Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

Jeffrey D. Lebensburger; Gary R. Cutter; Thomas H. Howard; Paul Muntner; Daniel I. Feig

doi:10.1007/s00467-017-3658-8

HMOX1 and Acute Kidney Injury in Sickle Cell Anemia

Blood ◽

10.1182/blood.v130.suppl_1.686.686 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 686-686

Author(s):

Santosh L. Saraf ◽

Maya Viner ◽

Ariel Rischall ◽

Binal Shah ◽

Xu Zhang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Risk Factor ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Kidney Injury ◽

Ckd Progression ◽

Kdigo Guidelines

Abstract Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear. We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium <1% or BUN-to-creatinine ratio >20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level >1.5 times over the baseline value at the time of enrollment (12%). Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment. We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as >25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04). Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03). In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. Disclosures Gordeuk: Emmaus Life Sciences: Consultancy.

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Risk Factors and Complications Among Pediatric Patients With Sickle Cell Anemia: A Single Tertiary Center Retrospective Study

Cureus ◽

10.7759/cureus.12440 ◽

2021 ◽

Author(s):

Fatma Alzahrani ◽

Anas M Fallatah ◽

Fatimah M Al-Haddad ◽

Shahad T Khayyat ◽

Wasayf M AlMehmadi ◽

...

Keyword(s):

Risk Factors ◽

Retrospective Study ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Pediatric Patients ◽

Tertiary Center

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APOL1 , α-thalassemia, and BCL11A variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia

Haematologica ◽

10.3324/haematol.2016.154153 ◽

2016 ◽

Vol 102 (1) ◽

pp. e1-e6 ◽

Cited By ~ 22

Author(s):

Santosh L. Saraf ◽

Binal N. Shah ◽

Xu Zhang ◽

Jin Han ◽

Bamidele O. Tayo ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Genetic Risk ◽

Risk Profile

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582. Risk Factors for Progression to Hospitalization in Adolescents Presenting with Mild or Moderate COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.780 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S393-S394

Author(s):

Melanie Dubois ◽

Jeffrey Campbell ◽

Gabriella S Lamb ◽

Mari M Nakamura

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Sickle Cell Disease ◽

Kidney Disease ◽

Sickle Cell ◽

Inhaled Corticosteroids ◽

Antibody Therapy ◽

Cell Disease ◽

Mild Disease ◽

Race Ethnicity

Abstract Background Most adolescents (age 12-17 years) with COVID-19 have mild disease. However, certain comorbidities may be risk factors for disease progression, and hospitalization rates for this age group have increased. Adolescents and adults with mild to moderate COVID-19 are eligible for monoclonal antibody therapy. To identify subgroups likely to benefit from this intervention, we evaluated the relationship between comorbidities and need for hospitalization in US adolescents presenting with mild to moderate COVID-19. Methods We analyzed presence of comorbidities and need for hospitalization within 28 days of diagnosis for adolescents in the PIDTRAN registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes (DM), immunosuppressive disease or treatment (IS), sickle cell disease (SCD), congenital/acquired heart disease (CHD), neurologic disease/neurodevelopmental disorders (ND), medical-related technology dependence (MTD), and pulmonary disease requiring daily inhaled corticosteroids (PD). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. Results 1574 patients met inclusion criteria, of whom 180 (11.4%) were hospitalized within 28 days of COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: IS (OR 10.8 [95%CI 5.4 – 21.7]); CKD (OR 5.1 [95%CI 1.0 – 25.6]); DM (OR 4.2 [95%CI 1.7 – 10.6]); SCD (OR 3.4 [95%CI 1.1 – 10.6]). ND (OR 3.0 [95%CI 1.7 – 5.4]); and obesity (OR 2.0 [95%CI 1.1 – 3.9]). Notably, CHD, MTD, and PD were not independently associated with hospitalization. There was no effect modification of race/ethnicity on the association between obesity or DM and hospitalization. Table 1: Characteristics of adolescents in our cohort Figure 1. Association between comorbidities and hospitalization. Model 1: comorbidities only. Model 2: comorbidities, adjusted for race/ethnicity. Abbreviations: CKD – chronic kidney disease; SCD – sickle cell disease; ICS – inhaled corticosteroids. Conclusion IS, CKD, DM, SCD, ND, and obesity were associated with increased odds of hospitalization in adolescents presenting with mild to moderate COVID-19. Adolescents with these comorbidities should be prioritized for consideration of treatment with monoclonal antibodies. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

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Genetic Modifiers Influencing the Development of Albuminuria in Children with Sickle Cell Anemia

Blood ◽

10.1182/blood.v126.23.3393.3393 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3393-3393

Author(s):

Beverly A Schaefer ◽

Jonathan M Flanagan ◽

Banu Aygun ◽

Ofelia A. Alvarez ◽

Stephen C Nelson ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Candidate Genes ◽

Genetic Polymorphisms ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Genetic Variants ◽

Research Funding ◽

Increased Risk

Abstract Background: Nephropathy in sickle cell anemia (SCA) begins in childhood and portends chronic kidney disease, renal failure, and early mortality among affected adults. Individuals of African descent have disproportionately higher rates of developing non-diabetic renal disease. Several candidate genetic variants have been identified, including some specific to African Americans, which are associated with the development of albuminuria and renal disease. The influence of genetic polymorphisms on albuminuria and elevated glomerular filtration rate (GFR) in children with SCA, both early signs of sickle nephropathy, has not been investigated. Objectives: To determine the influence of selected single nucleotide polymorphisms (SNPs) on the development of albuminuria and elevated GFR in children with SCA; to identify novel genetic variants influencing albuminuria and GFR by whole exome sequencing (WES). Design/Methods: Genomic DNA was collected on children with SCA enrolled in two prospective studies with pre-hydroxyurea renal assessments (n=185): (1) Hydroxyurea Study of Long-Term Effects (HUSTLE, NCT00305175, n=79) with no prior disease-modifying therapy; and (2) Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH, NCT 01425307, n=106) on chronic transfusions for abnormal TCD velocities. Albuminuria was defined as ≥30mg albumin/gm creatinine on the pre-hydroxyurea urine specimen. GFR was measured in HUSTLE using plasma DTPA (technetium 99m-labeled diethylenetriaminepentaacetic acid) clearance, and estimated GFR (eGFR) in TWiTCH based on serum creatinine. DNA samples were genotyped for 8 candidate SNPs previously associated with renal disease, using PCR-based allelic discrimination, bidirectional Sanger sequencing, and analysis of variable number tandem repeats (VNTR). Associations between albuminuria and genetic polymorphisms were tested using an additive model and correlation trend test. Linked WES data from the same patients were analyzed to identify other variants associated with albuminuria and GFR. Results: Albuminuria was present in 13.1% of patients, including 16.3% in HUSTLE and 11.0% in TWiTCH. APOL1 genetic variants were common (G1 allele frequency = 21.9%, G2 allele = 16.0%, Table) and similar to published cohorts. Children with two APOL1 G1 alleles had an increased risk of albuminuria that approached statistical significance (p=0.053). Conversely, the presence of the DARC SNP that confers Duffy antigen expression had a protective effect (p=.038). WES analysis did not identify additional non-synonymous APOL1 variants linked with albuminuria. However, 93 non-synonymous variants were associated with DTPA GFR (p<0.001). Using patients with eGFR as a validation cohort, 7 variants in FUBP1, ZFAND4, CD163, GMFG and HLA-E maintained their association with kidney filtrative function (p<0.05). In particular, two variants in CD163, which is a macrophage scavenger receptor for hemoglobin-haptoglobin complexes, were strongly associated with increased GFR in both patient cohorts. Table 1. Candidate genes associated with microalbuminuria. All SNPs were tested with either an additive or recessive genetic model. *The eNOS VNTR was analyzed by the chi-square method. Gene SNP Location MAF Albuminuria (Additive) Variant frequency Cases Controls APOL1 G1 rs73885319 22q12 21.9% 0.053 32.0% 20.3% APOL1 G2 rs71785313 22q12 16.0% 0.445 10.0% 16.0% DARC rs2814778 1q23 13.6% 0.038 4.2% 15.7% eNOS 4a VNTR 7q35 31.2% 0.333* 31.5% 22.7% eNOS rs1799983 7q35 12.5% 0.663 14.6% 12.2% eNOS rs2070744 7q35 15.6% 0.299 10.4% 16.3% CUBN rs7918972 10p12 16.2% 0.457 12.5% 16.8% CUBN rs1801239 10p12 2.7% 0.199 0.0% 3.1% Conclusion: Genetic polymorphisms associated with chronic kidney disease in African American adults may influence the development of early-onset albuminuria among children with SCA, including an increased risk among children with ≥1 APOL1 G1 alleles and a decreased risk associated with the DARC SNP. Previously published eNOS and CUBN variants had no measureable effects. WES analysis suggests novel genetic variants including CD163 SNPs may influence the development of elevated GFR in children with SCA, and provide candidate genes for future research. Disclosures Off Label Use: Hydroxyurea is FDA approved for the treatment of sickle cell anemia in adults, but has not yet been approved in children. . Nottage:Janssen Pharmaceuticals: Employment. Ware:Biomedomics: Research Funding; Bristol Myers Squibb: Research Funding; Bayer Pharmaceuticals: Consultancy; Eli Lilly: Other: DSMB membership.

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Urinary orosomucoid is associated with progressive chronic kidney disease stage in patients with sickle cell anemia

American Journal of Hematology ◽

10.1002/ajh.25036 ◽

2018 ◽

Vol 93 (4) ◽

pp. E107-E109 ◽

Cited By ~ 6

Author(s):

Marina Jerebtsova ◽

Santosh L. Saraf ◽

Simran Soni ◽

Nowah Afangbedji ◽

Xionghao Lin ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Chronic Kidney Disease Stage ◽

Disease Stage

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Burden and Risk Factors of Chronic Kidney Disease in Children with Sickle Cell Anaemia Aged 5 – 16 Years at the University Teaching Hospital, Lusaka - Zambia

University of Zambia Journal of Agricultural and Biomedical Sciences ◽

10.53974/unza.jabs.4.3.397 ◽

2020 ◽

Vol 4 (3) ◽

pp. 40-48

Author(s):

Nchimunya Machila ◽

◽

Chishala Chabala ◽

Chisambo Mwaba ◽

Catherine Chunda-Liyoka ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Sickle Cell ◽

Teaching Hospital ◽

Sickle Cell Anaemia ◽

Age At Diagnosis ◽

University Teaching ◽

Dipstick Urinalysis ◽

The University

Background: Improved medical care has led to the improved life expectancy of sickle cell anaemia (SCA) patients hence complications associated with SCA such as chronic kidney disease (CKD) are being seen more frequently. Globally, nephropathy of varying severity occurs in 5 to 18 % of the SCA population across all age groups with a third of the adults proceeding to develop CKD while over 30 % of paediatric SCA patients have CKD in Africa. The mortality rate in SCA patients CKD is high. This study sought to determine the prevalence and risk factors of CKD in SCA, information that was not available in Zambia prior to this study. This information will guide in targeting and timing of screening for CKD in SCA in children in our population. Objectives: To determine the prevalence of haematuria, proteinuria, abnormal estimated glomerular filtration rate (eGFR), CKD, and risk factors of CKD among the steady-state SCA patients aged 5 to 16 years at the University Teaching Hospital (UTH), Lusaka. Methodology: This was a prospective cross-sectional study of 197 children aged 5 to 16 years with SCA at the UTH - Lusaka conducted from August 2014 to July 2015. Demographic and clinical data were collected using a structured questionnaire. Urine and blood samples were used to determine the urine albumin creatinine ratio (ACR) and full blood count /blood biochemistry respectively. CKD was defined and determined using the Kidney Disease Outcome Quality Initiative 2012 guidelines employing urine ACR, dipstick urinalysis and eGFR. In this study, spot urine ACR and dipstick urinalysis were done and repeated three months later if initial tests were abnormal. Data was analysed using SPSS version 21. Chi-square and t-test were used to compare proportions between groups. Relation between study variables and CKD were examined using logistic regression. Results: The mean age of the participants was 9.6 years (SD ±3.6). Male to female ratio was 1:1. The median age at diagnosis of SCA was 22 months (IQR = 44). The prevalence of haematuria, proteinuria and CKD among the study participants was 14.2%, 36% and 36 % respectively. Low haemoglobin and elevated mean corpuscular volume (MCV) were associated with CKD-AOR 0.62, 95% CI; 0.46-0.84 and 1.04, 95% CI; 1.01 – 1.08 respectively. Recurrent admissions (due to VOCs, severe anaemia and febrile illness) were also risk factors associated with CKD- AOR 0.52, 95% CI; 0.27-0.98. CKD was not associated with age at enrolment, sex, age at diagnosis of SCA, recurrent Vaso-occlusive crisis (VOCs) or abnormal liver function tests. Conclusion: The prevalence of CKD among the SCA patients at UTH- Lusaka is high (36%) with lower Haemoglobin, elevated MCV and recurrent admissions being risk factors for developing CKD. SCA patients should be screened for CKD routinely at least once a year. Interventions such as the early introduction of hydroxyurea, proactive blood transfusions and ACE inhibitors can reduce the risk of CKD and its progression to end-stage renal disease.

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CHRONIC KIDNEY DISEASE AMONGST SICKLE CELL ANAEMIA PATIENT AT THE UNIVERSITY OF MAIDUGURI TEACHING HOSPITAL, NORTH EASTERN NIGERIA: A STUDY OF PREVALENCE AND RISK FACTORS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.010 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 4

Author(s):

Audu Abdullahi Bukar ◽

Mohammad Maina Sulaiman ◽

Adama Isa Ladu ◽

Aisha Mohammed Abba ◽

Mohammed Kabir Ahmed ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Sickle Cell ◽

Sickle Cell Anaemia ◽

Laboratory Data ◽

Transfusion Therapy ◽

Haematological Profile ◽

Stage Renal Disease

ABSTRACTIntroduction: Involvement of the kidneys in patient with sickle cell anaemia is a well recognized chronic complication of this disorder. The index study seeks to determine the prevalence of chronic kidney disease in patients with homozygous sickle cell disease (HbSS) and to identify risk factors associated with its development.Methodology: The subjects consisted of adolescents and adults with HbSS recruited sequentially from the adult haematology outpatient clinic and Day care ward of the unit. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crisis and transfusion therapy, as well as laboratory data including haematological profile, renal function test were obtained from routine blood result. The glomerular filtration rate was estimated (eGFR) using the ‘modification of diet in renal disease’ (MDRD) formula..Results: Two hundred and eighty-four HbSS patients were recruited. The prevalence of CKD amongst them was 38.9%. Further stratification of the patients based on eGFR showed that sixty-nine (26.8%) had hyperfiltration; 35 (13.6%) stage 1 CKD; 53 (20.6%) stage 2 CKD; 61 (23.7%) stage 3 CKD; 30 (11.7%) stage 4 CKD and 9 (3.5%) had end stage renal disease. There was significant association between eGFR and clinical parameters such as age (r -0.353, p=0.000), SBP (r -0.148, p= 0.021), DBP (r -0.213, p=0.001) and total number of blood received (r -0.276, p=0.000); and laboratory parameters such as PCV (r 0.371, p=0.000); urea ( r 0.527, p=000 ); creatinine (r 0.625, p=0.000) and uric acid ( r -0.419, p=0.000).ConclusionThe present study has revealed a high prevalence of CKD amongst patients with SCA in this region. Various clinical and laboratory predictors of eGFR were also identified. Monitoring and detection of early stages of these groups of patients may allow for interventions which may delay progression into advance stages and ESRD.

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Orosomucoid As a Biomarker for Chronic Kidney Disease Associated with Sickle Cell Anemia

Blood ◽

10.1182/blood-2018-99-119477 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2352-2352

Author(s):

Ammanuel Taye ◽

Nathan Smith ◽

Nowah Kokou Apeadoufia Afangbedji ◽

Xiaomei Niu ◽

James G. Taylor ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Research Funding ◽

Urine Samples ◽

Cell Disease ◽

Howard University ◽

Ckd Stage ◽

Stage 1

Abstract BACKGROUND: Chronic kidney disease (CDK) is a serious and highly prevalent complication of Sickle cell anemia (SCA). Proteinuria and microalbuminuria can be under-detected in SCA because of the renal concentrating defect. Hence, complementary diagnostic biomarkers are necessary for early detection of CKD in patient with SCA. Our recent study identified alpha 1-acid glycoprotein (orosomucoid, ORM) (1) as potential biomarker of CKD. ORM is a major acute phase inflammatory protein synthesized by the liver and its presence in urine may indicate underlying inflammation in SCA patients. OBJECTIVES: We aimed to validate ORM as biomarker for CKD in a cohort of SCA patients recruited at Howard University. METHODS: We analyzed samples collected from patients enrolled in a sickle cell disease registry study at Center for Sickle Cell Disease, Howard University. Plasma and urine samples were collected and stored at -80°C. Plasma samples were assayed for creatinine and cystatin C. Urine samples were analyzed for albumin, creatinine and ORM. Multistix was used to determine protein, blood, pH and specific gravity (SG) in urine samples. Estimated GFR (eGFR) was calculated using CKD-EPI creatinine-cystatin equation. CKD stages were assigned according to the National Kidney Foundation, Kidney Disease Outcomes Quality Initiatives (K/DOQI) guidelines: stage 0 - eGFR>60 ml/min/1.73m2 and AL/CRE<30 mg/g; stage 1- eGFR>90 ml/min/1.73m2 and AL/CRE≥30 mg/g; stage 2 - eGFR 60-89 ml/min/1.73m2 and AL/CRE≥30 mg/g, stage 3 - eGFR 30 - 59 /1.73m2; stage 4 - eGFR 15 - 29 ml/min/1.73m2 and stage 5 - eGFR < 15 ml/min/1.73m2. Glomerular hyperfiltration was defined as eGFR>130 ml/min/1.73 m2 for females and eGFR>140 ml/min/1.73 m2 for males. RESULTS: The Howard University registry study group consisted of 96 patients (mean age 38.1 years, range 18 - 67 years, 55% females) and included 65.6% HbSS, 21.8% HbSC, 7.2% HbS β+thalassemia, 4.1% HbS β0 thalassemia. Based on urinary dipstick test, proteinurea was detected in 16.5% patient. Hyperfiltration was detected in 45 patients (56.3%). CDK (combined stage 1-4) was detected in 35.8% patients. No difference was found between females and males in CKD prevalence. Prevalence of CKD in HbSC patients was 11% whereas it was 37% in HbSS patients. Prevalence of CDK increased with the age. The overall urinary ORM/CRE levels demonstrated modest correlation with CKD stage (R2=0.22). Next we stratified samples based on the levels of ORM/CRE. The samples were separated into two groups: (i) samples with no or mild inflammation (ORM/CRE<10μg/mg) and (ii) samples that displayed significant inflammation (ORM/CRE>10 μg/mg). We observed strong inverse correlation between the percentage of samples without inflammation and CKD stage (R2=0.996). We also observed strong correlation of CDK progression with number of samples with significant inflammation (R2=0.996). Sensitivity of ORM/CRE was 53.8%, specificity 70.2% and odds ratio OR 2.72 for samples with CKD stages 1-4 compared to the samples without CKD (stage 1). CONCLUSIONS: In our cohort, determination of proteinurea evaluated by dipstick (16%) grossly underestimated CKD prevalence (35%) determined by eGFR and AL/CRE ratios. Subjects with HbSC had 3-fold less prevalence of CKD comparing to the patients with HbSS. ORM/CRE levels correlated with the stages of CKD stages (OR 2.72). Further longitudinal study is needed to determine whether ORM/CRE ratio can be used as a prognostic marker of renal disease development. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants 1P50HL118006, 1R01HL125005 and 5G12MD007597. AT was supported by ASH MMSAP summer program. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI, NIMHD or NIH. REFERENCES: Jerebtsova, M., Saraf, S. L., Soni, S., Afangbedji, N., Lin, X., Raslan, R., Gordeuk, V. R., and Nekhai, S. (2018) Urinary orosomucoid is associated with progressive chronic kidney disease stage in patients with sickle cell anemia. American journal of hematology93, E107-E109 Disclosures Taylor: Pfizer: Research Funding; NHLBI: Research Funding. Nekhai:NIAID, NIH: Research Funding; NIMHD, NIH: Research Funding; NHLBI, NIH: Research Funding.

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