The trigger-maintenance model of persistent mild to moderate hyperoxaluria induces oxalate accumulation in non-renal tissues.
The trigger-maintenance model of persistent mild to moderate hyperoxaluria induces oxalate accumulation in non-renal tissues.
复制标题
持续性轻度至中度高草酸尿症的触发维持模型会诱导非肾组织中草酸盐的积累。
DOI：
10.1007/s00240-013-0584-5
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发表时间：
2013
期刊：
影响因子：
3.1
通讯作者：
Romani,AndreaMP
中科院分区：
文献类型：
--
作者：
Marengo,SusanRuth;Zeise,BrianS;Wilson,ChristopherG;MacLennan,GregoryT;Romani,AndreaMP
持续性轻度至中度高草酸尿症 (PMMH) 是减肥手术的常见副作用。然而，PMMH 在草酸钙 (CaOx) 尿石症进展中的作用及其对非肾组织的潜在影响尚不清楚。为了解决这些问题，在大鼠中开发了 PMMH 触发 + 维持 (T + Mt) 模型（实验 1）。触发因素是一个 IP。注射 PBS (TPBS) 或 288 μmol 草酸钠 (T288)。通过每天分配 PBS 或 7.5–30 μmol 草酸钾的微型泵进行维持 (Mt)，持续 28 天。尿草酸范围为 TPBS+ MtPBS 的 7.7 ± 0.8 μmol/天到 T288+ Mt30 的 18.2 ± 1.5 μmol/天（p≤ 0.0005）。所有接受 T288 的大鼠均出现 CaOx 肾钙质沉着症，许多大鼠出现“结石”。对于未使尿草酸盐升高至高于 TPBS+ MtPBS (p> 0.1) 的 Mt 剂量以及 T288 后未检测到尿草酸盐激增的大鼠来说也是如此。当给予 TPBS 时，无论 Mt 剂量如何，即使尿草酸盐与 TPBS+ MtPBS 相比升高，CaOx 肾钙质沉着症也不会发生（p≤0.0005）。与 PMMH 相关的风险之一是组织内草酸盐的积累。因此，在第二组实验（实验 2）中，通过微型泵施用用 14 C-草酸 (14C-Ox) 标记的不同剂量的草酸（Mt0.05、Mt15、Mt30）13 天。收获组织并通过闪烁计数评估 14 C-Ox 积累。 14 C-Ox 在骨、肾、肌肉、肝脏、心脏、肾、肺、脾和睾丸中以剂量依赖性方式（p≤0.004）积累。所有这些组织均表现出比血浆更高的 14 C-Ox 浓度（p≤0.05）。将我们的结果外推给患者表明，PMMH 患者应格外小心，避免饮食引起的草酸盐排泄高峰，以帮助预防 CaOx 肾钙质沉着症或结石形成。还可能需要监测易受草酸盐或氧化钙晶体损害的组织内草酸盐的积累。
Persistent mild to moderate hyperoxaluria (PMMH) is a common side effect of bariatric surgery. However, PMMH's role in the progression to calcium oxalate (CaOx) urolithiasis and its potential effects on non-renal tissues are unknown. To address these points, a trigger + maintenance (T + Mt) model of PMMH was developed in rats (Experiment 1). The trigger was an i.p. injection of PBS (TPBS) or 288 μmol sodium oxalate (T288). Maintenance (Mt) was given via minipumps dispensing PBS or 7.5–30 μmol potassium oxalate/day for 28 days. Urinary oxalate ranged from 7.7 ± 0.8 μmol/day for TPBS+ MtPBSto 18.2 ± 1.5 μmol/day for T288+ Mt30(p≤ 0.0005). All rats receiving T288developed CaOx nephrocalcinosis, and many developed ‘stones’. This was also true for Mt doses that did not elevate urinary oxalate above that of TPBS+ MtPBS(p> 0.1) and for rats that did not have a detectable surge in urinary oxalate post T288. When TPBSwas administered, CaOx nephrocalcinosis did not develop regardless of the Mt dose even if urinary oxalate was elevated compared to TPBS+ MtPBS(p≤ 0.0005). One of the risks associated with PMMH is oxalate accumulation within tissues. Hence, in a second set of experiments (Experiment 2) different doses of oxalate (Mt0.05, Mt15, Mt30) labeled with14C-oxalate (14C-Ox) were administered by minipump for 13 days. Tissues were harvested and14C-Ox accumulation assessed by scintillation counting.14C-Ox accumulated in a dose dependent manner (p≤ 0.004) in bone, kidney, muscle, liver, heart, kidney, lungs, spleen, and testis. All these tissues exhibited14C-Ox concentrations higher (p≤ 0.05) than the plasma. Extrapolation of our results to patients suggests that PMMH patients should take extra care to avoid dietary-induced spikes in oxalate excretion to help prevent CaOx nephrocalcinosis or stone development. Monitoring for oxalate accumulation within tissues susceptible to damage by oxalate or CaOx crystals may also be required.