Developing therapeutic 'arrows' with the precision of William Tell: the time has come for targeted therapies in kidney disease.

Abstract

PURPOSE OF REVIEW:

A core mission for modern medicine is the development of precision therapeutics. Cancer therapies have been at the leading edge of this effort, while nephrology has lagged on the path to precision medicine. Breaking the stalemate, recent work revealed CD80 (B7-1) as a candidate for targeted therapy in the treatment of resistant nephrotic syndrome. This review aims to summarize the current state of our understanding of podocyte CD80 biology, its therapeutic implications and the challenges that lie ahead in essential future validation studies.

RECENT FINDINGS:

The CD80 targeting agent abatacept (CTLA4-Ig), approved to treat rheumatoid arthritis, was shown to induce remission of nephrotic range proteinuria in four patients with recurrence of disease posttransplant and one patient with primary, treatment resistant nephrotic syndrome. The concept of 'CD80-positive' proteinuric kidney disease due to podocyte CD80 staining in patient kidney biopsies was introduced as a molecular biomarker to define disease and guide treatment. The mechanism of action of CTLA4-Ig in podocytes was shown to centre on β1 integrin activation in a T-cell independent fashion. Subsequent work revealed a putative role for podocyte CD80 in diabetic kidney disease.

SUMMARY:

These studies have direct implications for patient care, and intense interest has focused on validating these findings in upcoming clinical trials.

• Authors: Peter Mundel, Anna Greka
• Journal: Current opinion in nephrology and hypertension (Curr Opin Nephrol Hypertens) Vol. 24 Issue 4 Pg. 388-92 (Jul 2015) ISSN: 1473-6543 [Electronic] England
• PMID: 26050127 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Immunosuppressive Agents
• Abatacept

Topics

• Abatacept (therapeutic use)
• Animals
• Diabetic Nephropathies (drug therapy)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Nephrotic Syndrome (pathology, therapy)
• Podocytes (cytology, drug effects)
• Proteinuria (drug therapy)