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- Title
A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products.
- Authors
Zimanyi, M. A.; Denton, K. M.; Forbes, J. M.; Thallas-Bonke, V.; Thomas, M. C.; Poon, F.; Black, M. J.
- Abstract
Aims/hypothesis: The aim of this study was to investigate the effects of a secondary renal insult, due to chronic infusion of AGEs on renal function, and on early pathological markers in rats with a developmental nephron deficit. Methods: Female Wistar-Kyoto rats were fed a low-protein diet (LPD; 8.7% casein) or a normal-protein diet (NPD; 20% casein) during pregnancy and lactation. Nephron number was estimated in 4-week-old female offspring. Male offspring were allowed to grow to 20 weeks of age, when AGEs derived from BSA (AGEBSA) or BSA was infused subcutaneously (20 mg kg-1 day-1) for 4 weeks. At 24 weeks, blood pressure, renal function and circulating and renal AGEs were assessed. Real-time PCR was used to investigate early molecular markers of renal pathology. Results: As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring. This alone did not affect blood pressure or lead to hyperfiltration in adulthood. However, when coupled with the secondary renal insult, the expression of the genes encoding transforming growth factor-β1 and procollagen III was significantly upregulated in the kidneys. In addition, there was renal accumulation of AGEs in LPD offspring, and this was exacerbated by AGE infusion. Conclusions/interpretation: Our results demonstrate that the adult kidney with a reduced nephron endowment is more vulnerable to secondary renal insult from AGE-BSA. Since AGE formation is markedly elevated with hyperglycaemia, our findings suggest that a developmental or acquired deficit may render the kidney susceptible to diabetic renal disease.
- Subjects
KIDNEY tubules; FETAL growth retardation; KIDNEY diseases; CHRONIC kidney failure; DIET in disease; ENDOCRINOLOGY
- Publication
Diabetologia, 2006, Vol 49, Issue 4, p801
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-006-0175-x