Using nuclide renography, obesity was found to independently affect recovery in patients with renal damage (1). This study has revisited the paradigm of prenatal undernutrition in sheep, to include the effect of postnatal obesity on renal function in sheep as assessed with nuclear scintigraphy using Tc-99m DTPA. At day 23 gestation 37 ewes received either a control (C, 7 MJ/day; n=24) or nutrient restricted diet (NR, 50% C intake ~3.5 MJ/day; n=13) from day 30 to 80 gestation. Thereafter all sheep were fed to 100% requirements to term (12-13 MJ/day near term). Offspring delivered spontaneously and ewe reared as singletons (one twin being humanely put down) to weaning. From weaning to 1yr of age offspring were either barn reared (restricted activity; Obese controls OC, n=8 females; Obese nutrient restricted ONR, n=13(11 females, 2 males)) or pasture grazed (unrestricted activity; Lean controls LC, n=8 females). At this time a proportion of the offspring (LC, n=7; OC, n=3; ONR, n=3; all females) were catheterised for renography. At time zero 100MBq technetium-99 diethylenetriaminepentaacetic acid (Tc-99m DTPA) in 0.5ml NaCl was injected I.V. and left and right kidney renograms produced from analysis of 60 frames over 20min; derived indices of renal function were then calculated. GFR was determined by the 3-sample method (2). Data are means ± S.E.M. and were analysed by one-way ANOVA using SPSS v14. After weaning, physically inactive lambs (OC & ONR) gained weight rapidly and were 90 ± 2 and 89 ± 1 kg in OC and ONR, respectively vs. LC, 58 ± 4 kg at 12 months of age (P<0.001). Body fat at this time was 46 ± 2 and 49 ± 1% in OC and ONR, respectively vs. LC, 24±2% (P<0.001) as determined chemically (Direct Laboratories, Wolverhampton). Obese sheep had larger kidneys and a trend for higher uncorrected GFR (OC, 134 ± 17; ONR, 114 ± 17; vs. LC, 93 ± 9 ml min-1, P=0.07). However, corrected for kidney weight, ONR tended to have lower GFR (ONR, 68 ± 7; vs. OC, 84 ± 10; vs. LC, 84 ± 10 ml min-1 (100g kidney)-1, P=0.08). In both left and right kidneys the upslope (the positive slope of the renogram occurring before the peak and calculated as the X values (cpm) at 5 and 90% of the peak Y value) was significantly slower in obese sheep (right kidney data: OC, 48 ± 7; ONR, 38 ± 3; vs. LC, 130 ± 26 cpm, P<0.05) and time to peak tended to be longer (right kidney data: OC, 2.7 ± 0.2; ONR, 3.3 ± 0.4; vs. LC, 2.4 ± 0.2 min, P=0.05). Undernutrition over the period of nephrogenesis in sheep appears to impact upon GFR corrected for kidney weight. Obesity per se appears to markedly influence the renal handling of Tc-99m DTPA indicating increased renal resistance to uptake of nuclide.
University College London 2006 (2006) Proc Physiol Soc 3, PC207
Poster Communications: Prenatal undernutrition with postnatal obesity influences renal function in adult sheep
David Gardner1, Alan Perkins2, Michael Symonds2
1. School of Veterinary Medicine and Science, University of Nottingham, Loughborough, United Kingdom. 2. School of Human Development, University of Nottingham, Nottingham, United Kingdom.
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