Vallés P, Peralta M, Carrizo L, Martin L, Principi I, Gonzalez A, Manucha W
Instituto de Fisiopatología, Facultad de Medicina, Universidad Nacional de Cuyo, Centro Universitario 5500, Mendoza, Argentina.
Pediatr Nephrol. 2000 Dec;15(3-4):252-8. doi: 10.1007/s004670000472.
The aim of this study was to examine the compromise of proximal tubule cells in steroid-resistant nephrotic syndrome patients with a histologic diagnosis of focal segmental glomerulosclerosis (FSGS) through assessment of the urinary levels of beta 2-microglobulin (beta 2M) and N-acetyl-beta-D-glucosaminidase (NAG) during active disease and remission over a follow-up period of 3 years. We studied 34 children with nephrotic syndrome: 12 with steroid-resistant nephrotic syndrome (SRNS) and massive proteinuria, 7 with steroid-dependent nephrotic syndrome (SDNS) and 15 with steroid-sensitive nephrotic syndrome (SSNS). Of the SSNS patients, 8 children were in remission (RM) and 7 were in relapse (RL). Seven healthy children were included as controls. Urinary beta 2M, measured by enzyme-linked immunosorbent assay, was significantly increased in the SRNS group as compared to the SDNS group (P < 0.01), SSNS in remission (P < 0.01), and controls (P < 0.01). There were no differences between the SRNS group and SSNS in relapse. Analysis of urinary N-acetyl-beta-D-glucosaminidase (U-NAG) by colorimetric assay showed significantly higher values in the SRNS group of patients than in SDNS, SSNS, and control groups. A positive correlation between U-NAG and proteinuria was demonstrated (r = 0.73, P < 0.01). The SRNS group of patients (n = 12, 11 with a histologic diagnosis of FSGS and one with diffuse mesangial proliferation) was treated with the same protocol of i.v. methylprednisone and oral cyclophosphamide. Long-term follow-up showed a progressive decrease in U-beta 2M and U-NAG excretion to control values in the 3rd year, except in one patient who did not respond to the treatment. In the FSGS patients, evaluation of the contribution of structural interstitial histological abnormalities, including each of the histological parameters considered in interstitial scarring to the functional tubule abnormalities assessed by beta 2M and NAG excretion, was performed by multiple regression analysis. The r2 values for beta 2M and NAG were 53.99%, P = 0.19, and 57.90%, P = 0.14, respectively; neither was significant. We conclude that: (1) proximal tubule cell dysfunction, partially affected by massive albuminuria, may account for the higher values of beta 2M and NAG excretion in the SRNS patients and (2) urine beta 2M and NAG levels are not helpful in identifying histological evidence of structural tubulointerstitial damage in children with steroid-resistant nephrotic syndrome.
本研究旨在通过评估3年随访期内活动期疾病及缓解期类固醇抵抗型肾病综合征患者（组织学诊断为局灶节段性肾小球硬化症（FSGS））尿中β2-微球蛋白（β2M）和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）水平，来检测近端肾小管细胞的受损情况。我们研究了34例肾病综合征患儿：12例为类固醇抵抗型肾病综合征（SRNS）且有大量蛋白尿，7例为类固醇依赖型肾病综合征（SDNS），15例为类固醇敏感型肾病综合征（SSNS）。在SSNS患者中，8例患儿处于缓解期（RM），7例处于复发期（RL）。纳入7名健康儿童作为对照。通过酶联免疫吸附测定法测得，SRNS组尿β2M水平相较于SDNS组（P < 0.01）、缓解期的SSNS组（P < 0.01）及对照组（P < 0.01）显著升高。SRNS组与复发期的SSNS组之间无差异。通过比色法分析尿N-乙酰-β-D-氨基葡萄糖苷酶（U-NAG）显示，SRNS组患者的值显著高于SDNS组、SSNS组及对照组。U-NAG与蛋白尿之间呈正相关（r = 0.73，P < 0.01）。SRNS组患者（n = 12，11例组织学诊断为FSGS，1例为弥漫性系膜增生）接受相同方案的静脉注射甲泼尼龙和口服环磷酰胺治疗。长期随访显示，除1例对治疗无反应的患者外，第3年U-β2M和U-NAG排泄量逐渐降至对照值。对于FSGS患者，通过多元回归分析评估结构性间质组织学异常（包括间质纤维化中考虑的每个组织学参数）对通过β2M和NAG排泄评估的功能性肾小管异常的影响。β2M和NAG的r2值分别为53.99%，P =0.19，以及57.90%，P =0.14；两者均无统计学意义。我们得出结论：（1）近端肾小管细胞功能障碍，部分受大量蛋白尿影响，可能是SRNS患者β2M和NAG排泄值较高的原因；（2）尿β2M和NAG水平无助于识别类固醇抵抗型肾病综合征患儿结构性肾小管间质损伤的组织学证据。
