Ilham Youssry1,2, Samuel Makar3, Rania Fawzy4, Manal Wilson4, Ghada AbdAllah3, Eman Fathy4, Happy Sawires3. 1. Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. ilhamyoussry@yahoo.com. 2. Pediatric Hematology & BMT Unit, Department of Pediatrics, Faculty of Medicine, Cairo University, 1 Ben Kutiba Street, Section Seven, Nasr City, 11487, Cairo, Egypt. ilhamyoussry@yahoo.com. 3. Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. 4. Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
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.
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 SCDpatients 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 SCDpatients 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 SCDpatients with microalbuminuria compared to SCDpatients 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 SCDpatients compared to controls (p = 0.05). CONCLUSIONS: sFLT-1 may contribute to pathogenesis of albuminuria in SCDpatients and constitute a novel renal biomarker of SN.
Authors: Nan Hee Kim; Jeong Heon Oh; Ji A Seo; Kye Won Lee; Sin Gon Kim; Kyung Mook Choi; Sei Hyun Baik; Dong Seop Choi; Young Sun Kang; Sang Youb Han; Kum Hyun Han; Yi Hwa Ji; Dae Ryong Cha Journal: Kidney Int Date: 2005-01 Impact factor: 10.612
Authors: Giovana S Di Marco; Stefan Reuter; Uta Hillebrand; Susanne Amler; Maximilian König; Etienne Larger; Hans Oberleithner; Eva Brand; Hermann Pavenstädt; Marcus Brand Journal: J Am Soc Nephrol Date: 2009-07-16 Impact factor: 10.121
Authors: A Rajakumar; H M Michael; P A Rajakumar; E Shibata; C A Hubel; S Ananth Karumanchi; R Thadhani; M Wolf; G Harger; N Markovic Journal: Placenta Date: 2005-08 Impact factor: 3.481
Authors: Ann T Farrell; Julie Panepinto; Ankit A Desai; Adetola A Kassim; Jeffrey Lebensburger; Mark C Walters; Daniel E Bauer; Rae M Blaylark; Donna M DiMichele; Mark T Gladwin; Nancy S Green; Kathryn Hassell; Gregory J Kato; Elizabeth S Klings; Donald B Kohn; Lakshmanan Krishnamurti; Jane Little; Julie Makani; Punam Malik; Patrick T McGann; Caterina Minniti; Claudia R Morris; Isaac Odame; Patricia Ann Oneal; Rosanna Setse; Poornima Sharma; Shalini Shenoy Journal: Blood Adv Date: 2019-12-10
Authors: Shannon B Donnola; Connie M Piccone; Lan Lu; Joshua Batesole; Jane Little; Katherine M Dell; Chris A Flask Journal: NMR Biomed Date: 2018-01-19 Impact factor: 4.044