Correlation of Kidney Function, Volume and Imaging Findings, and PKHD1 Mutations in 73 Patients with Autosomal Recessive Polycystic Kidney Disease
Correlation of Kidney Function, Volume and Imaging Findings, and PKHD1 Mutations in 73 Patients with Autosomal Recessive Polycystic Kidney Disease
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DOI：
10.2215/cjn.07141009
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发表时间：
2010-06-01
影响因子：
9.8
通讯作者：
Gahl, William A.
中科院分区：
文献类型：
--
作者：
Gunay-Aygun, Meral;Font-Montgomery, Esperanza;Gahl, William A.
背景和目的：在分子确诊的常染色体隐性遗传性多囊肾病(ARPKD)患者中，肾功能和影像表现尚未得到全面和前瞻性的描述。设计、地点、参与者和测量：在美国国立卫生研究院临床中心对90名潜在的ARPKD患者进行了检查。73名患者符合临床诊断标准，至少有一个PKHD1突变，并通过磁共振成像(MRI)、高分辨率超声(HR-USG)以及肾小球和肾小管功能的测量进行前瞻性评估。结果：在31名围产期有症状的患者中，25%的人在11岁之前需要肾脏替代治疗；在42名症状超过1个月(非围产期)的患者中，25%的人需要在32岁之前进行肾移植。非围产期患者的肌酐清除量(103ml/-54ml/min/1.73m(2))高于围产期患者(62+/-33)(P=0.002)。与仅累及髓质(131+/-46)相比，HR-USG的皮髓受累与平均CrC1值(61+/-32)显著相关(P<；0.0001)。在肾脏增大的儿童中，体积与功能呈负相关，尽管差异很大。PKHD1突变的严重程度并不决定肾脏的大小或功能。35%的单纯髓质异常患者标准超声正常，HR-USG可发现病理改变。结论：ARPKD中，围产期表现和皮质髓质受累与肾脏疾病进展较快有关。HR-USG对轻度ARPKD的检出效果最佳。发生了不能用PKHD1突变类型解释的相当大的变异性。临床肾脏病5：972-984,2010。DOI：10.2215/CJN.07141009
Background and objectives: Renal function and imaging findings have not been comprehensively and prospectively characterized in a broad age range of patients with molecularly confirmed autosomal recessive polycystic kidney disease (ARPKD).Design, setting, participants, & measurements: Ninety potential ARPKD patients were examined at the National Institutes of Health Clinical Center. Seventy-three fulfilled clinical diagnostic criteria, had at least one PKHD1 mutation, and were prospectively evaluated using magnetic resonance imaging (MRI), high-resolution ultrasonography (HR-USG), and measures of glomerular and tubular function.Results: Among 31 perinatally symptomatic patients, 25% required renal replacement therapy by age 11 years; among 42 patients who became symptomatic beyond 1 month (nonperinatal), 25% required kidney transplantation by age 32 years. Creatinine clearance (CrCl) for nonperinatal patients (103 +/- 54 ml/min/1.73 m(2)) was greater than for perinatal patients (62 +/- 33) (P = 0.002). Corticomedullary involvement on HR-USG was associated with a significantly worse mean CrCl (61 +/- 32) in comparison with medullary involvement only (131 +/- 46) (P < 0.0001). Among children with enlarged kidneys, volume correlated inversely with function, although with wide variability. Severity of PKHD1 mutations did not determine kidney size or function. In 35% of patients with medullary-only abnormalities, standard ultrasound was normal and the pathology was detectable with HR-USG.Conclusions: In ARPKD, perinatal presentation and corticomedullary involvement are associated with faster progression of kidney disease. Mild ARPKD is best detected by HR-USG. Considerable variability occurs that is not explained by the type of PKHD1 mutation. Clin J Am Soc Nephrol 5: 972-984, 2010. doi: 10.2215/CJN.07141009