(2f) Removal of Parathyroid Hormone by Immunospecific Adsorption during Kidney Dialysis

Nearly all patients on kidney dialysis suffer from elevated levels of parathyroid hormone (PTH), a condition known as secondary hyperparathyroidism (SHPT). The symptoms of SHPT include a form of osteoporosis called renal osteodystrophy. As a consequence of renal osteodystrophy, kidney dialysis patients suffer from high rates of bone fracture, vascular calcification, and a rate of cardiovascular morbidity ten times that of the healthy population.

The restoration of normal PTH levels for kidney failure patients has to date proven to be a very challenging clinical problem. Conventional hemodialyzers are optimized to remove small molecular weight solutes such as urea and creatine (~100 Daltons). Middle molecular weight toxins such as PTH are of the order of 10,000 Daltons, and are poorly dialyzed. Meanwhile, drug therapies require weeks to months to lower serum PTH levels, allowing long periods of bone exposure to the hormone.

Affinity chromatography is a well-established technique to remove proteins from complex mixtures with high efficiency and specificity. To make use of its characteristic of high specific affinity between the antigen and antibody, a chromatographic column has been designed to reduce PTH levels to normal within one dialysis session. The removal is accomplished by a monoclonal antibody attached on the surface of the packing. The column is placed in series with a conventional hemodialyzer.

A mathematical model of the modified dialysis circuit was developed which reproduces an in vitro experiment with high accuracy. A simple, closed form, solution to the model was obtained, which was scaled up to the clinical scenario. The model indicates that the immunosorptive column will be effective in lowering PTH levels.