M Gandhi1, J L Olson, T W Meyer. 1. Division of Nephrology, VA Palo Alto Health Care System and Stanford University, California 94304, USA. mgandhi@leland.stanford.edu
Abstract
BACKGROUND: The remnant kidney model has been widely used to identify mechanisms responsible for the progression of renal disease. However, the structural changes associated with progressive loss of function in this model have not been well characterized. METHODS: Kidney function and structure were assessed at 10 weeks (REM 10) and 25 weeks (REM 25) after five-sixths renal ablation and in control rats (Control). Serial sections were examined to relate glomerular and tubular structure in individual nephrons. RESULTS: Remnant kidney function declined between 10 and 25 weeks after ablation (GFR 0.90 +/- 0.34 vs. 0.23 +/- 0.07 ml/min, REM 10 vs. REM 25, P < 0.05). This decline in function was associated with an increase in the prevalence of globally sclerotic glomeruli (14 +/- 10 vs. 0 +/- 0 vs. 0 +/- 0%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control). The decline in remnant kidney function between 10 and 25 weeks was also associated with the appearance of glomeruli that were atubular (48 +/- 14 vs. 9 +/- 8 vs. 3 +/- 5%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control) or connected to atrophic proximal tubule segments (26 +/- 10 vs. 11 +/- 6 vs. 1 +/- 2%, REM 25 vs. REM 10 vs. Control, P < 0.05 all comparisons). Atubular glomeruli, which usually had open capillary loops available for filtration, were more numerous than globally sclerotic glomeruli at 25 weeks after ablation. CONCLUSIONS: These findings indicate that tubular injury contributes to progressive loss of renal function following reduction in nephron number.
BACKGROUND: The remnant kidney model has been widely used to identify mechanisms responsible for the progression of renal disease. However, the structural changes associated with progressive loss of function in this model have not been well characterized. METHODS: Kidney function and structure were assessed at 10 weeks (REM 10) and 25 weeks (REM 25) after five-sixths renal ablation and in control rats (Control). Serial sections were examined to relate glomerular and tubular structure in individual nephrons. RESULTS: Remnant kidney function declined between 10 and 25 weeks after ablation (GFR 0.90 +/- 0.34 vs. 0.23 +/- 0.07 ml/min, REM 10 vs. REM 25, P < 0.05). This decline in function was associated with an increase in the prevalence of globally sclerotic glomeruli (14 +/- 10 vs. 0 +/- 0 vs. 0 +/- 0%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control). The decline in remnant kidney function between 10 and 25 weeks was also associated with the appearance of glomeruli that were atubular (48 +/- 14 vs. 9 +/- 8 vs. 3 +/- 5%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control) or connected to atrophic proximal tubule segments (26 +/- 10 vs. 11 +/- 6 vs. 1 +/- 2%, REM 25 vs. REM 10 vs. Control, P < 0.05 all comparisons). Atubular glomeruli, which usually had open capillary loops available for filtration, were more numerous than globally sclerotic glomeruli at 25 weeks after ablation. CONCLUSIONS: These findings indicate that tubular injury contributes to progressive loss of renal function following reduction in nephron number.