Glomerular Hyperfiltration in Adult Sickle Cell Anemia

Abstract

Background and objectives: Sickle cell anemia-associated nephropathy is a growing matter of concern because renal failure affects most aging sickle cell anemia patients. Glomerular damage is a common feature revealed by a microalbuminuria or a macroalbuminuria. Although glomerular hyperfiltration has been described for decades in this population, its prevalence in young adults is unknown.Design, setting, participants, & measurements: To address this issue, as well as the clinical and biologic correlates of hyperfiltration, a single-center, cross-sectional study of 280 homozygous SS disease patients was performed.Results: The prevalence of hyperfiltration assessed by Modification of Diet in Renal Disease estimated GFR was 51%. Among patients with hyperfiltration, 49% had hyperfiltration alone, whereas 36% and 15% had an associated microalbuminuria or macroalbuminuria, respectively. Estimated GFR sensitivity and specificity for hyperfiltration were 94% and 63%, respectively, in a selected subgroup of 48 patients (measured GFR was assessed by urinary 51 Cr EDTA clearance). In patients with no albuminuria, hyperfiltration status was significantly associated with a young age (years), the absence of alpha thalassemia, a lower hemoglobin level (g/dl), and a lower fetal hemoglobin. The role of chronic hemolysis was further strengthened by multivariate analysis showing a correlation between estimated GFR and a low plasma fetal hemoglobin level, a young age, and a high reticulocyte count (r 2 ‫؍‬ 0.54). Conclusions: Together, the data suggest that the pathophysiology of hyperfiltration would rather be attributable to the hemolysis-associated vasculopathy rather than a viscosity-vaso-occlusive process.

Carboxy-terminal fragment of fibroblast growth factor 23 induces heart hypertrophy in sickle cell disease

“…cFGF23 correlated negatively with hemoglobin and positively with GFR, suggesting that cFGF23 concentration correlates with the consequences of the SCD, anemia and glomerular hyperfiltration that is an early marker of SCD renal dysfunction. 8 In the present study, FGF23 elevation was not due to a decrease in GFR. Release of phosphate by hemolysis might have stimulated FGF23 release.…”

Association between hemolysis and albuminuria in adults with sickle cell anemia

“…They found that eGFR using the MDRD formula was a robust predictor of hyperfiltration when compared to the actual GFR. 15 Although our data have confirmed the downward trend of eGFR and upward trend of ACR as patients age, the exact temporal and pathological relationship between these two factors has not been fully investigated in individual patients, and further prospective studies are needed. The use of angiotensin-converting enzyme (ACE) inhibiting medications has been shown to reduce levels of proteinuria in small-scale trials and may prove to be beneficial in delaying the onset of CKD.…”

“…5,13 Similar studies in adults, however, have not replicated this finding, although an association between low hemoglobin levels and hyperfiltration have been reported. [14][15] More recently, Maier-Redelsperger et al utilized a marker of red cell survival derived from mature red blood cell hemoglobin (RBC Hb) and reticulocyte hemoglobin (RET Hb), and showed that the log (RBC Hb/RET Hb) was highly correlated with LDH, bilirubin and albuminuria. 16 In the present study, we have carried out a retrospective investigation of the prevalence of albuminuria and hyperfiltration in a larger cohort of adults with SCD.…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…While, renal replacement therapy with hemodialysis can extend survival, the start of dialysis is a poor prognostic factor with 1-year mortality of 26% [14,110]. Glomerular hypertension and hyper-filtration are characteristic of early sickle cell glomerulopathy, and albuminuria is its earliest clinical correlate [111][112][113]. Repeated cycles of sickling are thought to cause microinfarctions and renal medullary ischemia [114,115].…”