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Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study.
Am J Kidney Dis. 2019 07; 74(1):47-55.AJ

Abstract

RATIONALE & OBJECTIVE

Progression of chronic kidney disease (CKD) in sickle cell disease (SCD) and its risk factors remain poorly defined. We identified characteristics associated with CKD as well as decline in estimated glomerular filtration rate (eGFR) and presence of proteinuria over time in adults with SCD.

STUDY DESIGN

Retrospective observational study.

SETTING & PARTICIPANTS

Patients with SCD 18 years or older in a single center from 2004 to 2013.

PREDICTORS

Baseline clinical and laboratory measures, comorbid conditions, SCD-related complications, relevant treatments, and severity of genotypes defined as severe (homozygous SCD [HbSS]/sickle-β0-thalassemia [HbSβ0]) or mild (hemoglobin SC disease [HbSC]/sickle-β+-thalassemia [HbSβ+]-thalassemia).

OUTCOMES

Presence at baseline of CKD, defined here as eGFR<90mL/min/1.73m2 or proteinuria (≥1+) on urinalysis or current kidney transplant or dialysis therapy; change in eGFR; and presence of proteinuria over time.

ANALYTICAL APPROACH

Logistic regression for baseline CKD. Linear mixed-effects model for eGFR decline and generalized linear mixed-effects model for proteinuria during the study period evaluating for interaction with time. Stratified by genotype severity.

RESULTS

Among 427 patients, 331 had 2 or more measurements of creatinine. During a median follow-up of 4.01 (interquartile range, 1.66-7.19) years, annual eGFR decline was 2.05mL/min/1.73m2 for severe genotypes (P<0.001) and 1.16mL/min/1.73m2 (P=0.02) for mild genotypes. At baseline, 21.4% of patients with severe genotypes had CKD versus 17.2% of those with mild genotypes. For severe genotypes, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker use (OR, 6.10; 95% CI, 2.03-18.29; P=0.001) and avascular necrosis (OR, 0.40; 95% CI, 0.16-0.97; P=0.04) were associated with baseline CKD. Among those with mild genotypes, higher hemoglobin level was associated with lower probability of CKD (OR per 1-g/dL greater hemoglobin level, 0.63; 95% CI, 0.43-0.93; P=0.02). Rate of eGFR decline was inversely related to hemoglobin level (β = 0.46 [SE, 0.23]; P=0.04) within the severe genotype subgroup. No factors were identified to be associated with proteinuria over time.

LIMITATIONS

Retrospective observational study, limited direct measures of albuminuria.

CONCLUSIONS

Patients with SCD exhibit rapid decline in eGFR over time. Decline in eGFR is associated with markers of disease severity and associated comorbid conditions.

Authors+Show Affiliations

UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Charlotte, Charlotte, NC. Electronic address: vimal_derebail@med.unc.edu.Department of Medicine, University of North Carolina at Charlotte, Charlotte, NC.Department of Mathematics and Statistics, University of North Carolina at Charlotte, Charlotte, NC.Department of Medicine, Brody School of Medicine, East Carolina University, Greenville, NC.Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN. Electronic address: kataga@uthsc.edu.

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30797615

Citation

Derebail, Vimal K., et al. "Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: an Observational Cohort Study." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 74, no. 1, 2019, pp. 47-55.
Derebail VK, Ciccone EJ, Zhou Q, et al. Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study. Am J Kidney Dis. 2019;74(1):47-55.
Derebail, V. K., Ciccone, E. J., Zhou, Q., Kilgore, R. R., Cai, J., & Ataga, K. I. (2019). Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 74(1), 47-55. https://doi.org/10.1053/j.ajkd.2018.12.027
Derebail VK, et al. Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: an Observational Cohort Study. Am J Kidney Dis. 2019;74(1):47-55. PubMed PMID: 30797615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study. AU - Derebail,Vimal K, AU - Ciccone,Emily J, AU - Zhou,Qingning, AU - Kilgore,R Rosina, AU - Cai,Jianwen, AU - Ataga,Kenneth I, Y1 - 2019/02/21/ PY - 2018/06/07/received PY - 2018/12/17/accepted PY - 2019/2/25/pubmed PY - 2020/3/11/medline PY - 2019/2/25/entrez KW - Sickle cell disease KW - chronic kidney disease (CKD) KW - eGFR decline KW - estimated glomerular filtration rate (eGFR) KW - genotype KW - hyperfiltration KW - proteinuria KW - sickle hemoglobin KW - thalassemia SP - 47 EP - 55 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 74 IS - 1 N2 - RATIONALE & OBJECTIVE: Progression of chronic kidney disease (CKD) in sickle cell disease (SCD) and its risk factors remain poorly defined. We identified characteristics associated with CKD as well as decline in estimated glomerular filtration rate (eGFR) and presence of proteinuria over time in adults with SCD. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Patients with SCD 18 years or older in a single center from 2004 to 2013. PREDICTORS: Baseline clinical and laboratory measures, comorbid conditions, SCD-related complications, relevant treatments, and severity of genotypes defined as severe (homozygous SCD [HbSS]/sickle-β0-thalassemia [HbSβ0]) or mild (hemoglobin SC disease [HbSC]/sickle-β+-thalassemia [HbSβ+]-thalassemia). OUTCOMES: Presence at baseline of CKD, defined here as eGFR<90mL/min/1.73m2 or proteinuria (≥1+) on urinalysis or current kidney transplant or dialysis therapy; change in eGFR; and presence of proteinuria over time. ANALYTICAL APPROACH: Logistic regression for baseline CKD. Linear mixed-effects model for eGFR decline and generalized linear mixed-effects model for proteinuria during the study period evaluating for interaction with time. Stratified by genotype severity. RESULTS: Among 427 patients, 331 had 2 or more measurements of creatinine. During a median follow-up of 4.01 (interquartile range, 1.66-7.19) years, annual eGFR decline was 2.05mL/min/1.73m2 for severe genotypes (P<0.001) and 1.16mL/min/1.73m2 (P=0.02) for mild genotypes. At baseline, 21.4% of patients with severe genotypes had CKD versus 17.2% of those with mild genotypes. For severe genotypes, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker use (OR, 6.10; 95% CI, 2.03-18.29; P=0.001) and avascular necrosis (OR, 0.40; 95% CI, 0.16-0.97; P=0.04) were associated with baseline CKD. Among those with mild genotypes, higher hemoglobin level was associated with lower probability of CKD (OR per 1-g/dL greater hemoglobin level, 0.63; 95% CI, 0.43-0.93; P=0.02). Rate of eGFR decline was inversely related to hemoglobin level (β = 0.46 [SE, 0.23]; P=0.04) within the severe genotype subgroup. No factors were identified to be associated with proteinuria over time. LIMITATIONS: Retrospective observational study, limited direct measures of albuminuria. CONCLUSIONS: Patients with SCD exhibit rapid decline in eGFR over time. Decline in eGFR is associated with markers of disease severity and associated comorbid conditions. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/30797615/Progressive_Decline_in_Estimated_GFR_in_Patients_With_Sickle_Cell_Disease:_An_Observational_Cohort_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(19)30007-1 DB - PRIME DP - Unbound Medicine ER -