Policy: Kidney/Pancreas Post Transplant: Bone Disease Management Protocol Statement: Vision

Policy: Kidney/Pancreas Post Transplant: Bone Disease Management Protocol

Statement: Vision Strategy: Patient Care

Policy Statement: The Emory Transplant Center and all the solid organ transplant programs will comply with all applicable federal, state, and local laws, regulations, policies and protocols regarding the management of transplant patients.

Basis: Abnormalities of bone turnover and architecture are common after renal transplantation and as a result, renal transplant recipients (RTR) have a four-fold increased risk of fracture compared to the general population. The etiology of post transplant bone disease is multi factorial and encompasses pre-transplant renal osteodystrophy and osteoporosis (osteoporosis is present in up to 60% of RTR, frequently developing within the first 18 months of transplant) as well as other post-transplant factors including age, gonadal insufficiency, cigarette smoking, persistent hyperparathyroidism, immunosuppressive drugs (steroids/CNI), level of post-transplant renal function, hyperphosphaturia, hypophosphatemia, metabolic acidosis, and insufficient dietary calcium intake. Studies suggest that the risk of fracture is greatest within the first 3-5 years after transplantation. While correlation between bone mineral density as measured by DEXA scan and fracture rates are poor in the renal transplant population, this is likely a reflection of the fact that bone strength is determined not only by bone density, but also by bone quality which is harder to measure by non-invasive means. Efforts to restore bone health and prevent worsening of osteodystrophy and osteoporosis should begin soon after transplantation with measurement of bone density, serum calcium, vitamin D, and parathyroid hormone levels. Other testing including thyroid function tests and testosterone levels may be of benefit in select patients. Treatment for osteoporosis, vitamin D deficiency, secondary hyperparathyroidism, and electrolyte abnormalities should commence soon after transplantation and continue over the long term.

Admin Responsibility: All transplant program physicians, practitioners and clinical staff members are responsible for compliance with this clinical protocol.

Activation Date: 11/04/2009

Scope/Procedure:

SCREENING: I. Bone densitometry a. Performed within the first 3 months of transplantation and then at one year, 18 months, and 24 months post-transplant. After 2 years post transplantation, DEXA scans should be performed annually. II. Laboratory testing a. Measurement of the serum calcium, phosphorus, bicarbonate, and iPTH at the time of transplant, quarterly x one year post-transplant, and bi-annually thereafter. b. Measurement of a 25-OH Vitamin D level in all patients at 3 months post-transplant. PREVENTION: I. All patients (except those with hypercalcemia or significant hypophosphatemia) should receive Calcium and Vitamin D supplementation (1000-1500 mg Ca++/daily plus 400 IU Vitamin D/daily; i.e. 2 tabs po Qhs of either Caltrate 600+D or OsCal 500+D). II. Smoking cessation should be strongly encouraged. III. Patients should be encouraged to participate in weight bearing exercises in addition to regular daily exercise (walking/running on the treadmill/outside, stair-step machines, elliptical training machines, low or high impact aerobics). TREATMENT: I. Patients with low bone mineral density (except those with hypercalcemia) should be 25-OH Vitamin D replete. 25-OH Vitamin D insufficiency is common (studies have shown that up to 90% of RTRs may have vitamin D insufficiency). For 25-OH Vitamin D deficiency/insufficiency (level of ≤30 ng/ml), replete with ergocalciferol as follows: a. 25-OH D level of 16-30 ng/ml: 50,000 IU po q month x 6 months. b. 25-OH D level of 5-15 ng/ml: 50,000 IU po q week x 4 weeks then monthly to complete 6 months total. c. 25-OH D level of <5 ng/ml: 50,000 IU po q week x 12 weeks then monthly to complete 6 months total. Will need to check a f/u 25-OH Vitamin D level after repletion. II. Persistent Hyperparathyroidism:

Studies show that persistent hyperparathyroidism is common after renal transplant, but that the iPTH levels begin to fall shortly after successful transplantation. At 2 years post-transplant, >50% of patients have elevated iPTH levels and at 5 years post-transplant only 23% of patients having “normal” iPTH levels. The optimal iPTH level to be attained post-transplant is not clear and aggressive oversuppression of iPTH levels may lead to adynamic bone disease. Until further evidence is available, it is reasonable to target an iPTH level of ≤ 100 pg/ml in patients with good allograft function.

a. Patients who are on a calcimimetic prior to transplant, would continue the calcimimetic post-transplant and attempt to wean as iPTH level improves. b. Patients with an elevated iPTH in the setting of hypercalcemia may benefit from treatment with a calcimimetic. c. Patients who are >6 months post-transplant with persistent secondary/tertiary hyperparathyroidism in the setting of hypercalcemia that is refractory to medical therapy may benefit from parathyroidectomy. d. Patients with a GFR <60 ml/min, a persistently elevated iPTH, and normal serum calcium levels should be started on an oral vitamin D analog. III. Low Bone Mineral Density

Would recommend oral bisphosphonate therapy for the following patients with a CrCl of ≥35 ml/min: a. score ≤ -2.5 after appropriate therapy to exclude secondary causes. b. Prior fragility fracture and T score between -1 and -2.5. c. T score between -1 and -2.5 with a secondary cause for osteoporosis (steroid use) and decreasing bone mineral density post-transplant. d. Previous hip or vertebral fracture. e. T score between -1 and -2.5 and 10 year probability of hip fracture 3% or any major osteoporotic fracture 20% Determination of probability of fracture by FRAX calculation: http://www.shef.ac.uk/FRAX). IV. Mineral-Electrolyte Abnormalities (Serum calcium, phosphorus, magnesium and bicarbonate) Blood work including minerals and electrolytes should be ordered with each transplant clinic visit. Treatment includes:

a. Hypophosphatemia – Treatment with K-Phos Neutral 250 mg tablet three times daily, titrated based upon laboratory results. With treatment, hypophosphatemia usually resolves within a few months post-transplant. b. Hypercalcemia – Is usually asymptomatic. Calcium levels should be monitored in conjunction with parathyroid hormone (iPTH) levels. If hypercalcemia persists with an elevated iPTH level, consider treatment with a calcimimetic or para-thyroidectomy. c. Hypomagnesemia – Treatment with Magnesium Oxide 400 mg twice daily followed by titration of the dose based upon laboratory results. d. Metabolic Acidosis (low serum bicarbonate) – Treatment with sodium bicarbonate 1300 mg twice daily followed by titration of the dose based upon laboratory results to achieve a goal serum bicarbonate level of 21-22 mmol/L.

References: Approved by: Renal (Pancreas) Transplant Leadership Group

___Signature on File______Thomas C. Pearson, MD, DPhil Chair, Renal Transplant Leadership Group Director, Renal and Pancreas Transplant Programs

Approval: 11/04/2009