Safety in glomerular numbers

Abstract

A low nephron number is, according to Brenner's hyperfiltration hypothesis, associated with hypertension, glomerular damage and proteinuria, and starts a vicious cycle that ends in renal failure over the long term. Nephron endowment is set during foetal life, and there is no formation of nephrons after 34-36 weeks of gestation, indicating that many factors before that time-point may have an impact on kidney development and reduce nephron numbers. Such factors include maternal malnutrition, stress, diseases, such as diabetes, uteroplacental insufficiency, maternal and neonatal drugs and premature birth. However, other congenital anomalies, such as renal hypoplasia, unilateral renal agenesis or multicystic dysplastic kidney, may also lead to a reduced nephron endowment, with an increased risk for hypertension, renal dysfunction and the need for renal replacement therapy. This review focuses on the causes and consequences of a low nephron endowment and will illustrate why there is safety in glomerular numbers.

Fig. 1

Integration of causes and consequences of low nephron endowment due to programming of kidney development (upper) leading to glomerular hyperfiltration (lower). MCDK Multicystic dysplastic kidney, IUGR intrauterine growth restriction, GFR glomerular filtration rate, ESRD end-stage renal disease

Fig. 2

Different potential courses of albuminuria and glomerular filtration rare (GFR) in individuals with a congenital solitary functioning kidney, based on an integration of data from previous studies [13, 14, 16]. GFR (solid lines) may mature to normal two-kidney values (90–120 ml/min/1.73 m²) and gradually decrease during adulthood, with a gradual increase in albuminuria (dashed lines) into the microalbuminuria (30–300 mg/24 h) or macroalbuminuria (>300 mg/24 h) range. However, renal function may deteriorate much faster and lead to albuminuria in the first decade of life [13] and end-stage renal disease in early adulthood [16]