Impact of Custodial-N Cardioplegia on Acute Kidney Injury after Cardiopulmonary Bypass

Objectives: Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large cardiac ischemia-reperfusion animal model were compared.

Methods: Landrace pigs underwent median sternotomy, CPB at 34°C, 90 minutes of cardiac arrest, and 120 minutes of reperfusion. Animals were randomized for single-shot cardioplegia with either HTK (n = 10) or HTK-N (n = 10). The effects of the cardiac ischemia and reperfusion on kidney damage were investigated in renal biopsies and sera. AKI biomarkers, histological changes, and apoptosis marker were determined.

Results: Compared to HTK, HTK-N induced a decreased extent of proximal tubule swelling (48.3 ± 1.6 μm vs. 52.3 ± 1.1 μm, p = 0.05) and decreased cytochrome c release (0.26 ± 0.04 arb. units vs. 0.46 ± 0.08 arb. units, p = 0.04) without reaching statistical significance due to the Bonferroni correction. Comparing baseline and post-reperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK-N (Hb baseline: 6.0 ± 0.6 mmol/L, Hb reperfusion: 6.2 ± 0.7 mmol/L, p = 0.12; Ca²⁺ baseline: 1.36 ± 0.05 mmol/L, Ca²⁺ reperfusion: 1.28 ± 0.05 mmol/L, p = 0.16) compared to the HTK group (Hb baseline: 5.9 ± 0.4 mmol/L, Hb reperfusion: 4.7 ± 0.8 mmol/L, p < 0.01; Ca²⁺ baseline: 1.34 ± 0.07 mmol/L, Ca²⁺ reperfusion: 1.24 ± 0.06 mmol/L, p < 0.01).

Conclusion: HTK-N could positively affect the kidney during CPB by stabilizing Hb and calcium levels. A statistical trend was found showing that AKI-related proximal tubule swelling and cytochrome c release were diminished. Further investigations could prove whether HTK-N-mediated kidney protection is possible in humans.