Background and objectives

We have previously published the characteristics of kidney and liver disease in a cohort of 73 individuals with molecularly confirmed autosomal recessive polycystic kidney disease-congenital hepatic fibrosis, based upon cross-sectional data. Here, we present prospective data on the same cohort.

Design, setting, participants, and measurements

Comprehensive biochemical and imaging data on progression of kidney and liver disease in 60 of the 73 patients were prospectively collected at the NIH Clinical Center on multiple visits between 2003 and 2019.

Results and conclusions

Of the 73 patients, 23 received a renal allograft at an average age of 17.5 years and 10 underwent liver transplantation at an average age of 20.3 years. Patients who presented perinatally and those who had corticomedullary disease required kidney transplantation significantly earlier. The mean eGFR slope in patients with corticomedullary disease was −1.6 ml/min/1.73 m²/y, in comparison to −0.6 ml/min/1.73 m²/y in those with medullary disease. Kidney size remained the same over time and normalized to the upper limit of normal by 20–25 years of age. The extent of renal disease on ultrasound remained largely unchanged; no patient progressed from the “medullary” to the “corticomedullary” group. There was no correlation between eGFR slope and kidney size. The synthetic function of the liver remained largely intact even in patients with advanced portal hypertension. Based on spleen length/height ratio, two thirds of patients had portal hypertension which remained stable in 39% and worsened in 61%. Patients with portal hypertension had lower platelet counts and relatively higher levels of AST, GGT, direct bilirubin and ammonia. The progression rates of kidney and liver disease were independent of each other. Patients with bi-allelic non-truncating PKHD1 variants had similar progression of kidney and liver disease in comparison to those who were compound heterozygous for a non-truncating and a truncating variant.

中文翻译：

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常染色体隐性多囊肾病-先天性肝纤维化肾脏和肝脏疾病的前瞻性评估。

背景和目标

我们之前已经根据横断面数据，在 73 名分子确认常染色体隐性多囊肾病-先天性肝纤维化患者的队列中发表了肾脏和肝脏疾病的特征。在这里，我们提供了同一队列的前瞻性数据。

设计、设置、参与者和测量

2003 年至 2019 年期间，NIH 临床中心前瞻性收集了 73 名患者中 60 名患者肾脏和肝脏疾病进展的综合生化和影像数据。

结果和结论

在这 73 名患者中，23 人在平均年龄 17.5 岁时接受了同种异体肾移植，10 人在平均年龄为 20.3 岁时接受了肝移植。围产期和患有皮质髓质疾病的患者需要显着更早地进行肾移植。皮质髓质疾病患者的平均 eGFR 斜率为 -1.6 ml/min/1.73 m ² /y，相比之下为 -0.6 ml/min/1.73 m ²/y 在那些有髓质疾病的人中。肾脏大小随着时间的推移保持不变，并在 20-25 岁时恢复到正常上限。超声显示肾脏疾病的程度基本保持不变；没有患者从“髓质”组进展为“皮质髓质”组。eGFR 斜率与肾脏大小之间没有相关性。即使在晚期门静脉高压患者中，肝脏的合成功能也基本保持完整。根据脾长/高比，三分之二的患者有门脉高压，其中 39% 保持稳定，61% 恶化。门脉高压患者血小板计数较低，AST、GGT、直接胆红素和氨水平相对较高。肾脏和肝脏疾病的进展速度相互独立。双等位基因非截短患者与非截短和截短变异的复合杂合子相比，PKHD1变异具有相似的肾脏和肝脏疾病进展。