Atmaca Mustafa, Gulhan Bora, Korkmaz Emine, Inozu Mihriban, Soylemezoglu Oguz, Candan Cengiz, Bayazıt Aysun Karabay, Elmacı Ahmet Midhat, Parmaksiz Gonul, Duzova Ali, Besbas Nesrin, Topaloglu Rezan, Ozaltin Fatih
Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Pediatr Nephrol. 2017 Aug;32(8):1369-1375. doi: 10.1007/s00467-017-3634-3. Epub 2017 Mar 24.
ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration.
A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation.
Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m, proteinuria was 1,008 (IQR 281-1,567) mg/m/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m, P=0.61).
ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective.
与ADCK4相关的肾小球病是青少年激素抵抗型肾病综合征（SRNS）和/或病因不明的慢性肾脏病（CKD）的重要鉴别诊断。我们对青少年患者进行筛查，以确定ADCK4突变的频率以及早期给予辅酶Q10的疗效。
共筛查了146例年龄在10至18岁之间、新诊断为非肾病性蛋白尿、肾病综合征或病因不明的慢性肾衰竭和终末期肾病（ESKD）的索引患者的ADCK4突变情况。
确定了来自11个家庭的28例双等位基因突变个体。诊断时的中位年龄为12.4（四分位间距[IQR]8.04 - 19.7）岁。首次入院时，所有患者均有蛋白尿，18例患有CKD（6例ESKD）。8例是在索引病例确诊后通过对家庭成员进行筛查或在有移植同胞病史的个体进行蛋白尿基因调查期间确诊的。这8例患者的中位年龄为21.5（范围4.4 - 39）岁。基因诊断后给予辅酶Q10补充治疗。辅酶Q10给药前的中位估计肾小球滤过率（eGFR）为140（IQR 117 - 155）ml/min/1.73m²，蛋白尿为1008（IQR 281 - 1567）mg/m²/天。辅酶Q10给药后中位随访11.5（范围4 - 21）个月，蛋白尿显著降低（中位值363[IQR 175 - 561]mg/m²/天，P = 0.025），而eGFR保持不变（中位值137[IQR 113 - 158]ml/min/1.73m²，P = 0.61）。
在土耳其，ADCK4突变是青少年起病的病因不明的蛋白尿和/或CKD的最常见原因之一。补充辅酶Q10似乎对降低蛋白尿有效，因此可能具有肾脏保护作用。
