Numerous protein-bound solutes are cleared by the kidney with high efficiency.
Numerous protein-bound solutes are cleared by the kidney with high efficiency.
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DOI：
10.1038/ki.2013.154
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发表时间：
2013-09
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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作者：
肾脏从血浆中清除许多溶质;然而，当肾脏衰竭时，这些溶质的保留会导致尿毒症疾病。我们对哪些残留溶质是有毒的知之甚少，这限制了我们改善透析治疗的能力。为了探索这一点，我们采用非靶向质谱法来鉴定被肾脏有效清除的溶质。高分辨质谱法检测了5名肾功能正常者的尿液和血浆超滤液中的1808个特征。1082个峰的估计清除率大于肌酐清除率，表明肾小管分泌。进一步分析确定了90个特征，代表估计清除率大于肾血浆流量的溶质。定量质谱与稳定同位素稀释证实，这些溶质的有效清除是可能的结合血浆蛋白和肾小管分泌。串联质谱法确定了13种溶质的化学鉴别，包括马尿酸、硫酸吲哚酚和硫酸对甲酚。这13种有效清除的溶质被发现在血液透析患者的血浆中积累，其中除两种外，所有患者的游离水平均升高至正常水平的20倍以上。因此，进一步分析天然肾脏中通过分泌有效清除的溶质可能为鉴定尿毒症毒素提供潜在途径。
The kidney clears numerous solutes from the plasma; however, retention of these solutes causes uremic illness when the kidneys fail. We know remarkably little about which retained solutes are toxic and this limits our ability to improve dialysis therapies. To explore this we employed untargeted mass spectrometry to identify solutes that are efficiently cleared by the kidney. High resolution mass spectrometry detected 1808 features in the urine and plasma ultrafiltrate of 5 individuals with normal renal function. The estimated clearance rates of 1082 peaks were greater than the creatinine clearance indicating tubular secretion. Further analysis identified 90 features representing solutes with estimated clearance rates greater than the renal plasma flow. Quantitative mass spectrometry with stable isotope dilution confirmed that efficient clearance of these solutes is made possible by the combination of binding to plasma proteins and tubular secretion. Tandem mass spectrometry established the chemical identity of 13 solutes including hippuric acid, indoxyl sulfate, and p-cresol sulfate. These 13 efficiently cleared solutes were found to accumulate in the plasma of hemodialysis patients, with free levels rising to more than 20-fold normal for all but two of them. Thus, further analysis of solutes efficiently cleared by secretion in the native kidney may provide a potential route to the identification of uremic toxins.
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影响因子：
13.6
作者：
Aronov, Pavel A.;Luo, Frank J. -G.;Meyer, Timothy W.
通讯作者：
Meyer, Timothy W.
DOI：
10.1111/j.1365-2362.2010.02398.x
发表时间：
2011-03-01
影响因子：
5.5
作者：
Sato, Emiko;Kohno, Masahiro;Tanaka, Noriaki
通讯作者：
Tanaka, Noriaki
影响因子：
15
作者：
Feigenbaum, J;Neuberg, CA
通讯作者：
Neuberg, CA
影响因子：
13.6
作者：
Rhee, Eugene P.;Souza, Amanda;Gerszten, Robert E.
通讯作者：
Gerszten, Robert E.
影响因子：
2.5
作者：
Smith, CA;O'Maille, G;Siuzdak, G
通讯作者：
Siuzdak, G