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 (AGE-BSA) 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-beta(1) 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.
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 (AGE-BSA) 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-beta(1) 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.
Authors: J M Forbes; T Soulis; V Thallas; S Panagiotopoulos; D M Long; S Vasan; D Wagle; G Jerums; M E Cooper Journal: Diabetologia Date: 2001-01 Impact factor: 10.122
Authors: Josephine M Forbes; Vicki Thallas; Merlin C Thomas; Hank W Founds; Wendy C Burns; George Jerums; Mark E Cooper Journal: FASEB J Date: 2003-07-18 Impact factor: 5.191
Authors: Laura E Coats; Gwendolyn K Davis; Ashley D Newsome; Norma B Ojeda; Barbara T Alexander Journal: Curr Hypertens Rep Date: 2019-06-21 Impact factor: 5.369
Authors: Vladislava Zohdi; James T Pearson; Michelle M Kett; Paul Lombardo; Michal Schneider; M Jane Black Journal: Eur J Nutr Date: 2014-08-13 Impact factor: 5.614
Authors: Stephen P Gray; Kate M Denton; Luise Cullen-McEwen; John F Bertram; Karen M Moritz Journal: J Am Soc Nephrol Date: 2010-09-09 Impact factor: 10.121
Authors: Lina Gubhaju; Megan R Sutherland; Bradley A Yoder; Anthony Zulli; John F Bertram; M Jane Black Journal: Am J Physiol Renal Physiol Date: 2009-09-16
Authors: Noori Maka; John Makrakis; Helena C Parkington; Marianne Tare; Ruth Morley; M Jane Black Journal: Pediatr Nephrol Date: 2007-10-27 Impact factor: 3.714