Nephronophthis(NPHP)是一种慢性肾小管间质疾病,表现出常染色体隐性遗传形式,并导致儿童进行性肾衰竭。NPHP患者很少表现出尿路异常,水肿,或高血压。因此,NPHP通常仅在肾衰竭进展时才被检测到。根据终末期肾衰竭的年龄,NPHP可分为三种类型,即,婴儿类型(约5岁),青少年类型(大约13-14岁),和青少年类型(约19岁)。这里,我们报告一例在26岁时通过基因分析诊断为NPHP的不典型组织学异常.
一名26岁的妇女在每年的学校体检中没有表现出生长障碍或泌尿异常。然而,在26岁的体检中,患者出现肾功能不全(eGFR为26mL/min/1.73m2).尿检显示尿液比重低,但不是蛋白尿或镜下血尿。尿β2-微球蛋白高(805μg/L),进行肾活检以明确诊断。组织学发现在肾小球中没有明显发现。然而,在间质区域观察到中度纤维化,在小管中观察到中度萎缩。免疫荧光分析没有明显的发现,电子显微镜未检测到电子致密沉积物。尽管小管的囊肿样扩张尚不清楚,通过细胞角蛋白7染色,在远端小管中主要发现了管状萎缩。NPHP1基因的遗传分析显示该基因完全缺失,导致NPHP的明确诊断。
NPHP不仅仅是一种儿科疾病,而且在成人肾病发作终末期患者中发病率相对较高。在这种情况下,典型的组织学异常,如管状病变的囊肿样扩张,没有被观察到,通过对NPHP1基因的遗传分析来实现诊断,这是NPHP发作的原因。在肾衰竭患者中,肾小管间质疾病占优势,有必要区分NPHP,即使在成人的情况下。
Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13-14 years old), and adolescent type (approximately 19 years old). Here, we report a
case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities.
A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary β2-microglobulin was high (805 μg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP.
NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this
case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.