Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease

An Observational Cohort Study

Vimal K. Derebail, Emily J. Ciccone, Qingning Zhou, R. Rosina Kilgore, Jianwen Cai, Kenneth Ataga

Research output: Contribution to journalArticle

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 < 90 mL/min/1.73 m2 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 2.05 mL/min/1.73 m2 for severe genotypes (P < 0.001) and 1.16 mL/min/1.73 m2 (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.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume74
Issue number1
DOIs
StatePublished - Jul 1 2019

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Sickle Cell Anemia
Observational Studies
Glomerular Filtration Rate
Cohort Studies
Chronic Renal Insufficiency
Genotype
Proteinuria
Thalassemia
Hemoglobins
Hemoglobin SC Disease
Retrospective Studies
Albuminuria
Urinalysis
Angiotensin Receptor Antagonists
Angiotensins
Dialysis
Creatinine
Necrosis
Logistic Models
Transplants

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease : An Observational Cohort Study. / Derebail, Vimal K.; Ciccone, Emily J.; Zhou, Qingning; Kilgore, R. Rosina; Cai, Jianwen; Ataga, Kenneth.

In: American Journal of Kidney Diseases, Vol. 74, No. 1, 01.07.2019, p. 47-55.

Research output: Contribution to journalArticle

Derebail, Vimal K. ; Ciccone, Emily J. ; Zhou, Qingning ; Kilgore, R. Rosina ; Cai, Jianwen ; Ataga, Kenneth. / Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease : An Observational Cohort Study. In: American Journal of Kidney Diseases. 2019 ; Vol. 74, No. 1. pp. 47-55.
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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 < 90 mL/min/1.73 m2 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 2.05 mL/min/1.73 m2 for severe genotypes (P < 0.001) and 1.16 mL/min/1.73 m2 (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.",
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T1 - Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease

T2 - 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

PY - 2019/7/1

Y1 - 2019/7/1

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 < 90 mL/min/1.73 m2 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 2.05 mL/min/1.73 m2 for severe genotypes (P < 0.001) and 1.16 mL/min/1.73 m2 (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.

AB - 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 < 90 mL/min/1.73 m2 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 2.05 mL/min/1.73 m2 for severe genotypes (P < 0.001) and 1.16 mL/min/1.73 m2 (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.

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