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Novel marker for the detection of sickle cell nephropathy: soluble FMS-like tyrosine kinase-1 (sFLT-1)

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Abstract

Background

Given the burden and poor outcome of end-stage renal disease in sickle cell disease (SCD), early markers of sickle cell nephropathy (SN) are desirable. Disordered angiogenesis underlies many complications of SCD. We aimed to determine the relationship between serum FMS-like tyrosine kinase-1 (sFLT-1) and other biomarkers of renal damage for the early diagnosis of SN.

Methods

Forty-seven SCD patients and 49 healthy controls were enrolled. Microalbuminuria was determined in patient urine samples. Blood samples were tested for sFLT-1, serum creatinine, and various hemolysis and inflammation markers. Peripheral blood monocyte expression of sFLT-1 was measured using real-time polymerase chain reaction (PCR).

Results

The serum level of sFLT-1 (pg/ml) in SCD patients was higher than controls (median/range/IQR = 142/ 60–1300/61 pg/ml vs. 125/ 110–187/52 pg/ml, respectively) (p = 0.006). Median (range) of sFLT-1 level was higher in SCD patients with microalbuminuria compared to SCD patients with normoalbuminuria, 185 (140–1300) vs. 125 (60–189) mg/g, respectively) (p = 0.004). There was a significant positive correlation between serum sFLT-1 and microalbuminuria, lactate dehydrogenase (LDH), and indirect bilirubin (r = 0.59, 0.39, 0.30, and p = <0.001, 0.007, 0.041, respectively). sFLT-1 sensitivity in early detection of renal affection in SCD was 93.6 %, while specificity was 68.6 %. Finally, peripheral blood monocytes (PBM) sFLT-1 expression was significantly higher in SCD patients compared to controls (p = 0.05).

Conclusions

sFLT-1 may contribute to pathogenesis of albuminuria in SCD patients and constitute a novel renal biomarker of SN.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study protocol was approved by the Institutional Review Board.

Informed consent

Informed consent was obtained from the patients or the patients’ guardians.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt

    Ilham Youssry, Samuel Makar, Ghada AbdAllah & Happy Sawires

  2. Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Rania Fawzy, Manal Wilson & Eman Fathy

  3. Pediatric Hematology & BMT Unit, Department of Pediatrics, Faculty of Medicine, Cairo University, 1 Ben Kutiba Street, Section Seven, Nasr City, 11487, Cairo, Egypt

    Ilham Youssry

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  1. Ilham Youssry
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  2. Samuel Makar
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  3. Rania Fawzy
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  4. Manal Wilson
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  5. Ghada AbdAllah
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  6. Eman Fathy
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  7. Happy Sawires
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Correspondence to Ilham Youssry.

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Youssry, I., Makar, S., Fawzy, R. et al. Novel marker for the detection of sickle cell nephropathy: soluble FMS-like tyrosine kinase-1 (sFLT-1). Pediatr Nephrol 30, 2163–2168 (2015). https://doi.org/10.1007/s00467-015-3172-9

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  • DOI: https://doi.org/10.1007/s00467-015-3172-9

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