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Follow-up results of patients with ADCK4 mutations and the efficacy of CoQ10 treatment

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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.

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Acknowledgements

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 2012-305608 (EURenOmics).

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Authors and Affiliations

  1. Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Mustafa Atmaca

  2. Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey

    Bora Gulhan, Mihriban Inozu, Ali Duzova, Nesrin Besbas, Rezan Topaloglu & Fatih Ozaltin

  3. Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Emine Korkmaz & Fatih Ozaltin

  4. Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey

    Oguz Soylemezoglu

  5. Division of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey

    Cengiz Candan

  6. Division of Pediatric Nephrology, Cukurova University Faculty of Medicine, Adana, Turkey

    Aysun Karabay Bayazıt

  7. Pediatric Nephrology, Dr Faruk Sukan Maternity and Children’s Hospital, Konya, Turkey

    Ahmet Midhat Elmacı

  8. Adana Dr Turgut Noyan Training and Research Center, Başkent University, Adana, Turkey

    Gonul Parmaksiz

  9. Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey

    Fatih Ozaltin

Authors
  1. Mustafa Atmaca
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  2. Bora Gulhan
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  3. Emine Korkmaz
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  4. Mihriban Inozu
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  5. Oguz Soylemezoglu
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  6. Cengiz Candan
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  7. Aysun Karabay Bayazıt
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  8. Ahmet Midhat Elmacı
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  9. Gonul Parmaksiz
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  10. Ali Duzova
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  11. Nesrin Besbas
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  12. Rezan Topaloglu
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  13. Fatih Ozaltin
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Corresponding author

Correspondence to Fatih Ozaltin.

Ethics declarations

The study was approved by the ethics committee of Hacettepe University (HEK12/112-13). Written informed consent was obtained from the parents of all the patients.

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Atmaca, M., Gulhan, B., Korkmaz, E. et al. Follow-up results of patients with ADCK4 mutations and the efficacy of CoQ10 treatment. Pediatr Nephrol 32, 1369–1375 (2017). https://doi.org/10.1007/s00467-017-3634-3

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  • DOI: https://doi.org/10.1007/s00467-017-3634-3

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