{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:58:39Z","timestamp":1792047519094,"version":"4.4.0"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"framework of the European Reference Network on Rare Haematological Diseases","award":["101157011"],"award-info":[{"award-number":["101157011"]}]},{"name":"European Union within the framework of the Fourth EU Health Programme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. APOL1 was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while BCL11A variants were protective against albuminuria alone. The HMOX1 long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (CRYL1, VWF, and ADAMTS7) and nine loci were linked with eGFR (PKD1L2, TOR2A, CUBN, AGGF1, CYP4B1, CD163, LRP1B, linc02288, and FPGT-TNNI3K\/TNNI3K). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.<\/jats:p>","DOI":"10.3390\/ijms25105427","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T06:44:31Z","timestamp":1715841871000},"page":"5427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Systematic Review of Genetic Modifiers Associated with the Development and\/or Progression of Nephropathy in Patients with Sickle Cell Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-9274","authenticated-orcid":false,"given":"Veerle","family":"Labarque","sequence":"first","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Center for Molecular and Vascular Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Chide","family":"Okocha","sequence":"additional","affiliation":[{"name":"Haematology Department, Faculty of Basic Clinical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi PMB 5025, Anambra State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/01.md.0000189089.45003.52","article-title":"Outcome of Sickle Cell Anemia: A 4-Decade Observational Study of 1056 Patients","volume":"84","author":"Powars","year":"2005","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s11255-018-1803-3","article-title":"Sickle Cell Nephropathy: An Update on Pathophysiology, Diagnosis, and Treatment","volume":"50","author":"Hariri","year":"2018","journal-title":"Int. Urol. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"C733","DOI":"10.1152\/ajpcell.00021.2017","article-title":"Hemoglobin Inhibits Albumin Uptake by Proximal Tubule Cells: Implications for Sickle Cell Disease","volume":"312","author":"Eshbach","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/path.5011","article-title":"Podocytes Are New Cellular Targets of Haemoglobin-Mediated Renal Damage","volume":"244","author":"Yuste","year":"2018","journal-title":"J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/S0140-6736(11)60355-3","article-title":"Hydroxycarbamide in Very Young Children with Sickle-Cell Anaemia: A Multicentre, Randomised, Controlled Trial (BABY HUG)","volume":"377","author":"Wang","year":"2011","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/ajh.23762","article-title":"The Glomerulopathy of Sickle Cell Disease","volume":"89","author":"Ataga","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000494581","article-title":"Sickle Cell Nephropathy in the Pediatric Population","volume":"47","author":"Olaniran","year":"2019","journal-title":"Blood Purif."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"614","DOI":"10.7326\/0003-4819-115-8-614","article-title":"Chronic Renal Failure in Sickle Cell Disease: Risk Factors, Clinical Course, and Mortality","volume":"115","author":"Powars","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/bjh.14724","article-title":"Clinical and Genetic Predictors of Renal Dysfunctions in Sickle Cell Anaemia in Cameroon","volume":"178","author":"Geard","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.2215\/CJN.01600211","article-title":"Chronic Kidney Disease and Albuminuria in Children with Sickle Cell Disease","volume":"6","author":"Jabbar","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/bjh.12690","article-title":"Haemoglobinuria Is Associated with Chronic Kidney Disease and Its Progression in Patients with Sickle Cell Anaemia","volume":"164","author":"Saraf","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2165\/00128072-200204010-00004","article-title":"Renal Complications of Sickle Cell Disease: Managing for Optimal Outcomes","volume":"4","author":"Sesso","year":"2002","journal-title":"Paediatr. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.htct.2019.07.007","article-title":"Persistent Hematuria among Children with Sickle Cell Anemia in Steady State","volume":"42","author":"Akubuilo","year":"2020","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A Web and Mobile App for Systematic Reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sohani, Z.N., Meyre, D., de Souza, R.J., Joseph, P.G., Gandhi, M., Dennis, B.B., Norman, G., and Anand, S.S. (2015). Assessing the Quality of Published Genetic Association Studies in Meta-Analyses: The Quality of Genetic Studies (Q-Genie) Tool. BMC Genet., 16.","DOI":"10.1186\/s12863-015-0211-2"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1182\/bloodadvances.2022007451","article-title":"Genome-Wide Meta-Analysis Identifies New Candidate Genes for Sickle Cell Disease Nephropathy","volume":"7","author":"Garrett","year":"2023","journal-title":"Blood Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1681\/ASN.V1051014","article-title":"Evidence That Microdeletions in the \u03b1 Globin Gene Protect against the Development of Sickle Cell Glomerulopathy in Humans","volume":"10","author":"Guasch","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/ajh.20800","article-title":"Estimated Glomerular Filtration Rate in Sickle Cell Anemia Is Associated with Polymorphisms of Bone Morphogenetic Protein Receptor 1B","volume":"82","author":"Nolan","year":"2007","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1111\/j.1537-2995.2007.01622.x","article-title":"Lack of Duffy Antigen Expression Is Associated with Organ Damage in Patients with Sickle Cell Disease","volume":"48","author":"Kail","year":"2008","journal-title":"Transfusion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bcmd.2010.06.003","article-title":"Alpha-Thalassemia Is Associated with a Decreased Occurrence and a Delayed Age-at-Onset of Albuminuria in Sickle Cell Anemia Patients","volume":"45","author":"Nebor","year":"2010","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.clim.2010.02.023","article-title":"Association between Duffy Antigen Receptor for Chemokines Expression and Levels of Inflammation Markers in Sickle Cell Anemia Patients","volume":"136","author":"Nebor","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1365-2141.2011.08832.x","article-title":"MYH9 and APOL1 Are Both Associated with Sickle Cell Disease Nephropathy","volume":"155","author":"Okocha","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_24","first-page":"171","article-title":"Kidney Dysfunction and Beta S-Haplotypes in Patients with Sickle Cell Disease","volume":"35","author":"Rocha","year":"2013","journal-title":"Rev. Bras. Hematol. Hemoter."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98.e87","DOI":"10.3324\/haematol.2013.089243","article-title":"The Effect of Duffy Antigen Receptor for Chemokines on Severity in Sickle Cell Disease","volume":"98","author":"Drasar","year":"2013","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3324\/haematol.2015.124875","article-title":"Genetic Variants and Cell-Free Hemoglobin Processing in Sickle Cell Nephropathy","volume":"100","author":"Saraf","year":"2015","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/pbc.25234","article-title":"Endothelial Nitric Oxide Synthase Gene Intron 4 VNTR Polymorphism in Sickle Cell Disease: Relation to Vasculopathy and Disease Severity","volume":"62","author":"Tantawy","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1080\/10245332.2015.1111643","article-title":"Association between Duffy Antigen Receptor Expression and Disease Severity in Sickle Cell Disease Patients","volume":"21","author":"Farawela","year":"2016","journal-title":"Hematology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/bjh.14842","article-title":"Roles of APOL1 G1 and G2 Variants in Sickle Cell Disease Patients: Kidney Is the Main Target","volume":"179","author":"Kormann","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.3324\/haematol.2016.154153","article-title":"APOL1,\u03b1-Thalassemia, and BCL11A Variants as a Genetic Risk Profile for Progression of Chronic Kidney Disease in Sickle Cell Anemia","volume":"102","author":"Saraf","year":"2017","journal-title":"Haematologica"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E362","DOI":"10.1002\/ajh.25245","article-title":"A Common Functional PIEZO1 Deletion Allele Associates with Red Blood Cell Density in Sickle Cell Disease Patients","volume":"93","author":"Ilboudo","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s12288-018-1018-x","article-title":"VEGF Promoter Region 18-Bp Insertion-Deletion Polymorphism in Sickle Cell Disease Patients with Microalbuminuria: A Pilot Study","volume":"35","author":"Amle","year":"2019","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E385","DOI":"10.3324\/haematol.2018.212779","article-title":"Children with Sickle Cell Anemia and APOL1 Genetic Variants Develop Albuminuria Early in Life","volume":"104","author":"Zahr","year":"2019","journal-title":"Haematologica"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E125","DOI":"10.1002\/ajh.25763","article-title":"Prevalence and Risk Factors for Albuminuria and Glomerular Hyperfiltration in a Large Cohort of Children with Sickle Cell Anemia","volume":"95","author":"Belisario","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.htct.2020.01.009","article-title":"Polymorphisms in the Heme Oxygenase-1 and Bone Morphogenetic Protein Receptor Type 1b Genes and Estimated Glomerular Filtration Rate in Brazilian Sickle Cell Anemia Patients","volume":"43","author":"Chinedu","year":"2021","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"595702","DOI":"10.3389\/fgene.2021.595702","article-title":"Investigations of Kidney Dysfunction-Related Gene Variants in Sickle Cell Disease Patients in Cameroon (Sub-Saharan Africa)","volume":"12","author":"Belinga","year":"2021","journal-title":"Front. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/bjh.17647","article-title":"Generalization of a Genetic Risk Score for Time to First Albuminuria in Children with Sickle Cell Anaemia: SCCRIP Cohort Study Results","volume":"194","author":"Rashkin","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/bjh.17224","article-title":"Engulfment and Cell Motility 1 (ELMO1) and Apolipoprotein A1 (APOA1) as Candidate Genes for Sickle Cell Nephropathy","volume":"193","author":"Saraf","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/bjh.17832","article-title":"Clinical and Genetic Factors Are Associated with Kidney Complications in African Children with Sickle Cell Anaemia","volume":"196","author":"Adebayo","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1002\/ajh.26652","article-title":"The Pleiotropic Effects of \u03b1-Thalassemia on HbSS and HbSC Sickle Cell Disease: Reduced Erythrocyte Cation Co-Transport Activity, Serum Erythropoietin, and Transfusion Burden, Do Not Translate into Increased Survival","volume":"97","author":"Brewin","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_41","first-page":"5","article-title":"Effects of Senegal Haplotype (Xmn1-Rs7412844), Alpha-Thalassemia (3.7kb HBA1\/HBA2 Deletion), NPRL3-Rs11248850 and BCL11A-Rs4671393 Variants on Sickle Cell Nephropathy","volume":"13","author":"Ndour","year":"2022","journal-title":"Intl. J. Biochem. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10437","DOI":"10.34172\/npj.2022.10437","article-title":"IL1RN VNTR Polymorphism and Kidney Damage in Sickle Cell Anemia Patients","volume":"12","author":"Bhaskar","year":"2023","journal-title":"J. Nephropharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Schaefer, B.A., Flanagan, J.M., Alvarez, O.A., Nelson, S.C., Aygun, B., Nottage, K.A., George, A., Roberts, C.W., Piccone, C.M., and Howard, T.A. (2016). Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164364"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.kint.2020.02.038","article-title":"Transcription Factor MafB in Podocytes Protects against the Development of Focal Segmental Glomerulosclerosis","volume":"98","author":"Usui","year":"2020","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1093\/ndt\/14.12.2898","article-title":"Endothelial Nitric Oxide Synthase Gene Polymorphism in Intron 4 Affects the Progression of Renal Failure in Non-Diabetic Renal Diseases","volume":"14","author":"Wang","year":"1999","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40200-015-0144-3","article-title":"Association of 18bp Insertion\/Deletion Polymorphism, at -2549 Position of VEGF Gene, with Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients of North Indian Population","volume":"14","author":"Amle","year":"2015","journal-title":"J. Diabetes. Metab. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1464-5491.2005.01376.x","article-title":"Warren 3\/UK GoKind Study Group The TGF-Beta 1 Gene Codon 10 Polymorphism Contributes to the Genetic Predisposition to Nephropathy in Type 1 Diabetes","volume":"22","author":"Patel","year":"2005","journal-title":"Diabet. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1038\/s41467-019-11576-0","article-title":"Genome-Wide Association Meta-Analyses and Fine-Mapping Elucidate Pathways Influencing Albuminuria","volume":"10","author":"Teumer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/ki.1997.115","article-title":"Genetic Linkage Analysis of Growth Factor Loci and End-Stage Renal Disease in African Americans","volume":"51","author":"Freedman","year":"1997","journal-title":"Kidney Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1681\/ASN.2002010084","article-title":"Glomerular Involvement in Adults with Sickle Cell Hemoglobinopathies: Prevalence and Clinical Correlates of Progressive Renal Failure","volume":"17","author":"Guasch","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1193032","article-title":"Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans","volume":"329","author":"Genovese","year":"2010","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1681\/ASN.2011040388","article-title":"APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy","volume":"22","author":"Kopp","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/art.38220","article-title":"End-Stage Renal Disease in African Americans with Lupus Nephritis Is Associated with APOL1","volume":"66","author":"Freedman","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/ckj\/sfx058","article-title":"Prevalence and Determinants of Microalbuminuria in Children Suffering from Sickle Cell Anemia in Steady State","volume":"10","author":"Aloni","year":"2017","journal-title":"Clin. Kidney J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0002-9440(10)64037-0","article-title":"Oxidative Stress and Induction of Heme Oxygenase-1 in the Kidney in Sickle Cell Disease","volume":"158","author":"Nath","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1182\/blood-2002-12-3733","article-title":"Microsatellite Polymorphism in Heme Oxygenase-1 Gene Promoter Is Associated with Susceptibility to Oxidant-Induced Apoptosis in Lymphoblastoid Cell Lines","volume":"102","author":"Hirai","year":"2003","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1161\/ATVBAHA.110.207316","article-title":"Role of Heme Oxygenase-1 in Human Endothelial Cells: Lesson from the Promoter Allelic Variants","volume":"30","author":"Taha","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1086\/302729","article-title":"Microsatellite Polymorphism in the Heme Oxygenase-1 Gene Promoter Is Associated with Susceptibility to Emphysema","volume":"66","author":"Yamada","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1182\/blood.V84.2.643.643","article-title":"The Acute Chest Syndrome in Sickle Cell Disease: Incidence and Risk Factors. The Cooperative Study of Sickle Cell Disease","volume":"84","author":"Castro","year":"1994","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM199107043250103","article-title":"Pain in Sickle Cell Disease. Rates and Risk Factors","volume":"325","author":"Platt","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in Sickle Cell Disease. Life Expectancy and Risk Factors for Early Death","volume":"330","author":"Platt","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1073\/pnas.0804799105","article-title":"DNA Polymorphisms at the BCL11A, HBS1L-MYB, and Beta-Globin Loci Associate with Fetal Hemoglobin Levels and Pain Crises in Sickle Cell Disease","volume":"105","author":"Lettre","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.mce.2016.02.020","article-title":"A Novel Long Non-Coding RNA CYP4B1-PS1-001 Regulates Proliferation and Fibrosis in Diabetic Nephropathy","volume":"426","author":"Wang","year":"2016","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ygeno.2004.02.008","article-title":"Polycystin-1L2 Is a Novel G-Protein-Binding Protein","volume":"84","author":"Yuasa","year":"2004","journal-title":"Genomics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1002\/hsr2.267","article-title":"Comparison of Dipstick and Quantitative Tests for Proteinuria and Hematuria in Middle-Aged, Male Japanese Employees: A Single-Center Study","volume":"4","author":"Ikeda","year":"2021","journal-title":"Health Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.5001\/omj.2011.107","article-title":"A Comparison of Serum Cystatin C and Creatinine with Glomerular Filtration Rate in Indian Patients with Chronic Kidney Disease","volume":"26","author":"Kumaresan","year":"2011","journal-title":"Oman. Med. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41581-022-00540-9","article-title":"The Nephropathy of Sickle Cell Trait and Sickle Cell Disease","volume":"18","author":"Ataga","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"(2024). Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., 105, S117\u2013S314.","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E416","DOI":"10.1002\/ajh.26323","article-title":"The International Hemoglobinopathy Research Network (INHERENT): An International Initiative to Study the Role of Genetic Modifiers in Hemoglobinopathies","volume":"96","author":"Kountouris","year":"2021","journal-title":"Am. J. Hematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:43:20Z","timestamp":1760107400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":69,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105427"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105427","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,16]]}}}