Role of Inflammation in Polycystic Kidney Disease

ABSTRACT

Polycystic kidney disease (PKD) is a genetic disorder that is characterized by progressive growth of multiple cysts in the kidneys. Two forms of the disease exist, autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD). ADPKD is the most common form of genetic disorder of the kidney. In the United States about 600,000 people have PKD. This disease eventually leads to end stage kidney disease (ESKD) which may take as long as three decades to develop and requires renal replacement therapy. PKD is the fourth largest cause of kidney failure. Interstitial inflammation is a common component of chronic kidney disease (CKD) and, it is a better prognostic marker, than glomerular health, for progression of the disease or kidney function. PKD is no exception. Markers of inflammation are present much earlier than detectable cyst growth and correlate with the disease progression. While in other kidney diseases interstitial inflammation is mostly associated with interstitial fibrosis, in PKD inflammation is also linked to cyst progression. Inflammatory cells such as macrophages have been reported in both human and experimental animal models of PKD, with the degree of macrophage infiltrate associated with disease progression in humans. In animal models of PKD, macrophages have been associated with cyst growth and deteriorating renal function. What may differentiate PKD from the rest of the CKD is that experimental evidence suggests a direct role of PKD genes in regulating expression of some of the pro-inflammatory chemoattractants such as monocyte chemoattractant protein-1 (MCP-1) and other cytokines. Indeed, increased urinary levels of MCP-1 correlate with the progression of disease in humans. This chapter will highlight some of the work that provides evidence for the role of inflammation in disease progression in PKD.