Carstens J, Greisen J, Jensen K T, Vilstrup H, Pedersen E B
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
J Am Soc Nephrol. 1998 Aug;9(8):1489-98. doi: 10.1681/ASN.V981489.
This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.
本研究报告了短期（60分钟）低剂量（20纳克·千克⁻¹·分钟⁻¹）输注合成尿钠素（URO）对肝硬化患者的影响。URO是一种利钠肽。共有15例伴有腹水的肝硬化患者和9例无腹水的肝硬化患者参与了一项采用交叉设计的随机、双盲、安慰剂对照研究。通过使用放射性示踪剂的清除技术评估肾血流动力学，并采用锂清除率法评估肾小管对钠的处理。与输注安慰剂相比，尿钠素对肝硬化患者的肾脏影响表现为：无腹水患者的尿钠排泄率（UNa）和尿流率（V）显著增加（UNa：173%；V：94%），有腹水患者的尿钠排泄率（UNa：219%，P<0.01；V：42%，P<0.01）。钠排泄分数显著增加，表明尿钠素对钠处理有肾小管效应。滤过分数、锂清除率（近端液体输送的标志物）和锂排泄分数增加，近端肾小管钠重吸收分数降低，近端肾小管钠绝对重吸收不变，提示输注尿钠素期间近端小管等渗液体输送增加。此外，远端肾小管钠重吸收分数显著降低促成了利钠作用。总之，尿钠素通过增加近端小管的液体输送以及抑制远端肾单位的钠重吸收分数，改善了有腹水和无腹水的肝硬化患者的钠和尿量排出。
