Serum Amyloid P: A New Inhibitor of Renal Fibrosis?

Serum amyloid P (SAP)—a known inhibitor of pulmonary and cardiac fibrosis—may also have antifibrotic effects in the kidneys, according to a study published in Science Translational Medicine.

In experiments in two models of renal fibrosis in mice, administration of human SAP (hSAP) was associated with dose-dependent reductions in fibrosis. Although fibroblasts were still present in similar numbers, hSAP treatment was associated with down-regulation of fibrotic collagen gene transcription and collagen protein deposition. Further experiments suggested that hSAP selectively localized to the injured kidneys, mainly associated with apoptotic and necrotic cells. In humans, more severe kidney disease was associated with lower plasma concentrations of hSAP.

In the kidneys, fibrosis depends on inflammatory monocytes and macrophages, rather than fibroblasts. The antifibrotic effect of hSAP appeared to occur via monocyte/macrophage binding and suppression, dependent on interleukin-19 and regulated binding to Fcy receptors.

There is an urgent need for new treatments directed against chronic inflammation with fibrosis. A natural soluble pattern recognition receptor, SAP has been shown to recognize danger-associated molecular patterns (DAMPs) on the membranes of apoptotic cells and promote Fcy receptor-dependent phagocytosis.

The new results suggest that SAP acts as a natural inhibitor of fibrosis in response to inflammatory kidney injury. A recombinant form of hSAP is undergoing initial studies in humans [Castaño AP, Lin S-L, Surowy T, Nowlin BT, Turlapati SA, Patel T, Singh A, Li S, Lupher ML Jr, Duffield JS. Serum amyloid P inhibits fibrosis through Fcy R-dependent monocyte-macrophage regulation in vivo. Sci Transl Med. 2009; 1:5–13].