Developmental Origins of Kidney Disease

Low birthweight babies carry unique risks

Journal: Clinical Journal of the American Society of Nephrology
Date: January 2009

Kidneys are truly amazing. Within each one there is a world with millions of tiny filtering units called nephrons. These complex and delicate workhorses filter our blood and help remove waste and excess fluid from our bodies. Every day about 200 quarts of blood pass through our nephrons. The blood is filtered, cleaned and returned to our bloodstream. All except about two quarts, that is, which gets excreted as urine. Babies who are born small, whether premature or full-term with a low birthweight, have fewer of these filtering units. This puts them at risk for kidney disease later in life. However, there are ways to protect every precious nephron at birth and into childhood.

Nurturing our nephrons
Groups of nephrons develop much like onions do, in layers. This means that newly formed nephrons are on the outer layer, while the more developed nephrons become embedded deeper inside. Once the layering stops, at about 35 weeks gestational age, no new nephrons can be formed in our lifetime. Postnatal kidneys continue to grow larger to match our body size, as do nephrons, but the total number stays the same.
In the editorial, Developmental Origins of Renal Disease: Should Nephron Protection Begin at Birth?, author and nephrology specialist Susan Bagby, M.D. applies a DOHaD framework to make the case that it should. Since nephron number is proportional to birthweight, the first clinical clue to a reduced nephron endowment is whether the baby is premature or small at birth. And if care is taken to nurture those newborn nephrons through the first minutes, days, weeks and months, it can make a difference. 

Low birthweight implications
Premature and low birthweight babies are born with fewer layers of nephrons. This has implications for kidney disease later in life, as it sets the stage for a mismatch between body size and the kidney’s functional capacity. Over time, this causes a progressive loss of nephrons because of that mismatch. If a person’s body size increases to an extent that stresses the kidneys’ ability to handle the increased filtering load, it creates heightened pressure inside the nephron’s complex structure. This slowly damages and scars the nephrons over time. Low birthweight babies tend to grow rapidly in early childhood, and have an increased risk for being overweight and obese. Overweight and obesity increases their risk for kidney disease even more, because of the increased mismatch between kidney function and body size. It’s important to remember that this represents increased vulnerability to disease, and not actual disease per se. There are always opportunities in life to improve a person’s health.

Post-natal opportunities for protecting at-risk kidneys
Bagby points out there are postnatal opportunities to protect and help the kidneys of premature and low birthweight babies:

  • In premature babies (< 35 weeks), nephrons may (but do not always) continue developing for up to 40 days after birth, even if they never reach what would be considered normal levels. This potential for postnatal growth should be nurtured as much as possible by identifying what might harm or help the developing nephrons in the earliest days of life. The Neonatal Intensive Care Unit (NICU) experience, while critical for survival, is fraught with frequent exposures that are toxic for the kidneys. Many standard interventions were developed before there was an awareness of the potential for their effects on newborn kidneys. This topic needs to become a part of the training for neonatologists. In addition,  determining the optimum levels of macro- and micro-nutrients that would support postnatal nephron growth while in the NICU should be a high priority for the research community.
  • Another potentially critical period of kidney growth occurs during the first 18 months of life. Normally, kidneys continue to grow in size in relation to a person’s body size, even while nephron numbers remain set. However, kidney growth during this time period may remain poor in low birthweight and premature babies. So not only are they born with smaller kidneys, the kidneys may not grow as well as they should in the first 18 months of life. Understanding why this happens could reveal opportunities for early therapeutic interventions.
  • A third period warranting attention is when low birthweight babies rapidly gain weight in later childhood and adolescence. This accelerated growth often leads to obesity. Slowing and normalizing growth in childhood may not only prevent obesity, but it may prevent or delay the onset of kidney disease in those who are at risk. 

Bagby suggests a combination of early intervention strategies for at-risk newborns would be reasonable, including:

  • Adding birthweight and gestational age to the standard clinical history
  • Monitoring for signs of kidney dysfunction from birth (high blood pressure, urine protein, serum creatinine)
  • Educating parents and adult patients about their unique risks and the benefits of favorable lifestyle practices

While there are other known and unknown factors that affect kidney development, it’s clear that premature and low birthweight babies carry a unique risk for kidney disease later in life because they are born with fewer nephrons. This is a powerful case for addressing nephron protection at birth and throughout childhood, before kidney disease develops. Favorable lifestyle practices, combined with identifying and monitoring clinical symptoms, can help protect nephrons and optimize kidney health throughout life.

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The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

Bagby S.P., (2009). Developmental origins of renal disease: should nephron protection begin at birth? Clin J Am Soc Nephrol, Jan;4(1):10-3. PMID: 19129313. Retrieved from DOI: 10.2215/CJN.06101108