Abstract：
Autosomal recessive polycystic kidney disease (ARPKD) is associated with pathogenic variants in the PKHD1 gene. Autosomal dominant polycystic kidney disease (ADPKD) is mainly associated with pathogenic variants in PKD1 or PKD2. The present study aimed to identify the clinical and genetic features of Turkish pediatric ARPKD and ADPKD patients.
This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers. Demographic features, clinical, and laboratory findings at presentation and during 12-month intervals were recorded.
The median age of the ARPKD patients at diagnosis was lower than the median age of ADPKD patients (10.5 months [range: 0-15 years] vs. 5.2 years [range: 0.1-16 years], respectively, [p = 0.014]). At the time of diagnosis, the median eGFR in the ARPKD patients was lower compared to that of ADPKD patients (81.6 [IQR: 28.7-110.5] mL/min/1.73 m2 and 118 [IQR: 91.2-139.8] mL/min/1.73 m2, respectively, [p = 0.0001]). In total, 11 (52.4%) ARPKD patients had malnutrition; 7 (33.3%) patients had growth retardation at presentation; and 4 (19%) patients had both malnutrition and growth retardation. At diagnosis, 8 (16.7%) of the ADPKD patients had malnutrition, and 5 (10.4%) patients had growth retardation. The malnutrition, growth retardation, and hypertension rates at diagnosis were higher in the ARPKD patients than the ADPKD patients (p = 0.002, p = 0.02, and p = 0.0001, respectively). ARPKD patients with malnutrition and growth retardation had worse renal survival compared to the patients without (p = 0.03 and p = 0.01). Similarly, ADPKD patients with malnutrition had worse renal survival compared to the patients without (p = 0.002). ARPKD patients with truncating variants had poorer 3- and 6-year renal outcome than those carrying non-truncating variants (p = 0.017).
Based on renal survival analysis, type of genetic variant, growth retardation, and/or malnutrition at presentation were observed to be factors associated with progression to chronic kidney disease (CKD). Differentiation of ARPKD and ADPKD, and identification of the predictors of the development of CKD are vital for optimal management of patients with ARPKD or ADPKD.
This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers. Demographic features, clinical, and laboratory findings at presentation and during 12-month intervals were recorded.
The median age of the ARPKD patients at diagnosis was lower than the median age of ADPKD patients (10.5 months [range: 0-15 years] vs. 5.2 years [range: 0.1-16 years], respectively, [p = 0.014]). At the time of diagnosis, the median eGFR in the ARPKD patients was lower compared to that of ADPKD patients (81.6 [IQR: 28.7-110.5] mL/min/1.73 m2 and 118 [IQR: 91.2-139.8] mL/min/1.73 m2, respectively, [p = 0.0001]). In total, 11 (52.4%) ARPKD patients had malnutrition; 7 (33.3%) patients had growth retardation at presentation; and 4 (19%) patients had both malnutrition and growth retardation. At diagnosis, 8 (16.7%) of the ADPKD patients had malnutrition, and 5 (10.4%) patients had growth retardation. The malnutrition, growth retardation, and hypertension rates at diagnosis were higher in the ARPKD patients than the ADPKD patients (p = 0.002, p = 0.02, and p = 0.0001, respectively). ARPKD patients with malnutrition and growth retardation had worse renal survival compared to the patients without (p = 0.03 and p = 0.01). Similarly, ADPKD patients with malnutrition had worse renal survival compared to the patients without (p = 0.002). ARPKD patients with truncating variants had poorer 3- and 6-year renal outcome than those carrying non-truncating variants (p = 0.017).
Based on renal survival analysis, type of genetic variant, growth retardation, and/or malnutrition at presentation were observed to be factors associated with progression to chronic kidney disease (CKD). Differentiation of ARPKD and ADPKD, and identification of the predictors of the development of CKD are vital for optimal management of patients with ARPKD or ADPKD.
摘要：
背景：常染色体隐性遗传性多囊肾病（ARPKD）与PKHD1基因的致病变异有关。常染色体显性遗传性多囊肾病（ADPKD）主要与PKD1或PKD2的致病变异有关。本研究旨在确定土耳其儿童ARPKD和ADPKD患者的临床和遗传特征。
方法：这个多中心，回顾性队列研究纳入了来自7个儿科肾脏病中心的21例遗传证实的ARPKD和48例遗传证实的ADPKD患者.人口统计特征，临床,并记录了演示时和12个月间隔期间的实验室检查结果.
结果：诊断时ARPKD患者的中位年龄低于ADPKD患者的中位年龄（10.5个月[范围：0-15岁]与5.2年[范围：0.1-16年]，分别,[p=0.014])。在诊断的时候,ARPKD患者的eGFR中位数低于ADPKD患者(分别为81.6[IQR:28.7-110.5]mL/min/1.73m2和118[IQR:91.2-139.8]mL/min/1.73m2,[p=0.0001])。总的来说,11例（52.4％）ARPKD患者营养不良；7例（33.3％）患者出现生长迟缓；4例（19％）患者营养不良和生长迟缓。诊断时,8例(16.7%)ADPKD患者存在营养不良,生长迟缓5例(10.4%)。营养不良，生长迟缓,ARPKD患者诊断时的高血压发生率高于ADPKD患者(分别为p=0.002,p=0.02和p=0.0001).与没有营养不良和生长迟缓的ARPKD患者相比，营养不良和生长迟缓的ARPKD患者的肾脏生存率较差（p=0.03和p=0.01）。同样，与没有营养不良的ADPKD患者相比，营养不良的ADPKD患者的肾脏生存率较差（p=0.002）。具有截断变体的ARPKD患者的3年和6年肾脏结局比携带非截断变体的患者差（p=0.017）。
结论：基于肾脏生存分析，遗传变异的类型，生长迟缓,和/或出现时的营养不良被认为是进展为慢性肾脏病(CKD)的相关因素.ARPKD和ADPKD的分化，确定CKD发展的预测因子对于ARPKD或ADPKD患者的最佳治疗至关重要。
方法：这个多中心，回顾性队列研究纳入了来自7个儿科肾脏病中心的21例遗传证实的ARPKD和48例遗传证实的ADPKD患者.人口统计特征，临床,并记录了演示时和12个月间隔期间的实验室检查结果.
结果：诊断时ARPKD患者的中位年龄低于ADPKD患者的中位年龄（10.5个月[范围：0-15岁]与5.2年[范围：0.1-16年]，分别,[p=0.014])。在诊断的时候,ARPKD患者的eGFR中位数低于ADPKD患者(分别为81.6[IQR:28.7-110.5]mL/min/1.73m2和118[IQR:91.2-139.8]mL/min/1.73m2,[p=0.0001])。总的来说,11例（52.4％）ARPKD患者营养不良；7例（33.3％）患者出现生长迟缓；4例（19％）患者营养不良和生长迟缓。诊断时,8例(16.7%)ADPKD患者存在营养不良,生长迟缓5例(10.4%)。营养不良，生长迟缓,ARPKD患者诊断时的高血压发生率高于ADPKD患者(分别为p=0.002,p=0.02和p=0.0001).与没有营养不良和生长迟缓的ARPKD患者相比，营养不良和生长迟缓的ARPKD患者的肾脏生存率较差（p=0.03和p=0.01）。同样，与没有营养不良的ADPKD患者相比，营养不良的ADPKD患者的肾脏生存率较差（p=0.002）。具有截断变体的ARPKD患者的3年和6年肾脏结局比携带非截断变体的患者差（p=0.017）。
结论：基于肾脏生存分析，遗传变异的类型，生长迟缓,和/或出现时的营养不良被认为是进展为慢性肾脏病(CKD)的相关因素.ARPKD和ADPKD的分化，确定CKD发展的预测因子对于ARPKD或ADPKD患者的最佳治疗至关重要。
