Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study

Am J Kidney Dis. 2019 Jul;74(1):47-55. doi: 10.1053/j.ajkd.2018.12.027. Epub 2019 Feb 21.


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.

Keywords: Sickle cell disease; chronic kidney disease (CKD); eGFR decline; estimated glomerular filtration rate (eGFR); genotype; hyperfiltration; proteinuria; sickle hemoglobin; thalassemia.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Anemia, Sickle Cell* / complications
  • Anemia, Sickle Cell* / diagnosis
  • Anemia, Sickle Cell* / epidemiology
  • Creatinine / blood
  • Disease Progression
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Kidney Transplantation* / methods
  • Kidney Transplantation* / statistics & numerical data
  • Male
  • Proteinuria / diagnosis
  • Proteinuria / etiology
  • Renal Dialysis* / methods
  • Renal Dialysis* / statistics & numerical data
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / etiology
  • Renal Insufficiency, Chronic* / therapy
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • United States / epidemiology


  • Creatinine