Compensatory responses to nephron deficiency: Adaptive or maladaptive?

Abstract

This is a comprehensive review on our current understanding of postnatal functional and structural maturation of a kidney. We further explore how these adaptations in the setting of abnormal kidney development or loss of a kidney which result in low nephron number can lead to maladaptive phenotypes such as renal failure and hypertension later in life. ABSTRACT:Compensatory renal growth is a characteristic adaptation to reduced renal mass that appears to recapitulate the normal pattern of maturation of the kidney during the postnatal period. Hypertrophy of tubules (predominantly the proximal tubule) and glomeruli is accompanied by increased single nephron glomerular filtration rate and tubular reabsorption of sodium. We propose that the very factors, which contribute to the increase in growth and function of the renal tubular system, are, in the long term, the precursors to the development of hypertension in those with a nephron deficit. The increase in single nephron glomerular filtration rate is dependent on multiple factors, including reduced renal vascular resistance associated with an increased influence of nitric oxide, and a rightward shift in the tubuloglomerular feedback curve, both of which contribute to the normal maturation of renal function. The increased influence of nitric oxide appears to contribute to the reduction in tubuloglomerular feedback sensitivity and facilitate the initial increase in glomerular filtration rate. The increased single-nephron filtered load associated with nephron deficiency may promote hypertrophy of the proximal tubule and so increased reabsorption of sodium, and thus a rightward shift in the pressure natriuresis relationship. Normalization of sodium balance can then only occur at the expense of chronically increased arterial pressure. Therefore, alterations/adaptations in tubules and glomeruli in response to nephron deficiency may increase the risk of hypertension and renal disease in the long-term.

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

“…[21][22][23][24] Adaptive changes in glomeruli and tubules in response to nephron deficiency can increase the risk of hypertension and renal disease in the long run. 12 Many biochemical parameters were found to be activated during compensatory renal hypertrophic responses, such as angiotensin II, p-aminohippurate, nitric oxide, growth factors and proto-oncogenes. 4,12,25,26 At the histopathologic level, kidney weight was used as the main most prominent indicator of the compensatory hypertrophy.…”

“…12 Many biochemical parameters were found to be activated during compensatory renal hypertrophic responses, such as angiotensin II, p-aminohippurate, nitric oxide, growth factors and proto-oncogenes. 4,12,25,26 At the histopathologic level, kidney weight was used as the main most prominent indicator of the compensatory hypertrophy. 3,8 The compensatory growth can affect the glomeruli, proximal and distal convoluted tubules and also the cortical collecting ducts, 7,[27][28][29][30] with reports specifying that this growth occurs primarily in the cortex, especially confined to the proximal convoluted tubules.…”

“…11 According to the studies by Fong et al, the adaptive enlargement of the renal tubules and glomeruli that occurs in response to the decreased renal mass during the postnatal and prenatal phases varies from the adaptation that follows when there is a reduction in the renal tissue in adulthood. 12 This alteration occurs faster with a better result in younger animals compared to adults. [13][14][15] After unilateral nephrectomy, the major instant functional adaptation is a gradual increase in the mean glomerular filtration rate.…”

“…11 The growth pattern resembles that of the natural growth of kidney during the postnatal period where hypertrophy of the proximal tubules is more than that of distal tubules. 12 Glomerular podocytes are highly differentiated cells with a complex cytoarchitecture that lines the outer aspect of the glomerular basement membrane. Various human and experimental renal diseases affect the glomerular podocytes that form the final filtration barrier, leading to proteinuria.…”

Clinical characteristics and follow-up results of unilateral renal agenesis and hypoplasia of children

“…Tek taraflı agenezik ve hipoplazik böbrekli hastalar uzun dönemde, azalmış nefron sayısını kompanse etmek için gelişen glomerüler hiperfiltrasyona ve artmış glomerül boyutuna sekonder gelişen fokal segmental glomerüloskleroz (FSGS) nedeni ile kronik böbrek yetmezliği gelişme riskini artırır. Bu olguların yaklaşık %25'i son dönem böbrek yetmezliğine ilerler (3)(4)(5)(6) . Bu çalışmada, tek taraflı agenezik ve hipoplazik böbreği olan hastaların klinik özelliklerinin ve izlem sonuçlarının değerlendirilmesi planlandı.…”