Glomerular diseases最新文献

{"title":"Viral Glomerulopathy.","authors":"Margaret Deoliveira, Hridyesh Sikri, Samuel Mon-Wei Yu, John Cijiang He","doi":"10.1159/000531434","DOIUrl":"10.1159/000531434","url":null,"abstract":"<p><strong>Background: </strong>The association between viral infections and glomerular diseases, commonly known as \"viral glomerulopathies,\" has been described in various clinical scenarios for decades. Despite advancements in diagnostic tools, it remains challenging to establish a causative link fully.</p><p><strong>Summary: </strong>Data from mouse models have substantiated clinical observations and implicate direct viral infection in the pathogenesis of viral glomerulopathy, particularly in human immunodeficiency virus-associated nephropathy. In addition to the traditional concept of direct viral effects on kidneys, other factors such as <i>APOL1</i> risk alleles can further modify the clinical outcomes or presentations of different viral glomerulopathies. Newly developed antiviral drugs are now applicable to a wider range of patients with lower kidney function and fewer side effects.</p><p><strong>Key message: </strong>Efforts focusing on vaccines and antiviral treatments have significantly reduced the incidence of viral glomerulopathies. However, the most recent pandemic caused by severe acute respiratory syndrome coronavirus 2 infection complicated by COVID-associated nephropathy illustrates our susceptibility to novel viruses. Ongoing research is pivotal to deciphering the mechanisms behind viral glomerulopathies and discovering therapeutics in a collaborative approach.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"148-154"},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unusual Case of Seronegative Cryoglobulinemic Glomerulonephritis with Dominant Organized IgA Deposits Associated with Staphylococcal Infection: Casual or Causal Relationship?","authors":"José C De La Flor Merino, Jacqueline Apaza, Francisco Díaz, Edna Sandoval, Francisco Valga, Daniel Villa, Alexander Marschall, María Luisa Abascal, Andrea Rivas, Michael Cieza","doi":"10.1159/000531737","DOIUrl":"10.1159/000531737","url":null,"abstract":"<p><strong>Introduction: </strong>Cryoglobulinemia refers to the presence of cryoglobulins (CGs) in the serum, encompassing a group of diseases caused by the type of circulating GC. Cryoglobulinemic glomerulonephritis (CryoGN) is the principal manifestation of renal involvement. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of CG in the serum. However, cases of CryoGN without serological evidence of CGs are not uncommon in clinical practice, often diagnosed by anatomopathological findings in the renal biopsy.</p><p><strong>Case presentation: </strong>We report the case of an 86-year-old male who developed renal impairment, nephritic syndrome, and nephrotic-range proteinuria, without serological evidence of CGs, associated with staphylococcal bacteremia without apparent focus. Renal biopsy and pathological examination showed a membranoproliferative glomerulonephritis pattern with CD61-negative pseudothrombi. Immunofluorescence microscopy showed atypical IgA-dominant deposits. Electron microscopy revealed amorphous subendothelial and mesangial deposits and organized electrodense deposits within capillary loops (pseudothrombi) with microtubular substructure measuring 20-40 nm in thickness. These findings were consistent with seronegative CryoGN and microtubular organized atypical IgA-dominant deposits.</p><p><strong>Discussion: </strong>In this report, we discuss the clinical, analytical, and histopathological findings of a rare case of CryoGN without serological evidence of CGs. Regarding the etiology that triggered the glomerular disease in our patient, we conducted an exhaustive study in order to determine the underlying cause of CryoGN. At the time of biopsy, the patient had an active staphylococcal bacteremia. There are reports that postulate that staphylococcal antigens drive activation of immune system and in consequence, could cause this rare form of IgA-dominant glomerulonephritis with cryoglobulinemic features. After ruling out other causes of cryoglobulinemia, we discuss a plausible causal relationship of the staphylococcal infection in the pathogenesis of CryoGN in our patient.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"140-147"},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CureGN-Diabetes Study: Rationale, Design, and Methods of a Prospective Observational Study of Glomerular Disease Patients with Diabetes.","authors":"Amy K Mottl, Andrew S Bomback, Laura H Mariani, Gaia Coppock, J Charles Jennette, Salem Almaani, Debbie S Gipson, Sara Kelley, Jason Kidd, Louis-Philippe Laurin, Krzysztof Mucha, Andrea Oliverio, Matthew Palmer, Dana Rizk, Neil Sanghani, M Barry Stokes, Katalin Susztak, Shikha Wadhwani, Cynthia C Nast","doi":"10.1159/000531679","DOIUrl":"10.1159/000531679","url":null,"abstract":"<p><p>Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"155-164"},"PeriodicalIF":0.0,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing an Edema Clinician-Reported Outcome Measure for Nephrotic Syndrome.","authors":"Debbie S Gipson,&nbsp;Maisha Pal,&nbsp;Hailey Desmond,&nbsp;Charles Anderson,&nbsp;Liron Walsh,&nbsp;Howard Trachtman,&nbsp;Susan F Massengill,&nbsp;Patrick Gipson,&nbsp;Panduranga S Rao,&nbsp;Joshua Thurman,&nbsp;Jeffrey Kopp,&nbsp;Elaine Kamil,&nbsp;Jennifer Lamothe,&nbsp;Laura H Mariani,&nbsp;Paula LaFleur,&nbsp;Suzanne Vento,&nbsp;Michelle O'Shaughnessy,&nbsp;Youssef M K Farag,&nbsp;Christine Simon,&nbsp;Noelle E Carlozzi","doi":"10.1159/000531505","DOIUrl":"https://doi.org/10.1159/000531505","url":null,"abstract":"<p><strong>Introduction: </strong>Edema is a common manifestation of proteinuric kidney diseases, but there is no consensus approach for reliably evaluating edema. The objective of this study was to develop an edema clinician-reported outcome measure for use in patients with nephrotic syndrome.</p><p><strong>Methods: </strong>A literature review was conducted to assess existing clinician-rated measures of edema. Clinical experts were recruited from internal medicine, nephrology, and pediatric nephrology practices to participate in concept elicitation using semi-structured interviews and cognitive debriefing. Qualitative analysis methods were used to collate expert input and inform measurement development. In addition, training and assessment modules were developed using an iterative process that also utilized expert input and cognitive debriefing to ensure interrater reliability.</p><p><strong>Results: </strong>While several clinician-rated measures of edema have been proposed, our literature review did not identify any studies to support the reliability or validity of these measures. Fourteen clinician experts participated in the concept elicitation interviews, and twelve participated in cognitive debriefing. A clinician-reported outcome measure for edema was developed. The measure assesses edema severity in multiple individual body parts. An online training module and assessment tool were generated and refined using additional clinician input and investigative team expertise.</p><p><strong>Conclusion: </strong>The Edema ClinRO (V1) measure is developed specifically to measure edema in nephrotic syndrome. The tool assesses edema across multiple body parts, and it includes a training module to ensure standardized administration across raters. Future examination of this measure is ongoing to establish its reliability and validity.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"132-139"},"PeriodicalIF":0.0,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sporadic Case of Heterozygous X-Linked Alport Syndrome.","authors":"Jonathan E Zuckerman,&nbsp;Rachana Srivastava","doi":"10.1159/000530994","DOIUrl":"https://doi.org/10.1159/000530994","url":null,"abstract":"<p><p>Alport syndrome is a genetically and phenotypically heterogeneous disorder that can be transmitted in an X-linked, autosomal recessive, or autosomal dominant fashion and can affect glomerular, cochlear, and ocular basement membranes. The disorder results from mutations in the collagen IV genes <i>COL4A5</i> (X chromosome), <i>COL4A3</i>, and <i>COL4A4</i>. Alport patients are at lifetime risk for kidney failure, sensorineural deafness, and ocular abnormalities. Males with Alport syndrome typically present with severe phenotype with progression to end-stage kidney disease and/or sensorineural deafness and eye changes. Females generally having less severe presentation and diagnosis of X-linked Alport syndrome are generally not considered. Here, we report a case of a 3-year-old girl with gross hematuria, proteinuria, and chronic kidney disease who was found to have features of Alport syndrome on kidney biopsy and a sporadic heterozygous pathogenic <i>COL4A5</i> deletion on molecular testing. This case report emphasizes the importance of kidney biopsy and molecular testing in the work up of pediatric patients with hematuria, proteinuria, and/or chronic kidney disease. It is also a poignant illustration that females with heterozygous X-linked <i>COL4A5</i> mutations are often affected patients. It further illustrates the phenomenon of sporadic occurrence of genetic kidney disease in the absence of family history of kidney disease.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"126-131"},"PeriodicalIF":0.0,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"14th Biennial International Podocyte Conference","authors":"","doi":"10.1159/000530913","DOIUrl":"https://doi.org/10.1159/000530913","url":null,"abstract":"not applicable as these are abstracts","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78699500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients.","authors":"Elenjickal Elias John, Sanjeet Roy, Anup J Devasia, Reka Karuppusami, Nisha Jose, Selvin Sundar Raj Mani, Jeethu Joseph Eapen, Sabina Yusuf, Athul Thomas, Anna T Valson, Vinoi George David, Vikram Mathews, Biju George, Santosh Varughese, Suceena Alexander","doi":"10.1159/000529699","DOIUrl":"10.1159/000529699","url":null,"abstract":"<p><strong>Introduction: </strong>Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes.</p><p><strong>Material and methods: </strong>Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients.</p><p><strong>Results: </strong>The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft \"mesangiolysis\" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, <i>p</i> = 0.04). \"Associated extra-renal GvHD\" occurred in 11/19 (57.9%) allogenic recipients. Patients with \"associated extra-renal GvHD\" had significantly more deaths (6/11, 60% vs. 0, <i>p</i> = 0.02) but comparable renal outcomes.</p><p><strong>Conclusion: </strong>Renal GvHD can present with or without \"associated extra-renal GvHD\" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"98-115"},"PeriodicalIF":0.0,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9316893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Genetic Risk Score Distinguishes Different Types of Autoantibody-Mediated Membranous Nephropathy.","authors":"Sanjana Gupta, Mallory Lorraine Downie, Chris Cheshire, Stephanie Dufek-Kamperis, Adam Paul Levine, Paul Brenchley, Elion Hoxha, Rolf Stahl, Neil Ashman, Ruth Jennifer Pepper, Sean Mason, Jill Norman, Detlef Bockenhauer, Horia Constantin Stanescu, Robert Kleta, Daniel Philip Gale","doi":"10.1159/000529959","DOIUrl":"10.1159/000529959","url":null,"abstract":"<p><strong>Introduction: </strong>Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults and is characterized by detectable autoantibodies against glomerular antigens, most commonly phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain containing 7A (THSD7A). In Europeans, genetic variation in at least five loci, <i>PLA2R1</i>, <i>HLA-DRB1</i>, <i>HLA-DQA1, IRF4, and NFKB1,</i> affects the risk of disease. Here, we investigated the genetic risk differences between different autoantibody states.</p><p><strong>Methods: </strong>1,409 MN individuals were genotyped genome-wide with a dense SNV array. The genetic risk score (GRS) was calculated utilizing the previously identified European MN loci, and results were compared with 4,929 healthy controls and 422 individuals with steroid-sensitive nephrotic syndrome.</p><p><strong>Results: </strong>GRS was calculated in the 759 MN individuals in whom antibody status was known. The GRS for MN was elevated in the anti-PLA2R1 antibody-positive (<i>N</i> = 372) compared with both the unaffected control (<i>N</i> = 4,929) and anti-THSD7A-positive (<i>N</i> = 31) groups (<i>p</i> < 0.0001 for both comparisons), suggesting that this GRS reflects anti-PLA2R1 MN. Among PLA2R1-positive patients, GRS was inversely correlated with age of disease onset (<i>p</i> = 0.009). Further, the GRS in the dual antibody-negative group (<i>N</i> = 355) was intermediate between controls and the PLA2R1-positive group (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong>We demonstrate that the genetic risk factors for PLA2R1- and THSD7A-antibody-associated MN are different. A higher GRS is associated with younger age of onset of disease. Further, a proportion of antibody-negative MN cases have an elevated GRS similar to PLA2R1-positive disease. This suggests that in some individuals with negative serology the disease is driven by autoimmunity against PLA2R1.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"116-125"},"PeriodicalIF":0.0,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pSTAT1 Is Activated during the Progression of IgA Nephropathy.","authors":"Jianling Tao,&nbsp;Neeraja Kambham,&nbsp;Shirley Kwok,&nbsp;Richard A Lafayette","doi":"10.1159/000526056","DOIUrl":"https://doi.org/10.1159/000526056","url":null,"abstract":"<p><strong>Introduction: </strong>IgA nephropathy is the most common primary glomerular disease. Its pathogenesis is still poorly understood. Alterations of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway may play an important role in IgA nephropathy.</p><p><strong>Methods: </strong>We evaluated the clinical features, pathology, and tissue staining for lymphocytes and phosphorylated STAT1 (pSTAT1) in 43 patients with biopsy proven IgA nephropathy. They were followed to determine their disease outcomes. All had biopsy tissue and multiple laboratory measurements to assess their kidney disease progression. Sixteen patients underwent repeat kidney biopsy to further assess their clinical status.</p><p><strong>Results: </strong>The median eGFR at baseline was 61 mL/min/1.73 m² and the median proteinuria was 2,600 mg/d. The median follow-up was 5 years with an average annual decline in eGFR of 2.25 mL/min/1.73 m². There was significant inflammation and atrophy seen in the first biopsy, which progressed among those who undertook a 2nd biopsy. Compared to healthy kidney tissue, glomeruli and tubulointerstitium demonstrated increased lymphocyte (CD3+) infiltrates and increased pSTAT1 staining by immunohistochemistry. Increased CD3 (<i>p</i> = 0.001) staining and increased pSTAT1 (<i>p</i> = 0.03) correlated with reduced eGFR levels. In repeat biopsy samples, increasing pSTAT1 staining correlated with loss of eGFR over time (<i>p</i> = 0.02).</p><p><strong>Conclusion: </strong>These findings support the hypothesis that pSTAT1 is activated in IgA nephropathy and may play a role in the progression toward kidney failure.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"12-18"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0c/94/gdz-0003-0012.PMC9936761.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9314488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOL1 and APOL1-Associated Kidney Disease: A Common Disease, an Unusual Disease Gene - Proceedings of the Henry Shavelle Professorship.","authors":"Martin R Pollak,&nbsp;David J Friedman","doi":"10.1159/000529227","DOIUrl":"https://doi.org/10.1159/000529227","url":null,"abstract":"<p><strong>Background: </strong>Genetic variants in APOL1 are a major contributor to the increased risk of kidney disease in people of recent African ancestry.</p><p><strong>Summary: </strong>Two alleles in the APOL1 gene, referred to as G1 and G2, confer increased risk of kidney disease under a recessive model of risk inheritance. Disease risk is inherited as a recessive trait: People with genotypes G1/G1, G2/G2, and G1/G2 (i.e., a risk allele from each parent) have increased risk for what we refer to here as APOL1-associated kidney disease. In the USA, about 13% of the self-identified African-American population has a high-risk genotype. As we discuss below, APOL1 is an unusual disease gene. Most studies to date have suggested that the G1 and G2 variants have toxic, gain-of-function effects on the encoded protein.</p><p><strong>Key message: </strong>In this article, we review key concepts critical to understanding APOL1-associated kidney disease, emphasizing ways in which it is highly atypical for a human disease-causing gene.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"3 1","pages":"75-87"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/dc/gdz-0003-0075.PMC10126737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9364661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}