Lai Silvia, Mastroluca Daniela, Perrotta Adolfo Marco, Muscaritoli Maurizio, Lucciola Sara, Felli Maria Pia, Izzo Paolo, Rotondi Silverio, Izzo Sara, Tartaglione Lida, Belli Roberta, Ramaccini Cesarina, Izzo Luciano, De Intinis Claudia, Panebianco Valeria, Mazzaferro Sandro
Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
J Nephrol. 2025 Jan;38(1):153-162. doi: 10.1007/s40620-024-01965-0. Epub 2024 Jul 5.
Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5-10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss.
We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression ([RP], n 15) and Non-rapid disease progression ([NRP], n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV).
The expression of h-miR17-5p was higher (p < 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m/year) (p < 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm) and height-adjusted total fibrotic volume (cm/m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p (p < 0.05), but not to total kidney volume (cm) and height-adjusted total kidney volume (cm/m).
The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis.
常染色体显性多囊肾病（ADPKD）是一种遗传性肾脏疾病，可能进展为肾衰竭，占所有终末期肾病（ESKD）患者的5% - 10%。临床数据以及分子遗传学和先进的成像技术已经提供了替代预后生物标志物来预测肾功能的快速下降，尽管如此，仍需要增强的工具来评估ADPKD的预后。本研究的目的是分析参与ADPKD发病机制和肾纤维化发展的特定微小RNA，评估它们作为肾功能丧失预测指标的潜在作用。
我们通过估计肾小球滤过率（eGFR）评估了32例处于不同肾病阶段的ADPKD患者在T0时以及24个月随访后（T1）的肾功能。根据梅奥诊所分类标准，将患者分为两组：疾病快速进展组（[RP]，n = 15）和疾病非快速进展组（[NRP]，n = 17）。在T0时，ADPKD患者接受血浆采样，使用定量逆转录 - 聚合酶链反应（qRT-PCR）方法对h-miR-17-5p、h-miR-21-5p和h-miR-199a-5p微小RNA表达进行定量分析，并使用先进的MRI成像方案进行3T磁共振成像（MRI），以量化总肾体积（TKV）、总灌注体积（TPV）和总纤维化体积（TFV）。
疾病快速进展的ADPKD患者中h-miR17-5p的表达更高（p < 0.05）。h-miR-17-5p、h-miR-21-5p和h-mir-199-5p与eGFR斜率（mL/min/1.73 m²/年）呈正相关且具有显著相关性（p < 0.05），但与T0和T1时的eGFR均无相关性。总纤维化体积（cm³）和身高校正后的总纤维化体积（cm³/m）与h-miR 21-5p和h-miR 199-5p呈正相关且具有显著相关性（p < 0.05），但与总肾体积（cm³）和身高校正后的总肾体积（cm³/m）无相关性。
我们研究的微小RNA与纤维化和肾损伤相关，表明它们可能作为生物标志物，能够识别无论肾功能程度如何都有疾病快速进展高风险的ADPKD患者，因此适合药物治疗，并且可能有助于揭示囊肿形成背后的新分子机制。
