Therapy of Secondary Hyperparathyroidism With 19-Nor -1, 25-Dihydroxyvitamin D 2 Kevin J. Martin, MB, BCh, FACP, Esther A. Gonza ´ lez, MD, Mary E. Gellens, MD, L. Lee Hamm, MD, Hanna Abboud, MD, and Jill Lindberg, MD ● Secondary hyperparathyroidism contributes to significant morbidity in patients with chronic renal failure. The treatment of this disorder with vitamin D compounds, such as calcitriol, although effective at suppressing parathyroid hormone (PTH) secretion, may promote the development of hypercalcemia and hyperphosphatemia, thus increasing the risk for metastatic calcification. A new vitamin D analogue, 19-nor-1,25-(OH) 2 D 2 (paricalcitol; Zemplar, Abbott Laboratories, Inc, Chicago, IL) has recently been developed for the treatment of secondary hyperparathyroidism, and, in experimental animals, it was found to be less calcemic and phosphatemic than calcitriol. In double-blind clinical trials, paricalcitol effectively decreased the levels of PTH by 60%, yet the mean serum calcium values remained within the normal range. The few episodes of hypercalcemia that occurred in the paricalcitol-treated patients (8 of 400 determinations H11.0 mg/dL in 7 patients) were associated with marked decreases in PTH levels (87%  2% less than baseline) and absolute values of PTH less than 100 pg/mL in four of the seven patients. PTH values less than 100 pg/mL, however, occurred in 15 patients, but were not invariably associated with frank hypercalcemia, although serum calcium levels increased to 10.63  0.3 mg/dL, slightly greater than the upper limits of normal. Additional studies to evaluate the conversion from calcitriol to paricalcitol therapy showed that a dose ratio of 1:4 (calcitriol:paricalcitol) could maintain control of high levels of PTH without significant alterations in serum calcium and phosphorus levels. These studies indicate that effective control of hyperparathyroidism can be achieved with paricalcitol therapy with minimal perturbation of serum calcium and phosphorus levels, and may have a therapeutic advantage over current treatment strategies.  1998 by the National Kidney Foundation, Inc. INDEX WORDS: Hyperparathyroidism; vitamin D; calcitrol analogues. S ECONDARY hyperparathyroidism contin- ues to be a significant complication of chronic renal failure. 1,2 Because of the impor- tance of phosphorous retention and low levels of calcitriol in its pathogenesis, current therapy involves the use of dietary phosphorous restric- tion, phosphate-binding antacids to limit the ab- sorption of ingested phosphorus, and the admin- istration of vitamin D metabolites, such as calcitriol. 3-5 Because of the marked effect of calcitriol in increasing intestinal calcium absorp- tion, the concomitant use of calcitriol with large doses of calcium-containing phosphate-binding antacids increases the risk for hypercalcemia. Similarly, because calcitriol also increases intes- tinal phosphorus absorption, hyperphosphatemia may be aggravated during therapy with cal- citriol. 6 The need to improve our therapies for second- ary hyperparathyroidism has led to a search for analogues of vitamin D that might have less effect on the absorption of calcium and phospho- rous, and yet retain the effects of vitamin D on the suppression of parathyroid hormone (PTH) synthesis. Several new vitamin D analogues have been evaluated in this regard. One such ana- logue, 19-nor-1,25-dihydroxyvitamin D 2 (pari- calcitol), has been shown in experimental ani- mals to suppress PTH levels as effectively as calcitriol, but with lesser effects on serum cal- cium and phosphorous levels. 7 On the basis of these results in experimental animals, paricalci- tol has been evaluated in patients with secondary hyperparathyroidism and end-stage renal disease undergoing maintenance hemodialysis. 8 PATIENTS AND METHODS Studies of Safety and Effıcacy Seventy-eight patients with end-stage renal disease (ESRD) were studied in three identical double-blind, placebo- controlled, randomized, multicenter trials to evaluate the safety and efficacy of paricalcitol. The results of such studies are described in detail elsewhere. 8 All patients had ESRD and received hemodialysis three times a week. The study protocol is shown in diagrammatic form in Fig 1. In brief, if From the Division of Nephrology, Saint Louis University, St Louis, MO; Section of Nephrology, Tulane University; Department of Nephrology, Ochsner Clinic, New Orleans, LA; and the Division of Nephrology, University of Texas at San Antonio, TX. Supported in part by Abbott Laboratories, Abbott Park, IL. Address reprint requests to Kevin J. Martin, MB, BCh, FACP, Saint Louis University Health Sciences Center, Divi- sion of Nephrology (9-FDT), 3635 Vista Ave, St Louis, MO 63110. E-mail: martinkj@wpogate.slu.edu  1998 by the National Kidney Foundation, Inc. 6386/98/3204-0207$3.00/0 American Journal of Kidney Diseases, Vol 32, No 4, Suppl 2 (October), 1998: pp S61-S66 S61