Puthumana Jeremy, Hall Isaac E, Reese Peter P, Schröppel Bernd, Weng Francis L, Thiessen-Philbrook Heather, Doshi Mona D, Rao Veena, Lee Chun Geun, Elias Jack A, Cantley Lloyd G, Parikh Chirag R
Program of Applied Translational Research, Department of Medicine and.
Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
J Am Soc Nephrol. 2017 Feb;28(2):661-670. doi: 10.1681/ASN.2016010091. Epub 2016 Jul 22.
Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.
急性肾损伤(AKI)死亡供体的肾脏常因担心移植效果不佳而被丢弃。能够预测移植后肾脏恢复情况的供体生物标志物可改善器官选择并减少丢弃。在一项涉及来自五个器官获取组织的死亡肾脏供体的前瞻性队列研究中,我们测试了供体尿液中修复期蛋白YKL-40水平较高是否与受体更好的结局相关。我们测量了1301名供体(111名患有AKI,定义为血清肌酐翻倍)尿液中YKL-40的浓度,并确定了相应2435名受体的结局,其中756名经历了移植肾功能延迟恢复(DGF)。患有AKI的供体尿液中YKL-40浓度更高(P<0.001),且获取活检时有急性肾小管坏死(P=0.05)。在完全调整分析中,供体尿液YKL-40浓度升高与AKI供体肾脏受体和非AKI供体肾脏受体发生DGF的风险降低相关(最高与最低YKL-40三分位数相比,调整后的相对风险,AKI供体肾脏受体为0.51[95%置信区间(95%CI),0.32至0.80],非AKI供体肾脏受体为0.79[95%CI,0.65至0.97])。此外,在发生DGF的情况下,供体尿液YKL-40浓度升高与6个月估算肾小球滤过率(eGFR)较高(每1.73 m²为6.75[95%CI,1.49至12.02]ml/min)及移植失败风险较低相关(调整后的风险比,0.50[95%CI,0.27至0.94])。这些发现表明,YKL-40是对肾小管损伤的反应产物,且与从AKI和DGF中恢复独立相关。如果最终被确认为一种预后生物标志物,在确定供体肾脏是否适合移植时应考虑尿液YKL-40。