A 48-year-old man comes to the office for intractable lower extremity bone pain. He has end-stage renal disease due to focal segmental glomerulosclerosis and has been on hemodialysis 3 times a week for the past 4 years. Approximately 3 months ago, adjustments in his medications and hemodialysis regimens were made after the patient was found to have high serum calcium, phosphorus, and parathyroid hormone levels; however, these adjustments did not lead to any significant improvements in laboratory values. Temperature is 36.9 C (98.4 F), blood pressure is 190/100 mm Hg, and pulse is 88/min. Oral examination shows pallor of the mucous membranes. Lungs have decreased sounds at both bases. Cardiovascular examination shows a 2/6 systolic ejection murmur at the left upper sternal border and a palpable thrill over an arteriovenous fistula in the left forearm. Laboratory results are as follows: Chest x-ray reveals cardiomegaly with calcification of the ascending aorta. Which of the following treatments would be most beneficial for this patient's current condition?

Question

A 48-year-old man comes to the office for intractable lower extremity bone pain.  He has end-stage renal disease due to focal segmental glomerulosclerosis and has been on hemodialysis 3 times a week for the past 4 years.  Approximately 3 months ago, adjustments in his medications and hemodialysis regimens were made after the patient was found to have high serum calcium, phosphorus, and parathyroid hormone levels; however, these adjustments did not lead to any significant improvements in laboratory values.  Temperature is 36.9 C (98.4 F), blood pressure is 190/100 mm Hg, and pulse is 88/min.  Oral examination shows pallor of the mucous membranes.  Lungs have decreased sounds at both bases.  Cardiovascular examination shows a 2/6 systolic ejection murmur at the left upper sternal border and a palpable thrill over an arteriovenous fistula in the left forearm.  Laboratory results are as follows:  Chest x-ray reveals cardiomegaly with calcification of the ascending aorta.  Which of the following treatments would be most beneficial for this patient's current condition?

Quizplus · Accepted Answer

Explanation: 11ec2b69_bfdd_6268_8f63_c7f2279b1e5a_MD0005_00 This patient with chronic kidney disease (CKD), bone pain, vascular calcifications, and elevated calcium, phosphorus, and parathyroid hormone (PTH) levels has tertiary hyperparathyroidism. CKD affects parathyroid metabolism due to several factors: CKD causes phosphate retention due to a decrease in the filtered phosphate load. Binding of calcium by phosphate can lower free serum calcium levels, leading to a compensatory rise in PTH. CKD decreases renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, leading to decreased calcium absorption in the intestine. 1,25-dihydroxyvitamin D production is also suppressed by fibroblast growth factor 23, which is produced by osteocytes in response to hyperphosphatemia and falling free calcium concentrations. The net result is secondary hyperparathyroidism characterized by elevated PTH levels, low/low-normal calcium levels, and low 1,25-dihydroxyvitamin D levels (despite adequate 25-hydroxyvitamin D stores). Over time, this can lead to autonomous PTH secretion unresponsive to rising calcium levels, resulting in hypercalcemia with very high PTH levels. This tertiary hyperparathyroidism can be associated with metabolic bone disease with bone pain and an elevated bone-specific alkaline phosphatase (due to high bone turnover). Indications for parathyroidectomy in tertiary hyperparathyroidism include: Persistently elevated calcium (eg, >10.5 mg/dL), phosphorus, or PTH (eg, >800 pg/mL) levels Soft tissue calcification or calciphylaxis (vascular calcification with skin necrosis) Intractable bone pain or pruritus (Choice A) Bisphosphonates are generally not recommended in end-stage renal disease as they reduce bone turnover, leading to osteomalacia, mixed uremic osteodystrophy, and adynamic bone disease. They can also cause a worsening of hyperparathyroidism. (Choice B) Intravenous hydration is used for the acute treatment of severe hypercalcemia. However, it is not helpful in patients with end-stage renal disease and tertiary hyperparathyroidism as it is less effective in increasing urinary calcium excretion and can lead to fluid overload. (Choice D) Tertiary hyperparathyroidism is neither an indication nor a contraindication to renal transplantation. However, parathyroidectomy is recommended before renal transplantation when PTH levels are >800 pg/mL as hyperparathyroidism is unlikely to improve following transplantation. (Choice E) Peritoneal dialysis is effective in controlling calcium, phosphorus, and PTH levels in early secondary hyperparathyroidism. However, in severe secondary or tertiary hyperparathyroidism, peritoneal dialysis is not superior to hemodialysis. Educational objective: Chronic kidney disease is associated with phosphate retention, reduced free serum calcium levels, and decreased 1,25-dihydroxyvitamin D levels. This leads to a compensatory rise in parathyroid hormone (PTH) levels (secondary hyperparathyroidism). Over time, this can lead to autonomous PTH secretion (tertiary hyperparathyroidism). Indications for parathyroidectomy in tertiary hyperparathyroidism include persistent hypercalcemia or hyperphosphatemia, very high PTH levels, soft tissue calcification or calciphylaxis, and intractable bone pain. References: Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. (http://www.ncbi.nlm.nih.gov/pubmed/21454719)

A 48-Year-Old Man Comes to the Office for Intractable Lower