Kashtan C E, Gubler M C, Sisson-Ross S, Mauer M
University of Minnesota Medical School, Department of Pediatrics, Minneapolis 55455, USA.
Pediatr Nephrol. 1998 May;12(4):269-74. doi: 10.1007/s004670050451.
We investigated the onset of renal scarring in 62 males (aged 4-26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant correlation between age and Vv (interstitium/cortex) was observed in normal subjects (r = +0.47, slope = 0.0009, P = 0.07). In the Alport patients, age was significantly correlated with Vv (interstitium/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) < 0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m2 occurred more frequently in patients with Vv (interstitium/cortex) values > 0.2 (P < 0.0001) and in patients with > 10% globally sclerosed glomeruli (P < 0.001). Patients < or = or > 10 years of age differed in Vv (interstitium/cortex) [0.13 +/- 0.09 (mean +/- SD) vs. 0.24 +/- 0.026, P < 0.001], the frequency of Vv (interstitium/cortex) > 0.2 (3/32 vs. 15/31, P < 0.0001), the frequency of > 10% globally sclerosed glomeruli (3/33 vs. 11/30, P < 0.05), mean creatinine clearance (113 +/- 7 vs. 84 +/- 10 ml/min per 1.73 m2, P = 0.057), and the frequency of creatinine clearance < 80 ml/min per 1.73 m2 (1/20 vs. 11/23, P < 0.01). Thus, reduced creatinine clearance in males with Alport syndrome is associated with Vv (interstitium/cortex) > 0.2 and > 10% globally sclerosed glomeruli. These are frequently detectable in the 2nd decade. We hypothesize that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function.
我们通过测量肾活检中皮质间质体积分数[Vv（间质/皮质）]和整体肾小球硬化百分比，研究了62例患有Alport综合征的男性（年龄4 - 26岁）肾瘢痕形成的起始情况。9例男性儿童供肾和7例成年供肾作为对照。43例Alport患者在活检时可获得肌酐清除率数据。在正常受试者中，年龄与Vv（间质/皮质）之间观察到无统计学意义的相关性（r = +0.47，斜率 = 0.0009，P = 0.07）。在Alport患者中，年龄与Vv（间质/皮质）显著相关（r = +0.49，斜率 = 0.01，P = 0.001）以及与整体肾小球硬化显著相关（r = +0.41，P = 0.01），并且与肌酐清除率呈负相关（r = -0.33，P = 0.04）。肌酐清除率与Vv（间质/皮质）呈负相关（r = -0.78，P = 0.001）以及与整体肾小球硬化呈负相关（r = -0.74，P = 0.001）。对于高于正常范围的Vv（间质/皮质）值，即> 0.2，与肌酐清除率的相关性尤为强烈（r = -0.82，P = 0.001），而对于Vv（间质/皮质）< 0.2则不存在相关性（r = -0.119，P = 0.55）。Vv（间质/皮质）值> 0.2的患者（P < 0.0001）以及整体硬化肾小球> 10%的患者（P < 0.001）中，肌酐清除率值低于80 ml/min per 1.73 m2的情况更频繁出现。年龄≤10岁或> 10岁的患者在Vv（间质/皮质）方面存在差异[0.13 ± 0.09（均值±标准差）对0.24 ± 0.026，P < 0.001]，Vv（间质/皮质）> 0.2的频率（3/32对15/31，P < 0.0001），整体硬化肾小球> 10%的频率（3/33对11/30，P < 0.05），平均肌酐清除率（113 ± 7对84 ± 10 ml/min per 1.73 m2，P = 0.057），以及肌酐清除率< 80 ml/min per 1.73 m2的频率（1/20对11/23，P < 0.01）。因此，Alport综合征男性患者中肌酐清除率降低与Vv（间质/皮质）> 0.2以及整体硬化肾小球> 10%相关。这些情况在第二个十年中经常可检测到。我们推测，大多数Alport男性患者在第一个十年期间需要进行干预，以最佳地保护肾功能。
