In all patients with chronic kidney disease (CKD) stages 3–5, regular monitoring of serum markers of CKD-mineral and bone disorder, including calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 25-hydroxyvitamin D, and alkaline phosphatase, is recommended. Target ranges for these markers are endorsed by guidelines. The principles of therapy for secondary hyperparathyroidism include control of hyperphosphataemia, correction of hypocalcaemia, use of vitamin D sterols, use of calcimimetics, and parathyroidectomy.
of hyperphosphataemia is crucial and may be achieved by means of dietary P restriction, use of P binders, and P removal by dialysis. Dietary P restriction requires caution, as it may be associated with protein malnutrition. Aluminium salts are effective P binders, but they are not recommended for long-term use, as Aluminium toxicity (though from contaminated dialysis water rather than oral intake) may cause cognitive impairment, osteomalacia, refractory microcytic anaemia, and myopathy. Ca-based P binders are also quite effective, but should be avoided in patients with hypercalcaemia, vascular calcifications, or persistently low PTH levels. Non-aluminium, non-Ca binders, like sevelamer and lanthanum carbonate, may be more adequate for such patients; however, they are expensive and may have several side effects. Furthermore, comparative trials have failed so far to provide conclusive evidence on the superiority of these newer P binders over Ca-based binders in terms of preventing vascular calcifications, bone abnormalities, and mortality. P removal is about 1800–2700 mg per week with conventional thrice-weekly haemodialysis, but may be increased by using haemodiafiltration or intensified regimens, such as short daily, extended daily or three times weekly nocturnal haemodialysis.
Several vitamin D derivatives are currently used for the treatment of secondary hyperparathyroidism. In comparison with the natural form calcitriol, the vitamin D analogue paricalcitol seems to be more fast-acting and less prone to induce hypercalcaemia and hyperphosphataemia, but whether these advantages translate into better clinical outcomes is unknown.
Calcimimetics such as cinacalcet can significantly reduce PTH, Ca, and P levels, but they have failed to definitively prove any benefits in terms of mortality and cardiovascular events in dialysis patients.
Parathyroidectomy is often indicated in CKD patients with severe persistent hyperparathyroidism, refractory to aggressive medical treatment with vitamin D analogues and/or calcimimetics. This procedure usually leads to rapid improvements in biochemical markers (i.e. significant lowering of serum Ca, P, and PTH) and clinical manifestations (such as pruritus and bone pain); however, the long-term benefits are still unclear.
Long-term control of secondary hyperparathyroidism by combination therapy with cinacalcet hydrochloride and intravenous active vitamin D