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Am J Hematol 2021 Jun 10. Epub 2021 Jun 10.

Service d'Explorations Fonctionnelles Multidisciplinaires, Paris, France.

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients responsible for a high morbidity and mortality. However, sickle cell nephropathy natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Read More

Sci Rep 2021 Jun 3;11(1):11682. Epub 2021 Jun 3.

Department of Internal Medicine, Centre de reference de la drepanocytose (AP-HP), Centre Hospitalier Universitaire Tenon, Sorbonne Université, rue de la Chine, 75020, Paris, France.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Read More

Nature 2021 Jun 2. Epub 2021 Jun 2.

Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Sickle cell disease (SCD) is caused by a mutation in the β-globin gene HBB. We used a custom adenine base editor (ABE8e-NRCH) to convert the SCD allele (HBB) into Makassar β-globin (HBB), a non-pathogenic variant. Ex vivo delivery of mRNA encoding the base editor with a targeting guide RNA into haematopoietic stem and progenitor cells (HSPCs) from patients with SCD resulted in 80% conversion of HBB to HBB. Read More

Front Mol Biosci 2021 13;8:681676. Epub 2021 May 13.

Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China.

Ischemia/reperfusion (I/R) injury is characterized by limiting blood supply to organs, then restoring blood flow and reoxygenation. It leads to many diseases, including acute kidney injury, myocardial infarction, circulatory arrest, ischemic stroke, trauma, and sickle cell disease. Autophagy is an important and conserved cellular pathway, in which cells transfer the cytoplasmic contents to lysosomes for degradation. Read More

Pediatr Nephrol 2021 May 29. Epub 2021 May 29.

Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.

The life expectancy of individuals with sickle cell disease has increased over the years, majorly due to an overall improvement in diagnosis and medical care. Nevertheless, this improved longevity has resulted in an increased prevalence of chronic complications such as sickle cell nephropathy (SCN), which poses a challenge to the medical care of the patient, shortening the lifespan of patients by 20-30 years. Clinical presentation of SCN is age-dependent, with kidney dysfunction slowly beginning to develop from childhood, progressing to chronic kidney disease and kidney failure during the third and fourth decades of life. Read More

Emerg Radiol 2021 May 12. Epub 2021 May 12.

Department of Emergency Medicine, Mount Sinai Medical Center, New York, NY, USA.

Objective: The objectives of this study are to determine the efficacy of a roster of clinical factors in identifying risk for renal insufficiency in emergency department (ED) patients requiring intravenous contrast-enhanced CT scan (IVCE-CT) and to help mitigate potential for developing contrast-induced nephropathy (CIN).

Methods: A review was conducted of consecutive ED patients who received IVCE-CT during a 4-month period in our urban ED. The values of ED serum creatinine (SCr) performed were tabulated. Read More

J Bras Nefrol 2021 May 3. Epub 2021 May 3.

Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Pediatria, Disciplina de Hematologia, São Paulo, SP, Brasil.

Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD).

Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Read More

Cell Rep Med 2021 Apr 20;2(4):100247. Epub 2021 Apr 20.

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.

Sickle cell disease (SCD) is caused by a 20A > T mutation in the β-globin gene. Genome-editing technologies have the potential to correct the SCD mutation in hematopoietic stem cells (HSCs), producing adult hemoglobin while simultaneously eliminating sickle hemoglobin. Here, we developed high-efficiency viral vector-free non-footprint gene correction in SCD CD34 cells with electroporation to deliver SCD mutation-targeting guide RNA, Cas9 endonuclease, and 100-mer single-strand donor DNA encoding intact β-globin sequence, achieving therapeutic-level gene correction at DNA (∼30%) and protein (∼80%) levels. Read More

Rambam Maimonides Med J 2021 Apr 29;12(2). Epub 2021 Apr 29.

The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, USA.

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Read More

Sci Transl Med 2021 Apr;13(591)

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Hematopoietic stem cell gene therapy for hemoglobin disorders, including sickle cell disease, requires high-efficiency lentiviral gene transfer and robust therapeutic globin expression in erythroid cells. Erythropoietin is a key cytokine for erythroid proliferation and differentiation (erythropoiesis), and truncated human erythropoietin receptors (thEpoR) have been reported in familial polycythemia. We reasoned that coexpression of thEpoR could enhance the phenotypic effect of a therapeutic vector in erythroid cells in xenograft mouse and autologous nonhuman primate transplantation models. Read More

Indian J Pediatr 2021 06 21;88(6):540-541. Epub 2021 Apr 21.

Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Lab Chip 2021 04;21(8):1433-1453

Department of Engineering Science, National Cheng Kung University, Tainan, 701, Taiwan.

Lab-on-paper, or microfluidic paper-based analytical devices (μPADs), use paper as a substrate material, and are patterned with a system of microchannels, reaction zones and sensing elements to perform analysis and detection. The sample transfer in such devices is performed by capillary action. As a result, external driving forces are not required, and hence the size and cost of the device are significantly reduced. Read More

Br J Pharmacol 2021 Apr 17. Epub 2021 Apr 17.

Cyclerion Therapeutics Inc., Boston, Massachusetts, USA.

Background And Purpose: Reduced bioavailability of NO, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso-occlusion and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyses synthesis of cGMP in response to NO. cGMP-amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate TNFα-induced inflammation in wild-type C57BL/6 mice and in 'humanised' mouse models of SCD. Read More

Lancet Haematol 2021 05 7;8(5):e306-e307. Epub 2021 Apr 7.

Department of Pediatric Hematology and Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.

Mol Ther Methods Clin Dev 2021 Jun 3;21:121-132. Epub 2021 Mar 3.

Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.

Gene editing with the CRISPR-Cas9 system could revolutionize hematopoietic stem cell (HSC)-targeted gene therapy for hereditary diseases, including sickle cell disease (SCD). Conventional delivery of editing tools by electroporation limits HSC fitness due to its toxicity; therefore, efficient and non-toxic delivery remains crucial. Integrating lentiviral vectors are established for therapeutic gene delivery to engraftable HSCs in gene therapy trials; however, their sustained expression and size limitation preclude their use for CRISPR-Cas9 delivery. Read More

Front Physiol 2021 19;12:653545. Epub 2021 Mar 19.

Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.

Red cells from patients with sickle cell anaemia (SCA) contain the abnormal haemoglobin HbS. Under hypoxic conditions, HbS polymerises and causes red cell sickling, a rise in intracellular Ca and exposure of phosphatidylserine (PS). These changes make sickle cells sticky and liable to lodge in the microvasculature, and so reduce their lifespan. Read More

Ann Hematol 2021 Jun 2;100(6):1401-1409. Epub 2021 Apr 2.

Department of Clinical Pathology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait City, Kuwait.

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). Read More

Front Genet 2021 15;12:595702. Epub 2021 Mar 15.

Division of Human Genetics, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Background: Renal dysfunctions are associated with increased morbidity and mortality in sickle cell disease (SCD). Early detection and subsequent management of SCD patients at risk for renal failure and dysfunctions are essential, however, predictors that can identify patients at risk of developing renal dysfunction are not fully understood.

Methods: In this study, we have investigated the association of 31 known kidney dysfunctions-related variants detected in African Americans from multi-ethnic genome wide studies (GWAS) meta-analysis, to kidney-dysfunctions in a group of 413 Cameroonian patients with SCD. Read More

Front Mol Biosci 2020 8;7:558982. Epub 2021 Mar 8.

Department of Material and Bioprocess Engineering, School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, Brazil.

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) - the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. Read More

Pediatr Hematol Oncol 2021 Mar 16:1-16. Epub 2021 Mar 16.

Pediatric Department, Faculty of Medicine, Zagazig University, Sharkia, Egypt.

Cardiovascular complications represent the main determinant of survival in patients with hemoglobinopathies. Serum cystatin C is a well-known marker of nephropathy in sickle cell disease (SCD) and β-thalassemia patients that has recently emerged as a strong predictor of cardiovascular dysfunction in patients with and without kidney disease. We performed a case control study to determine the role of cystatin C as a predictor of subclinical cardiovascular dysfunction in SCD and β-thalassemia patients. Read More

J Phys Chem B 2021 04 16;125(14):3452-3467. Epub 2021 Mar 16.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States.

Modern experimental kinetics of protein folding began in the early 1990s with the introduction of nanosecond laser pulses to trigger the folding reaction, providing an almost 10-fold improvement in time resolution over the stopped-flow method being employed at the time. These experiments marked the beginning of the "fast-folding" subfield that enabled investigation of the kinetics of formation of secondary structural elements and disordered loops for the first time, as well as the fastest folding proteins. When I started to work on this subject, a fast folding protein was one that folded in milliseconds. Read More

Nefrologia (Engl Ed) 2021 Mar 10. Epub 2021 Mar 10.

Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Instituto Maimónides de Investigaciones Biomédicas de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, España. Electronic address:

Kidney problems are among the most common complications in sickle cell disease (SCD). They occur early in childhood and are one of the main factors related to mortality in these patients. The main underlying pathogenic mechanisms are vaso-occlusion and haemolysis. Read More

BMJ Case Rep 2021 Mar 5;14(3). Epub 2021 Mar 5.

Pediatria, Hospital de Santa Maria, Lisboa, Lisboa, Portugal.

Nephropathy is a common under-recognised complication of sickle cell disease (SCD) and one of the main factors of poor prognosis in these patients. The association between nephrotic syndrome and SCD in children is rare. Strategies for sickle cell nephropathy prevention are still poorly established. Read More

Adv Exp Med Biol 2021 ;1321:147-162

Department of Chemical Pathology, National Health Laboratory Services, University of the Witwatersrand, Johannesburg, South Africa.

The novel corona virus 2019 (COVID-19) outbreak which started in Hubei province in China has now spread to every corner of the earth. While the pandemic started later in Africa, it is now found in all African countries to varying degrees. It is thought that the prevalence and severity of disease is influenced by a number of non-communicable diseases (NCDs) which are all becoming increasingly prevalent in sub-Saharan Africa (SSA). Read More

Bioorg Chem 2021 Apr 9;109:104709. Epub 2021 Feb 9.

Laboratório Multidisciplinar de Pesquisa, Universidade São Francisco, Bragança Paulista, SP, Brazil. Electronic address:

The sickle cell disease (SCD) has a genetic cause, characterized by a replacement of glutamic acid to valine in the β-chain of hemoglobin. The disease has no effective treatment so far, and patients suffer a range from acute to chronic complications that include chronic hemolytic anemia, vaso-occlusive ischemia, pain, acute thoracic syndrome, cerebrovascular accident, nephropathy, osteonecrosis and reduced lifetime. The oxidation in certain regions of the hemoglobin favors the reactive oxygen species (ROS) formation, which is the cause of many clinical manifestations. Read More

Curr Pain Headache Rep 2021 Feb 25;25(3):19. Epub 2021 Feb 25.

Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, New York, NY, 10065, USA.

Purpose Of Review: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. Read More

Haematologica 2021 Jun 1;106(6):1535-1544. Epub 2021 Jun 1.

Department of General Pediatrics and Pediatric Infectious Diseases, Reference Center for Sickle Cell Disease, Necker Hospital for Sick Children, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Paris; Laboratory of Excellence GR-Ex, Paris; Institut National de la Transfusion Sanguine (INTS), Université de Paris, Inserm U1134, Paris.

Median life expectancy of patients with sickle cell disease has increased to up to 55 years but there are still frequent cases of premature death, mostly in patients with pre-existing organ failure such as pulmonary hypertension, kidney injury, and cerebral vasculopathy. Most organ injuries remain asymptomatic for a long time and can only be detected through early systematic screening. Protocols combining assessment of velocities on transcranial Doppler and regular transfusions in patients with abnormal velocities have been demonstrated to dramatically reduce the risk of stroke. Read More

Am J Physiol Regul Integr Comp Physiol 2021 05 24;320(5):R630-R640. Epub 2021 Feb 24.

Section of Cardio-renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Despite advancements in disease management, sickle cell nephropathy, a major contributor to mortality and morbidity in patients, has limited therapeutic options. Previous studies indicate hydroxyurea, a commonly prescribed therapy for sickle cell disease (SCD), can reduce renal injury in SCD but the mechanisms are uncertain. Because SCD is associated with reduced nitric oxide (NO) bioavailability, we hypothesized that hydroxyurea treatment would improve NO bioavailability in the humanized sickle cell mouse. Read More

Foods 2021 Feb 10;10(2). Epub 2021 Feb 10.

School of Food Science and Environmental Health, College of Sciences and Health, Technological University Dublin-City Campus, Grangegorman, 7 Dublin, Ireland.

SARS-CoV-2 or COVID-19 is a novel coronavirus, which is the cause of the current pandemic with 107,411,561 infections and 2,351,195 death worldwide so far. There are multiple symptoms that are linked with the infection of COVID-19 such as coughing, shortness of breath, congestion together with fatigue, fever, loss of taste or smell, headaches, diarrhea, vomiting, and loss of appetite. The lack of or early stage of development of a cure for COVID-19 illness, there is need for insuring the best possible position of health to be able to fight the virus naturally through a robust immune system to limit severe complication. Read More

Cell Stem Cell 2021 02;28(2):191-208

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Division of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address:

Sickle cell disease (SCD) is caused by a well-defined point mutation in the β-globin gene and therefore is an optimal target for hematopoietic stem cell (HSC) gene-addition/editing therapy. In HSC gene-addition therapy, a therapeutic β-globin gene is integrated into patient HSCs via lentiviral transduction, resulting in long-term phenotypic correction. State-of-the-art gene-editing technology has made it possible to repair the β-globin mutation in patient HSCs or target genetic loci associated with reactivation of endogenous γ-globin expression. Read More