Kidney Week

Abstract: SA-PO569

Follow Up of Patients with ADCK4 Associated Glomerulopathy and the CoQ10 Treatment

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Rao, Jia, Children's Hospital of Fudan university, Shanghai, China

Jia Rao,

• Song, Xiaoxiang, Children''s hospital of Suzhou university, Suzhou, China

Xiaoxiang Song,

• Shen, Qian, Children's Hospital of Fudan University, Shanghai, China

Qian Shen,

• Xu, Hong, Children''s Hospital of Fudan university, Shanghai, China

Hong Xu,

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. ADCK4 interacts with components of the coenzyme Q10 (CoQ10) biosynthesis pathway.

Methods

The incidence and phenotypes of patients with ADCK4 mutations were investigated in a cohort of Chinese pediatric patients with SRNS non-nephrotic proteinuria, or CKD.

Results

We identified 12 patients from 11 families with bi-allelic mutations of ADCK4. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, two subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 7.6 years) with nephrotic-range proteinuria in 58.3% of patients and advanced CKD in 63.6% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. ESRD occurred almost after age of 6 in patients with ADCK4 nephropathy. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 120.4 (IQR 69.5-135.9) ml/min/1.73m², proteinuria was evaluated by the ratio of urinary protein and creatinine (Up/cre) showing 3.9 (IQR 2.4-6.0). After a median follow-up of 21 (range 12–24) months following CoQ10 administration, proteinuria was significantly decreased (median Up/cre 2.2, IQR 1.5-2.5)，whereas the eGFR was preserved (median eGFR 128.0 ml/min/1.73m², IQR 68.2-137.4).

Conclusion

ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknownetiology in China. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective.

Fig1 Urinary protein level over the time following CoQ10 initiation in idividuals genetic diagnosed with ADCK4 mutation.