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Haptoglobin (HP) is an acute-phase protein and the main scavenger of cell-free hemoglobin. When HP is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of patients with SCD, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode or acute chest syndrome. With a median follow-up of 6.8 years, acute chest syndrome occurred in 42% (n = 163) and multiorgan failure in 14% (n = 53) of 391 patients with SCD with a minimum follow-up of 6 months. The HP 1 allele was independently associated with lower risk of developing multiorgan failure during acute chest syndrome (additive model hazard ratio, 0.5; P < .001). Future studies assessing the regulation of HP concentrations and ability to bind cell-free hemoglobin according to the HP genotype may help to identify patients with SCD at high risk for multiorgan failure and to guide interventions, such as rapid initiation of exchange transfusion or HP replacement therapy.

Glomerular hyperfiltration is common in young sickle cell anemia patients and precedes development of overt kidney disease. In this multicenter pooled cohort, we characterized hyperfiltration and its decline to normal range in adult patients. Glomerular filtration rate (GFR) was estimated using the creatinine-based 2009 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation omitting race adjustment and the 2021 CKD-EPI equation. Using CKD-EPI–2009, 506 patients had baseline estimated GFR (eGFR) ≥90 mL/min per 1.73 m2, median age of 24 (interquartile range [IQR], 19-34) years and 5.17 years of follow-up. The prevalence of hyperfiltration (eGFR ≥140 and ≥130 mL/min per 1.73 m2 for men and women, respectively) was 38.3%. Using CKD-EPI–2009, baseline hyperfiltration was less likely with older age (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.73-0.83; P < .0001), male sex (OR, 0.32; 95% CI, 0.18-0.58; P = .0002), and higher weight (OR, 0.96; 95% CI, 0.94-0.99; P = .001). Using CKD-EPI–2021, hyperfiltration was similarly less likely with older age (OR, 0.75; 95% CI, 0.70-0.81; P < .0001), male sex (OR, 0.24; 95% CI, 0.13-0.44; P < .0001), and higher weight (OR, 0.97; 95% CI, 0.95-0.99; P = .004). In patients with baseline hyperfiltration, eGFR declined to normal values at a median age of 26.2 years. Using CKD-EPI–2009, this decline was associated with male sex (HR, 2.20; 95% CI, 1.26-3.87; P = .006), systolic blood pressure (hazard ratio [HR], 1.02; 95% CI, 1.01-1.04; P = .01), and hydroxyurea use (HR, 1.74; 95% CI, 1.002-3.03; P = .05). Using CKD-EPI–2021, decline of eGFR to normal was only associated with male sex (HR, 3.39; 95% CI, 2.01-5.69; P < .0001). Decline to normal eGFR range from hyperfiltration occurs earlier in males, those on hydroxyurea, and with higher systolic blood pressure.

Aims Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. Methods and results Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when ∼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. Conclusion In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m(2) in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations were unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.

Disordered iron and mineral homeostasis are interrelated complications of chronic kidney disease that may influence cardiovascular and kidney outcomes. In a prospective analysis of 3747 participants in the Chronic Renal Insufficiency Cohort Study, we investigated risks of mortality, heart failure, end-stage kidney disease (ESKD), and atherosclerotic cardiovascular disease according to iron status, and tested for mediation by C-terminal fibroblast growth factor 23 (FGF23), hemoglobin and parathyroid hormone. Study participants were agnostically categorized based on quartiles of transferrin saturation and ferritin as: “Iron Replete” (27.1% of participants; referent group for all outcomes analyses), “Iron Deficiency” (11.1%), “Functional Iron Deficiency” (7.6%), “Mixed Iron Deficiency” (iron indices between the Iron Deficiency and Functional Iron Deficiency groups; 6.3%), “High Iron” (9.2%), or “Non-Classified” (the remaining 38.8% of participants). In multivariable-adjusted Cox models, Iron Deficiency independently associated with mortality (hazard ratio 1.28, 95% confidence interval 1.04–1.58) and heart failure (1.34, 1.05–1.72). Mixed Iron Deficiency associated with mortality (1.61, 1.27–2.04) and ESKD (1.33, 1.02–1.73). High Iron associated with mortality (1.54, 1.24–1.91), heart failure (1.58, 1.21–2.05), and ESKD (1.41, 1.13–1.77). Functional Iron Deficiency did not significantly associate with any outcome, and no iron group significantly associated with atherosclerotic cardiovascular disease. Among the candidate facilitators, FGF23 most significantly mediated the risks of mortality and heart failure conferred by Iron Deficiency. Thus, alterations in iron homeostasis associated with adverse cardiovascular and kidney outcomes in patients with chronic kidney disease.

Non-myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim-mobilized peripheral blood HPC and sirolimus. The median follow-up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft-versus-host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle-related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well-tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.

Sickle cell syndromes, including sickle cell disease (SCD) and sickle cell trait (SCT), are associated with multiple kidney abnormalities. Young patients with SCD have elevated effective renal plasma flow and glomerular filtration rates (GFR), which decrease to normal ranges in young adulthood and subnormal levels with advancing age. The pathophysiology of SCD-related nephropathy is multifactorial — oxidative stress, hyperfiltration and glomerular hypertension are all contributing factors. Albuminuria, which is an early clinical manifestation of glomerular damage, is common in individuals with SCD. Kidney function declines more rapidly in individuals with SCD than in those with sickle cell trait or in healthy individuals. Multiple genetic modifiers, including APOL1, HMOX1, HBA1 and HBA2 variants are also implicated in the development and progression of SCD-related nephropathy. Chronic kidney disease and rapid decline in estimated glomerular filtration rate are associated with increased mortality in adults with SCD. Renin–angiotensin–aldosterone system inhibitors are the standard of care treatment of albuminuria in SCD, despite a lack of controlled studies demonstrating their long-term efficacy. Multiple studies of novel therapeutic agents are ongoing, and patients with SCD and kidney failure should be evaluated for kidney transplantation. Given the high prevalence and severe consequences of kidney disease, additional studies are needed to elucidate the pathophysiology, natural history and treatment of SCD-related nephropathy.

BACKGROUND: People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. METHODS: This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ(0)-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ(+)-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. RESULTS: Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m(2), respectively) and moderate (52 and 102 ml/min per 1.73 m(2), respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m(2)). CONCLUSIONS: We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

Not available.

Hydroxyurea, indicated for managing sickle cell anemia (SCA), and L-glutamine, indicated for treating sickle cell disease (SCD), were the only pharmacotherapeutic options in this patient population before the approval of crizanlizumab by the U.S. Food and Drug Administration in November 2019 to reduce vaso-occlusive crisis (VOC) frequency. This article reviews the evidence pertaining to crizanlizumab in SCD by searching records in Medline, Embase, and International Pharmaceutical Abstracts. Crizanlizumab, a P-selectin inhibitor, mitigates the microvascular vaso-occlusion in SCD. In the multicenter randomized double-blind SUSTAIN trial, a higher dose of crizanlizumab decreased the incidence of VOCs by 45% and prolonged the median time to the first and second VOC. A post hoc subgroup analysis demonstrated that the proportion of patients who had no VOC incidence during the study period was greater in the crizanlizumab group, and this benefit was consistent regardless of concomitant hydroxyurea use, prior categorized history of VOC frequency, or SCD genotype. Crizanlizumab had a safety profile comparable with placebo. Multiple ongoing clinical trials are trying to establish its roles in pediatric patients with SCD and its effects on alleviating other SCD-related complications. As the first parenteral option for SCD, providers need to formulate administration logistics to improve patients' access to crizanlizumab. Current available data suggest crizanlizumab is a promising agent to reduce VOC in patients with SCD.

Voxelotor, a sickle hemoglobin polymerization inhibitor, was approved by the U.S. Food and Drug Administration to treat sickle cell disease (SCD) in November 2019. This article reviews published data about voxelotor treatment of SCD based on a search of MEDLINE, Embase, and International Pharmaceutical Abstracts. In a phase I/II trial, voxelotor demonstrated a dose-dependent pharmacokinetic and pharmacodynamic response and was well tolerated in healthy volunteers and patients with SCD. In a multi-center, randomized, double-blind, phase III trial (HOPE trial), a significantly higher percentage of patients randomized to voxelotor had increased hemoglobin (> 1 g/dl from baseline) compared to placebo. A greater reduction of hemolytic markers was also observed in the voxelotor-treated group, whereas the incidence of adverse effects was comparable. Three case series or reports also demonstrated the efficacy and safety of voxelotor use in a limited number of SCD patients in the real-world situation, although one patient with SCD, severe anemia, and a history of autoantibody-mediated hemolysis failed to respond to voxelotor. An ongoing trial (HOPE-KIDS) is designed to establish the use of voxelotor in younger pediatric patients with SCD. There is a theoretical concern that voxelotor may impair oxygen delivery, due to modification of the oxygen affinity of hemoglobin, which needs to be further evaluated. As a first-in-class hemoglobin modulator, voxelotor offers a new treatment option targeting the root cause of SCD.

Few studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD).Prospective cohort study.We studied 2,720 self-identified Black or White participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study from July 1, 2013, to December 31, 2017.Self-reported race (Black vs White).Hospitalized AKI (≥50% increase from nadir to peak serum creatinine).Cox regression models adjusting for demographics (age and sex), prehospitalization clinical risk factors (diabetes, blood pressure, cardiovascular disease, estimated glomerular filtration rate, proteinuria, receipt of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers), and socioeconomic status (insurance status and education level). In a subset of participants with genotype data, we adjusted for apolipoprotein L1 gene (APOL1) high-risk status and sickle cell trait.Black participants (n = 1,266) were younger but had a higher burden of prehospitalization clinical risk factors. The incidence rate of first AKI hospitalization among Black participants was 6.3 (95% CI, 5.5-7.2) per 100 person-years versus 5.3 (95% CI, 4.6-6.1) per 100 person-years among White participants. In an unadjusted Cox regression model, Black participants were at a modestly increased risk of incident AKI (HR, 1.22 [95% CI, 1.01-1.48]) compared with White participants. However, this risk was attenuated and no longer significant after adjusting for prehospitalization clinical risk factors (adjusted HR, 1.02 [95% CI, 0.83-1.25]). There were only 11 AKI hospitalizations among individuals with high-risk APOL1 risk status and 14 AKI hospitalizations among individuals with sickle cell trait.Participants were limited to research volunteers and potentially not fully representative of all CKD patients.In this multicenter prospective cohort of CKD patients, racial disparities in AKI incidence were modest and were explained by differences in prehospitalization clinical risk factors.

BACKGROUND. Hemolysis and vaso-occlusion underlie multi-organ system complications in sickle cell disease (SCD). METHODS. We assessed real-world biomarkers in University of Illinois adult SCD patients, categorized as severe (HbSS/Sβ(0)-thalassemia; n=342) or mild (HbSC/Sβ(+)-thalassemia; n=100) genotypes and stratified according to treatment. African-American controls from the National Health and Nutrition Examination Survey (NHANES) were matched with each genotype category. RESULTS. Most measures of hemolysis, anemia, inflammation, and function of kidneys, liver and lungs differed markedly in untreated severe genotype patients compared to NHANES controls. These same biomarkers were significantly closer to the NHANES control range in untreated mild versus severe genotype patients, but they were not improved in severe genotype patients receiving treatment with hydroxyurea or blood transfusions, except that hemoglobin and HbF were higher with hydroxyurea. Systolic blood pressures did not differ among the SCD and NHANES groups, but diastolic pressures were higher in mild genotype patients. Ferritin in severe genotype patients on chronic transfusions was 50-fold higher than NHANES controls. DISCUSSION. The cross-sectional real-world biomarkers of patients on hydroxyurea or transfusions were not markedly improved compared to untreated patients. This may be due partly to poor compliance or more severe disease. Our findings highlight the need for more effective treatments.

Background Whether race/ethnicity plays a role in hematopoietic stem/progenitor cells (HSPC) mobilization in autologous donors has not been studied. We hypothesize that donor characteristic including race/ethnicity, age, sex, body mass index, and diagnostic groups influences HSPC mobilization. Diagnostic groups include healthy allogeneic donors, autologous multiple myeloma (MM) and non-MM donors. Study design and methods Here, we conducted a single-center retrospective study in 64 autologous patients and 48 allogeneic donors. Autologous donors were patients diagnosed with MM or non-MM. All donors were grouped as African American (AA), White (W), or "Other"(O). Results Multivariate analysis demonstrated diagnostic group differences for CD34+ cell yields between race/ethnicity. Specifically, non-MM patients had the lowest CD34+ cell yields in AA and O, but not in W. For pre-apheresis peripheral blood (PB) CD34+ cell numbers, race/ethnicity had a significant effect both in bivariate and multivariate analyses. Non-MM patients had the lowest, and AA patients had the highest PB CD34+ cells. The results support the view that past therapies used in MM are likely more conducive of recovery of HSPC. Conclusions Our study shows that race/ethnicity and diagnostic group differences influenced CD34+ cell mobilization response across donor types. Interestingly, autologous MM donors with the aid of plerixafor displayed comparable CD34 yields to allogeneic donors. Even though both MM and non-MM donors received plerixafor, non-MM donors had significantly lower CD34 yields among AA and O donors but not in W donors. Larger studies would be required to validate the role of diagnostic groups and race/ethnicity interactions.

Conflicting evidence exists on the epidemiology of type 2 diabetes mellitus (T2DM) among patients with sickle cell disease (SCD). This study measured the prevalence, incidence and clinical outcomes associated with T2DM in a large US population of commercially-insured adults aged ≥20 years with SCD between 2009 and 2014. Among 7070 patients with SCD, the mean age (median) was 39 (37) years and 60·8% were female. The standardized prevalence of T2DM among patients with SCD showed a modest increase, from 15·7% to 16·5% (P trend = 0·026), and was comparable to African-American respondents to the National Health and Nutrition Examination Survey (18·2%). Over 17 024 person-years, the crude incidence rate for T2DM was 25·4 per 1000 person-years. Incident T2DM was associated with comorbid hypertension (hazard ratio [HR] = 1·45, 95% confidence interval [CI] 1·14-1·83), and dyslipidaemia (HR = 1·43, 95%CI 1·04-1·96). Compared to SCD patients without T2DM, more SCD patients with T2DM had diagnoses of nephropathy (28·0% vs. 9·5%; P < 0·001), neuropathy (17·7% vs. 5·2%; P < 0·001) and stroke (24·1% vs. 9·2%; P < 0·001). Prevalence of T2DM in SCD patients is similar to the general African American population with an increasing trend in recent years. These trends support routine screening for T2DM in aging patients with SCD, especially those with comorbid hypertension and/or dyslipidaemia.

BACKGROUND Patients with sickle cell disease (SCD) experience significant medical and psychological stressors that affect their mental health, well-being, and disease outcomes. Digital cognitive behavioral therapy (CBT) has been used in other patient populations and has demonstrated clinical benefits. Although evidence-based, nonpharmacological interventions for pain management are widely used in other populations, these treatments have not been well studied in SCD. Currently, there are no adequately powered large-scale clinical trials to evaluate the effectiveness and dissemination potential of behavioral pain management for adults with SCD. Furthermore, some important details regarding behavioral therapies in SCD remain unclear—in particular, what works best for whom and when. OBJECTIVE Our primary goal is to compare the effectiveness of two smartphone–delivered programs for reducing SCD pain symptoms: digital CBT versus pain and SCD education (Education). Our secondary goal is to assess whether baseline depression symptoms moderate the effect of interventions on pain outcomes. We hypothesize that digital CBT will confer greater benefits on pain outcomes and depressive symptoms at 6 months and a greater reduction in health care use (eg, opioid prescriptions or refills or acute care visits) over 12 months. METHODS The CaRISMA (Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications) study is a multisite comparative effectiveness trial funded by the Patient-Centered Outcomes Research Institute. CaRISMA is conducted at six clinical academic sites, in partnership with four community-based organizations. CaRISMA will evaluate the effectiveness of two 12-week health coach–supported digital health programs with a total of 350 participants in two groups: CBT (n=175) and Education (n=175). Participants will complete a series of questionnaires at baseline and at 3, 6, and 12 months. The primary outcome will be the change in pain interference between the study arms. We will also evaluate changes in pain intensity, depressive symptoms, other patient-reported outcomes, and health care use as secondary outcomes. We have 80% power to detect a difference of 0.37 SDs between study arms on 6-month changes in the outcomes with 15% expected attrition at 6 months. An exploratory analysis will examine whether baseline depression symptoms moderate the effect of the intervention on pain interference. RESULTS This study will be conducted from March 2021 through February 2022, with results expected to be available in February 2023. CONCLUSIONS Patients with SCD experience significant disease burden, psychosocial stress, and impairment of their quality of life. CaRISMA proposes to leverage digital technology and overcome barriers to the routine use of behavioral treatments for pain and depressive symptoms in the treatment of adults with SCD. The study will provide data on the comparative effectiveness of digital CBT and Education approaches and evaluate the potential for implementing evidence-based behavioral interventions to manage SCD pain. CLINICALTRIAL ClinicalTrials.gov NCT04419168; https://clinicaltrials.gov/ct2/show/NCT04419168. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/29014

Background Point‐of‐care (POC) International Normalized Ratio (INR) measurement provides efficient monitoring of warfarin therapy; however, its reliability may be affected in patients with anemia, such as those with sickle cell disease (SCD). Objectives To evaluate the correlation of POC‐INR to clinical laboratory INR (CL‐INR) in SCD and use of a correction factor. Patient/Methods In this retrospective study, the accuracy of POC‐INR compared to CL‐INR was evaluated in a cohort of patients with SCD and in a non‐SCD Black cohort. Results Despite the difference in anemia, the SCD cohort showed a similar percentage of in‐range POC‐INR values as observed in the non‐SCD cohort (37% vs 42%). The SCD cohort was randomly divided to form discovery and validation cohorts. In the discovery cohort, 86% of POC‐INRs were in range when the POC‐INRs were ˂4.0, but only 24% were in range if POC‐INRs were ≥4.0. A linear regression of CL‐INR versus POC‐INR for POC‐INR values ≥4.0 yielded a coefficient of 0.72 (95% confidence interval, 0.69‐0.75); Multiplying POC‐INR by this correction factor, rounded to 0.7 for ease of use in clinical practice, improved the proportion of in‐range POC‐INR values ≥4.0 from 24% to 100% in the SCD discovery cohort and from 19% to 95% in the SCD validation cohort. Similar findings applied to analyses of the non‐SCD cohort. Conclusions POC‐INR and CL‐INR in patients with SCD are similar when POC‐INR is

Introduction: Initial studies from Wuhan, China reported patients infected with SARS-CoV-2 have uncontrolled coagulopathy and an increased risk for thrombotic complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), and arterial thrombosis.1 The incidence of thrombosis attributed to coronavirus disease 2019 (COVID-19) ranged from 9.5% in all hospital-admitted patients to 31% in the critically ill.2,3 COVID-19 has had a major impact on the Chicago metropolitan area with over 121,000 confirmed cases as of August 2020, Cook county being the 4th highest affected county after Maricopa, Miami-Dade and Los Angeles counties.4 The primary goal of this study is to describe the rate of thrombotic events in the Chicago metropolitan area, highlighting an ethnically diverse population, and identify new risk factors for thrombosis between three university health systems. Methods: We conducted a retrospective analysis between three university health systems in the Chicago metropolitan area: Loyola University Health System (LUHS): comprised of one tertiary and two community hospitals, Rush University System for Health (RUSH): comprised of one tertiary and two community hospitals, and University of Illinois-Chicago (UIC): a tertiary hospital. All patients had positive SARS-CoV-2 testing and were hospitalized for COVID-19. PE, DVT or arterial thrombosis were confirmed by supportive imaging modalities. Wilcoxon rank sum test were used to test the associations of continuous variables; Chi-square test or Fisher's exact test were used to test the associations of categorical variables. All analyses were performed with SAS 9.4 and two-sided p-value < .05 were deemed statistically significant. Results: Between March and May 2020, 2,180 patients from LUHS, RUSH and UIC were hospitalized for COVID-19 and were included in our analysis. Baseline patient demographics are described in Table 1. Race/ethnicity demographics are as follows: Hispanics (H)/ African Americans (AA) represented 47%/17% of LUHS patients, 32%/42% of RUSH patients, and 36%/51% of UIC patients, respectively (Figure 1). Intensive care admissions were needed in 33% of all patients. Documented total thrombotic events are as follows: LUHS = 5.4% (41 VTE/PE, 10 arterial and 5 with both venous and arterial); RUSH = 9.7% (70 VTE/PE, 7 arterial and 4 with both venous/arterial); UIC = 6% (14 VTE/PE, 4 arterial and 0 with both venous/arterial). Patients that developed a thrombotic event were similar by age, sex, and BMI to those without a thrombotic event. Anticoagulation prophylaxis was given to 82% of pts at LUHS and UIC at time of admission. Collectively, those with thrombotic events (N=156) had higher incidence of intensive care admission, elevated white blood cell (WBC) count and a d-dimer >5X upper limit normal (ULN) at presentation. Furthermore, a higher proportion of pts that had a thrombotic event were diabetic at LUHS and RUSH (Table 2). Mortality in COVID-19 patients was 13-16% and patients that had a thrombotic event had a higher risk of death in the RUSH and UIC cohorts. Conclusions: In a racially diverse, multi-institutional cohort of patients, we demonstrate that 7.2% of COVID-19 patients had a thrombotic event. Consistent risk factors for thrombosis across the different centers included an initial d-dimer levels >5X ULN, elevated initial WBC count, diabetes, and being critically ill. Mortality differences and anticoagulation practices between the institutions as well as race/ethnicity differences regarding thrombosis will be explored in future combined multivariate analyses. Finally, based off these risk factors, identification of patients at most risk for thrombosis is needed to reduce the morbidity and mortality when diagnosed with COVID-19. References -Tang et. al. J Thromb Haemost. 2020;18:844-847. -Klock et. Al. Thrombosis Research 2020;191:145-147. -Al-Samkari H, Laef RS, Dzik WH et. Al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. -https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/county-map.html; accessed 8/7/20. Disclosures Arain: Astellas: Other: Spouse is employed. Stiff:Macrogenics: Research Funding; Delta-Fly: Research Funding; Unum: Research Funding; Atara: Research Funding; Kite, a Gilead Company: Research Funding; Amgen: Research Funding; Gamida Cell: Research Funding. Saraf:Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Pfizer, Global Blood Therapeutics, Novartis: Research Funding.

Introduction: Chronic kidney disease (CKD) is a prevalent complication of sickle cell anemia (SCA). Hyperfiltration that delayed detection of CKD is common in SCA patients. Identification of novel urinary biomarkers correlating with glomerular filtration rates may help to detect and predict progression of renal disease. Methods: Reanalysis of mass spectra of urinary samples obtained from University of Illinois at Chicago identified kringle domain-containing protein HGFL. Results: HGFL levels correlated with hyperfiltration, were significantly reduced at CKD stage 1 compared to stage 0, negatively correlated with progression of CKD and were suitable for differentiation of stage 1. Better prediction of CKD progression to stage 2 was observed for HGFL-based risk prediction compared to the estimated glomerular filtration rate (eGFR)-based prediction. Results from a Howard University patient cohort supported the utility of HGFL-based test for the differentiation of stage 1 of CKD. Conclusion: Urinary HGFL may contribute additional information beyond eGFR and improve diagnosis of early-stage CKD in SCA patients.

Background: In the general population, genetic risk for elevated blood pressure has been associated with cardiovascular disease but not kidney function or incident chronic kidney disease. These relationships have not been studied longitudinally in participants with chronic kidney disease. We examined whether blood pressure genetic risk predicts cardiovascular disease and kidney disease progression in patients with chronic kidney disease. Methods: We included 1,493 African and 1,581 European ancestry participants from the Chronic Renal Insufficiency Cohort who were followed for 12 years. We examined associations of blood pressure genetic risk scores with development of cardiovascular disease (myocardial infarction, congestive heart failure, or stroke) and chronic kidney disease progression (incident end stage kidney disease or halving of estimated glomerular filtration rate) using Cox proportional hazards models. Analyses were stratified by race and included adjustment for age, sex, study site, and ancestry principal components. Results: Each standard deviation increase in systolic blood pressure and pulse pressure genetic risk score conferred respective 15% [95% confidence interval: 4%, 27%] and 11% (95% confidence interval: 1%, 23%) higher risks of cardiovascular disease, with a similar marginally significant trend for diastolic blood pressure, among European ancestry participants. Among African ancestry participants, each standard deviation increase in systolic and diastolic blood pressure genetic risk score conferred 10% (95% confidence interval: 1%, 20%) and 9% (95% confidence interval: 0%, 18%) higher risk of cardiovascular disease. Higher genetic risk was not associated with chronic kidney disease progression. Conclusions: Genetic risk for elevation in blood pressure was associated with increased risk of cardiovascular disease but not chronic kidney disease progression.

Not available.