Compensatory Growth of Congenital Solitary Kidneys in Pigs Reflects Increased Nephron Numbers Rather Than Hypertrophy

Abstract

BackgroundPatients with unilateral MultiCystic Kidney Dysplasia (MCKD) or unilateral renal agenesis (URA) have a congenital solitary functioning kidney (CSFK) that is compensatory enlarged. The question whether this enlargement is due to increased nephron numbers and/or to nephron hypertrophy is unresolved. This question is of utmost clinical importance, since hypertrophy is associated with a risk of developing hypertension and proteinuria later in life with consequent development of CKD and cardiovascular disease.Methodology/Principal FindingsIn a cohort of 32,000 slaughter pigs, 7 congenital solitary functioning kidneys and 7 control kidneys were identified and harvested. Cortex volume was measured and with a 3-dimensional stereologic technique the number and volume of glomeruli was determined and compared. The mean total cortex volume was increased by more than 80% and the mean number of glomeruli per kidney was 50% higher in CSFKs than in a single control kidney, equaling 75% of the total nephron number in both kidneys of control subjects. The mean total glomerular volume in the CSFKs was not increased relative to the controls.Conclusions/SignificanceThus, in pigs, compensatory enlargement of a CSFK is based on increased nephron numbers. Extrapolation of these findings to the human situation suggests that patients with a CSFK might not be at increased risk for developing hyperfiltration-associated renal and cardiovascular disease in later life due to a lower nephron number.

Clinical Implications of the Solitary Functioning Kidney

“…Animal studies confirmed that a compensatory increase in nephron number is present in congenital solitary functioning kidney (27,28). Nevertheless, the total nephron number identified is still lower than in two kidney controls (Table 2).…”

Prenatal compensatory renal growth in unilateral renal agenesis

“…Van Vuuren used pig kidneys as a model for human kidneys for accurate determination of nephron size and number in a comparative analysis in slaughterhouse pigs with one or two kidneys. The mean total weight, cortex volume and mean number of glomeruli were 84%, 83% and 50% higher in the compensatory CSFKs than in the control kidneys respectively.…”

“…They observed a 45% increase in the number of nephrons in the kidneys from the unilaterally nephrectomized. In their study, and in contrast to the results of Van Vuuren et al , the mean glomerular volume in the unilaterally nephrectomized sheep was 26% lower than in controls and total glomerular volume per individual kidney was comparable in both groups. These findings may suggest differences in prenatal and postnatal compensatory mechanisms – increase in nephron number during fetal development and hypertrophic glomerular growth after birth.…”

“…An interesting observation made by Van Vuuren et al was the increased number of medullary papillae in the congenital solitary functioning kidneys as compared with normal control kidneys. Nephron number is reported to be influenced by ureteric bud arborization downstream of PAX2, RET and the ALD‐H1A2 OSR1 allele activity .…”

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

“…This is a plausible explanation as reduced nephron endowment has long been postulated to correlate with risk for hypertension as well as renal disease. 33 In contrast to the HSRA model, many studies using other models of congenital solitary kidney (rat 34 or pig 35 ) have observed compensatory nephrogenesis (i.e., increased nephron number). Similarly, studies in a novel sheep fetal nephrectomy model also demonstrated compensatory nephrogenesis.…”