Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle cell anemia

Abstract

Despite a normal or increased eGFR, KI biomarkers were detected in the urine of individuals with SCA. NAG, KIM-1 and urine hemosiderin correlated with the presence of albuminuria.

Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy

“…20,[52][53][54][55][56][57] KIM-1 is a transmembrane protein whose expression and release by proximal tubular cells is increased after exposure to inflammatory stimuli. 58 Consistent with other studies, 59,60 we observed that concentrations of urine KIM-1 were increased in SCD patients with albuminuria. A unique finding of our study is that KIM-1 concentration significantly correlated with cell-free hemoglobin concentration in the urine of patients with SCD and in the supernatant of HK-2 cells exposed to cell-free hemoglobin.…”

Intravascular hemolysis and the pathophysiology of sickle cell disease

“…Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias. (24)(25)(26). In contrast, as mentioned earlier, other complications were associated with lower hemolysis rates and higher steady-state hemoglobin levels, including the rate of vaso-occlusive painful episodes, ACS, and osteonecrosis (Table 1).…”

Sickle Cell Nephropathy in the Pediatric Population

“…Furthermore, hemoglobin dimers released during hemolysis promote albuminuria by inhibiting the reuptake of albumin in the proximal tubule [56]. Levels of albuminuria in SCN also correlate with hemolysis and markers of tubular injury [24].…”

“…Risk factors that have been associated with the development of pediatric SCN are older age, early severe anemia, severe hemolysis, Central African Republic sickle haplotype, elevated blood pressure for age, priapism, and hyperuricemia [1,13,17,[19][20][21][22][23][24].…”

“…Table 3. Biomarkers investigated for use in sickle cell nephropathy Proposed potential markers for early detection and monitoring progression of SCN Urine microalbumin/creatinine ratio Urine total protein/creatinine ratio Urine N-acetyl-beta-D-glucosaminidase (NAG) [24,89] Urine kidney injury molecule-1 [24,89] Urine ceruloplasmin [90] Urine free hemoglobin [29] Urine nephrin [91] Plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) [92] Plasma cystatin C [89,93] Measured glomerular filtration rate using iohexol clearance [94] Markers with conflicting or negative data on association with proteinuria in SCN Urine neutrophil gelatinase-associated lipocalin (NGAL) [63,89,95] Urine transforming growth factor beta (TGFβ) [63,89,95] Urine liver-type fatty acid binding protein (L-FABP) [89] Urine endothelin-1 [24] Olaniran/Eneanya/Nigwekar/VelaParada/Achebe/Sharma/Thadhani Non-Pharmacologic Therapies The evidence for the non-pharmacological therapies in SCN is sparse. In particular, chronic blood transfusions early in childhood have been shown to be reno-protective in children [15], but it is not clear how long this effect lasts.…”