Mild vitamin A deficiency leads to inborn nephron deficit in the rat

Abstract

We conclude that vitamin A supply to the fetus is critical in determining the number of nephrons. Data available thus far on the frequency of mild VAD during pregnancy and on the long-term consequences of inborn nephron deficit highlight the clinical relevance of the present study.

Retinoids Regulate the Repairing Process of the Podocytes in Puromycin Aminonucleoside-induced Nephrotic Rats

“…In the 1940s, Wilson et al (6) demonstrated that pregnant rats fed with a diet lacking in vitamin A showed diverse renal abnormalities such as hypoplastic or ectopic ureters, horseshoe kidney, and renal hypoplasia. Even mild vitamin A deficiency induces a reduction of the nephron number, while other organs develop in a normal way (7). Recently, it is reported that a role of vitamin A in the nephrogenesis is to regulate epithelial/mesenchymal interactions through the expression of c-ret, a receptor for glial cell linederived neurotrophic factor (GDNF), and to induce branching of the ureteric bud (8 -10).…”

Chronic Kidney Disease: A Life Course Health Development Perspective

“…Mice born 1-2 days prematurely develop a CKD phenotype by the time they are 5 weeks old, exhibiting hypertension, albuminuria, and reduced nephron number (Stelloh et al 2012). In other mouse studies, prenatal exposure to low protein and low vitamin A supply, perinatal exposure to gentamicin, and antenatal exposure to steroids all reduce nephron number in offspring (Gilbert et al 1990;Lelievre-Pegorier et al 1998;Sutherland et al 2012a;Ortiz et al 2001). Rats with 5/6 nephrectomy have been used as a model system to study the mechanisms by which low nephron number results in glomerular hyperfiltration, hypertension, albuminuria, and glomerulosclerosis (Brenner and Anderson 1987).…”

“…In infancy/childhood, the most overt cause of CKD and end-stage renal disease is birth defects or congenital anomalies of the kidney and urinary tract that result in inadequate renal mass to provide internal physiologic homeostasis for the provision of growth and development (NAPRTCS 2011;Chen et al 2012;Bagby 2015;Puddu et al 2009;Chiang et al 2010;Hsu et al 2014;Greenbaum et al 2011;Horbar et al 2012;Hack et al 2002;Stelloh et al 2012;Gilbert et al 1990;Lelievre-Pegorier et al 1998;Sutherland et al 2012a;Ortiz et al 2001;Brenner and Anderson 1987;Reidy and Kaskel 2007;Fogo 2007;Lopez-Hernandez and Lopez-Novoa 2012;Gubhaju et al 2009;Sutherland et al 2012b;White et al 2009;Bacchetta et al 2009;KeijzerVeen et al 2010;Rademacher and Sinaiko 2009;Salgado et al 2009; Centers for Disease Control and Prevention (CDC) 2007; Hodgin et al 2009a;Harambat et al 2012;Warady and Chadha 2007;Tabel et al 2010;Sanna-Cherchi et al 2009). The long-term consequences of prematurity on renal mass are more subtle but, as mentioned above, are becoming increasingly clear.…”

“…Genetic studies of children with congenital anomalies of the kidney and urinary tract and animal studies have enabled investigators to identify multiple molecular signaling pathways that are required for normal kidney and urinary tract development. These include Wnts, bone morphogenetic proteins (BMPs), fibroblast growth factor (FGF), sonic hedgehog, RET/glial cellderived neurotrophic factor, and Notch pathways (Horbar et al 2012;Hack et al 2002;Stelloh et al 2012;Gilbert et al 1990;Lelievre-Pegorier et al 1998;Sutherland et al 2012a;Ortiz et al 2001; Westland et al 2011;Spencer et al 2011;BertoliAvella et al 2008;Nishimura et al 1999;Song and Yosypiv 2011;Paces-Fessy et al 2012;Reidy and Rosenblum 2009). These signaling pathways regulate the outgrowth of the ureteric bud (from the Wolffian duct), the subsequent ureteric bud branching, and the reciprocal interactions between the tips of the ureteric bud and metanephric mesenchyme that lead to nephron and hence kidney formation.…”

Midkine Promotes Selective Expansion of the Nephrogenic Mesenchyme during Kidney Organogenesis

“…8 Midkine, 15,16 a third secreted polypeptide growth factor identified in G401 CM 17,18 is a retinoic acid inducible gene implicated in the regulation of Wilms' tumor growth and differentiation which is expressed during kidney development. 19 Since retinoic acid plays an essential role in development of the kidney, 10,[20][21][22][23] we reasoned that Midkine might play an important role during kidney organogenesis. Although genetic inactivation of the Midkine gene did not result in overt developmental abnormalities of the kidney, 24 anti-Midkine neutralizing antibodies have recently been shown to inhibit metanephric kidney development in organ culture 25 suggesting that this growth factor may have important functions when conditions for organ development are sub-optimal.…”