Follow-up results of patients with ADCK4 mutations and the efficacy of CoQ10 treatment.
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.
Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Mustafa
M
Atmaca
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Bora
B
Gulhan
Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Emine
E
Korkmaz
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Mihriban
M
Inozu
Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey.
Oguz
O
Soylemezoglu
Division of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey.
Cengiz
C
Candan
Division of Pediatric Nephrology, Cukurova University Faculty of Medicine, Adana, Turkey.
Aysun Karabay
AK
Bayazıt
Pediatric Nephrology, Dr Faruk Sukan Maternity and Children's Hospital, Konya, Turkey.
Ahmet Midhat
AM
Elmacı
Adana Dr Turgut Noyan Training and Research Center, Başkent University, Adana, Turkey.
Gonul
G
Parmaksiz
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Ali
A
Duzova
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Nesrin
N
Besbas
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
Rezan
R
Topaloglu
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey. fozaltin@hacettepe.edu.tr.|Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey. fozaltin@hacettepe.edu.tr.|Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey. fozaltin@hacettepe.edu.tr.
Fatih
http://orcid.org/0000-0003-1194-0164
F
Ozaltin
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000652:urine; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005919:Glomerular Filtration Rate; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D009154:Mutation; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D014421:Turkey; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult
D005938:Glucocorticoids; D014815:Vitamins; D014451:Ubiquinone; C586096:COQ8B protein, human; D011494:Protein Kinases; C024989:coenzyme Q10
ADCK4 mutation; Adolescent; Chronic kidney disease; CoQ10 supplementation; Nephrotic syndrome