Effects of age at the time of unilateral nephrectomy and dietary protein on long-term renal function in rats
- 31 Downloads
- 8 Citations
Abstract
Glomerular filtration rate (GFR) and urinary protein excretion (UpV) were studied in male rats with a uninephrectomy at 3 (UNX-3) or 15 weeks of age (UNX-15) and fed a low (12%, LP), normal (24%, NP) or high (36%, HP) protein diet. Measurements were made every 12 weeks throughout the entire life-span. The UNX rats were compared with sham-operated (2K) rats of the same age and on the same diets. At 12 weeks after surgery, the GFR of UNX rats, corrected for differences in body weight, age and protein intake (GFRcor), ranged between 73% and 77% of that of 2K rats. On the HP and NP diet, UpV was higher in UNX-3 than in UNX-15 rats. On the LP diet, UpV was equally low in both groups. Long-term follow-up indicated that the GFR of UNX rats on the HP diet started to decline first, followed by those on an NP diet, while those on an LP diet had the longest period of stable GFR. For UNX rats, the time to reach a GFRcor of 50% was used as an indicator of the length of renal survival. Analysis of variance of the renal survival times indicated a highly significant interaction between the protein diet and age at the time of UNX. On the HP diet, UNX-3 rats have a shorter renal survival time than UNX-15, while on the LP diet UNX-3 rats have a longer renal survival time. This indicates that the long-term outcome of UNX at young age depends on the protein intake. Simultaneous stimulation of renal growth by HP intake and compensatory growth, during the period of normal kidney growth, results in early damage of the remaining kidney.
Key words
Unilateral nephrectomy Developing kidney Glomerular filtration rate Proteinuria Chronic renal failure Protein diet RatsPreview
Unable to display preview. Download preview PDF.
References
- 1.Hayslett JP (1979) Functional adaptation to reduction in renal mass. Physiol Rev 59: 137–163Google Scholar
- 2.Fine LG (1986) The biology of renal hypertrophy. Kidney Int 29: 619–634Google Scholar
- 3.Provoost AP, De Keijzer MH, Molenaar JC (1989) Effect of protein intake on lifelong changes in renal function of rats unilaterally nephrectomized at young age. J Lab Clin Med 114: 19–26Google Scholar
- 4.Brenner BM (1985) Nephron adaptation to renal injury or ablation. Am J Physiol 249: F324-F337Google Scholar
- 5.Provoost AP, Baudoin P, De Keijzer MH, Van Aken M, Molenaar JC (1991) The role of nephron loss in the progression of renal failure: experimental evidence. Am J Kidney Dis 17 [Suppl 1]: 27–32Google Scholar
- 6.Jakobsson B, Celsi G, Lindblad BS, Aperia A (1987) Influence of different protein intake on renal growth in young rats. Acta Paediatr Scand 76: 293–299Google Scholar
- 7.Hostetter TH, Meyer TW, Rennke HG, Brenner BM (1986) Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int 30: 509–517Google Scholar
- 8.De Keijzer MH, Provoost AP (1990) Effects of dietary protein on the progression of renal failure in the fawn-hooded rat. Nephron 55: 203–209Google Scholar
- 9.Kleinknecht C, Salusky I, Broyer M, Gubler M-C (1979) Effect of various protein diets on growth, renal function, and survival of uremic rats. Kidney Int 15: 534–541Google Scholar
- 10.Hostetter TH, Olson JL, Rennke HG, Venkatachalam M, Brenner BM (1981) Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 241: F85-F93Google Scholar
- 11.Kenner CH, Evan AP, Blomgren P, Luft FC (1985) Effect of protein intake on renal function and structure in partially nephrectomized rats. Kidney Int 27: 739–750Google Scholar
- 12.Provoost AP, De Keijzer MH, Molenaar JC (1990) The effect of protein intake on the lifelong changes in renal function of rats with a solitary kidney damaged at young age. J Urol 144: 567–573Google Scholar
- 13.Lalich JJ, Burkholder PM, Paik WCW (1975) Protein overload nephropathy in rats with unilateral nephrectomy. Arch Pathol 99: 72–79Google Scholar
- 14.Larsson L, Aperia A, Wilton P (1980) Effect of normal development on compensatory renal growth. Kidney Int 18: 29–35Google Scholar
- 15.Celsi G, Jakobsson B, Aperia A (1986) Influence of age on compensatory renal growth in rats. Pediatr Res 20: 347–350Google Scholar
- 16.O'Donnell M, Kasiske B, Raij L, Keane WF (1985) Age is a determinant of the glomerular morphologic and functional responses to chronic nephron loss. J Lab Clin Med 106: 308–313Google Scholar
- 17.Celsi G, Bohman S-O, Aperia A (1987) Development of focal glomerulosclerosis after unilateral nephrectomy in infant rats. Pediatr Nephrol 1: 290–296Google Scholar
- 18.Ikoma M, Yoshioka T, Ichikawa Y, Fogo A (1990) Mechanism of the unique susceptibility of deep cortical glomeruli of maturing kidneys to severe focal glomerular sclerosis. Pediatr Res 28: 270–276Google Scholar
- 19.Provoost AP, De Keijzer MH, Wolff ED, Molenaar JC (1983) Development of renal function in the rat. The measurement of GFR and ERPF and correlation to body and kidney weight. Renal Physiol 6: 1–9Google Scholar
- 20.Cox DR (1972) Regression models and life tables. J Roy Stat Soc B Met 34: 187–220Google Scholar
- 21.Hayslett JP (1983) The effect of age on compensatory renal growth. Kidney Int 23: 599–602Google Scholar
- 22.Harris RC, Seifter JL, Brenner BM (1984) Adaptation of Na+-H+ exchange in renal microvillus membrane vesicles. Role of dietary protein and uninephrectomy. J Clin Invest 74: 1979–1987Google Scholar
- 23.El Nahas AM, Le Carpentier JE, Bassett AH, Hill DJ (1989) Dietary protein and insulin-like growth factor-I content following unilateral nephrectomy. Kidney Int 36: [Suppl 27]: S15-S19Google Scholar
- 24.Kanwar YS (1984) Biophysiology of glomerular filtration and proteinuria. Lab Invest 51: 7–21Google Scholar