Response to parathyroid hormone in normal human kidney donors before and after uninephrectomy

Normal human kidney donors represent a unique model of loss of renal mass without progressive disease. We studied such individuals to define the changes in mineral metabolism and renal responses to PTH that occur in mild renal insufficiency. PTH was infused for 24 h [0.132 microU/kg.(0.475 U/kg.h) synthetic human PTH, 1-34 fragment] before and after uninephrectomy in nine donors. Plasma 1,25-dihydroxyvitamin D levels were lower after uninephrectomy. However, the percent change from the preinfusion baseline was not different before and after uninephrectomy. With loss of a kidney, there was increased per nephron excretion of phosphate, calcium, and magnesium. Although serum carboxy-terminal levels were elevated after uninephrectomy, no changes in endogenous amino-terminal PTH levels were found. However, the levels of infused human PTH-(1-34) were higher after surgery because the MCR was lower. Serum carboxy-terminal PTH levels decreased in parallel with increased whole blood ionized calcium during PTH infusion, indicating appropriate parathyroid gland responsiveness. At this level of renal insufficiency, renal compensatory changes, rather than changes in parathyroid function, are the predominant factors in the maintenance of mineral homeostasis.