When I think back over the time that I have been in nephrology, I am struck by how many advances we have made in our understanding of kidney function and the pathogenesis of kidney disease. In no particular order, a (very) incomplete list includes: the enormous new insights into the biology of the podocyte and its importance as a target of kidney disease; the regulation of the renin-angiotensin system, its role in kidney diseases, and the effectiveness of its targeting in slowing progression; the role of inflammatory cells in kidney diseases; insights into the underlying pathophysiology of numerous genetic kidney diseases (e.g., PKD, Alport’s syndrome, cystinosis, Bartter’s syndrome, Liddle’s syndrome, Gordon’s syndrome); elucidation of underlying causes of glomerular diseases (e.g., IgA nephropathy, membranous nephropathy); the discovery of a genetic predisposition of certain populations to glomerular disease (ApoL1); spectacular success in developing more effective immunosuppression so that both patient and transplanted kidney survival have significantly improved; and immunotherapy for a variety of glomerular diseases.
Still, there remain concerns about the relative lack of success at developing new therapies for our patients, and the paucity of randomized controlled trials. We lag behind other specialties in implementation of new trials.
There are certain obvious reasons for this discrepancy:
First, designing trials for interventions in kidney diseases can be difficult because of the variability of individual patient rates of GFR decline and the necessity to use significant loss of renal function as a hard outcome. Everyone recognizes that to design and implement more effective clinical trials, we need better biomarkers and better understanding of how to stratify patients into “fast” and “slow” progressors. More generally, in order to identify the most effective targets, we need to better understand the underlying pathogenesis of human kidney diseases.
Second, there is insufficient funding for both preclinical and clinical research for kidney disease. While NIH has committed $2978 per patient with AIDS and $568 per patient with cancer, it commits only $29 per patient for kidney disease, even though there are more patients living with kidney disease in the US than with cancer and AIDS combined. This disparity is even starker when one considers that the amount spent by the government on the Medicare ESRD program is more than the entire NIH budget. Think how much more could be accomplished if we had the sort of funding that is lavished on these other diseases.
Recently, there have been two exciting developments that we hope will spur further successful research into approaches to prevent and treat kidney diseases.
The NIDDK Kidney Precision Medicine Initiative aims to obtain human kidney tissue for molecular interrogation. Many of the recent advances in understanding cancer biology and development of targeted therapies have arisen from similar direct analysis of the human tissue, so this NIH initiative may provide similar insights for our field and aid in identification of new targets for therapy, development of more effective biomarkers, and provide a fuller understanding of the natural history and variability of human kidney diseases.
In addition, it is especially encouraging for our discipline that the White House recently convened a summit to discuss the shortage of organs for transplantation and the need for innovative alternatives to traditional dialytic therapies for ESRD patients. There has been an unfortunate lack of innovation in therapeutic options for renal replacement in patients with ESRD and an inadequate number of donor kidneys available for what is still the best option for our ESRD patients. Representatives from ASN, along with representatives from FDA representing KHI, the public-private partnership of ASN with FDA, attended and announced new commitments to further research to improve treatment options for patients with ESRD. Specifically, ASN has pledged the first $7 million toward a possible XPRIZE competition to achieve that goal. We hope that this White House Initiative will spur exciting new research and innovative approaches and will lead to better options for our patients.
ASN applauds the foresightedness that led to the development of these two initiatives. We are very optimistic that they will result in new and exciting approaches for nephrologists to continue to provide the best care for patients with kidney diseases.