Preserving Bone, Vascular, and Muscle Health in Patients with Chronic Kidney Disease: Meet the Disruptors

Mineral and bone disorders resulting from chronic kidney disease (CKD) is a common complication that affects many vital organ systems, including the skeleton, vasculature, skin, and muscles. Untreated, it can lead to bone fractures, circulatory conditions, and serious metabolic disequilibrium resulting in significant morbidity and mortality.

According to the CDC, an estimated 15% of the U.S. population — 37 million people — have chronic kidney disease, making it a growing public health concern.

Researchers in the department of medicine's division of nephrology are looking at the ways mineral metabolism affects the musculoskeletal and vascular systems in the presence of chronic kidney disease and have several exciting studies underway.

Mineral Metabolism and Musculoskeletal Disease

Drs. Michal Melamed and Matthew Abramowitz, professor and associate professor, respectively, in the department of medicine's division of nephrology, are evaluating the interrelationship of kidney disease, muscle, and the effects of treatment on the skeleton.

Metabolic Acidosis

Many people with kidney disease are unable to remove acid from their blood, which, in time, can affect the bones.

Dr. Melamed, along with investigators from CHAM, Columbia University Irving Medical Center, and the University of Pittsburgh, recently received funding from the National Institute of Diabetes and Digestive and Kidney Diseases to conduct a six-month pilot study of approximately 100 adults and children with less severe kidney disease putting them on potassium citrate or placebo and using a highly sensitive imaging modality — high resolution peripheral quantitative computed tomography — to measure bone changes after six months.

If effective, this will allow clinicians to start treating patients with potassium citrate at much earlier stages of their disease, helping to disrupt the progression of bone disorders associated with CKD. This will be a major advance for all patients, but particularly children since most bone growth and mineralization occurs during childhood.

Muscle Fibrosis

Patients with CKD experience progressively worsening muscle fibrosis causing muscle stiffness and reduced physical function that can interfere with the activities of daily living. With a five-year grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Dr. Abramowitz and his colleagues are testing whether earlier initiation of dialysis in select patients could improve outcomes by preventing physical function decline. What they have found so far is encouraging — that even in patients with severe CKD and extensive fibrotic changes, starting dialysis resulted in marked improvement in fibrosis, suggesting muscle regenerative potential.

A further aim of his study is to identify molecular and cellular predictors of fibrosis resolution using transcriptomic and proteomic analyses of skeletal muscle. If successful, muscle fibrosis could be an important indicator for physicians to start dialysis therapy, allowing for interventions that could alleviate muscle dysfunction in patients with CKD.

Vascular Calcification

Vascular calcification — calcium deposits in the blood vessels — is a devastating complication of chronic kidney disease. It is prevalent and accelerated in patients with CKD and contributes to high rates of cardiovascular morbidity and mortality. To date, there are no effective drugs that can slow or prevent vascular calcification.

Identifying novel biomarkers for vascular calcification and therapeutic targets is the mainstay of Dr. Wei Chen's work. Dr, Chen, an associate professor in the department of medicine's division of nephrology, received funding from the National Institute of Diabetes and Digestive and Kidney Diseases to study whether calciprotein particles, measured by the high throughput assay developed in her lab, are potential biomarkers for vascular calcification. In addition, Dr. Chen's lab is examining the effects of serum enzymes on human vascular cells, including both endothelial and vascular smooth muscle cells.

The goal of her research is to develop blood tests that can detect vascular calcification early and to identify new drugs for this life-threatening complication of CKD. This could dramatically reduce the incidence of cardiovascular complications, the leading cause of death in patients with CKD.

This is just a sampling of the innovative work the division of nephrology's physician-scientists are doing.

The good news, say the researchers, is that we have more to offer patients. There are promising options to treat the devastating effects of chronic kidney disease at all of its stages.