Chronic kidney disease

Progressive tubulo-interstitial fibrosis is the common end point leading to end-stage renal disease regardless of the etiology in experimental and clinical settings. Ureter obstruction due to nephrolithiasis, ureter occlusion by either enhanced scaring as radiation side effect or prostate hypertrophy in elder male patients or ureter valve insufficiency with urine congestion in young children with consecutive hydronephrosis can lead to progressive renal damage and chronic kidney disease (CKD). Also, acute kidney injury (AKI) in the context of major cardiac surgery is an important risk factor for progressive CKD. Currently, no effective treatment strategy to protect kidney function is available.

In Vivo Models

• AKI induced CKD model

Unilateral renal pedical clamping to induce ischemia reperfusion injury (IRI) for 45 min causes progressive CKD within 2 - 3 weeks. This model mimics the clinical situation of AKI induced CKD. Follow up is 3 - 4 weeks.

• Unilateral ureter obstruction (UUO) induced CKD model

Unilateral ureter obstruction (UUO) causes pressure induced progressive renal fibrosis. This model mimics the ureter obstruction due to nephrolithiasis, ureter occlusion by either enhanced scaring as radiation side effect or prostate hypertrophy in elder male patients or ureter valve insufficiency with urine congestion in young children with consecutive hydronephrosis. Follow up is 5 - 10 days.

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• 5/6 Nephrectomie induced CKD model

In this model the lower branch of the left renal artery is ligated to produce about one third area with visible renal ischemia; the upper pole of the left kidney is removed by cautery and the right kidney is decapsulated and nephrectomized to induce a total 5/6 nephrectomy. This leads to a progressive renal failure with severe glomerulosclerosis within 8-12 weeks. One important feature of renal injury in this particular model is hypertension, which alone perpetuates endothelial activation, inflammation, and proliferation, followed by vascular obliteration and glomerulosclerosis.

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Available Readouts

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1. Renal morphology

   • Tubular atrophy

   • Inflammation

   • Immunophenotyping of infiltrating leukocytes

   • Extracellular matrix protein deposition

2. Systemic and local inflammatory response

   • Cytokine / chemokine profile in serum and kidney tissue

3. Fibrosis

   • Immunohistochemistry for fibronectin, a-SMA, collagen IV

   • Expression of profibrotic mediators

4. Endothelial injury

   • Expression of adhesion molecule

5. Renal damage marker KIM-1 and NGAL expression

6. Immunohistochemistry for specific markers of interests

7. Apoptosis

8. Blood pressure​​​