Hemmelder M H, de Zeeuw D, de Jong P E
Groningen Institute for Drug Studies (GIDS), Department of Medicine, University Hospital, The Netherlands.
Nephrol Dial Transplant. 1997;12 Suppl 2:57-62.
Until now, the renal clearance index of IgG to IgG4 (IgG/IgG4) as well as pancreatic to salivary amylase (PA/SA) were separately used as parameters of renal charge selectivity in diabetic and non-diabetic albuminuria. The suitability of the IgG index may be questioned because urinary loss of IgG rather reflects a size selective defect. In contrast, the amylase index seems more appropriate to reflect renal charge selectivity because its molecular size is comparable to albumin. We questioned whether IgG/IgG4 and PA/SA reflect renal charge selectivity in a comparable way in subjects with non-diabetic albuminuria over a wide range.
Renal fractional clearances of albumin, IgG, IgG4, PA and SA were estimated from ambulatory 24-h urine samples in 12 subjects with normo-albuminuria (UAE 4 [3-17] micrograms/min), six with micro-albuminuria (UAE: 147[36-200] micrograms/min), and 20 with macro-albuminuria (UAE: 2301 [608-13611] micrograms/min).
Macro-albuminuria is associated with a reduced IgG/IgG4 and PA/SA, whereas micro-albuminuria is only associated with a reduced IgG/IgG4 compared to normo-albuminuria. A reduction of IgG/IgG4 (r = -0.75, P < 0.001) and PA/SA (r = -0.52, P < 0.001) correlates with an increased albuminuria. In addition, IgG/IgG4 correlates with PA/SA in the total population (r = 0.49, P < 0.01). IgG/IgG4 (r = 0.51, P < 0.05) correlates with the size selective index IgG/albumin in an opposite way to PA/SA (r = -0.52, P < 0.05) in 20 subjects with macro-albuminuria. Multiple regression analysis revealed IgG clearance to be the variable which contributes to the variance of albuminuria clearance for the greater part in our population.
Both charge selective indices do not appear to correlate in micro-albuminuria. In addition, the presence of a size selective defect has a opposing effect on both charge selective indices. Although the reduction of IgG/IgG4 and PA/SA with increasing albuminuria suggests a progressive charge selective defect, albuminuria in our population is almost entirely explained by urinary loss of IgG. These data seriously question whether either one or both charge selective indices IgG/IgG4 and PA/SA do specifically reflect glomerular charge selectivity.
迄今为止，IgG与IgG4的肾清除指数（IgG/IgG4）以及胰淀粉酶与唾液淀粉酶（PA/SA）分别被用作糖尿病和非糖尿病蛋白尿患者肾电荷选择性的参数。IgG指数的适用性可能受到质疑，因为IgG的尿丢失更反映出一种大小选择性缺陷。相比之下，淀粉酶指数似乎更适合反映肾电荷选择性，因为其分子大小与白蛋白相当。我们质疑在广泛范围内，IgG/IgG4和PA/SA在非糖尿病蛋白尿患者中是否以可比的方式反映肾电荷选择性。
从12例正常白蛋白尿患者（尿白蛋白排泄率[UAE]为4[3 - 17]微克/分钟）、6例微量白蛋白尿患者（UAE：147[36 - 200]微克/分钟）和20例大量白蛋白尿患者（UAE：2301[608 - 13611]微克/分钟）的24小时动态尿液样本中估算白蛋白、IgG、IgG4、PA和SA的肾分数清除率。
大量白蛋白尿与IgG/IgG4和PA/SA降低相关，而微量白蛋白尿与正常白蛋白尿相比仅与IgG/IgG4降低相关。IgG/IgG4（r = -0.75，P < 0.001）和PA/SA（r = -0.52，P < 0.001）的降低与蛋白尿增加相关。此外，在总体人群中IgG/IgG4与PA/SA相关（r = 0.49，P < 0.01）。在20例大量白蛋白尿患者中，IgG/IgG4（r = 0.51，P < 0.05）与大小选择性指数IgG/白蛋白呈负相关，与PA/SA（r = -0.52，P < 0.05）相反。多元回归分析显示，在我们的研究人群中，IgG清除率是导致蛋白尿清除率变化的主要变量。
在微量白蛋白尿中，这两个电荷选择性指数似乎不相关。此外，大小选择性缺陷的存在对这两个电荷选择性指数有相反的影响。尽管随着蛋白尿增加IgG/IgG4和PA/SA降低提示电荷选择性缺陷逐渐加重，但我们研究人群中的蛋白尿几乎完全由IgG的尿丢失所解释。这些数据严重质疑IgG/IgG4和PA/SA这两个电荷选择性指数是否能特异性反映肾小球电荷选择性。
