By Ellie Kelepouris, MD, FAHA

It is well recognized now that chronic kidney disease (CKD) involves different organ complications, including heart disease, anemia and bone disease. CKD has been classified as having five stages with Stage 1 being early kidney disease and Stage 5 being patients on dialysis.

As early as CKD Stage 3 (which means that patients have a kidney function that approximates half of normal) patients are at a greater risk of going on to get more severe kidney disease. Patients are also at an increased risk of getting heart disease or other illnesses affecting the entire body.

For example, as kidney disease progresses, phosphate in the blood will accumulate (since its excretion by the kidney is decreased). That will lower blood calcium levels and in response, a hormone named parathyroid hormone (PTH) will be produced in higher amounts by a neck gland – the parathyroid gland. This is a normal defense mechanism which is magnified in patients with kidney disease. We normally have four parathyroid glands, but there are people who may have even more, "accessory" parathyroid glands, localized in other parts of the body. The result of these high PTH levels is bone disease because PTH "leaches" calcium from bone.

Elevations in PTH levels first become evident when kidney function is reduced to almost half of the normal, as in CKD Stage 3. PTH will increase blood calcium and lower blood phosphorus by taking calcium from the bones. It also decreases renal calcium excretion, while increasing urinary phosphate excretion. Simply put, bones with less calcium are weaker bones, therefore more prone to be painful and to break or fracture. Another mechanism that is specific for renal patients is the deficiency of the active form of vitamin D. Vitamin D is formed in your skin under the action of daylight (the UV rays). However, in order to be fully active, it needs activation by a specific enzyme synthesized (blended) by the kidneys. In patients with renal failure, the amount of the active form of vitamin D that can be produced by their failing kidneys is consequently decreased, because less activating enzyme is produced.

The active form of vitamin D, plays very important roles in the calcium and phosphate balance in our body and is an essential vitamin for bone health. Under its action, the amount of calcium and phosphate absorbed from the gut will increase. There are direct interactions between vitamin D and PTH: PTH stimulates the activation of vitamin D while the active form of vitamin D decreases, via a feedback mechanism, PTH production.

There is enough evidence now that PTH and vitamin D also play important roles in heart health and immune defense. Abnormal levels may be associated with more patients dying. All these metabolic abnormalities can initially show no signs of disease. However, if kidney failure progresses to the stage when only half of kidney function is preserved, clinical findings and symptoms are present. Those include fractures, tendon rupture, bone pain, muscle pain, weakness and joint pains. As previously mentioned, other systems can be involved and more physicians are recognizing calcium deposits in blood vessels in kidney disease may play a central role in heart disease and mortality, the leading cause of death in patients with kidney failure.

Your nephrologist can order a few simple blood tests to evaluate you for renal bone disease: the PTH, calcium and phosphorus levels. A simple x-ray of bones is also useful. In very rare cases, and if specific indications are present, your doctor may suggest a bone biopsy. This is the "gold standard", the best test to assess and diagnose the different types of bone disease in patients with renal failure. It is invasive and painful. Since the blood tests are simple, largely available, and reliable enough to evaluate your bone health, a bone biopsy is reserved for special cases which don’t respond to treatment.

There is increasing interest in measurement of vitamin D levels since vitamin D is very important for your health in general. There is deficiency in vitamin D in a large percentage of the general population, but especially prevalent in the elderly, women, diabetics, renal patients and African Americans. You may be instructed to take a vitamin D supplement to correct the deficit. These supplements have to be taken only under your doctor’s direct supervision.

Treatment of patients with predialysis CKD is a complex therapeutic decision and you can become an active part of it.

First, you should choose a low phosphate diet. Nuts, beer, chocolate and dark/brown sodas all have a high phosphorus content. Dairy products also are high in phosphorus, but they are also a good source of vitamin D. Your dietitian or nutritionist can help you by outlining a healthy diet which is both nutritious and tasteful. If diet control is not effective, medications called "phosphate binders" can be prescribed. They bind phosphorus released from food in the gut, preventing phosphorus from being reabsorbed and entering the bloodstream. Phosphate binders should be taken with food, usually three times a day.

The kidneys are important in removing acids which are released when eating foods containing protein. In kidney failure, these acids accumulate in the body. Acid accumulation is bad for bone health and could be improved or corrected by drinking an alkaline solution or taking sodium bicarbonate pills.

As already mentioned, treatment with vitamin D is a very important part of the therapeutic strategy, both to correct deficient levels and to counteract persistently elevated PTH levels, in which case active vitamin D supplements are recommended.

As our understanding of renal bone disease advances, so does the effectiveness of therapeutic options. More importantly, by treating renal bone disease adequately, we may be able to improve quality of life and reduce the morbidity and the risk of death in patients with renal diseases.

Ellie Kelepouris, MD, is Professor of Medicine and Director of Doctoring and Clinical Skills at Temple University School of Medicine in Philadelphia,Pennsylvania. A principal investigator on several clinical studies, Dr. Kelepouris is currently focusing her research on chronic kidney disease and parathyroid function and bone disease in patients on dialysis.

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