[Frontiers in Bioscience S1, 1-12, June 1, 2009]

Chemokines and chemokine receptors as therapeutic targets in chronic kidney disease

Volker Vielhauer1, Hans-Joachim Anders1

1Medizinische Poliklinik, Klinikum der Universitat Munchen, Campus Innenstadt, Ludwig-Maximilians-University, Pettenkoferstr 8a, 80336 Munich, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Pathomechanisms and progression of chronic kidney disease
4. Immunosuppressive versus anti-inflammatory treatment strategies for chronic kidney disease
5. Experimental evidence for chemokines and chemokine receptors mediating glomerular and interstitial leukocyte influx and injury
5.1. Glomerulonephritis
5.2. Interstitial nephritis
6. Experimental evidence for a role of chemokines and chemokine receptors in the progression of chronic kidney disease
6.1. Focal segmental glomerulosclerosis
6.2. Lupus nephritis
6.3. Diabetic nephropathy
6.4 .Glomerulosclerosis in Alport nephropathy
7. Compartment-specific functions of chemokines and chemokine receptors in the kidney
8. Conflicting data on the role of chemokines and chemokine receptors in renal disease
9. Validating potential chemokine and chemokine receptors targets for therapeutic applications
10. Perspective - Data needed before approaching clinical trials
11. Acknowledgments
12. References

1. ABSTRACT

As other cytokine families, chemokines have multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage. Chemokines play important roles in leukocyte trafficking and leukocyte activation, hence, blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicate that additional roles of chemokines in the regulation of innate and adaptive immune responses may adversely affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential and possible adverse effects of anti-chemokine strategies in renal inflammation.