End stage kidney disease (ESKD) has a significant impact on the lives of people suffering from it and their families. Alongside requiring multiple medications to reduce their risk of heart disease and stroke, they need replacement of their kidney function from a kidney transplant or dialysis. Whilst kidney transplants are the optimal method of providing this, the need for kidney transplants outstrips their availability, meaning that people can wait a long time for their transplant. Dialysis is used for many people with ESKD but it requires regular visits to hospital, very frequent blood tests and invasive procedures and only 35% of people survive longer than 5 years on dialysis.
Considering that the prevalence of ESKD has almost doubled in Europe in recent years (from 480 to 807 per million age related population between 1992 and 20051), it is clear that new measures are urgently needed to prevent ESKD.
ESKD develops following acute kidney injury (AKI)2 and/or several years of worsening chronic kidney disease (CKD), which presents a window of opportunity to implement new therapies that delay or prevent progression to ESKD.
Therapies based on mesenchymal stromal cells (MSCs) are showing great promise in preclinical studies. MSCs are attractive because they have already been used in the clinic and therefore have high potential for clinical translation. However, a number of bottlenecks need to be overcome before these therapies can be routinely used in renal patients. Our aim is the develop the new tools and technologies that are necessary to address these bottlenecks, as listed below.
Diagnosis:
CKD has 5 stages, with stage 1 being almost normal and stage 5 representing ESKD. To have maximum effect, it is likely that MSCs will need to be administered before stage 3, when kidney function is about 50% of normal levels. The glomerular filtration rate (GFR) is the gold-standard indicator of renal function, but measuring the GFR is difficult and results are often influenced by many factors, making it unsuitable for routine screening. Creatinine is the most commonly used blood marker of kidney disease, but it can be within normal range and there can still be a significant reduction of GFR. Hence, there is a pressing need for new cost-effective and convenient methods for diagnosing and accurately monitoring kidney disease at the point-of-care. Learn more about our activities to develop new diagnostic tools.
Safety and efficacy of MSC therapies:
Safety and efficacy data are essential for determining the risk:benefit ratio of MSC therapies so as to judge whether they would be appropriate for clinical use. To assess safety, knowledge of MSC biodistribution is required so that any potential adverse effects on the body can be monitored. To assess efficacy, it is necessary to monitor the degree of kidney damage and the extent and persistence of any therapeutic response. Learn more about our activities to assess the safety and efficacy of MSCs.
Cell Potency and Mechanisms of Action:
The properties of MSCs differ depending on which tissue they are derived from. Most renal studies have used bone marrow-derived MSCs (BM-MSCs) however, other types of MSCs, such as adipose-derived MSCs (A-MSCs), umbilical cord-derived MSCs (UC-MSCs), and skin-derived MSCs (S-MSCs) could present attractive alternatives because they are much easier to source. Before these alternatives can be used, however, methods to determine their potency and the underlying mechanisms by which they act to repair or regenerate tissue are necessary. Learn more about our activities to assess the potency and mechanisms of action of MSCs.
1. Zoccali et al. (2010) Nephrol Dial Transplant 25:1731-3.
2. Belayev and Palevsky (2014) Curr Opin Nephrol Hypertens 23:149-54