Branten A J, Wetzels J F
Department of Medicine, Division of Nephrology, University Hospital Nijmegen, The Netherlands.
Nephron. 1999;81(3):329-33. doi: 10.1159/000045301.
Most filtered proteins are reabsorbed by the renal proximal tubule by a mechanism that involves binding to the brush border membrane and endocytosis. Under normal conditions the low-molecular-weight protein beta2-microglobulin (beta2M), which is used to detect tubular injury, is reabsorbed almost completely. However, in proteinuric patients an increased urinary excretion of beta2M may not simply reflect tubular damage but might also result from a decreased tubular reabsorption due to competitive mechanisms. To examine the magnitude of such an effect we have studied the renal effects of albumin infusion (40 g in 2 h of a 20% solution) in 10 patients with a glomerular disease and proteinuria >3.5 g/24 h. Before, during and after albumin infusion the GFR (inulin clearance), RPF (PAH clearance), blood pressure and the urinary excretion of albumin, IgG, transferrin and beta2M were measured. Albumin infusion resulted in a slight decrease of the GFR (72 +/- 11 ml/min before and 67 +/- 10 ml/min after infusion), an increase of the RPF (379 +/- 66 ml/min before and 445 +/- 83 ml/min after), a decrease of the filtration fraction (0.20 before and 0.17 after), and hemodilution. After infusion the urinary excretion of albumin increased from 4.5 +/- 0.7 to 8.4 +/- 1.6 mg/min (p < 0.05). The urinary excretion of IgG and transferrin increased, probably reflecting a change in glomerular size-selectivity. In contrast, the urinary excretion of beta2M did not change significantly (baseline 12 +/- 5 microg/min, end 13 +/- 6 microg/min, percentage change 16.8 +/- 11%). To correct for changes in tubular load we calculated the fractional reabsorption of beta2M. The initial rise in albuminuria during infusion did not affect fractional tubular reabsorption (Delta%: 0. 72 +/- 0.52%, median 0.005%). In the period after infusion a slight decrease was noted (median -0.33%, p < 0.01). A decrease in the fractional reabsorption was particularly observed in patients with pre-existing tubular damage.
infusion of albumin in proteinuric patients has no clinically relevant effect on the tubular reabsorption of beta2M. Therefore, beta2M is useful as a parameter to detect tubular injury and alterations in tubular handling of proteins in patients with proteinuria and glomerular diseases.
大多数滤过的蛋白质通过一种涉及与刷状缘膜结合和内吞作用的机制被近端肾小管重吸收。在正常情况下，用于检测肾小管损伤的低分子量蛋白质β2-微球蛋白（β2M）几乎被完全重吸收。然而，在蛋白尿患者中，β2M尿排泄增加可能不仅仅反映肾小管损伤，也可能是由于竞争机制导致肾小管重吸收减少所致。为了研究这种影响的程度，我们对10例肾小球疾病且蛋白尿>3.5g/24h的患者进行了白蛋白输注（20%溶液40g，2小时内）的肾脏效应研究。在白蛋白输注前、期间和之后，测量了肾小球滤过率（菊粉清除率）、肾血浆流量（对氨基马尿酸清除率）、血压以及白蛋白、IgG、转铁蛋白和β2M的尿排泄。白蛋白输注导致肾小球滤过率略有下降（输注前72±11ml/min，输注后67±10ml/min），肾血浆流量增加（输注前379±66ml/min，输注后445±83ml/min），滤过分数下降（之前0.20，之后0.17），以及血液稀释。输注后白蛋白尿排泄从4.5±0.7增加到8.4±1.6mg/min（p<0.05）。IgG和转铁蛋白的尿排泄增加，可能反映了肾小球大小选择性的变化。相比之下，β2M的尿排泄没有显著变化（基线12±5μg/min，结束时13±6μg/min，百分比变化16.8±11%）。为校正肾小管负荷的变化，我们计算了β2M的分数重吸收。输注期间白蛋白尿最初的升高并未影响肾小管分数重吸收（变化百分比：0.72±0.52%，中位数0.005%）。输注后期间观察到略有下降（中位数-0.33%，p<0.01）。在已有肾小管损伤的患者中尤其观察到分数重吸收下降。
蛋白尿患者输注白蛋白对β2M的肾小管重吸收没有临床相关影响。因此，β2M作为检测蛋白尿和肾小球疾病患者肾小管损伤及肾小管蛋白质处理改变的参数是有用的。
