Geurts Frank, van Heugten Martijn H, Blijdorp Charles J, Fenton Robert A, Chaker Layal, Hoorn Ewout J
Division of Nephrology and Transplantation, Erasmus Medical Center, Department of Internal Medicine, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Kidney360. 2025 Mar 1;6(3):451-460. doi: 10.34067/KID.0000000687. Epub 2024 Dec 23.
Donor nephrectomy reduced urinary EGF (uEGF) by half and correlated with the reduction in kidney volume, suggesting that uEGF reflects tubular mass. In the general population, lower uEGF/creatinine was associated with lower eGFR, lower serum magnesium, and higher BP. Lower uEGF/creatinine, was associated with incident CKD, and this association was stronger in people without hypertension.
EGF is expressed in the distal tubule and secreted in urine (urinary EGF [uEGF]) after cleavage of membrane-bound pro-EGF. Lower uEGF is associated with kidney disease progression. EGF also plays a role in the regulation of serum magnesium and BP, but whether uEGF is associated with these parameters is unknown. We hypothesized that uEGF is a distal tubule marker associated with serum magnesium, BP, and kidney outcomes.
We first used a cohort of kidney donors (=20) and measured uEGF to analyze the association with tubular mass and pro-EGF in urinary extracellular vesicles as proxy for tubular expression. Next, we measured uEGF in a population-based cohort (=2382) to investigate the associations with serum magnesium, hypertension, and kidney outcomes (incident eGFR <60 or <45 ml/min per 1.73 m, 40% loss of eGFR, or kidney failure).
Kidney donation decreased eGFR from 86 to 54 ml/min per 1.73 m (36% reduction; 95% confidence interval [CI], 31% to 42%), uEGF from 28 to 14 g/24 hours (49% reduction; 95% CI, 42% to 55%), and pro-EGF by 29% (95% CI, 12% to 45%). The decrease in uEGF correlated with the decrease in kidney volume. In the population cohort, lower uEGF was significantly associated with hypertension and lower serum magnesium. The association between uEGF and serum magnesium was stronger in participants with lower eGFR, hypertension, and diuretic use. Lower uEGF at baseline was also associated with worse kidney outcomes, and this association was stronger for normotensive participants.
uEGF is a marker of distal tubular mass that is not only associated with kidney disease progression, but also with serum magnesium and BP. Future studies should address whether normotensive people with low uEGF excretion represent a group that may benefit from kidney-protective treatment.
供体肾切除术使尿表皮生长因子（uEGF）降低了一半，且与肾体积减小相关，提示uEGF反映肾小管质量。在一般人群中，较低的uEGF/肌酐水平与较低的估算肾小球滤过率（eGFR）、较低的血清镁水平及较高的血压相关。较低的uEGF/肌酐水平与慢性肾脏病（CKD）的发生相关，且这种关联在无高血压的人群中更强。
表皮生长因子（EGF）在远端小管表达，膜结合型前EGF裂解后分泌到尿液中（尿表皮生长因子[uEGF]）。较低的uEGF与肾脏疾病进展相关。EGF在血清镁和血压的调节中也起作用，但uEGF是否与这些参数相关尚不清楚。我们假设uEGF是一种与血清镁、血压和肾脏结局相关的远端小管标志物。
我们首先对一组肾供体（n = 20）进行研究，测量uEGF以分析其与肾小管质量及尿细胞外囊泡中前EGF的关联，将尿细胞外囊泡中的前EGF作为肾小管表达的替代指标。接下来，我们在一个基于人群的队列（n = 2382）中测量uEGF，以研究其与血清镁、高血压和肾脏结局（新发eGFR<60或<45 ml/min/1.73 m²、eGFR下降40%或肾衰竭）的关联。
肾切除术后，eGFR从86降至54 ml/min/1.73 m²（降低36%；95%置信区间[CI]，31%至42%），uEGF从28降至14 μg/24小时（降低49%；95% CI，42%至55%），前EGF降低29%（95% CI，12%至45%）。uEGF的降低与肾体积的减小相关。在人群队列中，较低的uEGF与高血压和较低的血清镁显著相关。在eGFR较低、患有高血压和使用利尿剂的参与者中，uEGF与血清镁之间的关联更强。基线时较低的uEGF也与较差的肾脏结局相关，且这种关联在血压正常的参与者中更强。
uEGF是远端肾小管质量的标志物，不仅与肾脏疾病进展相关，还与血清镁和血压相关。未来的研究应探讨uEGF排泄量低的血压正常人群是否是可能从肾脏保护治疗中获益的群体。
