Garimella Pranav S, Sarnak Mark J
aDivision of Nephrology-Hypertension, University of California, San Diego, San Diego, California bDivision of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA.
Curr Opin Nephrol Hypertens. 2017 Mar;26(2):136-142. doi: 10.1097/MNH.0000000000000299.
Although uromodulin or Tamm-Horsfall protein was discovered over 60 years ago, its functional role in humans remains unclear. This review highlights new studies elucidating the clinical correlates of uromodulin, its association with kidney function decline, nephrolithiasis and urinary host defense.
Uromodulin is evolutionarily conserved and has multiple functional roles. In large population studies, higher levels of uromodulin are associated with higher estimated glomerular filtration rate (eGFR) and kidney size, possibly indicating greater kidney functional reserve. Greater uromodulin excretion is associated with markers of volume overload such as fractional excretion of uric acid, sodium and chloride, indicating a possible role in salt and water retention. Recent evidence also suggests that higher uromodulin levels are associated with lower risk of eGFR decline, death and possibly a lower risk of acute kidney injury. Higher levels of uromodulin are associated with lower risk of urinary tract infections in older adults. Serum uromodulin levels are positively associated with eGFR, although its functional role remains unclear.
Over the last decade, we have begun to understand the functional role of uromodulin in health and disease. Large prospective studies in generalizable populations are needed to confirm these preliminary results, evaluate the clinical utility of measuring uromodulin and examine whether levels of this biomarker can be altered for therapeutic benefit.
尽管尿调节素或Tamm-Horsfall蛋白在60多年前就已被发现，但其在人类中的功能作用仍不清楚。本综述重点介绍了阐明尿调节素临床相关性、其与肾功能下降、肾结石和尿路宿主防御关联的新研究。
尿调节素在进化上具有保守性且具有多种功能作用。在大型人群研究中，较高水平的尿调节素与较高的估计肾小球滤过率（eGFR）和肾脏大小相关，这可能表明肾脏功能储备更大。尿调节素排泄增加与容量超负荷标志物如尿酸、钠和氯的分数排泄相关，提示其在盐和水潴留中可能发挥作用。最近的证据还表明，较高的尿调节素水平与eGFR下降、死亡风险较低以及可能较低的急性肾损伤风险相关。较高水平的尿调节素与老年人尿路感染风险较低相关。血清尿调节素水平与eGFR呈正相关，但其功能作用仍不清楚。
在过去十年中，我们已开始了解尿调节素在健康和疾病中的功能作用。需要在可推广人群中开展大型前瞻性研究，以证实这些初步结果，评估检测尿调节素的临床实用性，并研究是否可以改变该生物标志物的水平以获得治疗益处。
