Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza, San Bortolo Hospital, Via Rodolfi, 37, 36100, Vicenza, Italy.
Department of Internal Medicine II, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany.
J Transl Med. 2022 May 10;20(1):204. doi: 10.1186/s12967-022-03410-x.
Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects.
The prospective "Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation" study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations.
The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI - 1.4, - 1.7] vs. - 3.3 [95% CI - 4.4, - 2.2] ml/min/1.73 m) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (- 8.0 [95% CI - 14.1, - 1.9] vs. - 18.6 [95% CI - 23.3, - 14.0] ml/min/1.73 m; p = 0.008). A dose-response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression.
A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).
心脏手术后急性肾损伤（AKI）与死亡率增加有关。高蛋白餐可增强肾血流量和肾小球滤过率（GFR），并可能保护肾脏免受急性缺血性损伤。因此，我们评估了术前高口服蛋白质负荷对心脏手术后肾功能的影响，并使用实验模型阐明了蛋白质刺激肾脏保护作用的机制。
前瞻性“术前肾功能储备预测心脏手术后 AKI 风险”研究的随访时间延长至术后 12 个月，共 109 例患者。使用 1:2 比例倾向评分匹配方法确定对照组（n=214），以比较术前蛋白质负荷和标准护理的效果。主要终点是 AKI 发展和术后 3 个月和 12 个月时的估计肾小球滤过率（eGFR）损失。我们还评估了组织金属蛋白酶抑制剂-2（TIMP-2）和胰岛素样生长因子结合蛋白 7（IGFBP7）的分泌，这些生物标志物在体外实验中被证明参与了介导人类肾小管细胞的肾脏保护机制，我们将其暴露于不同的蛋白质浓度下。
蛋白质负荷组和对照组的 AKI 发生率无差异（13.6% vs. 12.3%；p=0.5）。然而，术后 3 个月时前者的平均 eGFR 损失较低（0.1[95%CI-1.4，-1.7] vs.-3.3[95%CI-4.4，-2.2]ml/min/1.73m），术后 12 个月时也较低（-2.7[95%CI-4.2，-1.2] vs.-10.2[95%CI-11.3，-9.1]ml/min/1.73m；p<0.001）。基于 AKI 发展的分层分析显示，前者术后 12 个月时的 eGFR 损失也较低（-8.0[95%CI-14.1，-1.9] vs.-18.6[95%CI-23.3，-14.0]ml/min/1.73m；p=0.008）。体外培养的原发性近端和远端肾小管上皮细胞的蛋白质治疗剂量反应分析显示，IGFBP7 和 TIMP-2 的表达显著增加。
术前高口服蛋白质负荷并未降低 AKI 的发生，但与心脏手术后 12 个月时伴有和不伴有 AKI 的患者的肾功能保护有关。蛋白质负荷可能诱导肾脏保护反应的潜在作用机制可能包括肾管状上皮细胞的细胞周期抑制。
ClinicalTrials.gov：NCT03102541（2017 年 4 月 5 日前瞻性注册）和 ClinicalTrials.gov：NCT03092947（2017 年 3 月 28 日前瞻性注册）。
