How can these insights into the biology of BMP-7 impact on clinical nephrology?

Even though several open questions remain to be answered, three different scenarios of a clinical application of BMP-7 in the setting of chronic renal disease deserve consideration: (1) The utility of BMP-7 as a biomarker to monitor or even to predict the progression of chronic renal disease; (2) a use for BMP-7 to substitute for the loss of circulating BMP-7 in patients with CRF in order to prevent osteodystrophy and (3) a possible application of recombinant BMP-7 as a therapeutic drug to treat chronic progressive renal disease.

Due to the complex regulation of BMP-7 activity in the kidney it appears that quantification of BMP-7 expression and protein levels has limited utility to serve as a biomarker for CRF. However, the circulating BMP-7 levels deserve further consideration. Studies by Lund and co-workers [25] suggested that decreased BMP-7 levels directly correlate with a loss of viable renal mass. While reliable assays to measure circulating BMP-7 are not available yet, the possibility of measuring circulating BMP-7 as a marker for chronic renal fibrosis should be further explored. Similarly, the consequences of decreased systemic BMP-7 levels deserve further consideration.

The central question though remains, whether BMP-7 could function as a drug to treat chronic renal fibrosis. While current animal studies suggest that systemic BMP-7 administration appears to be safe (in our studies we did not observe ectopic bone formation after 4 months of treatment in mice), the question of efficacy can only be tested in relevant clinical trials. In this regard, novel insights into the complexity of the regulatory mechanisms of BMP-7 activity in the kidney raise the concern that reno-protective BMP- 7 pathways cannot be utilized in everyone (see aforesaid) and it can be envisioned that subsets of patients with a favourable receptor status are more likely to respond to treatment with BMP-7. Regulatory BMP-7 pathways in the kidneys in health and disease must be further explored.

http://ndt.oxfordjournals.org/cgi/content/full/21/3/568