2015 New Treatments, Target Identification, Kidney
2015 How High Iron Levels in the Kidney May Cause Lupus Nephritis
The study and what it means to patients
We are excited to test our hypothesis that kidney damage in lupus is caused by a build up of too much iron in the kidney tissue. If we are correct, medications that reduce iron levels or limit its damaging effects could be developed to protect patients who are at risk of lupus nephritis.
Iron is an essential mineral that helps red blood cells move oxygen from the lungs to the rest of the body. However, iron buildup can damage organs such as the liver or heart, causing the organ to malfunction. In humans, biomarkers of lupus nephritis include proteins that help the body metabolize iron, suggesting a role for iron in this condition.
We have discovered that mice with lupus have abnormal iron buildup in their kidneys. Now our LRI-funded research will explore 1) how and why iron collects in the kidneys of mice with lupus, 2) whether this iron buildup injures the kidneys and contributes to lupus nephritis, and 3) the potential impact of therapies that decrease iron levels in treating lupus nephritis. Several medicines are already available to reduce iron levels but none have been investigated for lupus nephritis.
Scientific Abstract: Iron and ER Stress in Lupus Nephritis
Lupus nephritis is a serious and common complication of systemic lupus erythematosus (SLE), and affects approximately 50% of SLE patients. Current treatments for lupus nephritis are only partially effective and have serious side effects, highlighting a need for new therapies.
Based on our novel findings of increased renal iron accumulation in a mouse model of SLE, and published evidence of iron metabolism proteins as biomarkers of lupus nephritis in humans, we propose increased renal iron accumulation as a novel mechanism of renal injury in SLE. Our preliminary data also show increased endoplasmic reticulum (ER) stress in the kidneys, providing an additional novel and possibly interrelated mechanism of injury. Using a mouse model of SLE, we will determine (1) the contribution of increased iron accumulation to renal injury in SLE; (2) the pathway(s) by which increased iron accumulation occurs; and (3) the contribution of ER stress to renal injury in SLE. In doing so, we will gain proof-of-concept data for reducing iron accumulation and ER stress as novel therapeutic strategies for lupus nephritis, and identify specific iron transport pathways to target. Agents that chelate iron and block ER stress are already FDA-approved, therefore our results have excellent translational potential.