Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis

Abstract

Glomerular hyperfiltration is common in young sickle cell anemia (SCA) 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 equation omitting race adjustment and the 2021 CKD-EPI equation. Using CKD-EPI-2009, 506 patients had baseline eGFR ≥90 mL/min/1.73 m2, median age of 24 (IQR: 19, 34) years and 5.17 years of follow-up. The prevalence of hyperfiltration (eGFR≥140 and ≥130 mL/min/1.73 m2 for men and women, respectively) was 38.3%. Using CKD-EPI-2009, baseline hyperfiltration was less likely with older age (OR: 0.78, 95%CI: 0.73, 0.83; p<0.0001), male sex (OR: 0.32, 95%CI: 0.18, 0.58; p=0.0002), and weight (OR: 0.96, 95%CI: 0.94, 0.99; p=0.001). Using CKD-EPI-2021, hyperfiltration was similarly less likely with older age (OR: 0.75, 95%CI: 0.70, 0.81; p<0.0001), male sex (OR: 0.24, 95%CI: 0.13, 0.44; p<0.0001) and higher weight (OR: 0.97, 95%CI: 0.95, 0.99; p=0.004). 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=0.006), systolic blood pressure (SBP) (HR: 1.02, 95%CI: 1.01, 1.04; p=0.01) and hydroxyurea use (HR: 1.74, 95%CI: 1.002, 3.03; p=0.05). 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<0.0001). Decline to normal eGFR range from hyperfiltration occurs earlier in males, those on hydroxyurea and with higher SBP.

Glomerular filtration rate abnormalities in sickle cell disease

“…The new equations slightly underestimate eGFR in African Americans and overestimate it in the general population. The new creatinine-cystatin C equations without race were more accurate than new 10.3389/fmed.2022.1029224 creatinine equations, with smaller differences between race groups (21,80). Also, because the tubular secretion is the predominant mode of creatinine excretion when the GFR is less than 40 ml/min/1.73 m 2 , serum creatinine levels will produce false values in assessing GFR in older SCD patients with reduced metabolism and tubular dysfunction (36,76,81,82).…”

“…Early studies demonstrated that glomerular changes in SCD patients are characterized by high renal blood flow and glomerular hyperfiltration and hypertrophy, starting in infancy and declining to a normal range during the first two decades of life (18)(19)(20)(21)(22). Glomerular hyperfiltration is defined as estimated glomerular filtration rate (eGFR) above 130 ml/min/1.73 m 2 for women and 140 ml/min/1.73 m 2 for men.…”

“…In the general population, obesity is a risk factor for the progression of renal disease. However, in SCD patients, a higher body mass index is associated with decreased odds of rapid eGFR decline (21,61).…”

Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia

“…Glomerular filtration rate was estimated using the 2021 creatinine‐based Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation 8 . Hyperfiltration was defined as eGFR >130 mL/min per 1.73 m 2 for women and >140 mL/min per 1.73 m 2 for men 9 . The study was approved by the University of Tennessee Health Science Center (UTHSC) at Memphis Institutional Review Board.…”

“…8 Hyperfiltration was defined as eGFR >130 mL/min per 1.73 m 2 for women and >140 mL/min per 1.73 m 2 for men. 9 The study was approved by the University of Tennessee Health Science Center (UTHSC) at Memphis Institutional Review Board. All participants gave written informed consent.…”