bims-sicedi 2025-06-29 papers

J Am Soc Nephrol. 2025 Jun 26.

Management of Kidney Disease with Sickle Cell Disease.

Momen Abbasi, Anand Srivastava, Santosh L Saraf.

ABSTRACT: Sickle cell disease is the most common inherited blood cell disorder in the United States. Vaso-occlusion and hemolysis are hallmark features of sickle cell disease that may lead to kidney damage through endothelial dysfunction, oxidative, and inflammatory stress. Manifestations of sickle cell disease-related kidney disease include hyperfiltration that occurs early in the disease course followed by albuminuria and a progressive decline in estimated glomerular filtration rate (eGFR). Patients with sickle cell disease have a faster rate of eGFR decline and the development of CKD leads to increased morbidity and early mortality. The assessment of kidney function is challenged by the transition from the hyperfiltration phase to reduced eGFR and by tubular creatinine secretion, which may lead to overestimation of the true GFR. Cystatin C-based and race-free estimating GFR equations reduce the overestimation but require further validation. Complications of kidney dysfunction include hyperkalemia and metabolic acidosis that occur at higher eGFR thresholds compared to the general population. Coinheritance of genetic variants, such as APOL1 G1 and G2 kidney risk variants, may help identify sickle cell disease patients at greater risk for CKD and guide treatment and screening strategies. Therapeutic approaches targeting the sickle cell disease pathophysiology, such as hydroxyurea, chronic red blood cell transfusions, and hematopoietic stem cell transplantation, have demonstrated some kidney protective effects but larger studies with longer follow up are needed. Novel agents, including endothelin receptor antagonists, pyruvate kinase activators, and APOL1 inhibitors, are currently under investigation. Kidney-protective therapies such as renin-angiotensin aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors offer promise but require prospective validation in sickle cell disease cohorts. Kidney transplantation confers a survival benefit and should not be withheld based solely on sickle cell disease diagnosis. Early identification, individualized management, and ongoing research are essential to improve kidney outcomes and reduce mortality in this high-risk population.

DOI: https://doi.org/10.1681/ASN.0000000804

Skeletal Radiol. 2025 Jun 21.

Musculoskeletal manifestations of sickle cell disease: an imaging perspective.

Vitor Neves Sato, Tatiane Lumi Moriwaki, Leonardo Kazunori Tsuji, Daisy Terumi Kase, Lucas Kenzo Miyahara, Andre Hiroki Suyama Tsuji, Adham do Amaral E Castro, Carolina Freitas Lins, André Fukunishi Yamada, Artur da Rocha Correa Fernandes, Marcello Henrique Nogueira-Barbosa, Júlio Brandão Guimarães, André Yui Aihara.

Sickle cell disease (SCD) is a spectrum of inherited blood disorders, leading to propensity to sickling disruption of red blood cells. Musculoskeletal complications are a common cause of acute and chronic morbidities, related to the main pathophysiological processes: (i) hemolysis and anemia, resulting in marrow hyperplasia and extramedullary hematopoiesis; and (ii) vaso-occlusion, leading to osteonecrosis/bone infarction, myonecrosis, and infection (osteomyelitis and septic arthritis). Knowing the pathophysiology and clinical manifestations is essential for imaging interpretation, but differentiation between acute osteomyelitis and bone infarction remains a clinical and imaging challenge, therefore requiring a multidisciplinary approach. Large subperiosteal fluid collections (≥ 4 mm in depth), in conjunction with elevated inflammatory markers and white blood counts, are more suggestive of osteomyelitis rather than isolated bone infarction. The unenhanced T1-weighted fat-suppressed sequence on MR images was also proposed to aid in this differentiation, but so far with controversial results. Future perspectives of MR imaging include the DIXON technique, which has shown promising results as a biomarker of morbidity of SCD, through evaluation of fat fraction (FF) of bone marrow in a single acquisition and noninvasive way.

Keywords: MRI; Osteomyelitis; Osteonecrosis; Sickle cell disease (SCD); Vaso-occlusion

DOI: https://doi.org/10.1007/s00256-025-04975-6

Haematologica. 2025 Jun 26.

Early detection and management of extracranial arteriopathy reduces the incidence of silent cerebral infarcts in sickle cell anemia: a long-term prospective cohort study.

Francoise Bernaudin, Cecile Arnaud, Annie Kamdem, Jenny Youn, Manuela Vasile, Isabelle Hau, Fouad Madhi, Aline Malterre, Celine Delestrain, Ralph Epaud, Camille Jung, Suzanne Verlhac.

Previous reports about the Creteil newborn-cohort (1988/Apr-2007) showed that the risk of silent cerebral infarcts (SCI) remained high (37.1%) by age 14 in children with sickle cell anemia (SCA) and intracranial time-averaged mean maximum velocity (TAMMV)≥200cm/s despite chronictransfusion. Systematic assessment of extracranial internal carotid artery (eICA) since June-2011 revealed that SCI-risk is associated with chronic or acute anemia and eICA-stenosis. Based on these results, SCA-children with eICA-TAMMV≥200cm/s or eICA-stenosis were placed on chronictransfusion and considered for allogeneic stem-cell transplantation (alloSCT). SCA-children with 160-199cm/s eICA-TAMMV were maintained on hydroxyurea. We hypothesized that detection/management of eICA-arteriopathy and wider use of hydroxyurea could reduce SCI-incidence. Comparison between the new cohort (May-2007/Dec-2014) eICA-assessed before age 4 with wider but not systematic use of hydroxyurea and the earlier cohort (1988/Apr-2007) never eICAassessed until the 2008 update, revealed a significant reduction of SCI-risk (Log-Rank, P=.009) associated with eICA-assessment but not with wider use of hydroxyurea. eICA-TAMMVs≥160cm/s, even with no eICA-stenosis, were risk-factors for SCI, suggesting that all SCA-children with eICATAMMV≥ 160cm/s should be placed on chronic-transfusion. Hydroxyurea initiation at an early age was associated with lower intracranial-arteriopathy incidence, but not with lower eICA-arteriopathy and SCI-incidence. In the overall cohort (1988-2014), including 332 SCA-children, all assessed/managed for eICA-arteriopathy after 2011, the cumulative-SCI-incidence by age 14 was 25.0% (95%CI:19.0%-31.0%). SCI-risk was associated with being older at first-neck-MRA and having high MCV on hydroxyurea. While the impact of hydroxyurea on SCI-incidence remains unclear, making controlled trials necessary, eICA-arteriopathy management by intensive therapy is effective at improving SCIprevention.

DOI: https://doi.org/10.3324/haematol.2025.287720

Pediatr Blood Cancer. 2025 Jun 25. e31881

Clinical Features and Outcomes of Pneumococcal Bacteremia in Children with Sickle Cell Disease in the Pneumococcal Conjugate Vaccine Era.

Marianne E Yee, Lindsey Abel, Grace Kalmus, Ashwin Patel, Mohnd Elmontser, Nitya Bakshi, Yun F Wang, Mark D Gonzalez, Thomas V Adamkiewicz, Inci Yildirim, Peter A Lane.

INTRODUCTION: Children with sickle cell disease (SCD) are at higher risk for invasive infection with Streptococcus pneumoniae compared with the general pediatric population. Penicillin prophylaxis, pneumococcal conjugate (PCV), and polysaccharide vaccines (PPSV) have reduced but not eliminated the risk of pneumococcal bacteremia.
METHODS: A single institution cohort of children with SCD aged <19 years was reviewed over the 14-year period since PCV13 licensure (January 2010-December 2023) to identify and characterize the clinical features and outcomes of S. pneumoniae bacteremia, including serotypes and antibiotic susceptibility.
RESULTS: The cohort included 4356 children with SCD (24,076 person-years). Thirty-eight patients with pneumococcal bacteremia were identified (32 HbSS, five HbSC, one HbSβ+-thalassemia), with median age 5.3 years. The median time to culture positivity was 10.6 h (range 3.4-20.2). Meningitis occurred in four (11%) and acute chest syndrome in 13 (34%). Serotype information, available for 36 (95%) isolates, included 16 (44%) PPSV23 serotypes and one (2.6%) PCV13 serotype (serotype 3). Penicillin nonsusceptibility occurred in 12 out of 31 (39%) at meningitis and one out of 31 (3%) at nonmeningitis breakpoints. Three (8%) deaths occurred (serotypes 12F, 23B, and 15B), all in children aged ≥5 years, who had discontinued prophylactic penicillin. Long-term sequelae occurred in five (14%) surviving children, including hearing loss, limb amputation, and motor and neurocognitive defects.
CONCLUSION: Pneumococcal bacteremia continues to be a concern in children with SCD, with a risk of rapid progression to severe disease. Pneumococcal prevention strategies, immunizations, and urgent empiric treatment for fever remain important for children and adolescents of all ages with SCD.

Keywords: immunization; pneumococcus; sickle cell disease

DOI: https://doi.org/10.1002/pbc.31881