Secondary hyperparathyroidism (SHPT) describes a complex alteration in bone and mineral metabolism that occurs as a direct result of chronic kidney disease (CKD). Bone disease, a well-recognized complication of SHPT, represents only a small concern in light of the evidence that correlates SHPT with cardiovascular disease and an increased risk of morbidity and mortality in patients with CKD. Patients with mild CKD may not show any symptoms and therefore may not be identified until the pathology of SHPT has begun. Early intervention may slow or arrest the progression of both bone and cardiac disease. Dietary concerns, pharmacotherapy, and patient adherence are all important considerations in creating a successful treatment plan.
Chronic kidney disease (CKD) is a highly prevalent health issue in the United States and is most often the consequence of chronic diseases, notably diabetes or hypertension. Because ∼ 40% of patients with diabetes develop nephropathy, diabetic patients alone will account for 12 million people with CKD. Five stages of CKD are used to stratify patients based on the degree of renal function and act as markers to predict the development of co-morbidities of CKD, such as secondary hyperparathyroidism (SHPT). Research has shown that CKD patients who are classified as Stage 3, Stage 4, or Stage 5 are at risk for, or may already have developed, SHPT. The early identification and treatment of SHPT is crucial to preventing or controlling the consequences of this complication.
Renal osteodystrophy refers to several bone disorders that accrue from the pathophysiology of bone and mineral metabolism in CKD: osteitis fibrosa cystica, osteomalacia, and adynamic bone disease. Osteitis fibrosa cystica is referred to as high-turnover bone disease and is associated with elevated PTH concentrations that stimulate osteoclast activity, bone breakdown, and resorption. Osteomalacia (“soft bone”) is characterized by a low turnover of bone and abnormal mineralization and has historically been associated with aluminum toxicity. Adynamic bone disease is referred to as low-turnover disease with normal mineralization and may result from low PTH levels. The prevalence of adynamic bone disease is increasing and may be the consequence of PTH over-suppression from the use of vitamin D agents, calcimimetics, and phosphate binders, singly or in combination.
The ultimate goals of treating SHPT are to normalize mineral metabolism, prevent bone disease, and prevent extraskeletal manifestations of the altered biochemical processes. The markers of calcium, phosphorus, vitamin D, and iPTH are used as surrogate measures of disease progression. It is important to identify SHPT early. Abnormalities can occur subtly, usually without any symptoms, and may progress to cause more complications if not detected early. Until recently, it was thought that hyperphosphatemia was the earliest sign of SHPT and bone metabolism disorders. However, when patients reach Stage 3 CKD, it is highly probable that none of the biochemical parameters routinely assessed will be abnormal. In fact, the iPTH level is often increased before clinical hyperphosphatemia occurs. For this reason, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KQODI) guidelines recommend that all patients with a GFR < 60 ml/min/1.73 m2 undergo evaluation of serum calcium, phosphorus, and iPTH levels. Additionally, if the iPTH concentration exceeds the CKD stage-specific target, the precursor of activated vitamin D should be assessed and treated. Hopefully, earlier identification and assessment of SHPT will improve bone and mineral metabolism in CKD and reduce its associated complications (e.g., fractures, pain, and cardiovascular calcification).
SHPT is a complex and challenging condition. Metabolic parameters such as calcium, phosphate, iPTH, and vitamin D must be maintained within target ranges to prevent bone disease and extraskeletal calcification, decrease cardiac disease risk, and maintain homeostasis of other body systems. Additionally, all of these parameters need to be controlled simultaneously to be successful.
Perhaps the most difficult challenge in the treatment of SHPT is that of patient acceptance and adherence. Complicated medication regimens that involve taking medicines multiple times each day, a high pill burden, co-morbid conditions, financial constraints, psychosocial issues, and dietary restrictions are all factors that increase the rate of non-adherence and thwart treatment success. Maintaining bone and mineral metabolism is a challenge, and requires a multidisciplinary team approach. Dietitians must play a crucial role in the management of SHPT to design nutrition plans that restrict the amount of phosphorus while providing optimal protein intake. They also may recommend protein supplements or other dietary aids for optimal nutritional balance. Pharmacists and social workers are involved in the complicated process of obtaining drugs for patients with limited resources or prescription drug benefits that have restrictions on certain agents. Some might work with insurance companies and physicians to obtain prior authorizations or access patient assistance programs through the pharmaceutical industry or community resources. Physicians, nurses, pharmacists, social workers, physical therapists, and nearly all other health care professionals can play a role in managing SHPT. Adhering to prescribed medication, diet, and exercise and staying positive is crucial to the successful management of secondary hyperparathyroidism.