Nephron最新文献

{"title":"The Complexity of Decisions in Genetics: Annotation of Three Novel Variants in the PKD1 and PKD2 Genes.","authors":"Rui Barata, Liliana Rocha, Isabel Tavares, Odete Pereira, Filipa Carvalho, João Paulo Oliveira","doi":"10.1159/000534969","DOIUrl":"10.1159/000534969","url":null,"abstract":"<p><p>As nephrology practice is evolving toward precision medicine, and genetic tests are becoming widely available, basic genetic literacy is increasingly required for clinical nephrologists. Yet, decisions based on results of genetic tests are seldom straightforward. We report a 37-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) who was referred for medically assisted reproduction with monogenic preimplantation genetic testing (PGT-M). The PKD1 and PKD2 genes were screened for pathogenic variants. Sequencing analysis revealed the presence of three novel missense single nucleotide variants, two in the PKD1 gene - c.349T&gt;G, p.(Leu117Val) and c.1736C&gt;T, p.(Pro579Leu); and the third in the PKD2 gene - c.1124A&gt;G, p.(Asn375Ser). Bioinformatic predictions of the functional effects of those three missense variants were inconsistent across different software tools. The family segregation analysis, which was mandatory to identify the relevant variant(s) for PGT-M, strongly supported that the disease-causing variant was PKD1 c.349T&gt;G p.(Leu117Val), while the other two were nonpathogenic or, at most, phenotypic modulators. Proving the pathogenicity of novel variants is often complex but is critical to guide genetic counseling and screening, particularly when discussing reproductive alternatives for primary prevention in the progeny of at-risk couples. The family reported herein illustrates those challenges in the setting of ADPKD, and the invaluable importance of a detailed family history and segregation analysis for proper clinical annotation of novel variants. Basic genetic knowledge and proper clinical annotation of novel allelic variants in genes associated with hereditary kidney disorders are increasingly necessary for the contemporary practice of clinical nephrology.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"503-507"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546718","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 Impact of C-Reactive Protein-To-Albumin Ratio on Mortality in Patients with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy: A Multicenter Retrospective Study.","authors":"You Hyun Jeon, Sung Woo Lee, Yena Jeon, Jang-Hee Cho, Jiyun Jung, Jangwook Lee, Jae Yoon Park, Yong Chul Kim, Tae Hyun Ban, Woo Yeong Park, Kipyo Kim, Hyosang Kim, Kyeong Min Kim, Jeong-Hoon Lim","doi":"10.1159/000534970","DOIUrl":"10.1159/000534970","url":null,"abstract":"<p><strong>Introduction: </strong>C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury requiring continuous renal replacement therapy (CRRT).</p><p><strong>Methods: </strong>We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).</p><p><strong>Results: </strong>In total, 3,995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all p &lt; 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, p &lt; 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, p = 0.003). CAR combined with Acute Physiology and Chronic Health Evaluation II or Sequential Organ Failure Assessment scores significantly increased the predictive power compared to each severity score alone for AUC, NRI, and IDI (all p &lt; 0.05).</p><p><strong>Conclusions: </strong>A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"379-389"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138461147","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 Glomerular Sieving Coefficient of Albumin Is Really Very Low.","authors":"George A Tanner","doi":"10.1159/000538281","DOIUrl":"10.1159/000538281","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":"148 8","pages":"584-586"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073307","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":"Severe Leptospirosis with Acute Kidney Injury: A Case Description and Literature Review.","authors":"Clara Daschner, Anna-Sophie Schübler, Matthias Jung, Niklas Ayasse, Gökhan Yücel, Faeq Husain-Syed, Jan Leipe, Bernhard K Krämer, Babak Yazdani","doi":"10.1159/000540300","DOIUrl":"10.1159/000540300","url":null,"abstract":"<p><strong>Introduction: </strong>Leptospirosis is a globally transmitted zoonotic disease caused by Leptospira spp., a highly mobile, obligate aerobic, spiral-shaped bacteria. Described first by Adolf Weil in 1886, leptospirosis in Germany is rare, leading to a delayed diagnosis due to diverse symptoms. Most cases are mild, but severe forms, like Weil's disease, cause life-threatening complications such as fever, jaundice, hemoptysis, and acute kidney injury (AKI). The aim of this work was to provide a literature review of leptospirosis with renal manifestation based on a case report.</p><p><strong>Case presentation: </strong>We report the case of an 81-year-old male patient with initially unclear oliguric AKI, bilateral pulmonary infiltrates, and jaundice. After excluding common AKI causes, the expanded patient history suggested possible rat contact in his chicken coop. Finally, we serologically identified an infection with Leptospira spp. by positive IgM, proving that the illness was compatible with classical Weil's disease. The patient underwent temporary hemodialysis and antibiotic treatment with intravenous penicillin G for 2 weeks. Under therapy, the AKI, hyperbilirubinemia, and clinical condition of the patient improved. The patient was discharged after 2 weeks. In the following controls, slightly impaired kidney function was observed, indicating a progress of his chronic kidney disease (CKD).</p><p><strong>Conclusion: </strong>Although leptospirosis is rare, there are some cases with a fulminant course. Impairment of renal function often correlates with severity of the disease requiring antibiotic treatment. In some cases, AKI progresses to CKD demonstrating the need to raise awareness for leptospirosis.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"832-839"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893865","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":"Brenner's Unforgettable Legacy: Transforming Medicine and Renal Science for Generations.","authors":"Giuseppe Remuzzi, David Warnock","doi":"10.1159/000541866","DOIUrl":"10.1159/000541866","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"731-733"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381308","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":"Phenotypic Discordance among Siblings with Autosomal Recessive Polycystic Kidney Disease: Case Report and Review of the Literature.","authors":"Marc Henein, Felicia Russo, Zachary T Sentell, Rémi Goupil, Thomas M Kitzler","doi":"10.1159/000540741","DOIUrl":"10.1159/000540741","url":null,"abstract":"<p><p>Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the extensive allelic heterogeneity within the PKHD1 gene, which encodes a 4074-amino-acid protein. We report the case of adult siblings with biallelic missense PKHD1 variants, c.4870C>T (p.Arg1624Trp) and c.8206T>G (p.Trp2736Gly), who presented with discordant phenotypes. Patient A developed progressive chronic kidney disease and Caroli syndrome in childhood requiring combined liver and kidney transplantation, while patient B remains minimally affected in the fourth decade of life with normal kidney function and signs of medullary sponge kidney on imaging. We review previously reported cases of phenotypic discordance among siblings and suggest that genotypes composed of at least one hypomorphic missense variant are more likely to lead to phenotypic discordance.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"823-831"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522493","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":"Regional Variation in the Use of Percutaneous Kidney Biopsy in Japan.","authors":"Yasuhiro Oda, Hiroshi Nishi, Masaomi Nangaku","doi":"10.1159/000534449","DOIUrl":"10.1159/000534449","url":null,"abstract":"<p><strong>Introduction: </strong>The regional variation in the use of percutaneous kidney biopsy in Japan remains unknown. There are several large datasets of kidney biopsies in Japan, but an exhaustive survey of kidney biopsies is lacking.</p><p><strong>Methods: </strong>We analyzed insurance claims for percutaneous kidney biopsies registered in the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which is the closest to a complete dataset of kidney biopsies performed in Japan. In combination with other nationwide survey results, the number of inpatient percutaneous kidney biopsies per population in each prefecture was calculated. Factors associated with the frequency of percutaneous kidney biopsies were also explored.</p><p><strong>Results: </strong>The database contained 22,419 health insurance claims for percutaneous kidney biopsy in the fiscal year 2020. The frequency of inpatient percutaneous kidney biopsies could be up to 4.8 times as frequent in one prefecture than in another, even after adjusting for age and sex. The frequency of inpatient percutaneous kidney biopsies showed a positive correlation with the number of annual kidney transplants and patients on peritoneal dialysis per population and a weak negative correlation with the prevalence of reduced kidney function in the population aged 40-74 years.</p><p><strong>Conclusion: </strong>We found a large regional variation in the frequency of inpatient percutaneous kidney biopsies. Kidney transplants and peritoneal dialysis might be offered more frequently in regions with a higher frequency of kidney biopsy. This is the first dataset that shows more than 20,000 kidney biopsies were performed per year in Japan, as of 2020.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"357-366"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154877","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":"Chronic Inflammation in Chronic Kidney Disease.","authors":"Zhipeng Yan, Tingting Shao","doi":"10.1159/000534447","DOIUrl":"10.1159/000534447","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is an increasingly prevalent disease that affects approximately 10-12% of the global population. Therefore, it is considered a public health priority. Persistent and systemic low-grade chronic inflammation (CI) is an important part of the poor prognosis in CKD, especially for patients with advanced disease. For example, CI worsens anemia and promotes atherosclerosis. Therefore, CI deserves our attention.</p><p><strong>Summary: </strong>The formation of CI in CKD involves many aspects. Among them, the decline in the glomerular filtration rate leads to the influence of substances or inflammatory cytokines that should be cleared in time. In addition, oxidative stress, the gut, and the gut microbiota are also influencing factors.</p><p><strong>Key messages: </strong>In this review, we highlight the mechanisms involved in the development of CI in CKD.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"143-151"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49679935","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":"Stewart as I Knew Him.","authors":"Giuseppe Remuzzi","doi":"10.1159/000534841","DOIUrl":"10.1159/000534841","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"124-126"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230200","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":"Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement.","authors":"Silvia Orisio, Marina Noris, Miriam Rigoldi, Elena Bresin, Norberto Perico, Matias Trillini, Roberta Donadelli, Annalisa Perna, Ariela Benigni, Giuseppe Remuzzi","doi":"10.1159/000530657","DOIUrl":"10.1159/000530657","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2.</p><p><strong>Methods: </strong>237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis.</p><p><strong>Results: </strong>Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1 truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1 non-truncating variants or PKD2-mutated patients.</p><p><strong>Conclusions: </strong>Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"273-291"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9893296","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}