Kabanda A, Vandercam B, Bernard A, Lauwerys R, van Ypersele de Strihou C
Nephrology Unit, Catholic University of Louvain, Medical School, Brussels, Belgium.
Am J Kidney Dis. 1996 Jun;27(6):803-8. doi: 10.1016/s0272-6386(96)90517-x.
To determine whether human immunodeficiency virus (HIV) infection is associated with incipient tubular or glomerular defects, we determined the urinary excretion of four low molecular weight proteins (LMWP); beta2-microglobulin (U-beta2-m), cystatin C (U-cyst C), Clara cell protein (U-CC16), and retinol-binding protein (U-RBP), the markers of tubular dysfunction, the excretion of albumin (U-Alb), a marker of glomerular defect, and the excretion of N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of structural damage of the proximal tubular epithelium. Their determinants have been assessed by stepwise regression analysis using as possible predictors age, sex, serum-beta2-m (S-beta2-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta2-m < 5 mg/L (Group B1), 20 with S-beta2-m > or = 5 mg/L (Group B2), and 30 HIV-negative controls. Fourteen patients (18.4%) had no abnormal urinary protein loss, and 62 (81.6%) had elevated urinary excretion of at least one protein (Alb, LMWP, or NAG). A single urinary protein was abnormal in 21 patients (U-beta2-m, n = 9; U-RBP, n = 2; U-CC16, n = 4; and U-Alb, n = 6). At least two LMWP were abnormal without increased U-Alb in 23 patients (12 with increased and 11 with normal U-NAG). Ten patients had an increased urinary excretion of at least one LMWP together with U-Alb (5 with increased and 5 with normal U-NAG). An increased urinary excretion of all proteins was observed in the last 8 patients. The average urinary excretion of all proteins (except cyst C) was significantly higher in HIV than in the control group. As expected, U-beta2-m and the prevalence of abnormal U-beta2-m values were higher in the B2 than in the B1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta2-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta2-m and CC16, whereas male sex was associated with increased U-CC16. S-beta2-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta2-m as a consequence of a close correlation between S-beta2-m and either HIV infection stage (r = -0.52, P = 0.0001), or CD4 count (r = -0.45, P = 0.0002). Over 80% of HIV-infected patients without overt renal disease have evidence of glomerular permeability defects or tubular dysfunction, whatever the stage of the disease. U-Alb, RBP, and CC16 appear as the most sensitive and reliable early markers of these abnormalities. Their cause and prognostic value remain to be determined.
为了确定人类免疫缺陷病毒（HIV）感染是否与早期肾小管或肾小球缺陷相关，我们测定了四种低分子量蛋白（LMWP）的尿排泄量，即β2-微球蛋白（U-β2-m）、胱抑素C（U-胱抑素C）、克拉拉细胞蛋白（U-CC16）和视黄醇结合蛋白（U-RBP），这些是肾小管功能障碍的标志物；测定了白蛋白（U-Alb）的排泄量，这是肾小球缺陷的标志物；还测定了N-乙酰-β-D-氨基葡萄糖苷酶（U-NAG）的排泄量，这是近端肾小管上皮结构损伤的标志物。通过逐步回归分析评估了它们的决定因素，将年龄、性别、血清β2-微球蛋白（S-β2-m）、CD4淋巴细胞计数、HIV感染阶段或治疗作为可能的预测指标。该研究纳入了76例无肾脏疾病的HIV感染患者，其中56例S-β2-m＜5mg/L（B1组），20例S-β2-m≥5mg/L（B2组），以及30例HIV阴性对照者。14例患者（18.4%）无异常尿蛋白丢失，62例（81.6%）至少有一种蛋白（Alb、LMWP或NAG）的尿排泄量升高。21例患者单一尿蛋白异常（U-β2-m，9例；U-RBP，2例；U-CC16，4例；U-Alb，6例）。23例患者至少两种LMWP异常且U-Alb未增加（12例U-NAG增加，11例U-NAG正常）。10例患者至少一种LMWP与U-Alb的尿排泄量均增加（5例U-NAG增加，5例U-NAG正常）。最后8例患者所有蛋白的尿排泄量均增加。HIV感染患者所有蛋白（除胱抑素C外）的平均尿排泄量显著高于对照组。正如预期的那样，B2组的U-β2-m及U-β2-m异常值的患病率高于B1组（P = 0.0001），而两个HIV组中Alb、LMWP（除β2-微球蛋白外）或NAG的平均尿排泄量及升高值的患病率相同。通过逐步回归分析，年龄是β2-微球蛋白和CC16尿排泄量的重要决定因素，而男性与U-CC16增加相关。S-β2-m、CD4淋巴细胞计数或HIV感染阶段仅作为U-β2-m的重要决定因素出现，这是由于S-β2-m与HIV感染阶段（r = -0.52，P = 0.0001）或CD4计数（r = -0.45，P = 0.0002）密切相关。超过80%无明显肾脏疾病的HIV感染患者有肾小球通透性缺陷或肾小管功能障碍的证据，无论疾病处于何阶段。U-Alb、RBP和CC16似乎是这些异常最敏感和可靠的早期标志物。它们的病因和预后价值仍有待确定。
