Abstract：
OBJECTIVE: Kidneys are vital for vitamin D metabolism, and disruptions in both production and catabolism occur in chronic kidney disease. Although vitamin D activation occurs in numerous tissues, the kidneys are the most relevant source of circulating active vitamin D. This study investigates extrarenal vitamin D activation and the impact of kidney transplantation on vitamin D metabolism in patients who are anephric.
METHODS: Case series.
METHODS: Adult patients with previous bilateral nephrectomy (anephric) not receiving active vitamin D therapy evaluated at the time of (N=38) and 1 year after (n=25) kidney transplantation.
METHODS: Chromatography with tandem mass spectrometry was used to measure vitamin D metabolites. Activity of CYP24A1 [24,25(OH)2D/25(OH)D] and CYP27B1 [1α,25(OH)2D/25(OH)D] is expressed as metabolic ratios. Differences between time points were evaluated by paired t-test or Wilcoxon matched-pairs signed-rank test.
RESULTS: At time of transplantation, 1α,25(OH)2D was detectable in all patients (4-36pg/mL). There was a linear relationship between 25(OH)D and 1α,25(OH)2D levels (r=0.58, P<0.001), with 25(OH)D explaining 34% of the variation in 1α,25(OH)2D levels. There were no associations between 1α,25(OH)2D and biointact parathyroid hormone (PTH) or fibroblast growth factor 23 (FGF-23). One year after transplantation, 1α,25(OH)2D levels recovered (+205%), and CYP27B1 activity increased (+352%). Measures of vitamin D catabolism, 24,25(OH)2D and CYP24A1 activity increased 3- to 5-fold. Also, at 12 months after transplantation, 1α,25(OH)2D was positively correlated with PTH (ρ=0.603, P=0.04) but not with levels of 25(OH)D or FGF-23.
CONCLUSIONS: Retrospective, observational study design with a small cohort size.
CONCLUSIONS: Low-normal levels of 1α,25(OH)2D was demonstrated in anephric patients, indicating production outside the kidneys. This extrarenal CYP27B1 activity may be more substrate driven than hormonally regulated. Kidney transplantation seems to restore kidney CYP27B1 and CYP24A1 activity, as evaluated by vitamin D metabolic ratios, resulting in both increased vitamin D production and catabolism. These findings may have implications for vitamin D supplementation strategies in the setting of kidney failure and transplantation.
UNASSIGNED: Vitamin D activation occurs in multiple tissues, but the kidneys are considered the only relevant source of circulating levels. This study investigates vitamin D activation outside the kidneys by measuring vitamin D metabolites in 38 patients without kidneys. Active vitamin D was detectable in all patients, indicating production outside of the kidneys. There was a strong relationship between active and precursor vitamin D levels, but no association with mineral metabolism hormones, indicating that vitamin D production was more substrate dependent than hormonally regulated. One year after kidney transplantation, active vitamin D levels increased 2-fold and breakdown products increased 3-fold, indicating that production and degradation of the hormone recovers after kidney transplantation. These findings are relevant for future research into vitamin D supplementation in kidney failure.
METHODS: Case series.
METHODS: Adult patients with previous bilateral nephrectomy (anephric) not receiving active vitamin D therapy evaluated at the time of (N=38) and 1 year after (n=25) kidney transplantation.
METHODS: Chromatography with tandem mass spectrometry was used to measure vitamin D metabolites. Activity of CYP24A1 [24,25(OH)2D/25(OH)D] and CYP27B1 [1α,25(OH)2D/25(OH)D] is expressed as metabolic ratios. Differences between time points were evaluated by paired t-test or Wilcoxon matched-pairs signed-rank test.
RESULTS: At time of transplantation, 1α,25(OH)2D was detectable in all patients (4-36pg/mL). There was a linear relationship between 25(OH)D and 1α,25(OH)2D levels (r=0.58, P<0.001), with 25(OH)D explaining 34% of the variation in 1α,25(OH)2D levels. There were no associations between 1α,25(OH)2D and biointact parathyroid hormone (PTH) or fibroblast growth factor 23 (FGF-23). One year after transplantation, 1α,25(OH)2D levels recovered (+205%), and CYP27B1 activity increased (+352%). Measures of vitamin D catabolism, 24,25(OH)2D and CYP24A1 activity increased 3- to 5-fold. Also, at 12 months after transplantation, 1α,25(OH)2D was positively correlated with PTH (ρ=0.603, P=0.04) but not with levels of 25(OH)D or FGF-23.
CONCLUSIONS: Retrospective, observational study design with a small cohort size.
CONCLUSIONS: Low-normal levels of 1α,25(OH)2D was demonstrated in anephric patients, indicating production outside the kidneys. This extrarenal CYP27B1 activity may be more substrate driven than hormonally regulated. Kidney transplantation seems to restore kidney CYP27B1 and CYP24A1 activity, as evaluated by vitamin D metabolic ratios, resulting in both increased vitamin D production and catabolism. These findings may have implications for vitamin D supplementation strategies in the setting of kidney failure and transplantation.
UNASSIGNED: Vitamin D activation occurs in multiple tissues, but the kidneys are considered the only relevant source of circulating levels. This study investigates vitamin D activation outside the kidneys by measuring vitamin D metabolites in 38 patients without kidneys. Active vitamin D was detectable in all patients, indicating production outside of the kidneys. There was a strong relationship between active and precursor vitamin D levels, but no association with mineral metabolism hormones, indicating that vitamin D production was more substrate dependent than hormonally regulated. One year after kidney transplantation, active vitamin D levels increased 2-fold and breakdown products increased 3-fold, indicating that production and degradation of the hormone recovers after kidney transplantation. These findings are relevant for future research into vitamin D supplementation in kidney failure.
摘要：
目的：肾脏对维生素D的代谢至关重要，在慢性肾脏疾病中会发生维生素D的产生和分解代谢的破坏。虽然维生素D激活发生在许多组织中，肾脏是循环活性维生素D的最相关来源。这项研究调查了肾外维生素D的激活以及肾移植对肾病患者维生素D代谢的影响。
方法：案例系列。
方法：在肾移植后（N=38）和1年（N=25）时，对既往双侧肾切除术（肾切除术）未接受活性维生素D治疗的成年患者进行评估。采用液相色谱-串联质谱法测定维生素D代谢产物。代谢比例分别为CYP24A1(24,25(OH)2D/25(OH)D)和CYP27B1(1α,25(OH)2D/25(OH)D)为活动。评价时间点之间的差异通过配对Student'st检验或Wilcoxon配对配对符号秩检验来评价。
结果：移植时，1α,在所有患者中均可检测到25（OH）2D（4至36pg/mL）。25(OH)D与1α呈线性关系,25（OH）2D水平（r=0.58，p<0.001），25（OH）D解释了1α变化的34％，25（OH）2D水平。1α之间没有关联，25(OH)2D和生物完整的PTH或FGF23。移植一年后,1α,25(OH)2D水平恢复(+205%),CYP27B1活性增加(+352%)。维生素D分解代谢的措施，24,25(OH)2D和CYP24A1活性增加3-5倍。同样在移植后12个月，1α,25(OH)2D与PTH呈正相关(rho=0.603,p=0.04),但不与25（OH）D或FGF23的水平。
结论：回顾性，小队列的观察性研究设计。
结论：1α的正常水平低，25（OH）2D在肾病患者中得到证实，表明肾脏外的生产。这种肾外CYP27B1活性可能比激素调节的更受底物驱动。肾移植似乎可以恢复肾脏CYP27B1和CYP24A1的活性，通过维生素D代谢比评估，导致维生素D产生和分解代谢增加。这些发现可能对肾衰竭和移植中的维生素D补充策略有影响。
方法：案例系列。
方法：在肾移植后（N=38）和1年（N=25）时，对既往双侧肾切除术（肾切除术）未接受活性维生素D治疗的成年患者进行评估。采用液相色谱-串联质谱法测定维生素D代谢产物。代谢比例分别为CYP24A1(24,25(OH)2D/25(OH)D)和CYP27B1(1α,25(OH)2D/25(OH)D)为活动。评价时间点之间的差异通过配对Student'st检验或Wilcoxon配对配对符号秩检验来评价。
结果：移植时，1α,在所有患者中均可检测到25（OH）2D（4至36pg/mL）。25(OH)D与1α呈线性关系,25（OH）2D水平（r=0.58，p<0.001），25（OH）D解释了1α变化的34％，25（OH）2D水平。1α之间没有关联，25(OH)2D和生物完整的PTH或FGF23。移植一年后,1α,25(OH)2D水平恢复(+205%),CYP27B1活性增加(+352%)。维生素D分解代谢的措施，24,25(OH)2D和CYP24A1活性增加3-5倍。同样在移植后12个月，1α,25(OH)2D与PTH呈正相关(rho=0.603,p=0.04),但不与25（OH）D或FGF23的水平。
结论：回顾性，小队列的观察性研究设计。
结论：1α的正常水平低，25（OH）2D在肾病患者中得到证实，表明肾脏外的生产。这种肾外CYP27B1活性可能比激素调节的更受底物驱动。肾移植似乎可以恢复肾脏CYP27B1和CYP24A1的活性，通过维生素D代谢比评估，导致维生素D产生和分解代谢增加。这些发现可能对肾衰竭和移植中的维生素D补充策略有影响。
