Pub Date : 2024-07-24DOI: 10.1053/j.ajkd.2024.05.014
Stefano Volpi, Maria L Angelotti, Giulia Palazzini, Giulia Antonelli, Fiammetta Ravaglia, Federica Garibotto, Anna Agrusti, Alice Grossi, Alberto Magnasco, Giovanni M Rossi, Carmela Errichiello, Francesco Peyronel, Elisa Buti, Lorenzo Lodi, Gian M Ghiggeri, Paola Romagnani, Augusto Vaglio
DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 variants impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 variants is poorly characterized. Herein, we describe the clinical course of 3 children with monogenic SLE due to DNASE1L3 variants who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (ie, membranous, endocapillary, and extracapillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN-I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. Two of the patients had increased expression of interferon-stimulated genes in the peripheral blood, and all 3 patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN-I-mediated kidney disorders and provide the rationale for IFN-I-directed therapies in order to improve the poor outcome of this rare condition.
DNASE1L3 是一种细胞外核酸酶，可消化凋亡细胞释放的染色质。DNASE1L3 基因突变会损害酶的功能，增强自身抗体的产生和 I 型干扰素（IFN-I）的反应，并导致不同的常染色体隐性遗传表型，从低补体荨麻疹性血管炎综合征到全面的系统性红斑狼疮（SLE）。DNASE1L3基因突变患者的肾脏受累情况尚不明确。在此，我们描述了三名因 DNASE1L3 基因突变而患单基因系统性红斑狼疮的儿童的临床病程，他们患上了难治性肾小球肾炎，导致肾衰竭。他们的肾脏组织病理形态各异（即膜性、毛细血管内和毛细血管外肾小球肾炎以及血栓性微血管病），均属于狼疮肾炎（LN）谱系。一名患者的表型为混合型，显示出系统性红斑狼疮和ANCA相关性血管炎的重叠。通过免疫荧光技术，我们检测到了 IFN I 诱导的人类肌瘤病毒抗性蛋白 1（MXA）在肾小球中的表达，这种表达在肾小球内皮细胞中尤为明显。2/3的患者外周血中干扰素刺激基因的表达增加，所有三名患者的血清DNA酶活性都降低了。我们的研究结果表明，DNASE1L3相关肾小球肾炎可被纳入IFN I介导的肾脏疾病谱，并为IFN I导向疗法提供了理论依据，以改善这种罕见疾病的不良预后。
{"title":"Lupus Nephritis Patterns and Response to Type I Interferon in Patients With DNASE1L3 Variants: Report of Three Cases.","authors":"Stefano Volpi, Maria L Angelotti, Giulia Palazzini, Giulia Antonelli, Fiammetta Ravaglia, Federica Garibotto, Anna Agrusti, Alice Grossi, Alberto Magnasco, Giovanni M Rossi, Carmela Errichiello, Francesco Peyronel, Elisa Buti, Lorenzo Lodi, Gian M Ghiggeri, Paola Romagnani, Augusto Vaglio","doi":"10.1053/j.ajkd.2024.05.014","DOIUrl":"10.1053/j.ajkd.2024.05.014","url":null,"abstract":"<p><p>DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 variants impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 variants is poorly characterized. Herein, we describe the clinical course of 3 children with monogenic SLE due to DNASE1L3 variants who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (ie, membranous, endocapillary, and extracapillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN-I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. Two of the patients had increased expression of interferon-stimulated genes in the peripheral blood, and all 3 patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN-I-mediated kidney disorders and provide the rationale for IFN-I-directed therapies in order to improve the poor outcome of this rare condition.</p>","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1053/j.ajkd.2024.05.007
Michael K Sullivan, Jennifer S Lees, Brenda M Rosales, Rachel Cutting, Melanie L Wyld, Mark Woodward, Angela C Webster, Patrick B Mark, Nicole De La Mata
<p><strong>Rationale & objective: </strong>Females have a higher prevalence of chronic kidney disease (CKD) than males but are less likely to be treated with kidney replacement therapy (KRT). We studied the interaction between sex and the association of cardiometabolic risk factors for the decline in kidney function over time.</p><p><strong>Study design: </strong>A population-based cohort study.</p><p><strong>Setting & participants: </strong>1,127,731 adults living in Wales, United Kingdom, within the Secure Anonymised Information Linkage Databank.</p><p><strong>Exposure: </strong>Sex and risk factors including age, estimated glomerular filtration rate (eGFR), cardiometabolic conditions, smoking, and socioeconomic deprivation. These risk factors were defined using primary care records.</p><p><strong>Outcome: </strong>The yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR<15mL/min/1.73m<sup>2</sup>.</p><p><strong>Analytical approach: </strong>Linear mixed effects models and Cox proportional hazards analysis.</p><p><strong>Results: </strong>The average decline in eGFR at age≤73 years was equal in males and females. After age 73 years, eGFR decline was faster in males than females, particularly for males with heart failure (males-1.22mL/min/1.73m<sup>2</sup> per year [95% CI, -1.25 to-1.20] vs females-0.87mL/min/1.73m<sup>2</sup> per year [95% CI, -0.89 to-0.85]) and current smokers (males-1.58mL/min/1.73m<sup>2</sup> per year [95% CI, -1.60 to-1.55] vs females-1.27mL/min/1.73m<sup>2</sup> per year [95% CI, -1.29 to-1.25]). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females aged>73 years, whereas cardiometabolic risk factors were more important among males. Older females at baseline were less likely to develop incident kidney failure than older males (P for age<0.001).</p><p><strong>Limitations: </strong>Study of people who were almost exclusively White and who had blood laboratory test data. Reliance on creatinine-based eGFR. Albuminuria and body mass index data were incomplete.</p><p><strong>Conclusions: </strong>The eGFR decline was faster in males than in females, especially in the setting of heart failure and smoking. Socioeconomic deprivation was an important risk factor associated with eGFR decline, particularly for females. further work is required to explore less well-recognized risk factors, but these findings may inform clinical management strategies of CKD overall and within sex-specific groups.</p><p><strong>Plain-language summary: </strong>Kidney function is known to decline at a faster rate among males than females. This study incorporated blood laboratory test results from the routine care of 1.1 million adults living in the United Kingdom and found that the decline in kidney function associated with risk factors varied by sex. Before and at the age of 73 years, the decline in kidney function was similar between males and femal
{"title":"Sex and the Relationship Between Cardiometabolic Risk Factors and Estimated GFR Decline: A Population-Based Cohort Study.","authors":"Michael K Sullivan, Jennifer S Lees, Brenda M Rosales, Rachel Cutting, Melanie L Wyld, Mark Woodward, Angela C Webster, Patrick B Mark, Nicole De La Mata","doi":"10.1053/j.ajkd.2024.05.007","DOIUrl":"10.1053/j.ajkd.2024.05.007","url":null,"abstract":"<p><strong>Rationale & objective: </strong>Females have a higher prevalence of chronic kidney disease (CKD) than males but are less likely to be treated with kidney replacement therapy (KRT). We studied the interaction between sex and the association of cardiometabolic risk factors for the decline in kidney function over time.</p><p><strong>Study design: </strong>A population-based cohort study.</p><p><strong>Setting & participants: </strong>1,127,731 adults living in Wales, United Kingdom, within the Secure Anonymised Information Linkage Databank.</p><p><strong>Exposure: </strong>Sex and risk factors including age, estimated glomerular filtration rate (eGFR), cardiometabolic conditions, smoking, and socioeconomic deprivation. These risk factors were defined using primary care records.</p><p><strong>Outcome: </strong>The yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR<15mL/min/1.73m<sup>2</sup>.</p><p><strong>Analytical approach: </strong>Linear mixed effects models and Cox proportional hazards analysis.</p><p><strong>Results: </strong>The average decline in eGFR at age≤73 years was equal in males and females. After age 73 years, eGFR decline was faster in males than females, particularly for males with heart failure (males-1.22mL/min/1.73m<sup>2</sup> per year [95% CI, -1.25 to-1.20] vs females-0.87mL/min/1.73m<sup>2</sup> per year [95% CI, -0.89 to-0.85]) and current smokers (males-1.58mL/min/1.73m<sup>2</sup> per year [95% CI, -1.60 to-1.55] vs females-1.27mL/min/1.73m<sup>2</sup> per year [95% CI, -1.29 to-1.25]). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females aged>73 years, whereas cardiometabolic risk factors were more important among males. Older females at baseline were less likely to develop incident kidney failure than older males (P for age<0.001).</p><p><strong>Limitations: </strong>Study of people who were almost exclusively White and who had blood laboratory test data. Reliance on creatinine-based eGFR. Albuminuria and body mass index data were incomplete.</p><p><strong>Conclusions: </strong>The eGFR decline was faster in males than in females, especially in the setting of heart failure and smoking. Socioeconomic deprivation was an important risk factor associated with eGFR decline, particularly for females. further work is required to explore less well-recognized risk factors, but these findings may inform clinical management strategies of CKD overall and within sex-specific groups.</p><p><strong>Plain-language summary: </strong>Kidney function is known to decline at a faster rate among males than females. This study incorporated blood laboratory test results from the routine care of 1.1 million adults living in the United Kingdom and found that the decline in kidney function associated with risk factors varied by sex. Before and at the age of 73 years, the decline in kidney function was similar between males and femal","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1053/j.ajkd.2024.06.003
{"title":"New Insights into Vitamin D Metabolism in Kidney Disease and Transplant","authors":"","doi":"10.1053/j.ajkd.2024.06.003","DOIUrl":"10.1053/j.ajkd.2024.06.003","url":null,"abstract":"","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0272638624008400/pdfft?md5=a41dd097a80b827684c2892548e01469&pid=1-s2.0-S0272638624008400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-20DOI: 10.1053/j.ajkd.2024.04.009
Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research.
{"title":"Evaluation and Management of Resistant Hypertension: Core Curriculum 2024","authors":"","doi":"10.1053/j.ajkd.2024.04.009","DOIUrl":"10.1053/j.ajkd.2024.04.009","url":null,"abstract":"<div><p>Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research.</p></div>","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0272638624007935/pdfft?md5=20bb34f3c168434ee3e8f3e3462314a6&pid=1-s2.0-S0272638624007935-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1053/j.ajkd.2024.05.012
Jesse C Ikeme, Rebecca Scherzer, Pranav S Garimella, Stein I Hallan, Ronit Katz, Michelle M Estrella, Joachim H Ix, Michael G Shlipak
{"title":"The Association of Plasma and Urine Uromodulin With Cardiovascular Disease in Persons With Hypertension and CKD.","authors":"Jesse C Ikeme, Rebecca Scherzer, Pranav S Garimella, Stein I Hallan, Ronit Katz, Michelle M Estrella, Joachim H Ix, Michael G Shlipak","doi":"10.1053/j.ajkd.2024.05.012","DOIUrl":"10.1053/j.ajkd.2024.05.012","url":null,"abstract":"","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1053/j.ajkd.2024.05.009
Samira S Farouk, Anshul Bhalla, Meera Harhay, Laila Lakhani, Luis Sanchez Russo, Scott Sanoff, Manpreet Samra, Matthew A Sparks, Niralee Patel, Fasika Tedla, Anju Yadav, Roslyn B Mannon
{"title":"More Exams, More Problems: Do We Really Need a New Accreditation System for Transplant Nephrology?","authors":"Samira S Farouk, Anshul Bhalla, Meera Harhay, Laila Lakhani, Luis Sanchez Russo, Scott Sanoff, Manpreet Samra, Matthew A Sparks, Niralee Patel, Fasika Tedla, Anju Yadav, Roslyn B Mannon","doi":"10.1053/j.ajkd.2024.05.009","DOIUrl":"10.1053/j.ajkd.2024.05.009","url":null,"abstract":"","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1053/j.ajkd.2024.05.005
{"title":"Visceral Abdominal Adiposity and Autosomal Dominant Polycystic Kidney Disease Progression: One More Step Toward Identifying Useful Biomarkers and Characterizing the Disease Metabolic Links","authors":"","doi":"10.1053/j.ajkd.2024.05.005","DOIUrl":"10.1053/j.ajkd.2024.05.005","url":null,"abstract":"","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0272638624008412/pdfft?md5=1a25a4393ec9a0ce70ae8ee2a11bc019&pid=1-s2.0-S0272638624008412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1053/j.ajkd.2024.05.008
Rachel Shulman, Wei Yang, Debbie L Cohen, Peter P Reese, Jordana B Cohen
<p><strong>Rationale & objective: </strong>The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD.</p><p><strong>Study design: </strong>Prospective cohort study.</p><p><strong>Setting & participants: </strong>1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.</p><p><strong>Exposure: </strong>Albuminuria stage at study entry.</p><p><strong>Outcome: </strong>Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death.</p><p><strong>Analytical approach: </strong>Linear mixed effects and Cox proportional hazards regression analyses.</p><p><strong>Results: </strong>Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m<sup>2</sup> per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m<sup>2</sup> per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m<sup>2</sup> per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively).</p><p><strong>Limitations: </strong>Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding.</p><p><strong>Conclusions: </strong>Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria.</p><p><strong>Plain-language summary: </strong>Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies o
理由和目标：对于正常白蛋白尿型慢性肾脏病（CKD）的临床轨迹，尤其是在无糖尿病的情况下，尚未进行深入研究。本研究评估了非糖尿病慢性肾脏病患者队列中肾脏和心血管预后与白蛋白尿水平的关系：前瞻性队列研究：参加慢性肾功能不全队列（CRIC）研究的1,463名非糖尿病慢性肾功能不全成人患者，无已知肾小球肾炎，被诊断为高血压肾硬化症或慢性肾功能不全原因不明：研究开始时的白蛋白尿分期：主要结果次要结局：(1) eGFR斜率；(2) 复合心血管疾病事件（因心力衰竭、心肌梗死、中风或全因死亡住院）；(3) 全因死亡：分析方法：线性混合效应和考克斯比例危险回归分析：结果：白蛋白尿水平较低与女性和年龄较大有关。就主要结果而言，与正常白蛋白尿相比，中度和重度白蛋白尿患者的肾脏结果（调整后危险比[aHR]3.3，95% CI 2.4-4.6；aHR 8.6，95% CI 6.0-12.0）和心血管结果（aHR 1.5，95% CI 1.2-1.9；aHR 1.5，95% CI 1.1-2.0）发生率较高。正常白蛋白尿患者（300 毫克/毫克，N=274；2.63 毫升/分钟/1.73 平方米/年）。在调整分析中，与正常白蛋白尿患者（9.3年）相比，中度（8.6年）和重度（7.3年）白蛋白尿患者出现肾脏疾病结果的平均时间更早，而各组白蛋白尿患者出现心血管疾病结果的平均时间相似（分别为8.2年、8.1年和8.6年）：局限性：CKD病因自我报告，未进行肾活检确诊。结论：正常白蛋白尿型非糖尿病慢性肾脏病患者的慢性肾脏病进展速度大大减缓，但心血管风险仅略低于白蛋白尿水平高的患者。这些发现为今后设计针对白蛋白尿水平较低人群的干预研究提供了参考。
{"title":"Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study.","authors":"Rachel Shulman, Wei Yang, Debbie L Cohen, Peter P Reese, Jordana B Cohen","doi":"10.1053/j.ajkd.2024.05.008","DOIUrl":"10.1053/j.ajkd.2024.05.008","url":null,"abstract":"<p><strong>Rationale & objective: </strong>The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD.</p><p><strong>Study design: </strong>Prospective cohort study.</p><p><strong>Setting & participants: </strong>1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.</p><p><strong>Exposure: </strong>Albuminuria stage at study entry.</p><p><strong>Outcome: </strong>Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death.</p><p><strong>Analytical approach: </strong>Linear mixed effects and Cox proportional hazards regression analyses.</p><p><strong>Results: </strong>Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m<sup>2</sup> per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m<sup>2</sup> per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m<sup>2</sup> per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively).</p><p><strong>Limitations: </strong>Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding.</p><p><strong>Conclusions: </strong>Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria.</p><p><strong>Plain-language summary: </strong>Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies o","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1053/j.ajkd.2024.05.010
Nora Franceschini, David L Feldman, Jonathan S Berg, Whitney Besse, Alexander R Chang, Neera K Dahl, Rasheed Gbadegesin, Martin R Pollak, Hila Milo Rasouly, Richard J H Smith, Cheryl A Winkler, Ali G Gharavi
About 37 million people in the United States have chronic kidney disease, a disease that encompasses multiple causes. About 10% or more of kidney diseases in adults and as many as 70% of selected chronic kidney diseases in children are expected to be explained by genetic causes. Despite the advances in genetic testing and an increasing understanding of the genetic bases of certain kidney diseases, genetic testing in nephrology lags behind other medical fields. More understanding of the benefits and logistics of genetic testing is needed to advance the implementation of genetic testing in chronic kidney diseases. Accordingly, the National Kidney Foundation convened a Working Group of experts with diverse expertise in genetics, nephrology, and allied fields to develop recommendations for genetic testing for monogenic disorders and to identify genetic risk factors for oligogenic and polygenic causes of kidney diseases. Algorithms for clinical decision making on genetic testing and a road map for advancing genetic testing in kidney diseases were generated. An important aspect of this initiative was the use of a modified Delphi process to reach group consensus on the recommendations. The recommendations and resources described herein provide support to nephrologists and allied health professionals to advance the use of genetic testing for diagnosis and screening of kidney diseases.
{"title":"Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group.","authors":"Nora Franceschini, David L Feldman, Jonathan S Berg, Whitney Besse, Alexander R Chang, Neera K Dahl, Rasheed Gbadegesin, Martin R Pollak, Hila Milo Rasouly, Richard J H Smith, Cheryl A Winkler, Ali G Gharavi","doi":"10.1053/j.ajkd.2024.05.010","DOIUrl":"10.1053/j.ajkd.2024.05.010","url":null,"abstract":"<p><p>About 37 million people in the United States have chronic kidney disease, a disease that encompasses multiple causes. About 10% or more of kidney diseases in adults and as many as 70% of selected chronic kidney diseases in children are expected to be explained by genetic causes. Despite the advances in genetic testing and an increasing understanding of the genetic bases of certain kidney diseases, genetic testing in nephrology lags behind other medical fields. More understanding of the benefits and logistics of genetic testing is needed to advance the implementation of genetic testing in chronic kidney diseases. Accordingly, the National Kidney Foundation convened a Working Group of experts with diverse expertise in genetics, nephrology, and allied fields to develop recommendations for genetic testing for monogenic disorders and to identify genetic risk factors for oligogenic and polygenic causes of kidney diseases. Algorithms for clinical decision making on genetic testing and a road map for advancing genetic testing in kidney diseases were generated. An important aspect of this initiative was the use of a modified Delphi process to reach group consensus on the recommendations. The recommendations and resources described herein provide support to nephrologists and allied health professionals to advance the use of genetic testing for diagnosis and screening of kidney diseases.</p>","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1053/j.ajkd.2024.06.004
{"title":"The Impact of Obesity on Glomerular Diseases Remains to be Determined","authors":"","doi":"10.1053/j.ajkd.2024.06.004","DOIUrl":"10.1053/j.ajkd.2024.06.004","url":null,"abstract":"","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0272638624008424/pdfft?md5=c6bd296b2dc76816268a052dcb34977b&pid=1-s2.0-S0272638624008424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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