A Quantitative Study of Normal Nephrogenesis in the Human Fetus: Its Implication in the Natural History of Kidney Changes due to Low Obstructive Uropathies

Abstract

An evaluation of nephrogenesis according to fetal age was performed by quantifying the state of the nephrogenic blastema (NB) and the number of glomeruli (GN) on frontal renal sections in 99 control fetuses (gestational age ranging from 9 to 40 weeks) and in 17 aborted fetuses with low urinary tract obstruction (gestational age ranging from 14 to 36 weeks). In the control group, GN increases slowly from the 10th to the 18th week, then abruptly from the 18th to the 32nd week, reaching an upper limit with NB disappearance by the 32nd week. In the uropathy group, the renal changes show a wide range of severity clearly accounted for by the impairment of both NB and GN. The dysplastic effect of urinary backpressure is the more consistent pathogeny with the spectrum of observed renal changes. It is likely, from GN used as a time-dependent marker of renal development, that the most severe dysplasia is the result of early obstruction with abnormal disappearance of NB and subsequent arrest of nephrogenesis.

Developmental Origins of Renal Disease

“…We know that the critical window of kidney development spans 9 to 35 wk gestational age (GA) (5), although the point of completion can vary from 32 to 35 wk (6,7). Nephrogenesis involves successive branching of the ingrowing ureteral bud, with new nephron units forming at branch tips via co-inductive crosstalk between the ureteral bud epithelium and surrounding undifferentiated mesenchyme.…”

Preterm Birth and Hypertension Risk

“…45,46 Although nephrogenesis continues postnatally after preterm birth, 47 the process is likely disrupted. [47][48][49] Nephron number is an important indicator of renal functional capacity, with impaired renal development (reduced nephron endowment), as well as later nephron loss, strongly correlated with the development of high blood pressure.…”

“…[106][107][108] In experimental studies, inflammatory challenges given periconception, midgestation and in the neonatal period led to increased visceral fat and metabolic syndrome in mice offspring in adulthood. [44][45][46] Furthermore, adult guinea pigs that were administered parenteral nutrition (a contributor to oxidative stress) as pups exhibited dyslipidemia, glucose intolerance, and energy deficiency. 70 In adult rats exposed to hyperoxic stress as neonates, increased vascular superoxide production has been observed.…”

Prenatal intervention for urinary obstruction and myelomeningocele

“…Primitive renal function begins between week 7 and 9, and by week 20, about 1/3 of the total number of nephrons are present. Nephrogenesis is complete by the 32nd week of fetal life, after which no demonstrable increase in the number of glomeruli is noted (8)(9)(10).…”

“…They include the time of onset, duration, and degree of urinary obstruction. In general the earlier the obstruction occurs the more disturbed the development of the fetal kidney (8). Renal dysplasia, the most severe form of renal injury and maldevelopment, has been attributed to a very early effect of elevated pressures in the urinary (2) and alternatively by ureteral bud malposition with subsequent misconnection between the bud and the metanephric blastema (4,11).…”