Hatch F E, Culbertson J W, Diggs L W
J Clin Invest. 1967 Mar;46(3):336-45. doi: 10.1172/JCI105535.
Free water reabsorption (T(c) (H2O)) measured during 10% mannitol diuresis and subsequently during 3% saline diuresis was compared in patients with sickle cell anemia and in normal subjects. During mannitol infusion, T(c) (H2O) progressively rose with increasing osmolar clearance (C(osm)) and reached a maximal level in both groups studied. During hypertonic saline diuresis, T(c) (H2O) progressively rose in the normal subjects and exceeded the maximal levels attained during mannitol diuresis, with no evidence of a maximal T(c) (H2O) level appearing. In contrast, none of the saline curves significantly exceeded the mannitol curves in the sickle cell patients but tended to parallel the mannitol curves at comparable rates of solute clearance. Since T(c) (H2O) is an index of both solute (sodium) transport from the loop of Henle and solute accumulation in the hypertonic medullary interstitium, tubular sodium handling was examined in both sickle cell patients and control subjects alike. No difference in the tubular transport of sodium could be demonstrated either under conditions of sodium loading or under conditions in which the tubular sodium load was low (water diuresis). These data support the conclusion that the defect in urinary concentration in sickle cell patients is caused by a limitation in maintaining a high concentration of solute in the medullary interstitium, thus limiting the rate of T(c) (H2O) from the collecting duct.
对镰状细胞贫血患者和正常受试者在10%甘露醇利尿期间以及随后在3%盐水利尿期间测量的自由水重吸收（T(c) (H2O)）进行了比较。在输注甘露醇期间，T(c) (H2O)随着渗透清除率（C(osm)）的增加而逐渐升高，并在两组研究对象中均达到最高水平。在高渗盐水利尿期间，正常受试者的T(c) (H2O)逐渐升高，并超过了甘露醇利尿期间达到的最高水平，且未出现T(c) (H2O)的最高水平。相比之下，镰状细胞病患者的盐水曲线均未显著超过甘露醇曲线，但在溶质清除率相当的情况下倾向于与甘露醇曲线平行。由于T(c) (H2O)是溶质（钠）从髓袢转运以及高渗髓质间质中溶质积聚的指标，因此对镰状细胞病患者和对照受试者的肾小管钠处理情况进行了检查。在钠负荷条件下或肾小管钠负荷较低（水利尿）的条件下，均未发现肾小管钠转运存在差异。这些数据支持以下结论：镰状细胞病患者尿液浓缩功能缺陷是由于维持髓质间质高浓度溶质的能力受限，从而限制了集合管的T(c) (H2O)速率。
