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Abstract：
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 .
摘要：
肌酸是一种天然的含氮有机酸，对能量代谢不可或缺，对正常的细胞功能至关重要。肾脏参与肌酸产生的第一步。肾移植是治疗终末期肾病的金标准,肾移植受者(KTR)可能存在肌酸合成受损的风险.我们旨在比较KTR和对照组之间的肌酸稳态。血浆和尿液中精氨酸的浓度，甘氨酸,胍基乙酸盐，在553名KTR和168名健康对照中检测了肌酸和肌酐.使用食物频率问卷评估肌酸摄入量。在157个KTR和167个对照的亚组中可获得Ithalamate测量的GFR数据。KTR和对照组的体重相当，身高和肌酸摄入量(均P>0.05)。然而,与对照组相比，KTR的总肌酸池降低了14%(651±178vs.753±239mmol，P<0.001)。与对照组相比，KTR的内源性肌酸合成率降低了22％（7.8±3.0vs.10.0±4.1mmol/天,P<0.001)。尽管GFR较低，与对照组相比，KTR的血浆胍乙酸盐和肌酸浓度分别降低了21％和41％（均P<0.001）。与对照组相比，KTR中胍基乙酸盐和肌酸的尿排泄分别降低了66％和59％（均P<0.001）。在KTR,但不是在控制中，较高的测得GFR与较高的内源性肌酸合成率相关(std.β：0.21，95%CI：0.08；0.33；P=0.002），以及较高的总肌酸池(性病。β：0.22，95%CI：0.11；0.33；P<0.001）。这些关联完全由尿胍乙酸盐排泄介导（93％和95％；P<0.001），这与作为限速因子的肌酸前体胍乙酸盐的产生一致。我们的发现强调，与对照组相比，KTR的肌酸稳态受到干扰。鉴于测量的GFR与内源性肌酸合成速率和总肌酸池的直接关系，补充肌酸可能对肾功能低下的KTR有益.试用注册ID：NCT02811835。试用注册URL：https://clinicaltrials.gov/ct2/show/NCT02811835。
