Rozhinskaya_nl2010p2

Editor's Notes

1. Immediate goals of therapy: In addition to controlling PTH level, immediate goals of therapy that have been recommended in secondary HPT include preventing phosphate retention and hyperphosphatemia, and maintaining normal serum calcium concentrations {Goodman 2001}. Long-term goals of therapy: Preventing parathyroid gland hyperplasia (through PTH control) {Cunningham 1999}. Maintaining normal skeletal function (by normalizing PTH, calcium, and phosphate levels) {Cunningham 1999}. Reducing morbidity & mortality rate associated with not only PTH elevations, but also calcium and phosphate elevations {Block 2000}. Block GA et al. Am J Kidney Dis. 2000;35:1226-1237. Cunningham J. Kidney Int. 1999;56(suppl 73):S59-S64. Goodman WG. Kidney Int. 2001;59:1187-1201.
2. Malberti and colleagues performed a prospective annual survey of 14,180 patients after renal replacement therapy in the Lombardy Registry of Dialysis and Transplantation {Malberti 2001}. Of the 7371 patients who were alive on December 31, 1996, the overall incidence of parathyroidectomy was 54.6 per 1,000 patient-years. Years of dialysis therapy was associated with an increased incidence of parathyroidectomy—patients with a >15-year duration of dialysis were more than 30 times as likely to require parathyroidectomy compared with patients who had <5-year duration of dialysis. Over time, the incidence of parathyroidectomy also increased among renal transplantation patients, but they had significantly lower rates of parathyroidectomy than dialysis patients (RR=0.15, P <0.001). Other risk factors for parathyroidectomy included young age of the patient and female gender; the incidence of parathyroidectomy was nearly twice as high in women as in men. These data suggest the need for new therapies that stop the progression of this disease. Malberti F et al. J Am Soc Nephrol. 2001;12:1242-1248.
3. Management of SHPT has included the use of active vitamin D or VDR activators for the suppression of PTH secretion, which are effective, but can cause hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, paricalcitol is shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia compared with placebo. Shown here are data from a double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients 263 patients with serum Ca x P <75 mg/dL, and a PTH level ≥300 pg/mL were randomly assigned to receive either paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product. Paricalcitol-treated patients achieved a ≥50% reduction from baseline PTH significantly faster than the calcitriol-treated patients (p=0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately Week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (p=0.008). Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy.
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5. Лечение вторичного гиперпаратиреоза заключается в подавлении избыточной секреции паратгормона. При умеренно выраженном вторичном гиперпаратиреозе возможно консервативное лечение этого вида ренальной остеодистрофии, которое складывается из ограничения потребления фосфата с пищей, назначения фосфат-связывающих гелей, синтетических метаболитов витамина D 3 -кальцитриола, рокальтрола [ 1,25(ОН) 2 D 3 ] , оксидевита 1  (ОН) D 3 , представляющего синтетический метаболит витамина D 3 , прошедший почечную, но не печеночную трансформацию и превращающийся в организме в [ 1,25(ОН) 2 D 3 ] , некальцемических аналогов витамина D 3 - 22-оксикальцитриола, паракальцитола и 1  (ОН) D 3 , менее склонных вызывать гиперкальциемию, а также кальциймиметиков – производных фенилалкиламинов, реагирующих с Ca- рецепторами паращитовидной железы и уменьшающих секрецию ПТГ.
6. Vitamin D supplementation A substantial proportion of patients do not respond to vitamin D therapy. 1–3 Resistant patients are probably those with advanced SHPT in whom nodular hyperplasia has reduced expression of VDRs and CaRs. For example, in one study involving 35 dialysis patients, 18 patients achieved the therapeutic goal of iPTH levels less than 260 pg/mL (27   pmol/L), but iPTH levels increased or remained unchanged in 14 of the 17 non-responders. 2 In addition to its effects on PTH synthesis, vitamin D has an indirect effect on PTH by facilitating the intestinal absorption of calcium and phosphorus. 1,4,5 Unfortunately, in practice, this means that it may induce episodes of hyperphosphataemia and/or hypercalcaemia. 1,2,6 High levels of phosphorus can prevent vitamin D-induced reduction in PTH. 7,8 Accordingly, vitamin D therapy may add to the risk of extra-skeletal calcification. 9 Phosphate-binding agents All varieties of phosphate binder are associated with high pill burdens – a factor that frequently leads to reduced patient compliance. 10 Phosphate binders can only reduce absorption of phosphate from the gut and they have no effect on systemically derived phosphorus that is released from bone. Calcium-based agents can unfortunately add to systemic calcium load and have been associated with increased risk of cardiovascular calcification by a number of authors. 11,12 1. Quarles LD et al . Kidney Int 1994;45:1710–21 2. Malberti F et al. Am J Kidney Dis 1996;28:704–12 3. Rodriguez M et al . Kidney Int 1999;56:306–17 4. Block GA et al . Am J Kidney Dis 1998;31:607–17 5. Cunningham J. Kidney Int 1999;56(Suppl 73):S59–64 6. Bechtel U et al . Am J Kidney Dis 1995;25:291–6 7. Tallon S et al. Kidney Int 1996;49:1441–6 8. Almaden Y et al. Kidney Int 2003;64:2311–7 9. Jono S et al . Circulation 1998;98:1302–6 10. Pflanz S et al . Nephrol Dial Transplant 1994;9:1121–4 11. Goodman WG et al . N Engl J Med 2000;342:1478–83 12. Guerin AP et al. Nephrol Dial Transplant 2000;15:1014–21
7. The only adverse events that were reported more frequently in the cinacalcet group were nausea and vomiting. 1 Quarles LD et al. J Am Soc Nephrol 2003;14:463A(SA-PO751) Amgen. Data on file.