Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study
Faeq Husain-Syed, David R Emlet, Jochen Wilhelm, Tommaso Hinna Danesi, Fiorenza Ferrari, Pércia Bezerra, Salvador Lopez-Giacoman, Gianluca Villa, Khodr Tello, Horst-Walter Birk, Werner Seeger, Davide Giavarina, Loris Salvador, Dana Y Fuhrman, John A Kellum, Claudio Ronco, IRRIV-AKI Study Group, Carlotta Caprara, Valentina Corradi, Massimo Cal, Carla Estremadoyro, Renhua Lu, Sara Samoni, Aashish Sharma, Lorenzo Tofani, Grazia Maria Virzì, Faeq Husain-Syed, David R Emlet, Jochen Wilhelm, Tommaso Hinna Danesi, Fiorenza Ferrari, Pércia Bezerra, Salvador Lopez-Giacoman, Gianluca Villa, Khodr Tello, Horst-Walter Birk, Werner Seeger, Davide Giavarina, Loris Salvador, Dana Y Fuhrman, John A Kellum, Claudio Ronco, IRRIV-AKI Study Group, Carlotta Caprara, Valentina Corradi, Massimo Cal, Carla Estremadoyro, Renhua Lu, Sara Samoni, Aashish Sharma, Lorenzo Tofani, Grazia Maria Virzì
Abstract
Background: 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.
Methods: 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.
Results: 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 m2) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m2; 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 m2; 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.
Conclusions: 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).
Keywords: Acute kidney injury; Chronic kidney disease; Kidney stress test; Renal recovery.
Conflict of interest statement
KT has received speaking fees from Actelion and Bayer outside the submitted work. WS has received speaker/consultancy fees from Pfizer and Bayer Pharma AG outside the submitted work. JAK discloses inventorship on a patent application held by the Universities of Pittsburgh, and Munster, and Astute Medical (US2018/074054A1) for use of TIMP-2 and IGFBP7 in conjunction with interventions to protect the kidney. CR reports support for acting as an advisory board member for ASAHI, Baxter, GE, Jafron, and Medtronic, and speaker’s fees from Astute, bioMérieux, B. Braun, Cytosorbents, ESTOR, FMC, and Toray, all unrelated to the submitted work. All other authors have declared that no conflict of interests exists.
© 2022. The Author(s).
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