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Updated: May 10, 2026
5/6 Nephrectomy Using Sharp Bipolectomy Via Midline Laparotomy in Rats
Published on: April 4, 2025
Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic
Joseph Satriano1, Kumar Sharma, Roland C Blantz
1Div. of Nephrology-Hypertension, O’Brien Kidney Center, University of California San Diego and Veterans Administration San Diego Healthcare System, La Jolla, California 92161, USA. jsatriano@ucsd.edu
Abstract:
The rat kidney ablation and infarction (A/I) model of subtotal or 5/6th nephrectomy is the most commonly studied model of nondiabetic chronic kidney disease (CKD). The A/I kidney at 1 wk exhibits reductions in kidney function, as determined by glomerular filtration rate, and diminished metabolic efficiency as determined by oxygen consumption per sodium transport (QO2/TNa). As renoprotective AMPK activity is affected by metabolic changes and cellular stress, we evaluated AMPK activity in this model system. We show that these early pathophysiological changes are accompanied by a paradoxical decrease in AMPK activity. Over time, these kidney parameters progressively worsen with extensive kidney structural, functional, metabolic, and fibrotic changes observed at 4 wk after A/I. We show that induction of AMPK activity with either metformin or 5-aminoimidazole-4-carboxamide ribonucleotide increases AMPK activity in this model and also corrects kidney metabolic inefficiency, improves kidney function, and ameliorates kidney fibrosis and structural alterations. We conclude that AMPK activity is reduced in the subtotal nephrectomy model of nondiabetic CKD, that altered regulation of AMPK is coincident with the progression of disease parameters, and that restoration of AMPK activity can suppress the progressive loss of function characteristic of this model. We propose that induction of AMPK activity may prove an effective therapeutic target for the treatment of nondiabetic CKD.
Insights
AMPK activity is reduced in nondiabetic chronic kidney disease (CKD) models. Restoring AMPK activity improves kidney function and reduces fibrosis, suggesting it as a therapeutic target for CKD.
Area of Science:
- Nephrology
- Metabolic pathways
- Cellular stress response
Background:
- The 5/6th nephrectomy (A/I) model is widely used for nondiabetic chronic kidney disease (CKD).
- Early stages of CKD show reduced kidney function and metabolic efficiency.
- AMP-activated protein kinase (AMPK) plays a role in metabolic regulation and cellular stress, making it relevant to CKD pathogenesis.
Purpose of the Study:
- To investigate AMPK activity in the A/I model of nondiabetic CKD.
- To determine if modulating AMPK activity impacts disease progression and kidney health.
Main Methods:
- Utilized the rat kidney ablation and infarction (A/I) model (5/6th nephrectomy).
- Assessed kidney function (glomerular filtration rate) and metabolic efficiency (QO2/TNa) at 1 and 4 weeks post-A/I.
- Evaluated AMPK activity.
- Administered metformin or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to induce AMPK activity.
- Quantified structural, functional, metabolic, and fibrotic changes.
Main Results:
- A paradoxical decrease in AMPK activity was observed early in the A/I model.
- Kidney function, metabolic efficiency, and structure progressively worsened over 4 weeks.
- Induction of AMPK activity with metformin or AICAR improved metabolic inefficiency, enhanced kidney function, and reduced fibrosis and structural damage.
Conclusions:
- AMPK activity is diminished in the subtotal nephrectomy model of nondiabetic CKD.
- Altered AMPK regulation correlates with CKD progression.
- Restoring AMPK activity shows therapeutic potential for suppressing functional loss in nondiabetic CKD.
