Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time
Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time
复制标题
DOI：
10.1152/ajprenal.00541.2007
复制
发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Navis, Gerjan
中科院分区：
文献类型：
--
作者：
Kramer, Andrea B.;van Timmeren, Mirjan M.;Navis, Gerjan
克雷默AB，货车Timmeren MM，Schuurs TA，Vaidya VS，Bonventre JV，货车古尔H，Navis G.阿霉素肾病蛋白尿减少与肾脏损伤分子（Kim-1）随时间减少相关。美国肾脏生理学杂志296：F1136-F1145，2009年。首次发表于2009年2月25日; doi：10.1152/ajprenal.00541.2007。肾小管间质病变在蛋白尿性肾病的进展中是重要的。肾小管肾损伤分子-1（Kim-1）在急性肾损伤中被诱导，并且作为自然过程是可逆的。Kim-1也存在于慢性肾损伤中;然而，Kim-1在慢性肾损伤中的动力学和抗蛋白尿治疗对Kim-1的影响尚不清楚。我们研究了Kim-1在阿霉素肾病（AN）中在肾素-血管紧张素系统阻断前后的表达。阿霉素注射后6周取肾活检，研究肾损伤和Kim-1表达。随后，给予ACE抑制剂（ACEi; n = 23）、血管紧张素II拮抗剂（AT（1A）; n = 23）或载体（n = 10）6周;健康大鼠作为对照（CON; n = 8）。在AN中，肾脏Kim-1 mRNA在第6周时被诱导为CON的26倍，在溶媒中进一步增加至第12周（40倍），但被ACEi和AT（1A）降低至CON的10倍和12倍（P < 0.05 vs.第6周）。Kim-1蛋白在CON中检测不到;在AN中，它存在于邻近间质病变区域的扩张小管的刷状缘中。肾脏Kim-1蛋白水平在溶媒组从第6-12周增加，而在ACEi和AT（1A）治疗组降低（P < 0.05）。在载体中，尿Kim-1增加（P < 0.05 vs. CON），ACEi和AT（1A）降低（P < 0.05 vs.载体）。肾和尿Kim-1与蛋白尿和间质损伤相关。蛋白尿减少与肾Kim- 1相关，但与肾小管间质纤维化的相应变化无关。总之，在抗蛋白尿治疗期间的纵向随访中，肾脏Kim-1表达增加与蛋白尿减少成比例是可逆的，可能反映了早期肾小管损伤的可逆性，支持其作为肾小管间质损伤和修复过程的生物标志物的潜力。
Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, Navis G. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol 296: F1136-F1145, 2009. First published February 25, 2009; doi:10.1152/ajprenal.00541.2007.-Tubulointerstitial lesions are important in the progression of proteinuric renal disease. Tubular kidney injury molecule-1 (Kim-1) is induced in acute renal injury and reversible as a natural course. Kim-1 is also present in chronic renal damage; however, the dynamics of Kim-1 in chronic renal damage and effects of antiproteinuric treatment on Kim-1 are unknown. We studied Kim-1 in adriamycin nephrosis (AN) before and after reninangiotensin system blockade. A renal biopsy was taken 6 wk after adriamycin injection to study renal damage and Kim-1 expression. Subsequently, ACE inhibition (ACEi; n = 23), angiotensin II antagonist (AT(1A); n = 23), or vehicle (n = 10) was given for 6 wk; healthy rats served as controls (CON; n = 8). In AN, renal Kim-1 mRNA was induced 26-fold vs. CON at week 6, with further increase in vehicle to week 12 (40-fold) but was reduced by ACEi and AT(1A) to 10- and 12-fold vs. CON (P < 0.05 vs. week 6). Kim-1 protein was undetectable in CON; in AN, it was present in brush border of dilated tubules in areas with adjacent interstitial lesions. Renal Kim-1 protein levels increased from weeks 6-12 in vehicle and decreased in ACEi- and AT(1A)-treated groups (P < 0.05). In vehicle, urinary Kim-1 was increased (P < 0.05 vs. CON), with a reduction by ACEi and AT(1A) (P < 0.05 vs. vehicle). Renal and urinary Kim-1 correlated with proteinuria and interstitial damage cross-sectionally. Reductions in proteinuria and renal Kim- 1 correlated, which was not associated by corresponding changes in tubulointerstitial fibrosis. In conclusion, on longitudinal follow-up during antiproteinuric treatment increased renal Kim-1 expression is reversible in proportion to proteinuria reduction, likely reflecting reversibility of early tubular injury, supporting its potential as a biomarker for tubulointerstitial processes of damage and repair.