Kambham N, Markowitz G S, Valeri A M, Lin J, D'Agati V D
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Kidney Int. 2001 Apr;59(4):1498-509. doi: 10.1046/j.1523-1755.2001.0590041498.x.
We report the first large renal biopsy-based clinicopathologic study on obesity-related glomerulopathy.
Obesity was defined as body mass index (BMI)> 30 kg/m2. Obesity-related glomerulopathy (ORG) was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly (O-FSGS; N = 57) or glomerulomegaly alone (O-GM; N = 14).
Review of 6818 native renal biopsies received from 1986 to 2000 revealed a progressive increase in biopsy incidence of ORG from 0.2% in 1986-1990 to 2.0% in 1996-2000 (P = 0.0001). Mean BMI in ORG was 41.7 (range 30.9 to 62.7). Indications for renal biopsy included proteinuria (N = 40) or proteinuria and renal insufficiency (N = 31). Seventy-one patients with ORG were compared to 50 patients with idiopathic FSGS (I-FSGS). Patients with ORG were older (mean 42.9 vs. 32.6 years, P < 0.001) and more often Caucasian (75% vs. 52%; P = 0.003). ORG patients had a lower incidence of nephrotic range proteinuria (48% vs. 66%; P = 0.007) and nephrotic syndrome (5.6% vs. 54%; P < 0.001), with higher serum albumin (3.9 vs. 2.9 g/dL; P < 0.001), lower serum cholesterol (229 vs. 335 mg/dL; P < 0.001), and less edema (35% vs. 68%; P = 0.003). On renal biopsy, patients with ORG had fewer lesions of segmental sclerosis (10 vs. 39%; P < 0.001), more glomerulomegaly (100% vs. 10%; P < 0.001), and less extensive foot process effacement (40 vs. 75%; P < 0.001). Glomerular diameter in ORG (mean 226 mu) was significantly larger than age- and sex-matched normal controls (mean 168 mu; P < 0.001). Follow-up was available in 56 ORG patients (mean 27 months) and 50 idiopathic FSGS controls (mean 38 months). A total of 75% of ORG patients received angiotensin-converting enzyme (ACE) inhibition or A2 blockade while 78% of the I-FSGS patients received immunosuppressive therapy. ORG patients had less frequent doubling of serum creatinine (14.3% vs. 50%; P < 0.001) and progression to ESRD (3.6% vs. 42%; P < 0.001). On multivariate analysis, presenting serum creatinine and severity of proteinuria were the only predictors of poor outcome in ORG.
ORG is distinct from idiopathic FSGS, with a lower incidence of nephrotic syndrome, more indolent course, consistent presence of glomerulomegaly, and milder foot process fusion. The ten-fold increase in incidence over 15 years suggests a newly emerging epidemic. Heightened physician awareness of this entity is needed to ensure accurate diagnosis and appropriate therapy.
我们报告了首例基于大型肾活检的肥胖相关性肾小球病临床病理研究。
肥胖定义为体重指数（BMI）>30kg/m²。肥胖相关性肾小球病（ORG）在形态学上定义为局灶节段性肾小球硬化和肾小球肿大（O-FSGS；n = 57）或仅肾小球肿大（O-GM；n = 14）。
回顾1986年至2000年接收的6818例原发性肾活检显示，ORG的活检发病率从1986 - 1990年的0.2%逐步上升至1996 - 2000年的2.0%（P = 0.0001）。ORG患者的平均BMI为41.7（范围30.9至62.7）。肾活检的指征包括蛋白尿（n = 40）或蛋白尿合并肾功能不全（n = 31）。将71例ORG患者与50例特发性FSGS（I-FSGS）患者进行比较。ORG患者年龄更大（平均42.9岁对32.6岁，P < 0.001），且更常为白种人（75%对52%；P = 0.003）。ORG患者肾病范围蛋白尿（48%对66%；P = 0.007）和肾病综合征（5.6%对54%；P < 0.001）的发生率较低，血清白蛋白较高（3.9对2.9g/dL；P < 0.001），血清胆固醇较低（229对335mg/dL；P < 0.001），水肿较少（35%对68%；P = 0.003）。肾活检时，ORG患者节段性硬化病变较少（10%对39%；P < 0.001），肾小球肿大较多（100%对10%；P < 0.001），足突消失范围较小（40%对75%；P < 0.001）。ORG患者的肾小球直径（平均226μm）显著大于年龄和性别匹配的正常对照（平均168μm；P < 0.001）。56例ORG患者（平均27个月）和50例特发性FSGS对照患者（平均38个月）有随访数据。共75%的ORG患者接受了血管紧张素转换酶（ACE）抑制剂或A2受体阻滞剂治疗，而78%的I-FSGS患者接受了免疫抑制治疗。ORG患者血清肌酐翻倍的频率较低（14.3%对50%；P < 0.001），进展至终末期肾病（ESRD）的比例较低（3.6%对42%；P < 0.001）。多因素分析显示，就诊时的血清肌酐和蛋白尿严重程度是ORG患者预后不良的唯一预测因素。
ORG与特发性FSGS不同，肾病综合征发生率较低，病程进展较缓慢，始终存在肾小球肿大，足突融合较轻。15年间发病率增加了10倍，提示这是一种新出现的流行病。需要提高医生对该疾病的认识，以确保准确诊断和适当治疗。
