A 58-year-old man comes to the office due to fatigue, decreased appetite, muscle cramps, and nausea. The patient has chronic kidney disease resulting from primary focal segmental glomerulosclerosis. His current medications include a vitamin D supplement. While his blood pressure is being obtained, the patient develops carpal spasm. Bilateral lower extremity pedal edema is noted. Laboratory evaluation shows a blood urea nitrogen level of 120 mg/dL, serum creatinine level of 10 mg/dL, and serum calcium level of 6 mg/dL. Which of the following is most likely contributing to this patient's carpal spasm?

Question

A 58-year-old man comes to the office due to fatigue, decreased appetite, muscle cramps, and nausea.  The patient has chronic kidney disease resulting from primary focal segmental glomerulosclerosis.  His current medications include a vitamin D supplement.  While his blood pressure is being obtained, the patient develops carpal spasm.  Bilateral lower extremity pedal edema is noted.  Laboratory evaluation shows a blood urea nitrogen level of 120 mg/dL, serum creatinine level of 10 mg/dL, and serum calcium level of 6 mg/dL.  Which of the following is most likely contributing to this patient's carpal spasm?

Quizplus · Accepted Answer

11ec160b_3b51_ca51_9249_6bcef8d3ac91_MD0001_00 This patient with chronic kidney disease (CKD) has developed carpal spasm secondary to hypocalcemia. In CKD, reduced filtration and excretion of phosphorus causes hyperphosphatemia, which induces hypocalcemia through the following mechanisms: Released phosphate binds to free calcium and precipitates in soft tissues (which, over the long term, can lead to vascular calcification and stiffness) Increased serum phosphate triggers the release of fibroblast growth factor 23 from bone, which acts to lower phosphate levels in part by inhibiting renal expression of 1-alpha hydroxylase. This reduces production of 1,25-hydroxyvitamin D (calcitriol), leading to reduced intestinal calcium absorption Hypocalcemia is also worsened by the progressive loss of functioning renal tissue in CKD, which further reduces calcitriol synthesis. Hypocalcemia can cause alterations in cellular membrane potentials and neuromuscular excitability. Manifestations include muscle cramps, Chvostek (facial twitching elicited by tapping on the facial nerve) and Trousseau (carpal spasm triggered by inflation of a blood pressure cuff around the arm) signs, hyperreflexia, QTc prolongation, and seizures. (Choice B) The hypocalcemia and hyperphosphatemia that occur in patients with CKD stimulate secretion of parathyroid hormone (ie, secondary hyperparathyroidism). By contrast, hypoparathyroidism is usually due to autoimmune disease or iatrogenic injury during thyroid surgery and is not a common finding in CKD. (Choice C) Serum calcium is composed of an ionized free calcium fraction and a protein-bound (largely to albumin) fraction; only ionized calcium is metabolically active. Hypoalbuminemia can occur in patients with nephrotic syndrome (eg, this patient with focal segmental glomerulosclerosis). However, although hypoalbuminemia lowers the bound fraction (and therefore total serum calcium), ionized calcium remains normal, and patients do not experience hypocalcemic symptoms. (Choice D) Fibroblast growth factor 23 levels are usually low in patients with normal phosphate metabolism but are increased in patients with renal failure in response to hyperphosphatemia. (Choice E) Vitamin D toxicity can occur in food faddists, patients with mental illness, and those inadvertently treated with excessive doses of vitamin D. However, this causes hypercalcemia, not hypocalcemia. Educational objective: In chronic kidney disease, reduced excretion of phosphate can cause hyperphosphatemia. This induces hypocalcemia directly by binding free calcium and depositing in tissues, and indirectly by triggering fibroblast growth factor 23 secretion (decreases calcitriol production and intestinal calcium absorption). The resulting hypocalcemia can manifest as neuromuscular excitability (eg, carpal spasm). __________ References: Pathophysiology of calcium, phosphorus, and magnesium dysregulation in chronic kidney disease. (http://www.ncbi.nlm.nih.gov/pubmed/26303319)

A 58-Year-Old Man Comes to the Office Due to Fatigue