A 56-year-old man with chronic kidney disease is seen for a routine follow-up visit. The patient also has type 2 diabetes, hypertension, and hyperlipidemia. His serum creatinine level has been increasing over the past 2 years. Blood pressure is 144/90 mm Hg and pulse is 88/min. Weight is 80 kg (176 lb). Physical examination is normal except for trace pitting ankle edema. Serum creatinine level is 1.8 mg/dL; 1 year ago, serum creatinine was 1.4 mg/dL. Serum calcium and phosphorus levels are in the normal range. Which of the following is most likely responsible for maintaining the serum phosphorus within normal range despite declining renal function?

Question

A 56-year-old man with chronic kidney disease is seen for a routine follow-up visit.  The patient also has type 2 diabetes, hypertension, and hyperlipidemia.  His serum creatinine level has been increasing over the past 2 years.  Blood pressure is 144/90 mm Hg and pulse is 88/min.  Weight is 80 kg (176 lb).  Physical examination is normal except for trace pitting ankle edema.  Serum creatinine level is 1.8 mg/dL; 1 year ago, serum creatinine was 1.4 mg/dL.  Serum calcium and phosphorus levels are in the normal range.  Which of the following is most likely responsible for maintaining the serum phosphorus within normal range despite declining renal function?

Quizplus · Accepted Answer

11ec160b_3cf7_d98d_9249_d72165968d1d_MD0001_00 Renal clearance of phosphate depends on adequate filtration of phosphate in the glomerulus. Patients with chronic kidney disease (CKD) and decreased glomerular filtration can experience inadequate phosphate excretion leading to hyperphosphatemia. Fibroblast growth factor 23 (FGF23) is secreted by osteocytes in response to hyperphosphatemia and binds the FGF23 receptor along with the coreceptor Klotho. In the kidneys, FGF23 suppresses 1-hydroxylase (which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the more active form), leading to reduced levels of 1,25-dihydroxyvitamin D. This causes decreased intestinal phosphate absorption and decreased renal phosphate reabsorption. Concurrently, FGF23 downregulates sodium/phosphate cotransporter IIa in the renal tubules, leading to an additional decrease in phosphate reabsorption. The net effect is greater elimination of phosphate in the urine and feces. FGF23 is one of the earliest counterregulatory factors in responding to hyperphosphatemia, and it may be elevated even before circulating phosphate levels are above laboratory reference ranges. Serum FGF23 levels are useful as an early marker for monitoring abnormal phosphate metabolism in patients with CKD. (Choice A) In contrast to the parathyroid glands, which have a significant role in calcium and phosphate homeostasis, the pituitary-thyroid axis (ie, thyrotropin, thyroid hormone) is not a major regulator of calcium and phosphate metabolism. (Choices B and E) Hypocalcemia and hyperphosphatemia in CKD induce secretion (not suppression) of parathyroid hormone (PTH) from the parathyroid glands. PTH causes release of calcium from bone, renal calcium retention, and increased renal phosphate excretion. Despite rising PTH levels in CKD (ie, secondary hyperparathyroidism), patients tend to develop hyperphosphatemia due to the declining glomerular filtration rate (reduces filtered phosphate load). (Choice C) As with phosphate, declining glomerular filtration generally leads to magnesium retention, not wasting. Moreover, clinically significant alterations in magnesium levels are typically seen only in patients with advanced CKD (ie, glomerular filtration rate <10-30 mL/min; serum creatinine >2-3 mg/dL). Educational objective: Patients with chronic kidney disease (CKD) can develop hyperphosphatemia due to decreased filtration of phosphate. Fibroblast growth factor 23 (FGF23) is secreted in response to hyperphosphatemia and lowers plasma phosphate by reducing intestinal absorption and renal reabsorption of phosphate. FGF23 levels are useful as an early marker of abnormal phosphate metabolism in patients with CKD. __________ References: FGF23 synthesis and activity. (http://www.ncbi.nlm.nih.gov/pubmed/31008021)

A 56-Year-Old Man with Chronic Kidney Disease Is Seen for a Routine