coenzyme-q10 and Proteinuria

Herein, a 3-year-old boy presented with hidden-onset isolated proteinuria was reported. The disease was induced by COQ8B (previously termed ADCK4) compound heterozygous variants, including c.[271C > T] and c.[737G > A], which were inherited from his father and mother, respectively.. The patient visited our clinic due to non-nephrotic range proteinuria for 3 months, but no obvious abnormality was detected in the vital signs or laboratory test results. Renal histopathology revealed mitochondrial nephropathy, which manifested as mild glomerular abnormalities under light microscope, together with mitochondrial proliferation and hypertrophy and crowded arrangement under electron microscope. As suggested by whole exome sequencing, the patient inherited the COQ8B compound heterozygous variants from both of his parents who showed normal phenotype. After literature review, it was confirmed that one of the variant site (c.[271C > T]) had not been reported among the East Asian populations so far.. Steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis are the most common phenotypes and renal histopathological manifestations of COQ8B variant. Nonetheless, our case shows that such variant may have hidden and mild clinical manifestations at the early onset. Therefore, early diagnosis will help to identify children at the early disease stage who have opportunity to benefit from oral coenzyme Q10 supplementation.

Topics: Child, Preschool; Family; Genotype; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Male; Mutation; Nephrotic Syndrome; Phenotype; Protein Kinases; Proteinuria; Ubiquinone

Mitochondrial nephropathy has a poor prognosis and often progresses to the end-stage renal disease. Renal pathology often is focal segmental glomerulosclerosis (FSGS) and does not respond to steroid therapy or immunosuppressive therapy. Some patients are benefited from the therapy of coenzyme Q10, which affect the synthesis pathway of coenzyme Q10.. Herein, we report 2 cases of children with proteinuria renal disease with ADCK4 mutation.. Proteinuria renal disease with ADCK4 mutation.. Compound heterozygous mutation in ADCK4 gene were detected with next-generation sequencing and confirmed by Sanger sequencing. Both of the patients were given coenzyme Q10 supplementation therapy.. The first patient showed a decreased proteinuria after coenzyme Q10 supplementation therapy, while the other was not improved.. Based on the cases we reported and from the literature, recognition of ADCK4 mutation through early and accurate genetic screening could be helpful in avoiding unnecessary toxicities and in preventing complications arising in mitochondrial nephropathy.

Topics: Child; Dietary Supplements; Female; Humans; Infant; Kidney Diseases; Mutation; Protein Kinases; Proteinuria; Treatment Outcome; Ubiquinone

Functional state of the kidneys, severity of metabolic disturbances, intensity of LPO, and activity of the antioxidant system in 30 patients (18-36 years old) with type 1 diabetes mellitus and diabetic nephropathy of different compensation were studied before and after standard therapy or combination treatment with coenzyme Q10. Similar parameters were evaluated in 20 healthy subjects of the same age group. The development of metabolic disturbances in patients with type 1 diabetes mellitus (decompensated form) was accompanied by activation of LPO and inhibition of the antioxidant system. These patients were characterized by oxidative stress, diabetic nephropathy with associated proteinuria, and impairment of water excretion, electrolyte excretion, and nitrogen excretion in the kidneys. Combination therapy with coenzyme Q10 had a positive effect on LPO and antioxidant system. This treatment was followed by the relief of hyperglycemia, decrease in the concentrations of glycosylated hemoglobin and LDL cholesterol, and improvement of nitrogen metabolism.

Topics: Adult; Antioxidants; Cholesterol, LDL; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Electrolytes; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney; Lipid Peroxidation; Male; Nitrogen; Proteinuria; Ubiquinone

Primary Coenzyme Q10 (CoQ

Topics: Ataxia; Dietary Supplements; Humans; Kidney; Mitochondrial Diseases; Muscle Weakness; Mutation; Nephrotic Syndrome; Proteinuria; Steroids; Ubiquinone

Coenzyme Q10 (CoQ10) is involved in the biosynthesis of adenosine triphosphate (ATP), and is most abundant in the mitochondrial membrane. The primary CoQ10 deficiency caused by. Clinical and pathological data and peripheral blood samples of 2 siblings with steroid-resistant nephrotic syndrome (SRNS) and their family members of a Chinese pedigree were collected. DNA was extracted and subjected to next-generation sequencing of target genes of hereditary nephropathy.. Compound heterozygous mutations of. The 2 cases harboring

Topics: Alkyl and Aryl Transferases; Child, Preschool; China; Female; Glomerulosclerosis, Focal Segmental; Humans; Infant; Male; Mitochondrial Diseases; Mutation; Nephrotic Syndrome; Pedigree; Proteinuria; Siblings; Ubiquinone

Atmaca M, Gülhan B, Atayar E, Karabay Bayazıt A, Candan C, Arıcı M, Topaloğlu R, Özaltın 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.

Topics: Adolescent; Adult; Asymptomatic Diseases; Child; Child, Preschool; Dietary Supplements; Early Diagnosis; Female; Follow-Up Studies; Genetic Markers; Humans; Male; Mutation; Nephrotic Syndrome; Protein Kinases; Proteinuria; Ubiquinone; Vitamins; Young Adult

Topics: Child; Follow-Up Studies; Humans; Mutation; Proteinuria; Siblings; Ubiquinone

Treatment of steroid resistant nephrotic syndrome is still a challenge for physicians. There are a growing number of studies exploring genetic background of steroid-resistant glomerulopathies.. We present the case of a 4-year-old girl with steroid-resistant glomerulopathy due to a COQ6 defect with no additional systemic symptoms. The disease did not respond for second-line therapy with calcineurin inhibitor, but it remitted completely after oral treatment with 30 mg/kg/d of coenzyme Q10 (CoQ10). The patient was identified to be a compound heterozygote for two pathogenic variants in COQ6 gene: a known missense substitution c.1078C > T (p.R360W) and a novel frameshift c.804delC mutation. After 12 months of CoQ10 therapy, the child remains in full remission, her physical development accelerated, frequent respiratory airways diseases subsided.. Genetic assessment of children with steroid-resistant nephrotic proteinuria enables therapy optimization. Proteinuria caused by a COQ6 gene defect can be successfully treated with CoQ10.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcineurin Inhibitors; Child, Preschool; Drug Therapy, Combination; Female; Genetic Testing; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Heterozygote; Humans; Mutation; Nephrosis, Lipoid; Proteinuria; Treatment Outcome; Ubiquinone

COQ2 mutations cause a rare infantile multisystemic disease with heterogeneous clinical features. Promising results have been reported in response to Coenzyme Q10 treatment, especially for kidney involvement, but little is known about the long-term outcomes.. We report four new patients from two families with the c.437G→A (p.Ser146Asn) mutation in COQ2 and the outcomes of two patients after long-term coenzyme Q10 treatment.. Index cases from two families presented with vomiting, nephrotic range proteinuria, and diabetes in early infancy. These patients were diagnosed with coenzyme Q10 deficiency and died shortly after diagnosis. Siblings of the index cases later presented with neonatal diabetes and proteinuria and were diagnosed at the first day of life. Coenzyme Q10 treatment was started immediately. The siblings responded dramatically to coenzyme Q10 treatment with normalized glucose and proteinuria levels, but they developed refractory focal clonic seizures beginning at three months of life that progressed to encephalopathy.. In our cohort with CoQ10 deficiency, neurological involvement did not improve with oral coenzyme Q10 treatment despite the initial recovery from the diabetes and nephrotic syndrome.

Topics: Adaptor Proteins, Vesicular Transport; Ataxia; Cohort Studies; Diabetes Mellitus; Family Health; Female; Humans; Infant; Kidney; Magnetic Resonance Imaging; Male; Mitochondrial Diseases; Muscle Weakness; Mutation; Proteinuria; Ubiquinone

Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 μM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis.

Topics: Acidosis, Lactic; Alkyl and Aryl Transferases; Ataxia; Consanguinity; Fatal Outcome; Female; Gene Expression; Hepatic Insufficiency; Humans; Infant, Newborn; Intellectual Disability; Mitochondria, Muscle; Mitochondrial Diseases; Muscle Weakness; Muscle, Skeletal; Point Mutation; Proteinuria; Renal Aminoacidurias; Sequence Analysis, DNA; Ubiquinone

Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes.. Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.. Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).. db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Glomerular Filtration Rate; Guanosine Diphosphate; Ion Channels; Kidney Glomerulus; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Oxygen Consumption; Proteinuria; Ubiquinone; Uncoupling Protein 2; Vitamins

Topics: Alkyl and Aryl Transferases; Female; Humans; Infant; Kidney Failure, Chronic; Male; Mitochondrial Encephalomyopathies; Mutation, Missense; Nephrotic Syndrome; Proteinuria; Ubiquinone

It has been reported that coenzyme Q10 (CoQ10) functions as an electron transfer carrier in mitochondria, and can produce an improvement in heart diseases such as congestive heart failure. Its (2Z)-isomer contains a cis-double bond at the 2-position of the decaprenyl side chain. As the original organic industrial synthesis of CoQ10 resulted in a product that contained a small amount of this isomer, the efficacy and safety of CoQ10 was determined using CoQ10 containing this isomer; however, no toxicity data have been reported for the (2Z)-isomer itself. Thus, we conducted single (2,000 mg/kg) and 4-wk repeated (1,000 mg/kg) oral dose toxicity studies in rats to compare the toxicological profiles of CoQ10 and its (2Z)-isomer. The two compounds displayed similar toxicological profiles, and it was concluded that neither CoQ10 nor its (2Z)-isomer produce toxic effects in rats in single or repeated doses.

Topics: Animals; Body Weight; Coenzymes; Dose-Response Relationship, Drug; Eating; Female; Hydrogen-Ion Concentration; Isomerism; Lung; Male; Organ Size; Platelet Count; Pleura; Proteinuria; Rats; Rats, Wistar; Ubiquinone; Urine