Supplementary Material for: Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History

<b><i>Background:</i></b> Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature. <b><i>Methods:</i></b> We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history. <b><i>Results:</i></b> The annual decline of renal function was faster in the patients with <i>PKD1</i>/<i>PKD2</i> mutation (<i>PKD1</i> truncating [–3.08; 95% CI –5.30 to –0.87, <i>p</i> = 0.007], <i>PKD1</i> nontruncating [–2.10; –3.82 to –0.38, <i>p</i> = 0.02], and <i>PKD2</i> [–2.31; –4.40 to –0.23, <i>p</i> = 0.03]) than in the other patients without <i>PKD1</i>/<i>PKD2</i> mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different <i>PKD1</i>/<i>PKD2</i> groups, but Kaplan-Meier analysis showed that progression to eGFR &lt; 15 mL/min/1.73 m² was significantly faster in <i>PKD1</i> truncating group (<i>p</i> = 0.05). The annual rate of TKV increase was larger in the patients with <i>PKD1</i>/<i>PKD2</i> mutation (<i>PKD1</i> truncating [4.63; 95% CI 0.62–8.64, <i>p</i> = 0.03], <i>PKD1</i> nontruncating [3.79; 0.55–7.03, <i>p</i> = 0.02], and <i>PKD2</i> [2.11; –1.90 to 6.12, <i>p</i> = 0.29]) than in the other patients without <i>PKD1</i>/<i>PKD2</i> mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP. <b><i>Conclusion:</i></b> Detection of <i>PKD1</i>/<i>PKD2</i> mutation, especially <i>PKD1</i> truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history.

**背景**：已有研究表明，无明确家族史的多囊肾病（polycystic kidney disease, PKD）患者的遗传学特征与有阳性家族史的患者存在差异。但目前文献中对无明确家族史的PKD患者的临床病程记录仍较为匮乏。**方法**：本研究针对62例无明确家族史的PKD患者，分析了其基因型与临床病程之间的关联。**结果**：携带PKD1/PKD2基因突变的患者，其肾功能年下降速率快于未携带该类突变的患者：其中PKD1截短突变组为（–3.08；95%置信区间：–5.30~–0.87，p=0.007）、PKD1非截短突变组为（–2.10；95%置信区间：–3.82~–0.38，p=0.02）、PKD2突变组为（–2.31；95%置信区间：–4.40~–0.23，p=0.03）。在校正性别、年龄、估算肾小球滤过率（estimated glomerular filtration rate, eGFR）、身高校正总肾体积（height-adjusted total kidney volume, TKV）及平均动脉压（mean arterial pressure, MAP）后，上述结果仍保持一致。不同PKD1/PKD2突变亚组间的肾功能年下降速率无显著差异，但卡普兰-迈耶分析显示，PKD1截短突变组患者进展至eGFR＜15 mL/min/1.73 m²的速度显著更快（p=0.05）。携带PKD1/PKD2基因突变的患者，其总肾体积年增长速率亦高于未携带该类突变的患者：其中PKD1截短突变组为（4.63；95%置信区间：0.62~8.64，p=0.03）、PKD1非截短突变组为（3.79；95%置信区间：0.55~7.03，p=0.02）、PKD2突变组为（2.11；95%置信区间：–1.90~6.12，p=0.29）。在校正性别、年龄、eGFR及MAP后，上述结果仍保持一致。**结论**：对无明确家族史的PKD患者检测PKD1/PKD2基因突变（尤其是PKD1截短突变），有助于预测其肾脏预后及总肾体积增长速率。