Ana Rita Martins, Sofia Azeredo-Lopes, Sofia Azeredo Pereira, Inês Moreira, André Luíz Weigert
ABSTRACT Background Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. Methods This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan–Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. Results A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270–0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203–0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055–41.606, P < .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140–0.906, P < .05) and lean mass (HR 0.187, 95% CI 0.042–0.829, P < .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. Conclusions Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.
背景:与普通人群相比，慢性肾脏疾病(CKD)患者心血管(CV)发病率和死亡率的风险更高。虽然有几个公认的传统心血管危险因素，但很少有研究涉及新的潜在危险因素，如α-Klotho、不对称二甲基精氨酸(ADMA)和瘦质量。方法:这是一项观察性、前瞻性、单中心、队列研究，纳入了流行的血液透析(在线血液透析)成人患者。通过单因素logistic回归模型、单因素和多因素Cox比例风险模型以及Kaplan-Meier分析，我们评估了α-Klotho、ADMA和瘦质量水平与这些患者外周血管疾病(PVD)、心血管事件和全因死亡率的关系。结果共纳入200例HD患者。我们发现，log-α-Klotho水平升高与PVD(比值比(OR) 0.521, 95%可信区间(CI) 0.270-0.954, P = 0.034)和CV事件(OR 0.415, 95% CI 0.203-0.790, P = 0.01)的发生率降低显著相关，而log- adma水平升高仅与PVD发生率升高显著相关(OR 13.482, 95% CI 5.055-41.606, P &措施)。我们还发现log-α-Klotho的水平(HR 0.357, 95% CI 0.140-0.906, P <0.05)和瘦肉质量(HR 0.187, 95% CI 0.042-0.829, P <0.05)，但log-ADMA与全因死亡率风险显著相关，即使在调整了可能的混杂变量后也是如此。结论新的长期临床关联支持α-Klotho和瘦质量是血液透析患者新的心血管危险因素。
{"title":"Klotho and lean mass as novel cardiovascular risk factors in hemodialysis patients","authors":"Ana Rita Martins, Sofia Azeredo-Lopes, Sofia Azeredo Pereira, Inês Moreira, André Luíz Weigert","doi":"10.1093/ckj/sfad166","DOIUrl":"https://doi.org/10.1093/ckj/sfad166","url":null,"abstract":"ABSTRACT Background Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. Methods This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan–Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. Results A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270–0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203–0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055–41.606, P &lt; .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140–0.906, P &lt; .05) and lean mass (HR 0.187, 95% CI 0.042–0.829, P &lt; .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. Conclusions Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135579806","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}
Carmine Zoccali, Francesca Mallamaci, Luca De Nicola, Roberto Minutolo
ABSTRACT Resistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics. Renal denervation is another option for treatment-resistant hypertension. New compounds targeting different pathways involved in RH—including inhibitors of aminopeptidase A, endothelin antagonists and selective aldosterone synthase inhibitors—have been tested in clinical trials in this condition. The centrally acting drug firibastat, targeting the brain renin–angiotensin system, failed to demonstrate significant effectiveness in reducing blood pressure (BP) in patients with difficult-to-treat and RH in the Firibistat in Resistant Hypertension (FRESH) trial. Aprocitentan, a dual endothelin A and B receptor antagonist, showed a moderate but statistically significant decrease in BP in patients with RH in the Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial. However, concerns remain about potential adverse events, such as fluid retention. The use of baxdrostat, a selective aldosterone synthase inhibitor, showed promising results in reducing BP in patients with treatment-resistant hypertension in the Baxdrostat in Resistant Hypertension (BrigHTN) trial. However, a subsequent trial, HALO, failed to meet its primary endpoint. The unexpected results may be influenced by factors such as patient adherence and white-coat hypertension. Despite the disappointing results from HALO, the potential benefits of inhibiting aldosterone synthesis remain to be fully understood. In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition.
{"title":"New trials in resistant hypertension: mixed blessing stories","authors":"Carmine Zoccali, Francesca Mallamaci, Luca De Nicola, Roberto Minutolo","doi":"10.1093/ckj/sfad251","DOIUrl":"https://doi.org/10.1093/ckj/sfad251","url":null,"abstract":"ABSTRACT Resistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics. Renal denervation is another option for treatment-resistant hypertension. New compounds targeting different pathways involved in RH—including inhibitors of aminopeptidase A, endothelin antagonists and selective aldosterone synthase inhibitors—have been tested in clinical trials in this condition. The centrally acting drug firibastat, targeting the brain renin–angiotensin system, failed to demonstrate significant effectiveness in reducing blood pressure (BP) in patients with difficult-to-treat and RH in the Firibistat in Resistant Hypertension (FRESH) trial. Aprocitentan, a dual endothelin A and B receptor antagonist, showed a moderate but statistically significant decrease in BP in patients with RH in the Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial. However, concerns remain about potential adverse events, such as fluid retention. The use of baxdrostat, a selective aldosterone synthase inhibitor, showed promising results in reducing BP in patients with treatment-resistant hypertension in the Baxdrostat in Resistant Hypertension (BrigHTN) trial. However, a subsequent trial, HALO, failed to meet its primary endpoint. The unexpected results may be influenced by factors such as patient adherence and white-coat hypertension. Despite the disappointing results from HALO, the potential benefits of inhibiting aldosterone synthesis remain to be fully understood. In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135580159","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}
Frederik Husum Mårup, Martin Bjergskov Thomsen, Henrik Birn
ABSTRACT Background Dapagliflozin and finerenone reduce albuminuria and slow CKD progression, but additive effects remain unstudied. We compared their individual and combined efficacy and safety in patients with non-diabetic CKD. Methods In an open-label, randomized clinical trial, we included patients aged 18–80 on maximal tolerated ACE inhibitor or angiotensin receptor blocker with eGFR 25–45 mL/min/1,73 m2 and albuminuria 150–2000 mg/g. Participants received either finerenone 20 mg/day or dapagliflozin 10 mg/day for four weeks, followed by combination therapy for four weeks. Data were collected at baseline, 4 and 8 weeks. Results Twenty patients (10 per group) with a mean mGFR of 34 mL/min/1,73 m2 and a mean urine albumin creatinine ratio (UACR) of 469 mg/g were included. Finerenone alone or in addition to dapagliflozin resulted in −24% (95% CI, −36% to −11%) and −34% (95% CI, −47% to −18%) change in UACR, respectively. Dapagliflozin alone or in addition to finerenone resulted in −8% (95% CI, −22 to 9%) and −10% (95% CI, −28% to 12%) change in UACR, respectively. Overall, UACR change after 8 weeks was −36% (95% CI, −46% to −24%). After 8 weeks, systolic blood pressure and mGFR were reduced by 10 mmHg (95% CI, 6–13 mmHg) and 7 mL/min/1,73 m2 (95% CI, 5–8 mL/min/1,73 m2). Adverse effects were minimal. Conclusions The combination of finerenone and dapagliflozin was safe and significantly reduced albuminuria. The effect of combination therapy was at least equal to the calculated, combined effect of each of the drugs, suggesting an additive effect on albuminuria. Larger studies assessing long-term effects and safety are warranted.
{"title":"Additive effects of dapagliflozin and finerenone on albuminuria in non-diabetic CKD: an open-label randomized clinical trial","authors":"Frederik Husum Mårup, Martin Bjergskov Thomsen, Henrik Birn","doi":"10.1093/ckj/sfad249","DOIUrl":"https://doi.org/10.1093/ckj/sfad249","url":null,"abstract":"ABSTRACT Background Dapagliflozin and finerenone reduce albuminuria and slow CKD progression, but additive effects remain unstudied. We compared their individual and combined efficacy and safety in patients with non-diabetic CKD. Methods In an open-label, randomized clinical trial, we included patients aged 18–80 on maximal tolerated ACE inhibitor or angiotensin receptor blocker with eGFR 25–45 mL/min/1,73 m2 and albuminuria 150–2000 mg/g. Participants received either finerenone 20 mg/day or dapagliflozin 10 mg/day for four weeks, followed by combination therapy for four weeks. Data were collected at baseline, 4 and 8 weeks. Results Twenty patients (10 per group) with a mean mGFR of 34 mL/min/1,73 m2 and a mean urine albumin creatinine ratio (UACR) of 469 mg/g were included. Finerenone alone or in addition to dapagliflozin resulted in −24% (95% CI, −36% to −11%) and −34% (95% CI, −47% to −18%) change in UACR, respectively. Dapagliflozin alone or in addition to finerenone resulted in −8% (95% CI, −22 to 9%) and −10% (95% CI, −28% to 12%) change in UACR, respectively. Overall, UACR change after 8 weeks was −36% (95% CI, −46% to −24%). After 8 weeks, systolic blood pressure and mGFR were reduced by 10 mmHg (95% CI, 6–13 mmHg) and 7 mL/min/1,73 m2 (95% CI, 5–8 mL/min/1,73 m2). Adverse effects were minimal. Conclusions The combination of finerenone and dapagliflozin was safe and significantly reduced albuminuria. The effect of combination therapy was at least equal to the calculated, combined effect of each of the drugs, suggesting an additive effect on albuminuria. Larger studies assessing long-term effects and safety are warranted.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135718683","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}
Alexandre Persu, Maria S Stoenoiu, Frédéric Maes, Reinhold Kreutz, Giuseppe Mancia, Sverre E Kjeldsen
ABSTRACT Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.
{"title":"Late outcomes of renal denervation are more favorable than early ones. Facts or fancies?","authors":"Alexandre Persu, Maria S Stoenoiu, Frédéric Maes, Reinhold Kreutz, Giuseppe Mancia, Sverre E Kjeldsen","doi":"10.1093/ckj/sfad231","DOIUrl":"https://doi.org/10.1093/ckj/sfad231","url":null,"abstract":"ABSTRACT Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136375733","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}
Anders Nordholm, Ida M H Sørensen, Sasha S Bjergfelt, Andreas Fuchs, Klaus F Kofoed, Nino E Landler, Tor Biering-Sørensen, Nicholas Carlson, Bo Feldt-Rasmussen, Christina Christoffersen, Susanne Bro
Abstract Background Plasma (p-)activin A is elevated in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined if p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality, and CKD-MBD complications in CKD patients. Methods The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with eGFR, coronary, and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance, and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results P-activin A was increased by CKD stage 3 (124 to 225pg/mL, P < 0.001) and correlated inversely with eGFR (r=−0.53, P < 0.01). P-activin A was associated with all-cause mortality (97 events, HR 1.55 [1.04;2.32], P < 0.05) after adjusting for age, sex, diabetes mellitus (DM), and eGFR. Median follow-up was 4.36 (IQR 3.64–4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM, and eGFR. No association with MACE, vascular calcification, or BMD was demonstrated.
背景血浆(p-)激活素A在慢性肾病-矿物质和骨骼疾病(CKD-MBD)中升高。激活素A抑制可改善啮齿动物CKD模型中的CKD- mbd并发症(血管钙化和骨病)。我们研究了p-激活素A是否与CKD患者的主要不良心血管事件(MACE)、全因死亡率和CKD- mbd并发症相关。方法该研究包括916名参与者(741名患者和175名对照)，来自哥本哈根前瞻性CKD队列。p-激活素A与eGFR、冠状动脉和胸主动脉Agatston评分、骨密度(BMD)的比较采用Spearman秩相关单变量线性回归、协方差分析和带调整的有序逻辑回归进行评估。通过aallen - johansen或Kaplan-Meier估计量评估p-活化素A与MACE和全因死亡率的关系，随后进行多重Cox回归分析。结果CKD 3期P活化素A升高(124 ~ 225pg/mL);0.001)，与eGFR呈负相关(r= - 0.53, P <0.01)。P活化素A与全因死亡率相关(97例，HR 1.55 [1.04;2.32]， P <在调整了年龄、性别、糖尿病(DM)和eGFR后，0.05)。中位随访时间为4.36年(IQR为3.64-4.75)。eGFR调整后与MACE的相关性不显著。Agatston评分和BMD与p-激活素A无关。结论p-激活素A随肾功能下降而升高，与年龄、性别、糖尿病和eGFR无关的全因死亡率相关。与MACE、血管钙化或骨密度无关联。
{"title":"Plasma activin a rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease","authors":"Anders Nordholm, Ida M H Sørensen, Sasha S Bjergfelt, Andreas Fuchs, Klaus F Kofoed, Nino E Landler, Tor Biering-Sørensen, Nicholas Carlson, Bo Feldt-Rasmussen, Christina Christoffersen, Susanne Bro","doi":"10.1093/ckj/sfad238","DOIUrl":"https://doi.org/10.1093/ckj/sfad238","url":null,"abstract":"Abstract Background Plasma (p-)activin A is elevated in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined if p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality, and CKD-MBD complications in CKD patients. Methods The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with eGFR, coronary, and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance, and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results P-activin A was increased by CKD stage 3 (124 to 225pg/mL, P &lt; 0.001) and correlated inversely with eGFR (r=−0.53, P &lt; 0.01). P-activin A was associated with all-cause mortality (97 events, HR 1.55 [1.04;2.32], P &lt; 0.05) after adjusting for age, sex, diabetes mellitus (DM), and eGFR. Median follow-up was 4.36 (IQR 3.64–4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM, and eGFR. No association with MACE, vascular calcification, or BMD was demonstrated.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"89 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136376032","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}
Cynthia Ciwei Lim, Crystal Chong, Gavin Tan, Chieh Suai Tan, Carol Y Cheung, Tien Y Wong, Ching Yu Cheng, Charumathi Sabanayagam
ABSTRACT Backgraund Cardiovascular disease (CVD) and mortality is elevated in chronic kidney disease (CKD). Retinal vessel calibre in retinal photographs is associated with cardiovascular risk and automated measurements may aid CVD risk prediction. Methods Retrospective cohort study of 860 Chinese, Malay and Indian participants aged 40–80 years with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] who attended the baseline visit (2004–2011) of the Singapore Epidemiology of Eye Diseases Study. Retinal vessel calibre measurements were obtained by a deep learning system (DLS). Incident CVD [non-fatal acute myocardial infarction (MI) and stroke, and death due to MI, stroke and other CVD] in those who were free of CVD at baseline was ascertained until 31 December 2019. Risk factors (established, kidney, and retinal features) were examined using Cox proportional hazards regression models. Model performance was assessed for discrimination, fit, and net reclassification improvement (NRI). Results Incident CVD occurred in 289 (33.6%) over mean follow-up of 9.3 (4.3) years. After adjusting for established cardiovascular risk factors, eGFR [adjusted HR 0.98 (95% CI: 0.97–0.99)] and retinal arteriolar narrowing [adjusted HR 1.40 (95% CI: 1.17–1.68)], but not venular dilation, were independent predictors for CVD in CKD. The addition of eGFR and retinal features to established cardiovascular risk factors improved model discrimination with significantly better fit and better risk prediction according to the low (<15%), intermediate (15–29.9%), and high (30% or more) risk categories (NRI 5.8%), and with higher risk thresholds (NRI 12.7%). Conclusions Retinal vessel calibre measurements by DLS were significantly associated with incident CVD independent of established CVD risk factors. Addition of kidney function and retinal vessel calibre parameters may improve CVD risk prediction among Asians with CKD.
{"title":"A deep learning system for retinal vessel calibre improves cardiovascular risk prediction in Asians with chronic kidney disease","authors":"Cynthia Ciwei Lim, Crystal Chong, Gavin Tan, Chieh Suai Tan, Carol Y Cheung, Tien Y Wong, Ching Yu Cheng, Charumathi Sabanayagam","doi":"10.1093/ckj/sfad227","DOIUrl":"https://doi.org/10.1093/ckj/sfad227","url":null,"abstract":"ABSTRACT Backgraund Cardiovascular disease (CVD) and mortality is elevated in chronic kidney disease (CKD). Retinal vessel calibre in retinal photographs is associated with cardiovascular risk and automated measurements may aid CVD risk prediction. Methods Retrospective cohort study of 860 Chinese, Malay and Indian participants aged 40–80 years with CKD [estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2] who attended the baseline visit (2004–2011) of the Singapore Epidemiology of Eye Diseases Study. Retinal vessel calibre measurements were obtained by a deep learning system (DLS). Incident CVD [non-fatal acute myocardial infarction (MI) and stroke, and death due to MI, stroke and other CVD] in those who were free of CVD at baseline was ascertained until 31 December 2019. Risk factors (established, kidney, and retinal features) were examined using Cox proportional hazards regression models. Model performance was assessed for discrimination, fit, and net reclassification improvement (NRI). Results Incident CVD occurred in 289 (33.6%) over mean follow-up of 9.3 (4.3) years. After adjusting for established cardiovascular risk factors, eGFR [adjusted HR 0.98 (95% CI: 0.97–0.99)] and retinal arteriolar narrowing [adjusted HR 1.40 (95% CI: 1.17–1.68)], but not venular dilation, were independent predictors for CVD in CKD. The addition of eGFR and retinal features to established cardiovascular risk factors improved model discrimination with significantly better fit and better risk prediction according to the low (&lt;15%), intermediate (15–29.9%), and high (30% or more) risk categories (NRI 5.8%), and with higher risk thresholds (NRI 12.7%). Conclusions Retinal vessel calibre measurements by DLS were significantly associated with incident CVD independent of established CVD risk factors. Addition of kidney function and retinal vessel calibre parameters may improve CVD risk prediction among Asians with CKD.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135063759","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}
Gaye Hafez, Jolanta Malyszko, Aleksandra Golenia, Aleksandra Klimkowicz-Mrowiec, Ana Carina Ferreira, Mustafa Arici, Annette Bruchfeld, Dorothea Nitsch, Ziad A Massy, Marion Pepin, Giovambattista Capasso, Laila-Yasmin Mani, Sophie Liabeuf, Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Sophie Liabeuf, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji (Molla), Giorgos Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pepin, Andrzej Wiecek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian Konig, Ivan Rychlik, Michela Deleidi, George Reusz, Michele Farisco, Norberto Perico, Pedro Imenez Silva, Mickaël Bobot, Aleksandra Golenia, Alessandra Perna, Alma Idrizi, Brian Hansen, Mariadelina Simeoni
ABSTRACT There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood–brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects.
{"title":"Drugs with a negative impact on cognitive functions (Part 2): drug classes to consider while prescribing in CKD patients","authors":"Gaye Hafez, Jolanta Malyszko, Aleksandra Golenia, Aleksandra Klimkowicz-Mrowiec, Ana Carina Ferreira, Mustafa Arici, Annette Bruchfeld, Dorothea Nitsch, Ziad A Massy, Marion Pepin, Giovambattista Capasso, Laila-Yasmin Mani, Sophie Liabeuf, Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Sophie Liabeuf, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji (Molla), Giorgos Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pepin, Andrzej Wiecek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian Konig, Ivan Rychlik, Michela Deleidi, George Reusz, Michele Farisco, Norberto Perico, Pedro Imenez Silva, Mickaël Bobot, Aleksandra Golenia, Alessandra Perna, Alma Idrizi, Brian Hansen, Mariadelina Simeoni","doi":"10.1093/ckj/sfad239","DOIUrl":"https://doi.org/10.1093/ckj/sfad239","url":null,"abstract":"ABSTRACT There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood–brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135109756","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}
Sophie Liabeuf, Vesna Pesic, Goce Spasovski, Romaldas Maciulaitis, Mickaël Bobot, Ana Farinha, Carsten A Wagner, Robert J Unwin, Giovambattista Capasso, Inga Arune Bumblyte, Gaye Hafez, Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Sophie Liabeuf, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji (Molla), Giorgos Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pepin, Andrzej Wiecek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian Konig, Ivan Rychlik, Michela Deleidi, George Reusz, Michele Farisco, Norberto Perico, Pedro Imenez Silva, Mickaël Bobot, Aleksandra Golenia, Alessandra Perna, Alma Idrizi, Brian Hansen, Mariadelina Simeoni
ABSTRACT People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.
{"title":"Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease (CKD) as a risk factor","authors":"Sophie Liabeuf, Vesna Pesic, Goce Spasovski, Romaldas Maciulaitis, Mickaël Bobot, Ana Farinha, Carsten A Wagner, Robert J Unwin, Giovambattista Capasso, Inga Arune Bumblyte, Gaye Hafez, Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Sophie Liabeuf, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji (Molla), Giorgos Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pepin, Andrzej Wiecek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian Konig, Ivan Rychlik, Michela Deleidi, George Reusz, Michele Farisco, Norberto Perico, Pedro Imenez Silva, Mickaël Bobot, Aleksandra Golenia, Alessandra Perna, Alma Idrizi, Brian Hansen, Mariadelina Simeoni","doi":"10.1093/ckj/sfad241","DOIUrl":"https://doi.org/10.1093/ckj/sfad241","url":null,"abstract":"ABSTRACT People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135203039","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}
Julien Marro, Andrew J Chetwynd, Jennifer Hawkes, Sarah J Northey, Louise Oni
ABSTRACT Background IgA vasculitis (IgAV) is the most common form of childhood vasculitis. Nephritis (IgAVN) occurs in 50% of patients and 1–2% progress to chronic kidney disease stage 5. The pathophysiology of nephritis remains largely unknown, but recent evidence suggests that the complement system may be involved. The aim of this cross-sectional study was to explore whether there is evidence of alternative and/or lectin complement pathway activation in children with IgAVN. Methods Children with IgAV were recruited and grouped according to proteinuria: IgAVN or IgAV without nephritis (IgAVwoN). Age and sex-matched healthy controls (HCs) were also recruited. Cross-sectional urine and plasma concentrations of complement factor D (CFD), factor B (CFB), and MBL-associated protease 1 (MASP-1) were performed using commercially available enzyme-linked immunoassays. Results A total of 50 children were included (IgAVN, n = 15; IgAVwoN, n = 20, HCs, n = 15). The mean age was 8.5 ± 3.7 years old, male:female ratio was 1:1. Urinary CFD and CFB concentrations were statistically significantly increased in children with IgAVN (3.5 ± 5.4 μg/mmol; 25.9 ± 26.5 μg/mmol, respectively) compared to both IgAVwoN (0.4 ± 0.4 μg/mmol, P = 0.002; 9.2 ± 11.5 μg/mmol, P = 0.004) and HCs (0.3 ± 0.2 μg/mmol, P < 0.001; 5.1 ± 6.0 μg/mmol, P < 0.001). No statistically significant difference was reported for the plasma concentrations of CFD and CFB. Urinary MASP-1 concentrations were statistically significantly increased in IgAVN (116.9 ± 116.7 ng/mmol) compared to HCs (41.4 ± 56.1 ng/mmol, P = 0.006) and plasma MASP-1 concentrations were increased in IgAVwoN (254.2 ± 23.3 ng/mL) compared to HCs (233.4 ± 6.6 ng/mL, P = 0.046). Conclusion There is evidence of complement pathway products in the urine of children with IgAVN that warrants further investigation.
背景IgA血管炎(IgAV)是儿童血管炎最常见的形式。50%的患者发生肾炎(IgAVN)， 1-2%进展为慢性肾脏疾病第5期。肾炎的病理生理机制在很大程度上仍然未知，但最近的证据表明，补体系统可能参与其中。本横断面研究的目的是探讨IgAVN患儿是否存在替代和/或凝集素补体途径激活的证据。方法招募IgAV患儿，根据蛋白尿情况分为IgAVN型和IgAVwoN型(无肾炎)。还招募了年龄和性别匹配的健康对照(hc)。采用市售的酶联免疫分析法检测补体因子D (CFD)、补体因子B (CFB)和mbl相关蛋白酶1 (MASP-1)的横断面尿液和血浆浓度。结果共纳入50例患儿(IgAVN, n = 15;IgAVwoN, n = 20, hc, n = 15)。平均年龄8.5±3.7岁，男女比例1:1。IgAVN患儿尿CFD和CFB浓度显著升高(3.5±5.4 μg/mmol;25.9±26.5 μg/mmol)，与IgAVwoN(0.4±0.4 μg/mmol, P = 0.002;9.2±11.5 μg/mmol, P = 0.004)和HCs(0.3±0.2 μg/mmol, P <0.001;5.1±6.0 μg/mmol, P &0.001)。CFD和CFB的血浆浓度无统计学差异。IgAVN组尿MASP-1浓度(116.9±116.7 ng/mmol)高于hc组(41.4±56.1 ng/mmol, P = 0.006)， IgAVwoN组血浆MASP-1浓度(254.2±23.3 ng/mL)高于hc组(233.4±6.6 ng/mL, P = 0.046)。结论IgAVN患儿尿液中存在补体途径产物，值得进一步研究。
{"title":"Urinary markers of the alternative and lectin complement pathway are increased in IgA vasculitis nephritis","authors":"Julien Marro, Andrew J Chetwynd, Jennifer Hawkes, Sarah J Northey, Louise Oni","doi":"10.1093/ckj/sfad236","DOIUrl":"https://doi.org/10.1093/ckj/sfad236","url":null,"abstract":"ABSTRACT Background IgA vasculitis (IgAV) is the most common form of childhood vasculitis. Nephritis (IgAVN) occurs in 50% of patients and 1–2% progress to chronic kidney disease stage 5. The pathophysiology of nephritis remains largely unknown, but recent evidence suggests that the complement system may be involved. The aim of this cross-sectional study was to explore whether there is evidence of alternative and/or lectin complement pathway activation in children with IgAVN. Methods Children with IgAV were recruited and grouped according to proteinuria: IgAVN or IgAV without nephritis (IgAVwoN). Age and sex-matched healthy controls (HCs) were also recruited. Cross-sectional urine and plasma concentrations of complement factor D (CFD), factor B (CFB), and MBL-associated protease 1 (MASP-1) were performed using commercially available enzyme-linked immunoassays. Results A total of 50 children were included (IgAVN, n = 15; IgAVwoN, n = 20, HCs, n = 15). The mean age was 8.5 ± 3.7 years old, male:female ratio was 1:1. Urinary CFD and CFB concentrations were statistically significantly increased in children with IgAVN (3.5 ± 5.4 μg/mmol; 25.9 ± 26.5 μg/mmol, respectively) compared to both IgAVwoN (0.4 ± 0.4 μg/mmol, P = 0.002; 9.2 ± 11.5 μg/mmol, P = 0.004) and HCs (0.3 ± 0.2 μg/mmol, P &lt; 0.001; 5.1 ± 6.0 μg/mmol, P &lt; 0.001). No statistically significant difference was reported for the plasma concentrations of CFD and CFB. Urinary MASP-1 concentrations were statistically significantly increased in IgAVN (116.9 ± 116.7 ng/mmol) compared to HCs (41.4 ± 56.1 ng/mmol, P = 0.006) and plasma MASP-1 concentrations were increased in IgAVwoN (254.2 ± 23.3 ng/mL) compared to HCs (233.4 ± 6.6 ng/mL, P = 0.046). Conclusion There is evidence of complement pathway products in the urine of children with IgAVN that warrants further investigation.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135552840","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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