Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

Conditions

Cardiac Surgery

Keywords

kidney protection, acute kidney injury, cardiac surgery, amino acids, mortality, ICU

Brief summary

To date, no pharmacological agents are proven efficacious in treating perioperative AKI. There is a strong biological rationale for the administration of amino acid in the management of patients at risk of AKI with increases in renal blood flow and GFR of 25 to 60% for several hours after the administration of amino acids (Woods LL 1993) mediated by a afferent arteriolar dilation.(Meyer TW 1983) Moreover, animal models have demonstrated that an increase in renal blood flow in response to a short-term amino acid infusion can protect the kidney from acute ischemic insults. Finally, these nephro-protective effects are preserved in critical illness. Cardiac surgery appears to be the best setting to test the likely beneficial renal effects of amino acid because of pathophysiological principles and the ability to intervene before the injury has begun. Although the etiology of AKI in cardiac surgery is multifactorial, renal hypoperfusion is believed to play a major role in this development by decreasing renal perfusion through a reduction in renal blood flow and through the activation of the sympathetic nervous system and the renin-angiotensin system with afferent arteriolar vasoconstriction. In this setting, a global increase in renal blood flow by means of Amino Acid therapy appears a logical and promising intervention. The primary aim of the study is to determine whether providing continuous infusion of a balanced mixture of amino acids, compared to placebo (balanced crystalloid solution), reduces the incidence of acute kidney injury (AKI) in patients scheduled for cardiac surgery defined as KDIGO stage 1 or greater during hospital stay.

Alessandro Belletti, Antonio Pisano, Anna Mara Scandroglio, Eugenio Garofalo, Maria Grazia Calabró et al. (55 authors)

European Journal of Cardio-Thoracic Surgery2025-02-017 citations

10.1093/ejcts/ezaf035

A Randomized Trial of Intravenous Amino Acids for Kidney Protection

Giovanni Landoni, Fabrizio Monaco, Lian Kah Ti, Martina Baiardo Redaelli, Nikola Bradic et al. (48 authors)

New England Journal of Medicine2024-06-12139 citations

10.1056/nejmoa2403769

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

Landoni G, Brambillasca C, Baiardo Redaelli M, Bradić N, Ti LK, Povšić-Čevra Z, Nepomniashchikh VA, Zoccai GB, D'Ascenzo F, Romagnoli E, Scandroglio AM, Ballotta A, Rondello N, Franco A, Massaro C, Viscido C, Calabrò MG, Garofalo E, Canichella F, Monaco F, Severi L, Pisano A, Barucco G, Venditto M, Federici F, Licheri M, Paternoster G, Trompeo A, Belletti A, Mantovani LF, Perone R, Dalessandro G, Kroeller D, Haxhiademi D, Galbiati C, Tripodi VF, Giardina G, Lembo R, Nakhnoukh C, Guarracino F, Longhini F, Bove T, Zangrillo A, Bellomo R, Fominskiy E.

2022-08-2810 citations

10.1016/j.cct.2022.106898

Interventions

DRUGAmino Acids

Patients randomized to experimental arm receive a continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day (to a maximum 100 g/day) from the operating room admission up to either death, start of RRT, ICU discharge or 72 hours after treatment initiation, trough a central venous line

DRUGPlacebos

Placebo: standard treatment

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* age \> 18 years * scheduled cardiac surgery * expected to stay in ICU at least 1 night after surgery * signed informed consent

Exclusion criteria

* Patient currently enrolled into another randomized clinical trial * Patient currently receiving or scheduled for intermittent or continuous renal replacement therapy * Patients with CKD of equal or more than CKD stage IV (GFR\<30 ml/min/1.73 m2) * Patient with a kidney transplant * Patient is not expected to survive ICU or hospital discharge * Patient previously been enrolled and randomized into this study * Patient has severe liver disease (Child-Pugh score \>7 points) * Patient has a hypersensitivity (known allergy) to one or more of the included amino acids * Patient has a congenital alteration of amino acid metabolism * Pregnant or currently breastfeeding patients * Patients with any of the contraindications reported in the summary product characteristics.

Design outcomes

Primary

Measure	Time frame	Description
AKI incidence	Until hospital discharge, an average of 10 days	Incidence of Acute Kidney Injury during hospital stay

Secondary

Measure	Time frame	Description
RRT	180 days	Need and duration of renal replacement therapy
ICU stay	Until ICU discharge, an average of 2 days	Duration of Intensive Care Unit stay
Mortality	180 days	All-cause mortality at ICU discharge, hospital discharge, 30 and 90 and 180 days after randomization
Mechanical Ventilation	Until ICU discharge, an average of 2 days	Need and duration of mechanical ventilation
EQ-5D	180 days	Quality of life at 180 days after randomization as measured by the EQ-5D
Hospital stay	Until hospital discharge, an average of 10 days	Duration of hospital stay

Countries

Croatia, Italy, Singapore

Outcome results

None listed