Physiology and Pathophysiology of Compensatory Adaptations of a Solitary Functioning Kidney.

Zoe Mcardle,Reetu R Singh,Karen M Moritz,Kate M Denton,Michiel F Schreuder

doi:10.3389/fphys.2020.00725

Abstract

Children born with a solitary functioning kidney (SFK) have an increased risk of hypertension and kidney disease from early in adulthood. In response to a reduction in kidney mass, the remaining kidney undergoes compensatory kidney growth. This is associated with both an increase in size of the kidney tubules and the glomeruli and an increase in single nephron glomerular filtration rate (SNGFR). The compensatory hypertrophy and increase in filtration at the level of the individual nephron results in normalization of total glomerular filtration rate (GFR). However, over time these same compensatory mechanisms may contribute to kidney injury and hypertension. Indeed, approximately 50% of children born with a SFK develop hypertension by the age of 18 and 20–40% require dialysis by the age of 30. The mechanisms that result in kidney injury are only partly understood, and early biomarkers that distinguish those at an elevated risk of kidney injury are needed. This review will outline the compensatory adaptations to a SFK, and outline how these adaptations may contribute to kidney injury and hypertension later in life. These will be based largely on the mechanisms we have identified from our studies in an ovine model of SFK, that implicate the renal nitric oxide system, the renin angiotensin system and the renal nerves to kidney disease and hypertension associated with SFK. This discussion will also evaluate current, and speculate on next generation, prognostic factors that may predict those children at a higher risk of future kidney disease and hypertension.

Highlights

Congenital anomalies of the kidney and urinary tract (CAKUT) represent the primary cause of chronic kidney disease (CKD) in the pediatric population, accounting for approximately 50% of cases (Becherucci et al, 2016)
Common prognostic indicators of kidney injury [hypertension, proteinuria, estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2] have been observed in children born with an solitary functioning kidney (SFK) from as early as 10 years of age, early markers at time of diagnosis of SFK, that distinguish those at an elevated risk of kidney injury are needed (Schreuder et al, 2008; Westland et al, 2011, 2013a)
Since the increase in single nephron glomerular filtration rate (SNGFR) after reduction in kidney mass are greater in the young compared with the adult (Table 2), these data suggest that adaptive glomerular hyperfiltration and associated increases in fluid flow shear stress (FFSS) sustained from a younger age may cause degradation of the glomerular filtration barrier earlier in life, resulting in podocyte loss and may account for the greater incidence of kidney injury in children with a SFK compared with adult kidney donors (Figure 1)

Summary

Introduction

Congenital anomalies of the kidney and urinary tract (CAKUT) represent the primary cause of chronic kidney disease (CKD) in the pediatric population, accounting for approximately 50% of cases (Becherucci et al, 2016). In our ovine model of congenital SFK, fetal unilateral nephrectomy at 100 days of a 150-day gestation, resulted in a ∼45% greater nephron number in the SFK compared with a single kidney of a sham operated control sheep at 130 days of gestation but individual glomerular volumes were lower in the SFK compared with control at this age (Douglas-Denton et al, 2002).

Results

Conclusion