroyo, S. Kanduri, R. Justiniano, Pedro J. Martinez- Pitre, J. Velez
Background: It has been noted in observational and interventional studies that individuals exposed to fenofibrate can exhibit a rise in serum creatinine (sCr) concentration. However, it is not known to what extent this phenomenon impacts kidney function in patients who are referred to a nephrology clinic for consultation for chronic kidney disease (CKD). Methods: We conducted a prospective observational study of patients referred to our nephrology clinic for a new evaluation of a rise in sCr or worsening CKD and who were on fenofibrate therapy. We examined the effect of discontinuation of fenofibrate on kidney function, change in sCr, and estimated glomerular filtration (eGFR) at 3, 6, and 12 months. Results: A total of 22 patients (59% women, 86% White, 59% with type 2 diabetes, and 18% with peripheral arterial disease) were captured over 2.5 years. Median sCr at the time of fenofibrate discontinuation was 1.9 (1.1–3.3) mg/dL and eGFR, 32 (17–57) mL/min; proteinuria was absent in 17 (77%). Upon discontinuation of fenofibrate, median sCr decreased to 1.5 (0.9–2.4), 1.4 (1.0–2.5), and 1.4 (1.0–2.3) mg/dL at 3, 6, and 12 months, respectively (p < 0.05); whereas median eGFR increased to 44 (27–71), 45 (23–71), and 42 (21–71) mL/min, respectively (p < 0.05). A ≥30% rise in eGFR was observed in 59% of the patients at 3 months, and it persisted in 45% and 50% of patients at 6 and 12 months, respectively. Conclusion: Discontinuation of fenofibrate in patients referred for CKD evaluation can result in sustained reduction in sCr in about half of the patients and for up to 1 year. There is a need to raise awareness among primary practitioners about this phenomenon. Recognition of fenofibrate as a cause of rise in sCr could reduce unnecessary nephrology consultation and resource utilization.
{"title":"Improvement in Kidney Function after Discontinuation of Fenofibrate in Outpatient Nephrology Consultation for Chronic Kidney Disease","authors":"C. Hernandez-Arroyo, S. Kanduri, R. Justiniano, Pedro J. Martinez- Pitre, J. Velez","doi":"10.1159/000522081","DOIUrl":"https://doi.org/10.1159/000522081","url":null,"abstract":"Background: It has been noted in observational and interventional studies that individuals exposed to fenofibrate can exhibit a rise in serum creatinine (sCr) concentration. However, it is not known to what extent this phenomenon impacts kidney function in patients who are referred to a nephrology clinic for consultation for chronic kidney disease (CKD). Methods: We conducted a prospective observational study of patients referred to our nephrology clinic for a new evaluation of a rise in sCr or worsening CKD and who were on fenofibrate therapy. We examined the effect of discontinuation of fenofibrate on kidney function, change in sCr, and estimated glomerular filtration (eGFR) at 3, 6, and 12 months. Results: A total of 22 patients (59% women, 86% White, 59% with type 2 diabetes, and 18% with peripheral arterial disease) were captured over 2.5 years. Median sCr at the time of fenofibrate discontinuation was 1.9 (1.1–3.3) mg/dL and eGFR, 32 (17–57) mL/min; proteinuria was absent in 17 (77%). Upon discontinuation of fenofibrate, median sCr decreased to 1.5 (0.9–2.4), 1.4 (1.0–2.5), and 1.4 (1.0–2.3) mg/dL at 3, 6, and 12 months, respectively (p < 0.05); whereas median eGFR increased to 44 (27–71), 45 (23–71), and 42 (21–71) mL/min, respectively (p < 0.05). A ≥30% rise in eGFR was observed in 59% of the patients at 3 months, and it persisted in 45% and 50% of patients at 6 and 12 months, respectively. Conclusion: Discontinuation of fenofibrate in patients referred for CKD evaluation can result in sustained reduction in sCr in about half of the patients and for up to 1 year. There is a need to raise awareness among primary practitioners about this phenomenon. Recognition of fenofibrate as a cause of rise in sCr could reduce unnecessary nephrology consultation and resource utilization.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88787661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Glucocorticoids are one of the most commonly used drugs for treatment of inflammatory and autoimmune diseases. Sirtuin-1 (SIRT-1) belongs to the family of proteins involved in protection against inflammation and oxidative stress. A role of SIRT-1 in regulation of bone metabolism during high-dose steroid therapy is unknown. Objectives: The study assessed influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease. Methods: The study included 40 patients (25 M, 15 F; mean age 53.1 ± 14 years) with chronic kidney disease (mean estimated glomerular filtration rate, 58.9 ± 31.3 mL/min). The main inclusion criterion was clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24 h. The patients received intravenous pulses of methylprednisolone 20–30 mg/kg/day for three consecutive days followed by oral prednisone 0.8–1.0 mg/kg/day. The blood was taken before administration of methylprednisolone to assess plasma SIRT-1, sclerostin, calcium, phosphate, and parathormone; and first-morning urine sample was taken for measurement of calcium, phosphate, and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7, and 30 days during steroid therapy. Results: Plasma SIRT-1 increased significantly during steroid administration. Plasma sclerostin did not change significantly. There was a significant linear negative correlation between changes in SIRT-1 levels and sclerostin throughout the study. In a multiple regression model, changes of plasma sclerostin induced by steroid therapy explained the largest part of variance of respective changes of plasma SIRT-1. Conclusions: Plasma SIRT-1 increase during high-dose corticosteroid therapy is negatively related to the change of plasma sclerostin that may suggest a protective role of SIRT-1 against the negative effects of steroid therapy on bone.
{"title":"Effect of High-Dose Glucocorticoids on Markers of Inflammation and Bone Metabolism in Patients with Primary Glomerular Disease","authors":"Katarzyna Pęczek, M. Nowicki","doi":"10.1159/000524091","DOIUrl":"https://doi.org/10.1159/000524091","url":null,"abstract":"Background: Glucocorticoids are one of the most commonly used drugs for treatment of inflammatory and autoimmune diseases. Sirtuin-1 (SIRT-1) belongs to the family of proteins involved in protection against inflammation and oxidative stress. A role of SIRT-1 in regulation of bone metabolism during high-dose steroid therapy is unknown. Objectives: The study assessed influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease. Methods: The study included 40 patients (25 M, 15 F; mean age 53.1 ± 14 years) with chronic kidney disease (mean estimated glomerular filtration rate, 58.9 ± 31.3 mL/min). The main inclusion criterion was clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24 h. The patients received intravenous pulses of methylprednisolone 20–30 mg/kg/day for three consecutive days followed by oral prednisone 0.8–1.0 mg/kg/day. The blood was taken before administration of methylprednisolone to assess plasma SIRT-1, sclerostin, calcium, phosphate, and parathormone; and first-morning urine sample was taken for measurement of calcium, phosphate, and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7, and 30 days during steroid therapy. Results: Plasma SIRT-1 increased significantly during steroid administration. Plasma sclerostin did not change significantly. There was a significant linear negative correlation between changes in SIRT-1 levels and sclerostin throughout the study. In a multiple regression model, changes of plasma sclerostin induced by steroid therapy explained the largest part of variance of respective changes of plasma SIRT-1. Conclusions: Plasma SIRT-1 increase during high-dose corticosteroid therapy is negatively related to the change of plasma sclerostin that may suggest a protective role of SIRT-1 against the negative effects of steroid therapy on bone.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88602617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The present research analyzed the correlation between N6-methyladenosine (m6A) methylation and ferroptosis associated genes (FAGs) in acute kidney injury (AKI) patients. Methods: Bioinformatics analysis of microarray profiles (GSE30718) was performed to select differential expression genes (DEGs). FAGs are derived from systematic analysis of the aberrances and functional implications. The m6A methylation related genes were derived from the molecular characterization and clinical significance of m6A modulators. The multi-gene correlation of ferroptosis and M6A methylation modification was displayed. Then, the CIBERSORT algorithm was used to analyze the proportions of 22 immune cell infiltration. Results: In total, 349 DEGs were extracted between the AKI and control samples, among which 172 genes were upregulated and 177 were downregulated. FAGs (SLC1A5, CARS, SAT1, ACSL4, NFE2L2, TFRC, and MT1G) and m6A methylation related genes (YTHDF3, WTAP, and IGF2BP3) were significantly increased in AKI patients (p < 0.05). FAGs (SAT1, ACSL4, and NFE2L2) were positively correlated with the expression level of m6A methylation genes (p < 0.05). NFE2L2 has high diagnostic value, and the level of NFE2L2 was negatively correlated with the degree of follicular helper T (TFH) cell infiltration. Conclusion: Our research could provide a new theoretical basis for the pathogenesis and immune mechanism of AKI.
{"title":"The Correlation between Ferroptosis and m6A Methylation in Patients with Acute Kidney Injury","authors":"Lihua Ni, Rui Bai, Qi-Lin Zhou, C. Yuan, Le-ting Zhou, Xiaoyan Wu","doi":"10.1159/000524900","DOIUrl":"https://doi.org/10.1159/000524900","url":null,"abstract":"Objective: The present research analyzed the correlation between N6-methyladenosine (m6A) methylation and ferroptosis associated genes (FAGs) in acute kidney injury (AKI) patients. Methods: Bioinformatics analysis of microarray profiles (GSE30718) was performed to select differential expression genes (DEGs). FAGs are derived from systematic analysis of the aberrances and functional implications. The m6A methylation related genes were derived from the molecular characterization and clinical significance of m6A modulators. The multi-gene correlation of ferroptosis and M6A methylation modification was displayed. Then, the CIBERSORT algorithm was used to analyze the proportions of 22 immune cell infiltration. Results: In total, 349 DEGs were extracted between the AKI and control samples, among which 172 genes were upregulated and 177 were downregulated. FAGs (SLC1A5, CARS, SAT1, ACSL4, NFE2L2, TFRC, and MT1G) and m6A methylation related genes (YTHDF3, WTAP, and IGF2BP3) were significantly increased in AKI patients (p < 0.05). FAGs (SAT1, ACSL4, and NFE2L2) were positively correlated with the expression level of m6A methylation genes (p < 0.05). NFE2L2 has high diagnostic value, and the level of NFE2L2 was negatively correlated with the degree of follicular helper T (TFH) cell infiltration. Conclusion: Our research could provide a new theoretical basis for the pathogenesis and immune mechanism of AKI.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89430198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Thompson, N. Wiebe, M. Stickland, G. Gyenes, Rachelle Davies, J. Vallance, M. Graham
Introduction: Exercise is an effective strategy for blood pressure (BP) reduction in the general population, but its efficacy for the management of hypertension in chronic kidney disease (CKD) is not known. We evaluated the difference in 24-h ambulatory systolic BP (SBP) with exercise training in people with moderate to severe CKD. Methods: Participants with an estimated glomerular filtration rate (eGFR) of 15–44 mL/min per 1.73 m2 and SBP >120 mm Hg were randomized to receive thrice-weekly moderate-intensity aerobic-based exercise over 24 weeks, or usual care. Phase 1 included supervised in-center and home-based sessions for 8 weeks. Phase 2 was 16 weeks of home-based sessions. BP, arterial stiffness, cardiorespiratory fitness, and markers of cardiovascular (CV) risk were analyzed using mixed linear regression. Results: We randomized 44 people; 36% were female, the median age was 69 years, 55% had diabetes, and the median eGFR was 28 mL/min per 1.73 m2. Compared with usual care, there was no significant change in 24-ambulatory SBP at 8 weeks (2.96 mm Hg; 95% confidence interval (CI): −2.56, 8.49) or 24 weeks. Peak oxygen uptake improved by 1.9 mL/kg/min in the exercise group (95% CI: 0.03, 3.79) at 8 weeks with a trend toward higher body mass index 1.84 kg/m2 (95% CI: −0.10, 3.78) and fat free mass, but this was not sustained at 24 weeks. Markers of CV risk were unchanged. Conclusions: Despite an improvement in peak aerobic capacity and body composition, we did not detect a change in 24-h ambulatory SBP in people with moderate-to-severe CKD.
{"title":"Physical Activity in Renal Disease and the Effect on Hypertension: A Randomized Controlled Trial","authors":"S. Thompson, N. Wiebe, M. Stickland, G. Gyenes, Rachelle Davies, J. Vallance, M. Graham","doi":"10.1159/000524518","DOIUrl":"https://doi.org/10.1159/000524518","url":null,"abstract":"Introduction: Exercise is an effective strategy for blood pressure (BP) reduction in the general population, but its efficacy for the management of hypertension in chronic kidney disease (CKD) is not known. We evaluated the difference in 24-h ambulatory systolic BP (SBP) with exercise training in people with moderate to severe CKD. Methods: Participants with an estimated glomerular filtration rate (eGFR) of 15–44 mL/min per 1.73 m2 and SBP >120 mm Hg were randomized to receive thrice-weekly moderate-intensity aerobic-based exercise over 24 weeks, or usual care. Phase 1 included supervised in-center and home-based sessions for 8 weeks. Phase 2 was 16 weeks of home-based sessions. BP, arterial stiffness, cardiorespiratory fitness, and markers of cardiovascular (CV) risk were analyzed using mixed linear regression. Results: We randomized 44 people; 36% were female, the median age was 69 years, 55% had diabetes, and the median eGFR was 28 mL/min per 1.73 m2. Compared with usual care, there was no significant change in 24-ambulatory SBP at 8 weeks (2.96 mm Hg; 95% confidence interval (CI): −2.56, 8.49) or 24 weeks. Peak oxygen uptake improved by 1.9 mL/kg/min in the exercise group (95% CI: 0.03, 3.79) at 8 weeks with a trend toward higher body mass index 1.84 kg/m2 (95% CI: −0.10, 3.78) and fat free mass, but this was not sustained at 24 weeks. Markers of CV risk were unchanged. Conclusions: Despite an improvement in peak aerobic capacity and body composition, we did not detect a change in 24-h ambulatory SBP in people with moderate-to-severe CKD.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72583973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Chronic kidney disease (CKD) affects the crosstalk between organs in the body and vast majority of studies were devoted to the interactions between the kidneys and the cardiovascular system. As of today, there is more evidence of the kidney and the central nervous system connections. Summary: Indeed, CKD and in particular dialysis therapy is linked to the increased prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment, and depression. Both traditional cardiovascular risk factors (such as diabetes, hypertension, and lipid disorders), nontraditional risk factors (such as uremic toxins, anemia, and secondary hyperparathyroidism) may predispose CKD patients to neurological disorders. Likewise, cognitive problems occur more commonly in kidney transplant recipients, regardless of age, than in the general population, but the prevalence is still understudied. Cognitive impairment is associated with a higher risk of hospitalization, mortality, decreased quality of life, or health care costs in kidney transplant recipients. Here, we review (i) the potential clinical impact of kidney transplantation on cerebrovascular and neurological complications, (ii) evaluation of patients with cognitive impairment for kidney transplantation (iii) the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, and (iv) unmet medical needs. Key Messages: Cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem. The screening for cognitive declines after kidney transplantation is not yet a routine practice. Several prospective and cross-sectional studies reported improvement across some of the assessed cognitive domains after transplantation.
{"title":"Cognitive Impairment and Kidney Transplantation: Underestimated, Underrecognized but Clinically Relevant Problem","authors":"A. Golenia, J. Małyszko, J. Małyszko","doi":"10.1159/000521907","DOIUrl":"https://doi.org/10.1159/000521907","url":null,"abstract":"Background: Chronic kidney disease (CKD) affects the crosstalk between organs in the body and vast majority of studies were devoted to the interactions between the kidneys and the cardiovascular system. As of today, there is more evidence of the kidney and the central nervous system connections. Summary: Indeed, CKD and in particular dialysis therapy is linked to the increased prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment, and depression. Both traditional cardiovascular risk factors (such as diabetes, hypertension, and lipid disorders), nontraditional risk factors (such as uremic toxins, anemia, and secondary hyperparathyroidism) may predispose CKD patients to neurological disorders. Likewise, cognitive problems occur more commonly in kidney transplant recipients, regardless of age, than in the general population, but the prevalence is still understudied. Cognitive impairment is associated with a higher risk of hospitalization, mortality, decreased quality of life, or health care costs in kidney transplant recipients. Here, we review (i) the potential clinical impact of kidney transplantation on cerebrovascular and neurological complications, (ii) evaluation of patients with cognitive impairment for kidney transplantation (iii) the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, and (iv) unmet medical needs. Key Messages: Cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem. The screening for cognitive declines after kidney transplantation is not yet a routine practice. Several prospective and cross-sectional studies reported improvement across some of the assessed cognitive domains after transplantation.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76191039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Halouzková, J. Hartinger, V. Krátký, V. Tesar, O. Slanař
Background: The dosing of aminoglycosides (AGs) in patients with kidney disease is challenging due to their markedly prolonged half-life, which renders pulse dosing schedules unsuitable. We performed a review of the literature that describes the pharmacokinetics of, and dosing recommendations for, AG for patients with abnormal renal functions and various renal replacement therapy modalities, focusing on patients treated with intermittent hemodialysis (iHD). Summary: During one iHD session, dialysis removes a remarkable amount of the drug regardless of the dialyzer type. In patients with severely reduced kidney functions, the distribution phase is prolonged, which needs to be taken into account when drawing samples shortly after drug administration or following an iHD session. Key Messages: The doses recommended for the pulse dosing of patients without kidney disease leads to unacceptably high overall systemic exposure for patients with severely reduced kidney functions even with dosing intervals extended up to 48 h. Therefore, lower doses accompanied by extended dosing intervals must be applied for this patient group. The clinical evidence and current recommendations support the dosing of AG following, rather than before, HD sessions. In patients with end-stage kidney disease, the samples for TDM of AGs should not be drawn earlier than 2 h after end of the infusion and 4 h after the end of iHD session to allow full (re)distribution of the drug.
{"title":"Dosing of Aminoglycosides in Chronic Kidney Disease and End-Stage Renal Disease Patients Treated with Intermittent Hemodialysis","authors":"B. Halouzková, J. Hartinger, V. Krátký, V. Tesar, O. Slanař","doi":"10.1159/000523892","DOIUrl":"https://doi.org/10.1159/000523892","url":null,"abstract":"Background: The dosing of aminoglycosides (AGs) in patients with kidney disease is challenging due to their markedly prolonged half-life, which renders pulse dosing schedules unsuitable. We performed a review of the literature that describes the pharmacokinetics of, and dosing recommendations for, AG for patients with abnormal renal functions and various renal replacement therapy modalities, focusing on patients treated with intermittent hemodialysis (iHD). Summary: During one iHD session, dialysis removes a remarkable amount of the drug regardless of the dialyzer type. In patients with severely reduced kidney functions, the distribution phase is prolonged, which needs to be taken into account when drawing samples shortly after drug administration or following an iHD session. Key Messages: The doses recommended for the pulse dosing of patients without kidney disease leads to unacceptably high overall systemic exposure for patients with severely reduced kidney functions even with dosing intervals extended up to 48 h. Therefore, lower doses accompanied by extended dosing intervals must be applied for this patient group. The clinical evidence and current recommendations support the dosing of AG following, rather than before, HD sessions. In patients with end-stage kidney disease, the samples for TDM of AGs should not be drawn earlier than 2 h after end of the infusion and 4 h after the end of iHD session to allow full (re)distribution of the drug.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74053174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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