- Email: [email protected]
Our Kidneys: A Lot Is Riding on Their Shoulders
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Foreword Ou r K id ne y s : A Lo t Is R id in g o n T h e i r Sh o u l d e r s
Lucky Jain, MD, MBA Consulting Editor
Let us admit it: they don’t get the respect they deserve! At least not until they start to fail, which is when all sorts of alarm bells go off, and the renal squad gets called! Up until then, other needy organs overshadow the need to protect precious renal tissue. From blood pressure management to clearing infections, many of the most potent agents available to us are not very kind to the kidneys.1 We are just now beginning to understand the long-term effects on the kidneys of early neonatal disorders and the agents deployed to treat them.2 The kidneys are still developing when many preterm babies begin getting exposed to fairly nephrotoxic agents. Animal data and autopsy findings in preterm infants reveal morphologically abnormal glomeruli primarily in the outer renal cortex, suggesting nephrons impacted by the hostile environment after birth.2,3 Abnormalities observed in these studies include diminished capillarization, cystic Bowman’s space, and relatively immature form.3 Indeed, the majority of nephrons are still being formed in the third trimester. The loss and abnormal function of nephrons have far-reaching consequences with residual effects detected in adult life (Fig. 1). Observational studies in humans and studies in animal models point to the association between low birth weight and chronic renal disease in adulthood. These effects are not as readily seen in children and young animals. The precise reason for this finding is unclear; however, it may be related to the decreased final number of nephrons with the remaining (fewer) glomeruli compensating by hyperfiltrating, thus accelerating the normal age-related decline in nephron number and function.4 This follows Brenner’s hyperfiltration hypothesis connecting low nephron number with hypertension, glomerular injury, and proteinuria.5 Additional factors that may impair nephrogenesis in fetal life include maternal diet, stress, infections, diabetes, chronic utero-placental insufficiency, and medications. This story sounds very similar to what we already know about premature lungs and brain in that much growth of these organs is yet to occur and that injury can have
Clin Perinatol - (2014) -–http://dx.doi.org/10.1016/j.clp.2014.06.002 perinatology.theclinics.com 0095-5108/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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Foreword
Fig. 1. Overview of the factors that may contribute to the formation of abnormal glomeruli in kidneys from preterm infants and the health consequences of reduced nephron endowment at birth. (From Black MJ, Sutherland MR, Gubhaju L, et al. When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 2013;18:181; with permission.)
delayed and permanent consequences. In the case of the kidneys, we are lulled into complacence because of the large natural reserve in renal function, which masks manifestations until the damage is severe. It is for this same reason that our overall knowledge of the pathophysiology of renal disorders lags behind that of the lung and brain. Drs Greenbaum and Rheault are to be congratulated for pulling together a superb series of articles related to renal and urologic issues in the perinatal period with contributions from leaders in the fields of nephrology, urology, neonatology, and other related disciplines. I am confident that this issue of the Clinics in Perinatology will serve as a ready source of up-to-date information for our colleagues in neonatal perinatal medicine and restore (hopefully) a healthy level of respect for this vital organ system. Lucky Jain, MD, MBA Emory University School of Medicine & Children’s Healthcare of Atlanta 2015 Uppergate Drive Atlanta, GA 30322, USA E-mail address: [email protected]
REFERENCES
1. Ligi I, Boubred F, Grandvuillemin I, et al. The neonatal kidney: implications for drug metabolism and elimination. Curr Drug Metab 2013;14:174–7. 2. Black MJ, Sutherland MR, Gubhaju L, et al. When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 2013;18:180–2. 3. Maringhini S, Corrado C, Maringhini G, et al. Early origin of adult disease. J Matern Fetal Neonatal Med 2010;23:84–6.
Foreword
4. Vehaskari VM. Prenatal programming of kidney disease. Curr Opin Pediatr 2010; 22:176–82. 5. Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 1996;49:1774–7.
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Foreword Ou r K id ne y s : A Lo t Is R id in g o n T h e i r Sh o u l d e r s
Lucky Jain, MD, MBA Consulting Editor
Let us admit it: they don’t get the respect they deserve! At least not until they start to fail, which is when all sorts of alarm bells go off, and the renal squad gets called! Up until then, other needy organs overshadow the need to protect precious renal tissue. From blood pressure management to clearing infections, many of the most potent agents available to us are not very kind to the kidneys.1 We are just now beginning to understand the long-term effects on the kidneys of early neonatal disorders and the agents deployed to treat them.2 The kidneys are still developing when many preterm babies begin getting exposed to fairly nephrotoxic agents. Animal data and autopsy findings in preterm infants reveal morphologically abnormal glomeruli primarily in the outer renal cortex, suggesting nephrons impacted by the hostile environment after birth.2,3 Abnormalities observed in these studies include diminished capillarization, cystic Bowman’s space, and relatively immature form.3 Indeed, the majority of nephrons are still being formed in the third trimester. The loss and abnormal function of nephrons have far-reaching consequences with residual effects detected in adult life (Fig. 1). Observational studies in humans and studies in animal models point to the association between low birth weight and chronic renal disease in adulthood. These effects are not as readily seen in children and young animals. The precise reason for this finding is unclear; however, it may be related to the decreased final number of nephrons with the remaining (fewer) glomeruli compensating by hyperfiltrating, thus accelerating the normal age-related decline in nephron number and function.4 This follows Brenner’s hyperfiltration hypothesis connecting low nephron number with hypertension, glomerular injury, and proteinuria.5 Additional factors that may impair nephrogenesis in fetal life include maternal diet, stress, infections, diabetes, chronic utero-placental insufficiency, and medications. This story sounds very similar to what we already know about premature lungs and brain in that much growth of these organs is yet to occur and that injury can have
Clin Perinatol - (2014) -–http://dx.doi.org/10.1016/j.clp.2014.06.002 perinatology.theclinics.com 0095-5108/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
ii
Foreword
Fig. 1. Overview of the factors that may contribute to the formation of abnormal glomeruli in kidneys from preterm infants and the health consequences of reduced nephron endowment at birth. (From Black MJ, Sutherland MR, Gubhaju L, et al. When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 2013;18:181; with permission.)
delayed and permanent consequences. In the case of the kidneys, we are lulled into complacence because of the large natural reserve in renal function, which masks manifestations until the damage is severe. It is for this same reason that our overall knowledge of the pathophysiology of renal disorders lags behind that of the lung and brain. Drs Greenbaum and Rheault are to be congratulated for pulling together a superb series of articles related to renal and urologic issues in the perinatal period with contributions from leaders in the fields of nephrology, urology, neonatology, and other related disciplines. I am confident that this issue of the Clinics in Perinatology will serve as a ready source of up-to-date information for our colleagues in neonatal perinatal medicine and restore (hopefully) a healthy level of respect for this vital organ system. Lucky Jain, MD, MBA Emory University School of Medicine & Children’s Healthcare of Atlanta 2015 Uppergate Drive Atlanta, GA 30322, USA E-mail address: [email protected]
REFERENCES
1. Ligi I, Boubred F, Grandvuillemin I, et al. The neonatal kidney: implications for drug metabolism and elimination. Curr Drug Metab 2013;14:174–7. 2. Black MJ, Sutherland MR, Gubhaju L, et al. When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 2013;18:180–2. 3. Maringhini S, Corrado C, Maringhini G, et al. Early origin of adult disease. J Matern Fetal Neonatal Med 2010;23:84–6.
Foreword
4. Vehaskari VM. Prenatal programming of kidney disease. Curr Opin Pediatr 2010; 22:176–82. 5. Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 1996;49:1774–7.
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