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The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood

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Abstract

The advanced glycation end products/receptor for advanced glycation end products (AGE–RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = −0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.

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Abbreviations

AGEs:

Advanced glycation end products

DBP:

Diastolic blood pressure

DN:

Diabetic nephropathy

eGFR:

Estimated glomerular filtration rate

esRAGE:

Endogenous secretory receptor of advanced glycation end products

MA:

Microalbuminuria

SBP:

Systolic blood pressure

sRAGE:

Soluble receptor of advanced glycation end products

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Acknowledgements

We thank Dr. M Impicciatore of the Department of Radiology (Hospital of Guardiagrele, Chieti, Italy) for his collaboration in performing the ultrasound of the kidney.

Duality of interest

The authors declare that there are no competing financial interests.

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Authors and Affiliations

  1. Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy

    Cosimo Giannini, Ebe D’Adamo, Tommaso de Giorgis, Valentina Chiavaroli, Alberto Verrotti, Francesco Chiarelli & Angelika Mohn

  2. Clinical Research Center, University of Chieti, Chieti, Italy

    Cosimo Giannini, Francesco Chiarelli & Angelika Mohn

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  1. Cosimo Giannini
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  2. Ebe D’Adamo
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  6. Francesco Chiarelli
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Correspondence to Angelika Mohn.

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Giannini, C., D’Adamo, E., de Giorgis, T. et al. The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood. Pediatr Nephrol 27, 269–275 (2012). https://doi.org/10.1007/s00467-011-1988-5

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  • DOI: https://doi.org/10.1007/s00467-011-1988-5

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