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Method of renal mass reduction is a critical modulator of subsequent hypertension and glomerular injury
K A Griffin1, M Picken, A K Bidani
1Department of Medicine, Loyola University Medical Center, Maywood, IL.
Abstract:
The hypertension, proteinuria, and glomerulosclerosis that develop in the remnant kidney model (uninephrectomy plus infarction of approximately 2/3 of the other kidney) have been generally considered to represent the adverse consequences of a severe reduction in nephron number. To differentiate the blood pressure (BP) responses to infarction from those of reduced renal mass per se, BP was continuously monitored radiotelemetrically in rats whose total renal mass was reduced by 2/3 (infarction) and by 5/6 (infarction or surgical excision of both poles) and in sham-operated controls. Hypertension only developed in the two infarcted groups. Overall averages of systolic BP monitored every 10 min over 6 wk were 144 +/- 8 and 156 +/- 5 mm Hg in the 2/3 and 5/6 infarction groups (N = 10 each), respectively, as compared with 120 +/- 2 mm Hg (N = 12) in the approximately 5/6 surgical excision group (P < 0.01) and 117 +/- 5 mm Hg (N = 8) in controls. Changes in kidney weights, glomerular volumes, RBF, GFR, and renal autoregulatory ability after renal mass reduction by the two methods were qualitatively similar in additional animals from each group monitored for 2, 4, or 6 wk without radiotelemetry. Significant proteinuria and glomerulosclerosis only developed in the two infarction (hypertensive) groups. At 6 wk, 18 +/- 4 and 19 +/- 3% of the glomeruli exhibited injury in the 2/3 (N = 22) and the 5/6 infarction groups (N = 21), respectively, in contrast to 3 +/- 1% glomerular injury in the 5/6 surgical excision group (N = 24) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Renal infarction, not just reduced kidney mass, causes hypertension and kidney damage in rats. This study distinguishes the effects of infarction versus surgical reduction of renal mass on blood pressure and glomerulosclerosis.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Experimental Pathology
Background:
- The remnant kidney model is used to study kidney disease, but the specific role of renal infarction versus reduced renal mass is unclear.
- Hypertension, proteinuria, and glomerulosclerosis are common findings in this model, often attributed solely to nephron reduction.
Purpose of the Study:
- To differentiate the blood pressure (BP) responses and subsequent renal pathology caused by renal infarction from those caused by reduced renal mass per se.
- To investigate the impact of different methods of renal mass reduction on BP and glomerular injury.
Main Methods:
- Continuous radiotelemetric monitoring of BP in rats subjected to 2/3 or 5/6 renal infarction, 5/6 surgical excision, or sham operation over 6 weeks.
- Assessment of kidney weights, glomerular volumes, renal blood flow (RBF), glomerular filtration rate (GFR), and renal autoregulatory ability.
- Histopathological evaluation of glomeruli for injury (proteinuria and glomerulosclerosis).
Main Results:
- Hypertension developed exclusively in the infarcted groups, with systolic BP averaging 144 +/- 8 and 156 +/- 5 mm Hg for 2/3 and 5/6 infarction, respectively.
- The surgical excision group (5/6 renal mass reduction) and controls did not develop hypertension (BP 120 +/- 2 and 117 +/- 5 mm Hg, respectively).
- Significant proteinuria and glomerulosclerosis were observed only in the hypertensive, infarcted groups, with 18-19% glomerular injury compared to 3% in the surgical excision group.
Conclusions:
- Renal infarction, rather than simply a reduction in renal mass, is the primary driver of hypertension in this model.
- Infarction leads to significant glomerular injury, including glomerulosclerosis and proteinuria, which is not observed with surgical reduction of renal mass alone.
- These findings highlight the distinct pathological consequences of infarction versus nephron reduction in the context of chronic kidney disease research.