Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent

Flyvbjerg, Allan; Bennett, William F.; Rasch, Ruth; Neck, Johan W. van; Groffen, Cora; Kopchick, John J.; Scarlett, John A.

doi:10.1046/j.1523-1755.1999.00776.x

Cited by 46 publications

(42 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in agreement with other studies examining renal GHR/GHBP mRNA levels (Chen et al 1997, Flyvbjerg et al 1999b, Segev et al 1999. Our study may represent a compensatory upregulation of the GHR gene expression in response to the functional blockade of the GHR by the GHRA.…”

Section: Discussionsupporting

confidence: 93%

“…When GHRA transgenic animals were made diabetic, protection to GH-and IGF-I-induced renal damage was observed (Chen et al 1995(Chen et al , 1996. Furthermore, GHRA treatment protected diabetic mice from renal damage (Flyvbjerg et al 1999a, Segev et al 1999 and abolished compensatory renal growth in uninephrectomized mice (Flyvbjerg et al 1999b).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

Neck¹,

Dits²,

Cingel³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1·25, 2·5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2·5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups.In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

Neck¹,

Dits²,

Cingel³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Since ΔP cannot be measured directly, we assumed a level of 40 filtration may additionally be maintained by (a) compensatory glomerular hypertrophy, leading to an increase in the wholekidney K f ; (b) an increase in ΔP; or (c) some combination of both. Although the mechanism is contentious, glomerular hypertrophy is well described in both animal models, in which glomerular volume increases in proportion to the renocortical volume following uninephrectomy (16,17), and in biopsies of solitary human functioning kidneys (18). Our subjects had a mean 27% and 33% increase in renocortical volume from the pre-donation to early and late post-donation periods, respectively.…”

Section: Discussionmentioning

confidence: 85%

Longitudinal study of living kidney donor glomerular dynamics after nephrectomy

Lenihan¹,

Busque²,

Derby³

et al. 2015

J. Clin. Invest.

153

100

View full text Add to dashboard Cite

ResultsResponse to donor nephrectomy in healthy humans. Twenty-one subjects underwent clinical, physiological, and radiological assessments immediately before, early after (median, 0.8 years), and late after (median, 6.1 years) (hereafter, pre-donation, early post-donation, and late post-donation) living kidney donation. A morphometric evaluation of glomeruli was performed on renocortical tissue that was obtained by wedge biopsy at the time of donor nephrectomy in 19 subjects. Baseline demographic, physio-BACKGROUND. Over 5,000 living kidney donor nephrectomies are performed annually in the US. While the physiological changes that occur early after nephrectomy are well documented, less is known about the long-term glomerular dynamics in living donors. METHODS.We enrolled 21 adult living kidney donors to undergo detailed long-term clinical, physiological, and radiological evaluation pre-, early post-(median, 0.8 years), and late post-(median, 6.3 years) donation. A morphometric analysis of glomeruli obtained during nephrectomy was performed in 19 subjects.RESULTS. Donors showed parallel increases in single-kidney renal plasma flow (RPF), renocortical volume, and glomerular filtration rate (GFR) early after the procedure, and these changes were sustained through to the late post-donation period. We used mathematical modeling to estimate the glomerular ultrafiltration coefficient (K f ), which also increased early and then remained constant through the late post-donation study. Assuming that the filtration surface area (and hence, K f ) increased in proportion to renocortical volume after donation, we calculated that the 40% elevation in the single-kidney GFR observed after donation could be attributed exclusively to an increase in the K f . The prevalence of hypertension in donors increased from 14% in the early post-donation period to 57% in the late post-donation period. No subjects exhibited elevated levels of albuminuria. CONCLUSIONS.Adaptive hyperfiltration after donor nephrectomy is attributable to hyperperfusion and hypertrophy of the remaining glomeruli. Our findings point away from the development of glomerular hypertension following kidney donation.

show abstract

“…The GH-IGF-I system has been linked to sex differences in CKG in other studies, so its role was examined in the present experiments (6,27,28). Kidney IGF-I content increased approximately twofold after Unx and was not influenced by sex or genotype.…”

Section: Discussionmentioning

confidence: 92%

Compensatory kidney growth in estrogen receptor-α null mice

Sun¹,

Langer²,

Devish³

et al. 2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Females are relatively protected in many progressive kidney diseases. Processes of kidney scarring and growth are intricately linked, and female kidneys are smaller than male kidneys. To better understand links between sex, growth, and the kidney, we examined compensatory kidney growth (CKG) after uninephrectomy (Unx) in wild-type and estrogen receptor-α null mice (ERKO). Mice (10 wk old) underwent Unx or sham procedure, with removal of all remaining kidney(s) 48 h later. Studies included kidney weight, renal content of protein, DNA, and insulin-like growth factor-I (IGF-I), serum IGF-I, mean glomerular area, and immunostaining for proliferating cell nuclear antigen (PCNA). Sham Unx produced no differences between left and right kidneys. Unx altered kidney weight, glomerular area, DNA content, IGF-I content, and PCNA regardless of sex or genotype. Females showed greater increases in kidney weight (26 vs. 19%) and glomerular area (73 vs. 51%) than males. Differences in kidney weight were restricted to wild-type females (32% increase); ERKO females showed an increase in kidney weight similar to males (19%). Genotype did not influence glomerular growth in this model. Both male and female mice exhibit hyperplastic growth 48 h after Unx, with more pronounced enlargement in females. Lack of estrogen receptor-α is associated with reduced CKG in females, probably via suppression of proliferation. ERKO mice did not demonstrate any alterations in compensatory glomerular enlargement. Kidney IGF-I content doubled after Unx, regardless of sex or genotype, implicating other mechanisms with regard to these findings.

show abstract

Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent

Cited by 46 publications

References 22 publications

Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

Longitudinal study of living kidney donor glomerular dynamics after nephrectomy

Compensatory kidney growth in estrogen receptor-α null mice

Contact Info

Product

Resources

About