Abstract

Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population. The major late pathologic feature of CKD is interstitial fibrosis in the kidney characterized by extracellular matrix deposition but in early stage, several profibrotic and proinflammatory cytokines as well as growth factors are expressed. The renin-angiotensin and ET systems both play an important role in the pathogenesis of CKD and the blockade of these systems has been shown to suppress proinflammatory cytokines and to arrest the progression of CKD. We have demonstrated earlier also the renoprotective effect of physical activity on the experimental CKD progression (Pechter et al., 2003). Aim of the study was to investigate the effects of non-drug treatment, physical activity, to the extent of gene expression in experimental CKD and to compare with endothelin receptor blocker (ERB, sitaxentan) and standard nephroprotective drug, angiotensin receptor blocker (ARB, losartan) treatments. Expression of mRNA was assessed by real-time reverse transcription-polymerase chain reaction. CCL2/MCP-1 and nuclear factor-κB (NFκB) gene expression was measured in whole kidneys. Results revealed that CCL2/MCP-1 gene expression (data presented in poster presentation ASN Renal Week 2010, Pechter et al.) was increased in the 5/6 NPX rat kidneys, and the increase was lessened significantly after physical activity and losartan therapy. ERB treatment appeared less effective. Combined ARB and ERB treatment as well as drugs alone or physical therapy prevented the increase in systemic blood pressure, albuminuria and CCL2/MCP-1 as well as NFκB gene expression. We conclude that non-drug and drug treatments both were effective regarding the rate of the progression of experimental CKD measured by physiological and molecular biomarkers of chronic inflammation in kidney tissue.

Highlights

  • IntroductionChronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population [1]

  • We conclude that non-drug and drug treatments both were effective regarding the rate of the progression of experimental Chronic kidney disease (CKD) measured by physiological and molecular biomarkers of chronic inflammation in kidney tissue

  • Morphological studies revealed that significantly less focal-segmental glomerulosclerosis (FSGS) and interstitial fibrosis was found in remnant kidneys of the water therapy, ARB and ARB + ERB groups compared with untreated controls (p < 0.05)

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Summary

Introduction

Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population [1]. The renin-angiotensin-aldosterin system (RAAS) and ET systems both play an important role in the pathogenesis of CKD and despite the experimental and clinical first-line use of RAAS blockers in the management of CKD, there is still a great need to improve the prevention the progression of CKD. In early stage, several profibrotic and proinflammatory cytokines as well as growth factors are expressed in kidney tissue which is well-known phenomenon in CKD to the addition of progressive proteinuria and hypertension. Among key molecular factors that have been reported to have an important role in the pathogenesis of CKD are NFκB and CCL2, known as monocyte chemoattractant protein 1 (MCP-1) [3]. The blockade of RAAS and endothelin (ET) systems has been shown to suppress early proinflammatory cytokines and growth factors and to arrest the progression of CKD [4] [5]. We have demonstrated earlier the renoprotective effect of aquatic exercise on the experimental CKD progression [6]

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