Mustafa Atmaca1, Bora Gulhan2, Emine Korkmaz3, Mihriban Inozu2, Oguz Soylemezoglu4, Cengiz Candan5, Aysun Karabay Bayazıt6, Ahmet Midhat Elmacı7, Gonul Parmaksiz8, Ali Duzova2, Nesrin Besbas2, Rezan Topaloglu2, Fatih Ozaltin9,10,11. 1. Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. 2. Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey. 3. Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey. 4. Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey. 5. Division of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey. 6. Division of Pediatric Nephrology, Cukurova University Faculty of Medicine, Adana, Turkey. 7. Pediatric Nephrology, Dr Faruk Sukan Maternity and Children's Hospital, Konya, Turkey. 8. Adana Dr Turgut Noyan Training and Research Center, Başkent University, Adana, Turkey. 9. Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey. fozaltin@hacettepe.edu.tr. 10. Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey. fozaltin@hacettepe.edu.tr. 11. Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey. fozaltin@hacettepe.edu.tr.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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/1.73m2, proteinuria was 1,008 (IQR 281-1,567) mg/m2/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/m2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m2, P=0.61). CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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/1.73m2, proteinuria was 1,008 (IQR 281-1,567) mg/m2/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/m2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m2, P=0.61). CONCLUSIONS: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.
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