*2.2.4. Development of sickle cell nephropathy from infancy to adulthood*

Glomerular changes in SCD occur early in the first decade of life even though SCD patients remain asymptomatic. These are characterized by high renal blood flow, hyperfiltration and hypertrophy. Current data suggest that infants with SCD develop a hyperfiltration phase, which plateaus during early childhood. As early as the first year, renal enlargement is observed in correlation to hyperfiltration. Hyperfiltration is a well-known phenomenon in SCD even though the pathogenesis and pathophysiology is less well understood. As a result of hyperperfusion, increased amount of fluids is presented to the proximal tubule triggering more tubular reabsorption of sodium and water in order to restore glomerulotubular balance. Increased proximal tubular sodium reabsorption is associated with high metabolism and adaptive cellular response leading to overall renal enlargement. This complex phenomenon might be relevant to the glomerular hypertrophy that occurs in SCD [13]. Some studies show that for children with HbSS, there is an age-related increase in the estimated creatinine clearance in the first decade of life, with a decline toward normal values in the second decade [41–43]. In the study by Etteldorf and colleagues, children with SCD aged 4–11 years had a significantly higher mean measured glomerular filtration rate (mGFR) (169 mL/min/1.73 m2 ) than normal controls (128 mL/min/1.73 m2 ) [44]. In the BABY HUG trial, 176 children aged 9–19 months had a measured GFR at baseline of 125 mL/min/1.73 m2 [45], which was significantly higher than published normal values for the same age group [46].

In a cross-sectional study of 410 patients with SCD aged 2–21 (mean age 11) years, 23% of HbSS patients showed elevated urinary albumin excretion (≥30 mg/g), while other investigators have reported a HbSS prevalence of 16–27% in the childhood SCD population [47–49].

Further progressive kidney injury and CKD is reflected in a declining and abnormally low GFR. During adolescence, estimated glomerular filtration rate (eGFR) begins to decline in some patients, and aroud 10% of adolescent patients with SCD develop a GFR of <90 mL/ min/1.73 m2 [50]. Similarly, Bodas et al. recently reported a CKD prevalence of 8% in a cohort of patients with SCD aged 3–17 years [51].

The prevalence of end-stage renal disease (ESRD) in the pediatric SCD population is also not well described; however, childhood SCD accounts for only 0.3% of incident pediatric ESRD [52].

Eventually, renal failure develops in early adulthood (median age 23–37 years) in SCA and in mid-life (median age 50 years) in HbSC disease.
