Renal phosphate loss in long-term kidney transplantation

Abstract

Background and objectives: Renal phosphate wasting occurs early postkidney transplantation as a result of an accumulation of parathyroid hormone and fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney transplantation. What happens beyond this period is unknown.

Design, setting, participants, & measurements: Mineral parameters were obtained from 229 kidney transplant recipients at least 1 year posttransplantation; 46 normal subjects and 202 CKD patients with similar GFR served as controls. Factors associated with phosphate metabolism were analyzed.

Results: Despite the reduced graft function, most kidney transplant recipients had lower serum phosphate than normal subjects accompanied by renal phosphate loss. Fibroblast growth factor 23 was mostly lower or comparable with normal subjects, whereas parathyroid hormone was elevated in most patients. Hyperparathyroidism is also more common among kidney transplant recipients compared with CKD patients. Both parathyroid hormone and fibroblast growth factor 23 showed relationships with renal phosphate excretion, but only parathyroid hormone displayed an independent association. Parathyroid hormone showed the highest area under the curve in predicting renal phosphate leak. When patients were categorized according to parathyroid hormone and fibroblast growth factor 23 levels, only subset of patients with high parathyroid hormone had an increased renal phosphate excretion.

Conclusions: Relatively low serum phosphate from renal phosphate leak continued to present in long-term kidney transplantation. Both parathyroid hormone and fibroblast growth factor 23 participated in renal tubular phosphate handling, but persistent hyperparathyroidism seemed to have a greater influence in this setting.

Figure 1.

Comparisons of mineral parameters between normal subjects (white bars, n=46) and kidney transplantation (KT) recipients (black bars) categorized by the stages of kidney function (stages 1 and 2: n=99; stage 3: n=106; stages 4 and 5: n=23). (A) Serum phosphate, (B) 24-hour urine phosphate, (C) fractional excretion of phosphate, (D) tubular maximum phosphate reabsorption/GFR, (E) fibroblast growth factor 23 (FGF-23), (F) serum calcium, and (G) parathyroid hormone (PTH). P values in the graphs represent the significance of trends for allograft function stages 1–5. *P<0.05 versus normal subjects; **P<0.001 versus normal subjects.

Figure 2.

Receiver operating characteristic curves analyses of factors associated with renal tubular phosphate leak in KT recipients defined by fractional excretion of phosphate (FePi) and tubular maximum phosphate reabsorption/GFR (TmP/GFR) above and below the normal limits of normal subjects, respectively. (A) FePi and (B) TmP/GFR. AUC, area under the curve.

Figure 3.

Parameters of renal tubular phosphate excretion according to PTH and FGF-23 levels (low, below median; high, above median). (A) FePi and (B) TmP/GFR. *P<0.05 versus low PTH/low FGF-23. P values in the graphs represent the significance of trends of all groups.