Background Idiopathic Nephrotic Syndrome (NS) in children poses treatment challenges, with a subset developing Steroid-Resistant Nephrotic Syndrome (SRNS). Genetic factors play a role, yet data on pediatric SRNS genetics in India are scarce. We conducted a prospective study utilising whole-exome sequencing to explore genetic variants and their clinical correlations. Methods A single-centre prospective study (October 2018–April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. Results A total of 680 pediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.56%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed FSGS in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. Conclusion The study underscores the importance of genetic analysis in pediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasise the value of personalised approaches and further research in managing pediatric SRNS.
{"title":"Novel mutation patterns in children with steroid-resistant nephrotic syndrome","authors":"Narayan Prasad, Jeyakumar Meyyappan, Manoj Dhanorkar, Ravi Kushwaha, Kaushik Mandal, Vamsidhar Veeranki, Manas Behera, Manas Patel, Brijesh Yadav, Dharmendra Bhadauria, Anupama Kaul, Monika Yaccha, Mansi Bhatta, Vinita Agarwal, Monoj Jain","doi":"10.1093/ckj/sfae218","DOIUrl":"https://doi.org/10.1093/ckj/sfae218","url":null,"abstract":"Background Idiopathic Nephrotic Syndrome (NS) in children poses treatment challenges, with a subset developing Steroid-Resistant Nephrotic Syndrome (SRNS). Genetic factors play a role, yet data on pediatric SRNS genetics in India are scarce. We conducted a prospective study utilising whole-exome sequencing to explore genetic variants and their clinical correlations. Methods A single-centre prospective study (October 2018–April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. Results A total of 680 pediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.56%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed FSGS in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. Conclusion The study underscores the importance of genetic analysis in pediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasise the value of personalised approaches and further research in managing pediatric SRNS.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"353 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jet Milders, Chava L Ramspek, Yvette Meuleman, Willem Jan W Bos, Wieneke M Michels, Wanda S Konijn, Friedo W Dekker, Merel van Diepen
Background Prognostic uncertainty is a recurring theme among patients with chronic kidney disease (CKD). We developed a survey to explore whether CKD patients want to know more about their future, and if so, which topics they prioritize. In addition, we explored differences between several subgroups. Methods A survey was constructed and tested in collaboration with the Dutch Kidney Patients Association. The survey consisted of three parts: 1) demographics, 2) considerations about the future, and 3) prognostic information. The survey was distributed amongst CKD patients (all stages) through patient associations and via healthcare professionals in two Dutch hospitals. Descriptive statistics were used to summarize the results. All results were stratified by population, sex and age. Results A total of 163 patients (45 CKD, 26 dialysis and 92 kidney transplantation) participated in the survey. The mean age was 63.9 (SD 12.0) and 48.5% was male. Most patients think about their future with CKD occasionally (56.4%) or often (35.0%). Nearly half of the patients (49.7%) discuss the future with their nephrologist, some (19.6%) do not but would like to, and 20 (15.3%) prefer not to. Most patients (73.6%) want more prognostic information, regardless of it being positive or negative. Key topics to receive prognostic information about were laboratory values, symptoms, and physical well-being. Dialysis patients prioritized mental over physical well-being. CKD patients without KRT indicated thinking about, and discussing their future more regularly than KRT patients. Conclusions Patients with CKD contemplate their future regularly and express interest in receiving prognostic information on a variety of topics. One in five patients currently do not discuss their future with CKD with their nephrologist, despite wanting to do so. These findings underline the need to tailor prognostic information provision to patients’ preferences, advocating more attention to this subject both in research and clinical practice.
{"title":"Dealing with an uncertain future: a survey study on what patients with chronic kidney disease actually want to know","authors":"Jet Milders, Chava L Ramspek, Yvette Meuleman, Willem Jan W Bos, Wieneke M Michels, Wanda S Konijn, Friedo W Dekker, Merel van Diepen","doi":"10.1093/ckj/sfae225","DOIUrl":"https://doi.org/10.1093/ckj/sfae225","url":null,"abstract":"Background Prognostic uncertainty is a recurring theme among patients with chronic kidney disease (CKD). We developed a survey to explore whether CKD patients want to know more about their future, and if so, which topics they prioritize. In addition, we explored differences between several subgroups. Methods A survey was constructed and tested in collaboration with the Dutch Kidney Patients Association. The survey consisted of three parts: 1) demographics, 2) considerations about the future, and 3) prognostic information. The survey was distributed amongst CKD patients (all stages) through patient associations and via healthcare professionals in two Dutch hospitals. Descriptive statistics were used to summarize the results. All results were stratified by population, sex and age. Results A total of 163 patients (45 CKD, 26 dialysis and 92 kidney transplantation) participated in the survey. The mean age was 63.9 (SD 12.0) and 48.5% was male. Most patients think about their future with CKD occasionally (56.4%) or often (35.0%). Nearly half of the patients (49.7%) discuss the future with their nephrologist, some (19.6%) do not but would like to, and 20 (15.3%) prefer not to. Most patients (73.6%) want more prognostic information, regardless of it being positive or negative. Key topics to receive prognostic information about were laboratory values, symptoms, and physical well-being. Dialysis patients prioritized mental over physical well-being. CKD patients without KRT indicated thinking about, and discussing their future more regularly than KRT patients. Conclusions Patients with CKD contemplate their future regularly and express interest in receiving prognostic information on a variety of topics. One in five patients currently do not discuss their future with CKD with their nephrologist, despite wanting to do so. These findings underline the need to tailor prognostic information provision to patients’ preferences, advocating more attention to this subject both in research and clinical practice.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"63 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141741851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vincent Dupont, Constance Xhaard, Isabelle Behm-Ansmant, Emmanuel Bresso, Quentin Thuillier, Christiane Branlant, Marilucy Lopez-Sublet, Jean-François Deleuze, Faiez Zannad, Nicolas Girerd, Patrick Rossignol
Background Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving the patients’ management. Methods Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal STANISLAS cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of more than 15 mL/min/1.7m2) ways. We analyzed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119 765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. Bonferroni correction was applied. Results We found several proteins (including PLC, PGF, members of the tumor necrosis factor receptor superfamily), genes (including CCL18, SESN3) and a newly discovered miRNA—mRNA pair (MIR1205–DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodeling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease. Conclusions These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment.
{"title":"Multiomic profiling of new-onset kidney function decline: insights from the STANISLAS study cohort with a 20-year follow-up","authors":"Vincent Dupont, Constance Xhaard, Isabelle Behm-Ansmant, Emmanuel Bresso, Quentin Thuillier, Christiane Branlant, Marilucy Lopez-Sublet, Jean-François Deleuze, Faiez Zannad, Nicolas Girerd, Patrick Rossignol","doi":"10.1093/ckj/sfae224","DOIUrl":"https://doi.org/10.1093/ckj/sfae224","url":null,"abstract":"Background Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving the patients’ management. Methods Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal STANISLAS cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of more than 15 mL/min/1.7m2) ways. We analyzed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119 765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. Bonferroni correction was applied. Results We found several proteins (including PLC, PGF, members of the tumor necrosis factor receptor superfamily), genes (including CCL18, SESN3) and a newly discovered miRNA—mRNA pair (MIR1205–DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodeling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease. Conclusions These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"160 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wing-Chi G Yeung, Nigel D Toussaint, Sunil V Badve
In people with chronic kidney disease (CKD), physiology of vitamin D is altered and leads to abnormalities in bone and mineral metabolism which contribute to CKD Mineral and Bone Disorder (CKD-MBD). Observational studies show an association between vitamin D deficiency and increased risk of mortality, cardiovascular disease and fracture in CKD. Although vitamin D therapy is widely prescribed in people with CKD, clinical trials to date have failed to demonstrate a clear benefit of either nutritional vitamin D supplementation or active vitamin D therapy in improving clinical outcomes in CKD. This review provides an updated critical analysis of recent trial evidence on vitamin D therapy in people with CKD.
慢性肾脏病（CKD）患者体内维生素 D 的生理功能发生改变，导致骨骼和矿物质代谢异常，从而引发慢性肾脏病矿物质和骨骼紊乱（CKD-MBD）。观察性研究表明，维生素 D 缺乏与 CKD 患者死亡、心血管疾病和骨折风险增加之间存在关联。虽然维生素 D 治疗被广泛用于 CKD 患者，但迄今为止的临床试验未能证明营养性维生素 D 补充剂或活性维生素 D 治疗对改善 CKD 的临床疗效有明显的益处。本综述对近期有关 CKD 患者维生素 D 治疗的试验证据进行了最新的批判性分析。
{"title":"Vitamin D therapy in chronic kidney disease: a critical appraisal of clinical trial evidence","authors":"Wing-Chi G Yeung, Nigel D Toussaint, Sunil V Badve","doi":"10.1093/ckj/sfae227","DOIUrl":"https://doi.org/10.1093/ckj/sfae227","url":null,"abstract":"In people with chronic kidney disease (CKD), physiology of vitamin D is altered and leads to abnormalities in bone and mineral metabolism which contribute to CKD Mineral and Bone Disorder (CKD-MBD). Observational studies show an association between vitamin D deficiency and increased risk of mortality, cardiovascular disease and fracture in CKD. Although vitamin D therapy is widely prescribed in people with CKD, clinical trials to date have failed to demonstrate a clear benefit of either nutritional vitamin D supplementation or active vitamin D therapy in improving clinical outcomes in CKD. This review provides an updated critical analysis of recent trial evidence on vitamin D therapy in people with CKD.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"1 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carmine Zoccali, Giovanni Tripepi, Vianda Stel, Eduard L Fu, Francesca Mallamaci, Friedo Dekker, Kitty J Jager
Soluble Decoy receptors (DR) are circulating proteins that act as molecular traps for ligands that modulate various signalling pathways. These proteins can be exploited as biomarkers and, in some cases, as drugs in various disease contexts. Inflammation is a key area where DRs have shown significant potential. By binding to pro-inflammatory cytokines, inflammatory DRs, like soluble tumour necrosis factor receptors (sTNFRs), can inhibit downstream inflammatory signalling. This modulation of the inflammatory response holds promise for therapeutic interventions in various inflammatory conditions, including cardiovascular and chronic kidney diseases. Soluble DRs for advanced glycation end products (sRAGE) bind to advanced glycation end products (AGEs), reducing their detrimental effects on vascular function and atherosclerosis. High circulating sRAGE levels are associated with a lower risk for CV events, highlighting the potential of these soluble receptors for assessing the role of AGEs in CV diseases and managing the attendant risk. DRs may serve as biomarkers and therapeutic agents to advance our understanding of disease mechanisms and improve patients' outcomes. Their ability to modulate signalling pathways in a controlled manner opens new opportunities for therapeutic interventions in various diseases, ranging from inflammation to cardiovascular and renal disorders.
{"title":"Decoy receptors as biomarkers for exploring aetiology and designing new therapies","authors":"Carmine Zoccali, Giovanni Tripepi, Vianda Stel, Eduard L Fu, Francesca Mallamaci, Friedo Dekker, Kitty J Jager","doi":"10.1093/ckj/sfae222","DOIUrl":"https://doi.org/10.1093/ckj/sfae222","url":null,"abstract":"Soluble Decoy receptors (DR) are circulating proteins that act as molecular traps for ligands that modulate various signalling pathways. These proteins can be exploited as biomarkers and, in some cases, as drugs in various disease contexts. Inflammation is a key area where DRs have shown significant potential. By binding to pro-inflammatory cytokines, inflammatory DRs, like soluble tumour necrosis factor receptors (sTNFRs), can inhibit downstream inflammatory signalling. This modulation of the inflammatory response holds promise for therapeutic interventions in various inflammatory conditions, including cardiovascular and chronic kidney diseases. Soluble DRs for advanced glycation end products (sRAGE) bind to advanced glycation end products (AGEs), reducing their detrimental effects on vascular function and atherosclerosis. High circulating sRAGE levels are associated with a lower risk for CV events, highlighting the potential of these soluble receptors for assessing the role of AGEs in CV diseases and managing the attendant risk. DRs may serve as biomarkers and therapeutic agents to advance our understanding of disease mechanisms and improve patients' outcomes. Their ability to modulate signalling pathways in a controlled manner opens new opportunities for therapeutic interventions in various diseases, ranging from inflammation to cardiovascular and renal disorders.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"84 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maxime Ingwiller, Nicolas Keller, Thierry Krummel, Eric Prinz, Lydie Steinmetz, Thierry Hannedouche, Nans Florens
Background Establishing the optimal timing for creating vascular access in patients with chronic kidney disease (CKD) is a critical and challenging aspect of patient management. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines propose using a 40% 2-year threshold based on the Kidney Failure Risk Equation (KFRE) for this purpose. However, the effectiveness of this threshold compared to traditional methods, such as estimated Glomerular Filtration Rate (eGFR), is not well-established. Methods In this monocentric retrospective cohort study, we analyzed data from patients referred for vascular mapping before arteriovenous fistula (AVF) creation between April 2013 and June 2023. The study aimed to compare the ≥ 40% 2-year KFRE threshold with a <15 mL/min/m²73 eGFR threshold for predicting End Stage Kidney Disease (ESKD). We assessed the probability of ESKD, considering death before AVF creation as a competing risk. Discrimination between KFRE and eGFR was evaluated using C-statistics. Results The study included 238 patients with a mean age of 65.2 years and a mean eGFR of 13.3 mL/min/m²73. Over a median follow-up of 10.7 months, 178 patients developed ESKD, and 21 died before ESKD. Probability of ESKD at 1 year was 77.6% (95% CI, 69.9-85.3%) using a ≥ 40% 4 variables KFRE threshold versus 65.8% (95% CI, 58.3-73.3%) using a <15 mL/min/m²73 eGFR threshold. The C-statistics indicated better predictive ability for the 8-variable KFRE at 6 months (0.82 (95% CI: 0.76-0.88)),while both 4 and 8-variable KFRE models were effective for 1-year predictions (0.835 (95% CI :0.78-0.89) and 0.82 (95% CI : 0.76-0.875) respectively). Sensitivity and specificity analyses favored the ≥ 40% KFRE threshold over the eGFR threshold. Conclusions This study suggests that using a ≥ 40% 2-year KFRE threshold for planning vascular access in CKD patients is promising and potentially superior to the traditional <15 mL/min/m²73 eGFR threshold. This approach may offer a balance between minimizing premature AVF creation and the risk of starting dialysis via a central venous catheter.
{"title":"Enhancing Vascular Access Planning in CKD: Validating the 40% KFRE Threshold for predicting ESKD in a French Retrospective Cohort Study","authors":"Maxime Ingwiller, Nicolas Keller, Thierry Krummel, Eric Prinz, Lydie Steinmetz, Thierry Hannedouche, Nans Florens","doi":"10.1093/ckj/sfae220","DOIUrl":"https://doi.org/10.1093/ckj/sfae220","url":null,"abstract":"Background Establishing the optimal timing for creating vascular access in patients with chronic kidney disease (CKD) is a critical and challenging aspect of patient management. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines propose using a 40% 2-year threshold based on the Kidney Failure Risk Equation (KFRE) for this purpose. However, the effectiveness of this threshold compared to traditional methods, such as estimated Glomerular Filtration Rate (eGFR), is not well-established. Methods In this monocentric retrospective cohort study, we analyzed data from patients referred for vascular mapping before arteriovenous fistula (AVF) creation between April 2013 and June 2023. The study aimed to compare the ≥ 40% 2-year KFRE threshold with a &lt;15 mL/min/m²73 eGFR threshold for predicting End Stage Kidney Disease (ESKD). We assessed the probability of ESKD, considering death before AVF creation as a competing risk. Discrimination between KFRE and eGFR was evaluated using C-statistics. Results The study included 238 patients with a mean age of 65.2 years and a mean eGFR of 13.3 mL/min/m²73. Over a median follow-up of 10.7 months, 178 patients developed ESKD, and 21 died before ESKD. Probability of ESKD at 1 year was 77.6% (95% CI, 69.9-85.3%) using a ≥ 40% 4 variables KFRE threshold versus 65.8% (95% CI, 58.3-73.3%) using a &lt;15 mL/min/m²73 eGFR threshold. The C-statistics indicated better predictive ability for the 8-variable KFRE at 6 months (0.82 (95% CI: 0.76-0.88)),while both 4 and 8-variable KFRE models were effective for 1-year predictions (0.835 (95% CI :0.78-0.89) and 0.82 (95% CI : 0.76-0.875) respectively). Sensitivity and specificity analyses favored the ≥ 40% KFRE threshold over the eGFR threshold. Conclusions This study suggests that using a ≥ 40% 2-year KFRE threshold for planning vascular access in CKD patients is promising and potentially superior to the traditional &lt;15 mL/min/m²73 eGFR threshold. This approach may offer a balance between minimizing premature AVF creation and the risk of starting dialysis via a central venous catheter.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"43 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zijin Chen, Lin-lin Xu, Wen Du, Yan Ouyang, Xiangchen Gu, Zhengying Fang, Xialian Yu, Junru Li, Lin Xie, Yuanmeng Jin, Jun Ma, Zhaohui Wang, Xiaoxia Pan, Wen Zhang, Hong Ren, Weiming Wang, Xiaonong Chen, Xu-jie Zhou, Hong Zhang, Nan Chen, Jingyuan Xie
Background This study investigates the link between genetic variants associated with kidney function and IgA nephropathy (IgAN) progression. Methods We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. The clinical and renal pathological data were collected. The primary outcome was the time for ESRD. A healthy population was defined as eGFR > 60 ml/min/1.73m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical, pathologic indices, and treatment (adjusted Hazard Ratio, 2.10; 95% CI, 1.14 to 3.88). No significant differences in ESRD-free survival time among different genotypes in non-IgAN ESRD patients (log-rank, p = 0.480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (p = 0.009) was associated with faster IgAN progression. Conclusion The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.
{"title":"Uromodulin and Progression of IgA Nephropathy","authors":"Zijin Chen, Lin-lin Xu, Wen Du, Yan Ouyang, Xiangchen Gu, Zhengying Fang, Xialian Yu, Junru Li, Lin Xie, Yuanmeng Jin, Jun Ma, Zhaohui Wang, Xiaoxia Pan, Wen Zhang, Hong Ren, Weiming Wang, Xiaonong Chen, Xu-jie Zhou, Hong Zhang, Nan Chen, Jingyuan Xie","doi":"10.1093/ckj/sfae209","DOIUrl":"https://doi.org/10.1093/ckj/sfae209","url":null,"abstract":"Background This study investigates the link between genetic variants associated with kidney function and IgA nephropathy (IgAN) progression. Methods We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. The clinical and renal pathological data were collected. The primary outcome was the time for ESRD. A healthy population was defined as eGFR &gt; 60 ml/min/1.73m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical, pathologic indices, and treatment (adjusted Hazard Ratio, 2.10; 95% CI, 1.14 to 3.88). No significant differences in ESRD-free survival time among different genotypes in non-IgAN ESRD patients (log-rank, p = 0.480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (p = 0.009) was associated with faster IgAN progression. Conclusion The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"45 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141719224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Peyronel, Giovanni M Rossi, Giulia Palazzini, Ludovica Odone, Carmela Errichiello, Giacomo Emmi, Augusto Vaglio
Early-onset systemic lupus erythematous (SLE) is a distinct clinical entity characterised by the onset of disease manifestations during childhood. Despite some similarities with patients who are diagnosed during adulthood, early-onset SLE typically displays a greater disease severity, with aggressive multiorgan involvement, lower responsiveness to classical therapies, and more frequent flares. Lupus nephritis (LN) is one of the most severe complications of SLE and represents a major risk factor for long-term morbidity and mortality, especially in children. This review focuses on the clinical and histological aspects of early-onset LN, aiming at highlighting relevant differences with adult patients, emphasizing long-term outcomes and discussing the management of long-term complications. We also discuss monogenic lupus, a spectrum of conditions caused by single gene variants affecting the complement cascade, extracellular and intracellular nucleic acid sensing and processing, and occasionally other metabolic pathways. These monogenic forms typically develop early in life and often have clinical manifestations that resemble sporadic SLE, whereas their response to standard treatments is poor.
{"title":"Early-Onset Lupus Nephritis","authors":"Francesco Peyronel, Giovanni M Rossi, Giulia Palazzini, Ludovica Odone, Carmela Errichiello, Giacomo Emmi, Augusto Vaglio","doi":"10.1093/ckj/sfae212","DOIUrl":"https://doi.org/10.1093/ckj/sfae212","url":null,"abstract":"Early-onset systemic lupus erythematous (SLE) is a distinct clinical entity characterised by the onset of disease manifestations during childhood. Despite some similarities with patients who are diagnosed during adulthood, early-onset SLE typically displays a greater disease severity, with aggressive multiorgan involvement, lower responsiveness to classical therapies, and more frequent flares. Lupus nephritis (LN) is one of the most severe complications of SLE and represents a major risk factor for long-term morbidity and mortality, especially in children. This review focuses on the clinical and histological aspects of early-onset LN, aiming at highlighting relevant differences with adult patients, emphasizing long-term outcomes and discussing the management of long-term complications. We also discuss monogenic lupus, a spectrum of conditions caused by single gene variants affecting the complement cascade, extracellular and intracellular nucleic acid sensing and processing, and occasionally other metabolic pathways. These monogenic forms typically develop early in life and often have clinical manifestations that resemble sporadic SLE, whereas their response to standard treatments is poor.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"29 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141614400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Møller, Iain Bressendorff, Rikke Borg, Hans Dieperink, Jon W Gregersen, Helle Hansen, Kristine Hommel, Mads Hornum, Per Ivarsen, Karina H Jensen, Morten B Jørgensen, Tilde Kristensen, Dorrit Krustrup, Frank H Mose, Peter Rossing, Kjeld E Otte, Frederik Persson, Kristine D Schandorff, Ditte Hansen
Introduction This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments, and prognosis of kidney diseases. Methods Kidney biopsy reports from January 1st, 1998, to December 31st, 2018, were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen's kappa coefficient (κ) for the retrieved SNOMED codes were calculated. Results A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n = 368), tubulointerstitial disease (n = 67), renal vascular disease (n = 51), diabetic nephropathy (n = 51), and various renal disorders (n = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%), and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%), and other renal disorders (17%) showed lower PPVs. Conclusion and perspective SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy, and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research.
{"title":"The validity of pathology codes for biopsy-confirmed kidney disease in the Danish National Patobank","authors":"Marie Møller, Iain Bressendorff, Rikke Borg, Hans Dieperink, Jon W Gregersen, Helle Hansen, Kristine Hommel, Mads Hornum, Per Ivarsen, Karina H Jensen, Morten B Jørgensen, Tilde Kristensen, Dorrit Krustrup, Frank H Mose, Peter Rossing, Kjeld E Otte, Frederik Persson, Kristine D Schandorff, Ditte Hansen","doi":"10.1093/ckj/sfae203","DOIUrl":"https://doi.org/10.1093/ckj/sfae203","url":null,"abstract":"Introduction This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments, and prognosis of kidney diseases. Methods Kidney biopsy reports from January 1st, 1998, to December 31st, 2018, were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen's kappa coefficient (κ) for the retrieved SNOMED codes were calculated. Results A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n = 368), tubulointerstitial disease (n = 67), renal vascular disease (n = 51), diabetic nephropathy (n = 51), and various renal disorders (n = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%), and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%), and other renal disorders (17%) showed lower PPVs. Conclusion and perspective SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy, and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"55 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141587371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10eCollection Date: 2024-08-01DOI: 10.1093/ckj/sfae215
Firas F Alkaff, Rosa G M Lammerts, Mohamed R Daha, Stefan P Berger, Jacob van den Born
Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function.
{"title":"Apical tubular complement activation and the loss of kidney function in proteinuric kidney diseases.","authors":"Firas F Alkaff, Rosa G M Lammerts, Mohamed R Daha, Stefan P Berger, Jacob van den Born","doi":"10.1093/ckj/sfae215","DOIUrl":"10.1093/ckj/sfae215","url":null,"abstract":"<p><p>Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function.</p>","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"17 8","pages":"sfae215"},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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