NDT Plus最新文献

{"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 < .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.","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}

{"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}

{"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}

{"title":"Podocyte puzzles: IgA nephropathy","authors":"Joyita Bharati, Kiran Munir, Kenar D Jhaveri","doi":"10.1093/ckj/sfad244","DOIUrl":"https://doi.org/10.1093/ckj/sfad244","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"116 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061777","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}

{"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}

{"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 < 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.","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}

{"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) <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.","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}

{"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}

{"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}

{"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 < 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.","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}