Plasma phosphocreatine (PC) as a predictive biomarker for immune checkpoint inhibition in patients with refractory metastatic colorectal cancer (mCRC): Analysis of the CCTG CO.26 trial.

Xiaolu, Lucy; Loree, Jonathan M.; Jonker, Derek J.; Kennecke, Hagen F.; Berry, Scott; Couture, Felix; Ahmad, Chaudhary E.; Goffin, John R.; Kavan, Petr; Harb, Mohammed; Colwell, Bruce; Samimi, Setareh; Samson, Benoit; Abbas, Tahir; Aucoin, Nathalie; Aubin, Francine; Koski, Sheryl; Tu, Dongsheng; O’Callaghan, Christopher J.; Chen, Eric Xueyu

doi:10.1200/jco.2023.41.4_suppl.183

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is supported by a study into the pharmacokinetics of exogenous phosphocreatine, which previously demonstrated that all of the pre-dose plasma samples had phosphocreatine concentrations below the limit of quantitation of 1.96 µmol/L (He et al 2020 ). Plasma phosphocreatine concentrations of the same order of magnitude were found in metastatic colorectal cancer patients (Ma et al 2023 ). Furthermore, non-clinical pharmacokinetic study demonstrated that nearly three fourth of an intravenously administrated phosphocreatine dose was quickly converted into creatine (Xu et al 2014 ).…”

Section: Discussionmentioning

confidence: 72%

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls

Post,

Groothof,

Kremer

et al. 2024

Amino Acids

View full text Add to dashboard Cite

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

show abstract

Section: Discussionmentioning

confidence: 72%