Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

A broad clinical spectrum of PLCε1-related kidney disease and intrafamilial variability.

BACKGROUND: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. METHODS: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. RESULTS: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. CONCLUSION: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Predictors for the use of herbal and dietary supplements in children and adolescents with kidney and urinary tract diseases.

Complementary and alternative medicine are treatments administered alone or in combination with conventional medical treatments. Data on complementary and alternative medicine use in children with kidney and urinary tract diseases are limited. In this cross-sectional study, the frequency and preferred methods of complementary and alternative medicine use and factors associated with their use were evaluated in 201 patients (48% female; median age, 11 years; median disease duration, 5.1 years) with kidney and urinary tract diseases and 260 healthy (without chronic disease) controls. Data were collected through a questionnaire-based interview and patients' medical records. Herbal and dietary supplements, including fish oil, were the most commonly used complementary and alternative medicine agents in both groups. There was no difference in herbal and dietary supplement use between the groups when fish oil was excluded (29% vs. 28%; p = 0.88). Herbal and dietary supplements were mainly used to improve/mitigate renal disease (52%). Logistic regression analysis revealed that disease duration > 7 years (odds ratio (OR), 3.70; 95% confidence interval (CI), 1.48-9.20), current use of six or more drugs (OR, 5.6; 95% CI, 1.28-24.41), and recurrent urinary tract infection or nephrolithiasis (OR, 3.92; 95% CI, 1.02-15.09) were the independent risk factors for herbal and dietary supplement use, except fish oil. Middle socioeconomic status was associated with decreased herbal and dietary supplement use, except fish oil, compared with low socioeconomic status (OR, 0.30; 95% CI, 0.11-0.81). Herbal and dietary supplements were used by 78% patients, despite knowing that these products could have side effects; only 42% of the patients shared the information about herbal and dietary supplement use with their doctors.Conclusion: Herbal and dietary supplement use is frequent in children with kidney and urinary tract diseases. Educating health professionals regarding such use is mandatory for developing strategies to prevent critical consequences. What is Known: • Complementary and alternative medicine (CAM) practices are therapeutic approaches that do not have sufficient efficacy and safety evidence. • CAM is widely used in healthy children and in certain chronic diseases. What is New: • Herbal and dietary supplements (HDSs) were the most commonly used method in kidney and urinary tract diseases. • Duration of disease, number of drugs, and socioeconomic status are determinants of HDS use except fish oil.

Long-term follow-up results of patients with ADCK4 mutations who have been diagnosed in the asymptomatic period: effects of early initiation of CoQ10 supplementation.

Atmaca M, Gülhan B, Atayar E, Karabay Bayazit A, Candan C, Arici M, Topaloglu R, Özaltin F. Long-term follow-up results of patients with ADCK4 mutations who have been diagnosed in the asymptomatic period: effects of early initiation of CoQ10 supplementation. Turk J Pediatr 2019; 61: 657-663. ADCK4-related glomerulopathy is a recently recognized clinical entity associated with insidious onset in young children and a high potential to progress to chronic kidney disease in adolescents. Early initiation of exogenous coenzyme Q10 (CoQ10) supplementation in the asymptomatic period could be protective on renal functions. In the present study, we aimed to investigate long-term follow-up of patients that we have diagnosed during the asymptomatic period and in whom we started CoQ10 treatment. We analyzed long-term effects of CoQ10 on proteinuria and estimated glomerular filtration rate (eGFR) in this patient population. A total of 8 patients (4 female, 4 male) from 6 different families were included. The mean age at diagnosis and at last visit were 16.8±11.2 years and 20.7±11.7 years, respectively. None of the patients had extrarenal system involvement. At the time of initiation of treatment; median eGFR was 107.8 ml/min/1.73 m2, median proteinuria was 1008 mg/m2/day. After a median follow-up period of 25.3±5.8 months, median proteinuria decreased to 318.5 mg/m2/day (p=0.03) and median eGFR remained stable at 99.6 ml/min/1.73 m2 (p=0.21). Coenzyme Q10 treatment is effective for reducing proteinuria and seems to be renoprotective.

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.