Validation of an Experimental Model to Study Less Severe Chronic Renal Failure

J Invest Surg. 2016 Oct;29(5):309-15. doi: 10.3109/08941939.2015.1114689. Epub 2016 Mar 30.

Abstract

Purpose: The 5/6 nephrectomy, mimics the stages of human chronic renal failure (CRF), but the procedure causes severe renal functional and morphological damage that could interfere with the evaluation of therapies for slowing the progression of the disease. This study summarizes the results of renal function, histology, and immunohistochemical findings in rats undergoing a 2/3 nephrectomy.

Methods: The rats were distributed in groups according to the type of nephrectomy: CRF5/6: induced by a 5/6 renal mass reduction and CRF2/3: less severe CRF. The body weight and blood pressure were monitored, and the serum creatinine (SCr), creatinine clearance (CCr), urine osmolality, and 24-h proteinuria (PT24h) were measured. CRF progression was evaluated by the rate of decline of CCr (RCCr). Histology and immunohistochemistry were performed in the remnant kidneys. Statistical analysis was done by unpaired t-test, and a P-value < 0.05 was taken as a statistical significance.

Results: Compared to the CRF5/6 group, the CRF2/3 model had a lower SCr, PT24h, CCr, and variations of the SCr from baseline. The disease progression was also significantly slower. The renal histopathological findings revealed fewer chronic lesions in rats with CRF2/3. Similarly, we observed less macrophage accumulation as well as lower proliferative activity and expression of fibronectin and a-smooth muscle-actin in the CRF2/3 model.

Conclusions: The CRF2/3 model presented with a pattern of less severe CRF, functionally and morphologically, compared to the classical CRF5/6 model, and the CRF2/3 model may be useful for evaluating therapeutic interventions that target the early stages of CRF.

Keywords: chronic renal failure; experimental 5/6 nephrectomy; renal mass reduction.

Publication types

  • Validation Study

MeSH terms

  • Actins / metabolism
  • Animals
  • Blood Pressure
  • Disease Models, Animal
  • Disease Progression
  • Fibronectins / metabolism
  • Humans
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / physiopathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Nephrectomy / methods
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Actins
  • Fibronectins
  • Proliferating Cell Nuclear Antigen
  • smooth muscle actin, rat