Nephrology最新文献

{"title":"Autosomal dominant nephrogenic diabetes insipidus in one family caused by a novel AQP2 mutation","authors":"Hou‐Xuan Huang, Monika Sullivan, Paola Zayas Borges, Sabina Kennedy","doi":"10.1111/nep.14389","DOIUrl":"https://doi.org/10.1111/nep.14389","url":null,"abstract":"A 9‐month‐old male presented with vomiting and dehydration with mild hypernatremia in the context of failure to thrive. He was later diagnosed with nephrogenic diabetes insipidus (NDI) during this hospitalisation and was also found to have eosinophilic esophagitis (EoE). He has since been growing well after EoE and NDI were properly managed. Molecular genetic testing revealed an unreported deletion in <jats:italic>AQP2</jats:italic> which was deemed pathogenic and of autosomal dominant inheritance when correlated with his clinical findings and family history. This case report describes the clinical course of this patient in comparison to his family members and reviews current literature on autosomal dominant NDI caused by <jats:italic>AQP2</jats:italic> mutations.","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"186 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC12A1 variant c.1684+1 G>A causes Bartter syndrome type 1 by promoting exon 13 skipping","authors":"Wenke Yang, Yanjun Li, Zhenglong Guo, Yanxin Ren, Jianmei Huang, Huiru Zhao, Shixiu Liao","doi":"10.1111/nep.14390","DOIUrl":"https://doi.org/10.1111/nep.14390","url":null,"abstract":"BackgroundBartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss‐of‐function variants in the <jats:italic>SLC12A1</jats:italic> gene. It is characterized by metabolic alkalosis and prenatal‐onset polyuria leading to polyhydramnios.MethodsWe identified pathogenic gene in a 12‐day‐old newborn boy with Bartter syndrome type 1 using whole‐exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre‐mRNA splicing.ResultsWe found a compound heterozygous variants in the <jats:italic>SLC12A1</jats:italic> gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G&gt;A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G&gt;A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G&gt;A abolished a consensus splice donor site of <jats:italic>SLC12A1</jats:italic> intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of <jats:italic>SLC12A1</jats:italic> function.ConclusionUsing a cell‐based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant <jats:italic>SLC12A1</jats:italic> c.1684+1 G&gt;A on pre‐mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/nep14390-gra-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"60 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The risk factor for adverse pregnancy outcomes and its impact on clinical effect in IgA nephropathy: A retrospective observational study","authors":"Fengxia Zhang, Zhiyong Xie, Siqi Peng, Nan Jiang, Bohou Li, Boxi Chen, Shuting Deng, Ye Yuan, Qiong Wu, Sichun Wen, Yiming Tao, Jianchao Ma, Sijia Li, Ting Lin, Feng Wen, Zhuo Li, Renwei Huang, Zhonglin Feng, Chaosheng He, Wenjian Wang, Xinling Liang, Lixia Xu, Yue Shen, Niechao Hong, Ruiquan Xu, Shuangxin Liu","doi":"10.1111/nep.14387","DOIUrl":"https://doi.org/10.1111/nep.14387","url":null,"abstract":"AimIgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long‐term renal outcome of pregnant IgAN patients remained unclear.MethodsWe performed a retrospective observational study covering 2003–2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO.ResultsIn this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome.ConclusionPregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/nep14387-gra-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"6 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cell targeting in IgA nephropathy.","authors":"Yusuke Suzuki","doi":"10.1111/nep.14367","DOIUrl":"10.1111/nep.14367","url":null,"abstract":"<p><p>The \"multi-hit theory/4-hit theory\" pathogenesis hypothesis is widely accepted and IgA nephropathy (IgAN) is understood to be a disease originating from Hit 1, galactose deficient IgA1 (GdIgA1). The chronic repetitive activation of the complement pathway (alternative and lectin pathways) and the subsequent inflammation results in progressive glomerular damage that spills over into increased intraglomerular pressure and other hemodynamic changes, increased urinary protein, glomerulosclerosis, and tubulointerstitial fibrosis. The basic pathophysiology of this disease is the progression of a mixture of such acute and chronic pathologies. Currently, a number of new drugs has emerged as promising agents, such as complement regulators, endothelin receptor antagonists, and SGLT2 inhibitors, which are associated with each pathological step after glomerular deposition of GdIgA1/immune complexes. On the other hand, the molecular mechanisms of GdIgA1 production are gradually being elucidated, and the development of several novel therapeutic agents targeting the responsible B cells and their international clinical trials are progressing. These agents that inhibit or control the production of the Hit1, GdIgA1, are highly expected as essential therapies for this disease. The large body of clinical and basic research findings to date strongly suggest that nephritogenic GdIgA1 is a polymeric IgA1 of mucosal origin. In addition, the B cells involved in its nephritogenic GdIgA1 production are mainly differentiated mature B cells such as plasma cells, which may migrate to the bone marrow as well as the mucosa. The innate immune system in the mucosa, especially Toll-like receptors (TLRs), is thought to be involved in their production. Among TLRs, TLT9 and TLR7, which recognize bacterial and viral unmethylated DNA and RNA, have been reported to be involved. The mucosal activation of these TLRs is associated with the production of APRIL (A Proliferation Inducing Ligand) and BAFF (B cell activating factor), which are TNF superfamily cytokines involved in B cell maturation, survival, and IgA class switching, and may also be involved in the production of nephritogenic GdIgA1. It is still inconclusive whether APRIL or BAFF is more closely involved in the production of nephritogenic GdIgA1. Phenotypes in transgenic animal models suggest BAFF involvement, however, a genome wide association study (GWAS) analysis of human IgAN has identified APRIL, not BAFF, as a candidate gene. Based on the above background, several international clinical trials are underway for drugs such as TLR regulators (hydroxychloroquine), anti-APRIL drugs, anti-BAFF drugs, APRIL/BAFF receptor (TACI) binding inhibitors, and cytoreductive drugs (proteasome inhibitors, anti-CD38 antibodies) to inhibit nephritogenic GdIgA1 production in responsible B cells. This session will provide an overview of the responsible B cells, their GdIgA1 production mechanism, and ongoing drugs.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"29 Suppl 2 ","pages":"39-43"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgA nephropathy: Correlation between pathologic findings and complement activation.","authors":"Mark Haas","doi":"10.1111/nep.14342","DOIUrl":"10.1111/nep.14342","url":null,"abstract":"","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"29 Suppl 2 ","pages":"60-62"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of IgA nephropathy: Omics data inform glycomedicine.","authors":"Jan Novak","doi":"10.1111/nep.14350","DOIUrl":"10.1111/nep.14350","url":null,"abstract":"","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"29 Suppl 2 ","pages":"18-22"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.","authors":"Seyoung Ryou, Hyeran Park, Seung Yun Chae, Yaeni Kim, Yeong-Jin Choi, Cheol Whee Park","doi":"10.1111/nep.14298","DOIUrl":"10.1111/nep.14298","url":null,"abstract":"<p><p>Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":" ","pages":"607-611"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for risk stratification of IgA nephropathy.","authors":"Hitoshi Suzuki","doi":"10.1111/nep.14294","DOIUrl":"10.1111/nep.14294","url":null,"abstract":"","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"29 Suppl 2 ","pages":"23-24"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"My journey on the path to understanding IgA nephropathy: From bench to bedside.","authors":"Yasuhiko Tomino","doi":"10.1111/nep.14346","DOIUrl":"10.1111/nep.14346","url":null,"abstract":"<p><p>When Berger et al. first reported IgA nephropathy in 1968, the prognosis was generally thought to be benign. However, as more case data were accumulated, it became evident that not all patients with IgA nephropathy necessarily had a good prognosis. IgA nephropathy has a significant morbidity, culminating in end-stage kidney disease (ESKD) in about 40% of patients without treatment within 20 years of the diagnosis. Although almost 20% of patients remain stable in their renal function, 30%-40% of patients develop ESKD from its onset. The important factors of renal outcome in patients with IgA nephropathy is the severity of histopathological findings, heavy proteinuria, long duration of proteinuria, haematuria and hypertension.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"29 Suppl 2 ","pages":"51-54"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cultural diversity on COVID-19 vaccination hesitancy in kidney transplant recipients.","authors":"Rachel Frederick, Frank Ierino, Rey Lopez, David Goodman","doi":"10.1111/nep.14351","DOIUrl":"10.1111/nep.14351","url":null,"abstract":"<p><strong>Aim: </strong>To study COVID-19 vaccination status in kidney transplant recipients (KTRs), reasons for incomplete vaccination and the clinical impact of vaccination on patient outcomes.</p><p><strong>Methods: </strong>A single-centre retrospective analysis of KTR (n = 543) conducted between 1970 and December 2022. Data included baseline demographics, number of vaccinations, reason for incomplete vaccination and patient outcomes following COVID-19 infection. A completed course of COVID-19 vaccination was defined as four or more vaccine doses.</p><p><strong>Exclusion criteria: </strong>those deceased prior December 2019, managed by another health service, failed graft, or deceased secondary to non-COVID cause.</p><p><strong>Results: </strong>273 of 543 patients met inclusion criteria. Mean age was 58.1 ± 12.2 years, 66% were male. 58.2% of patients were fully vaccinated, 22.7% received three doses, 7.7% received two doses, 0.7% received one dose, 0.7% received zero doses, and 10% incomplete records. The most common reasons for incomplete vaccination were COVID-19 infection, concern for side effects, and patient unawareness of booster recommendations. Vaccination uptake was greater in Australian born patients compared with those born overseas, odds ratio 0.40 (95% CI 0.23-0.69). KTR with incomplete vaccination had poorer outcomes, higher rate of AKI, long COVID, and increased hospitalization.</p><p><strong>Conclusion: </strong>The majority of KTR were fully vaccinated. KTR with incomplete vaccination status had poorer outcomes with COVID-19 infection and other issues. Patient education is a major area for improvement targeting patients born overseas and better information regarding side effects. Potential interventions need to address improved communication, cultural relevancy, and language.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":" ","pages":"600-606"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}