Influence of Age on Compensatory Renal Growth in Rats

Abstract

ABSTRACT. Rats were nephrectomized (nx) or shamoperated (s) at the age of 5 days (young) or 55 days (adult). Nx and s rats from the same litters were studied a t various times 5-75 days after surgery with determination of kidney weight and of renal cortical DNA and protein content. In some protocols protein and DNA content were determined in a more homogenous population of proximal tubular cells. In s rats body weight, kidney weight, renal cortical DNA content, and proteinlDNA ratio increased until at least 80 days of age. Body growth was the same in nx and s rats. In young nx rats the remnant kidney was significantly enlarged 5 days after surgery. The difference in kidney size between nx and s rats increased continuously a t least until the age of 80 days. The remnant kidney was 125 2 9% enlarged 3 wk after nx and 175 + 18% enlarged 8 wk after nx. Five days after nx there was no increase in cortical DNA content but a significant increase in protein/DNA ratio. From 2 wk after nx on, the DNA content was significantly higher in nx than in s rats but the protein/ DNA ratio was the same in nx and s rats. In adult nx rats, the remnant kidney was enlarged to the same extent 3 and 8 wk after surgery (130 + 7 and 132 + 8%, respectively).The increase in kidney weight 8 wk after nx was significantly smaller in adult than in young rats. The cortical DNA content and protein/DNA ratio were both moderately but significantly increased in adult rats 8 wk after nx. In conclusion this study has established age-dependent differences regarding the degree, the nature and the duration of compensatory renal growth. These differences can probably be attributed to the high mitotic capacity that is unique in the young kidney. (Pediatr Res 20: 347-350,1986) Abbreviation CRG, compensatory renal growth Several methodological problems are involved in studies of the age dependence of CRG, since the rapid normal growth of the kidney and the body must be taken into account. To be conclusive, studies on the effect of age on CRG should be performed in large series of animals, where nephrectomized animals are compared to sham-operated littermates at various times after nephrectomy. In the present study we have used this approach and have determined the degree and duration of CRG and the proportion of hyperplasia and hypertrophy in the remnant kidney of rats nephrectomized in infancy and followed until adulthood. The degree and duration of CRG in rats nephrectomized in infancy has then been compared to the degree and duration of CRG in rats nephrectomized in adulthood. MATERIALS AND METHODSMale Sprague-Dawley rats ranging in age from 5 to 110 days were used. The rat pups were separated from their mothers at the age of 2 1 days. The rats were fed a standard diet containing 2 1 % protein. Water was provided ad libitum.Procedzrre. Animals in the same litter were randomly assigned for unilateral nephrectomy or sham-operation. The nephrectoiny was performed under light ether anesthesia. The left kidney was exposed through a flank incision and gently dis...

Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number.

“…For instance, a 20% nephron loss in utero, due to gentamicin toxicity or uterine arterial ligation in the mother, resulted in glomerulosclerosis in the offspring, whereas comparable nephron reduction in adult animals did not have adverse consequences (11,12,(40)(41)(42). The exact timing at which the reduction occurred was also shown to be critical in a series of experiments in metanephric cultures (43).…”

Uninephrectomy in Young Age or Chronic Salt Loading Causes Salt-Sensitive Hypertension in Adult Rats

“…In uninephrectomized animals, this compensation in kidney growth has been described as somewhat more pronounced in immature kidneys than in fully developed kidneys. 9,10 Compared with the controls, all of the hypertensive groups (ie, UNXϩHS, UNX, and HS groups) displayed reduced urine concentrating ability. This was associated with an increased diuresis on all of the diets and elevated osmolar excretion.…”

“…The compensatory increase in kidney weight and function after nephrectomy appears more pronounced in immature than in adult kidneys, as determined by experimental studies. 9,10 Furthermore, uninephrectomy, before completion of nephrogenesis, causes salt-sensitive hypertension and compromised renal function. [11][12][13] Therefore, it is considered that the immature kidney is more susceptible to the development of renal damage and that neonatal and adult nephrectomy differs with respect to effects on blood pressure.…”

Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

“…This compensatory adaptation to nephron loss was found to be age-dependent; the earlier the nephron loss, the greater the compensation (9)(10)(11)(12). There is also substantial evidence that, after renal mass ablation, the hyperfunctioning of the remaining nephrons, which at first appears beneficial, in fact has a harmful long-term effect because it accelerates the development of glomerular sclerosis (for review see Ref.…”