ubiquinone and Albuminuria

Chronic kidney disease (CKD) associates with increased cardiovascular disease (CVD) risk. Hypertension is a major determinant of progression of CKD. Omega-3 fatty acids (omger3FA) protect against CVD via improvements in blood pressure, heart rate, vascular reactivity and serum lipids. Coenzyme Q(10) (CoQ) may improve blood pressure and vascular function. This study determined whether omega3FA and CoQ have independent or additive effects in improving the cardiovascular profile, particularly blood pressure and heart rate, in nondiabetic patients with CKD stages 3-4.. In a double-blind, placebo-controlled intervention, patients were randomized to either omega3FA (4 g), CoQ (200 mg), both supplements or control (4 g), daily for 8 weeks.. Eighty-five patients aged 56.5 +/- 1.4 years; BMI 27.3 +/- 0.5 kg/m(2); supine blood pressure 125.0/72.3mmHg; and glomerular filtration rate 35.8 +/- 1.2 ml/min/1.73m(2), were randomized. Seventy-four completed the study. omega3FA, but not CoQ, reduced 24-h ambulatory heart rate (P<0.0001) and blood pressure (P<0.0001). Main effects for omega3FA on 24-h measurements were -3.3 +/- 0.7/ -2.9 +/- 0.5mmHg and -4.0 +/- 0.5 bpm. Postintervention blood pressure showed significant interactions between treatments. omega3FA reduced triglycerides 24% (P<0.001). There were no changes in glomerular filtration rate, urinary albumin or total protein excretion, cholesterol, HDL-cholesterol (C), LDL-C, glucose, insulin, or high-sensitivity C-reactive protein.. This study has shown that omega3FA reduce blood pressure, heart rate and triglycerides in patients with CKD. CoQ had no independent effect on blood pressure but increased heart rate. These results show that omega3FA lower blood pressure and may reduce cardiovascular risk in nondiabetic patients with moderate-to-severe CKD.

Topics: Adult; Aged; Albuminuria; Arteries; Blood Glucose; Blood Platelets; Blood Pressure; Diet; Double-Blind Method; Drug Synergism; Dyslipidemias; Echocardiography; Fatty Acids; Fatty Acids, Omega-3; Female; Heart Rate; Humans; Hypertension; Insulin; Life Style; Male; Middle Aged; Phospholipids; Renal Insufficiency, Chronic; Ubiquinone

Cyclosporine, a potent immunosuppressant, has nephrotoxic adverse effects that may be mediated by oxidative stress. The reduced form of coenzyme Q10 has antioxidant effects. The aim of the present study was to evaluate the effect of the reduced form of coenzyme Q10 on cyclosporine nephrotoxicity.. Six-week-old male Wistar rats were divided into 3 groups (10 animals each). Group 1 (control) received olive oil only. Group 2 received cyclosporine (30 mg/kg/d, which is an experimentally nephrotoxic dose). Group 3 received cyclosporine (30 mg/kg/d) and the reduced form of coenzyme Q10 (600 mg/kg/d). The cyclosporine and the reduced form of coenzyme Q10 were given orally for 4 weeks. Daily urinary albumin excretion, serum creatinine level, and urinary 8-hydroxydeoxyguanosine level were measured, and renal tissue was evaluated by immunohistochemistry.. In rats treated with cyclosporine and the reduced form of coenzyme Q10 (group 3), there were significantly less abnormalities in mean urinary albumin excretion (group 1: 2.8 ± 0.5; group 2: 41 ± 7; group 3: 21 ± 4 μg/d), serum creatinine (group 1: 1.0 ± 0.2; group 2: 1.8 ± 0.4; group 3: 1.4 ± 0.3 mg/dL), and urine 8-hydroxydeoxyguanosine levels (group 1: 7 ± 3; group 2: 10 ± 3; group 3: 7 ± 1 mg/mL creatinine) than rats treated with cyclosporine alone (group 2). There were 8-hydroxydeoxyguanosine deposits seen in the proximal tubular cells of group 2 that were not present in rats treated with the reduced form of coenzyme Q10 (group 3).. The reduced form of coenzyme Q10 may prevent or minimize cyclosporine nephrotoxicity by an antioxidant effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Albuminuria; Animals; Creatinine; Cyclosporine; Deoxyguanosine; Immunosuppressive Agents; Kidney; Male; Models, Animal; Oxidative Stress; Prevalence; Rats; Rats, Wistar; Ubiquinone

Cardiovascular benefits of ubiquinone have been previously demonstrated, and we administered it as a novel therapy in an experimental model of type 2 diabetic nephropathy. db/db and dbH mice were followed for 10 weeks, after randomization to receive either vehicle or ubiquinone (CoQ10; 10mg/kg/day) orally. db/db mice had elevated urinary albumin excretion rates and albumin:creatinine ratio, not seen in db/db CoQ10-treated mice. Renal cortices from db/db mice had lower total and oxidized CoQ10 content, compared with dbH mice. Mitochondria from db/db mice also contained less oxidized CoQ10(ubiquinone) compared with dbH mice. Diabetes-induced increases in total renal collagen but not glomerulosclerosis were significantly decreased with CoQ10 therapy. Mitochondrial superoxide and ATP production via complex II in the renal cortex were increased in db/db mice, with ATP normalized by CoQ10. However, excess renal mitochondrial hydrogen peroxide production and increased mitochondrial membrane potential seen in db/db mice were attenuated with CoQ10. Renal superoxide dismutase activity was also lower in db/db mice compared with dbH mice. Our results suggest that a deficiency in mitochondrial oxidized CoQ10 (ubiquinone) may be a likely precipitating factor for diabetic nephropathy. Therefore CoQ10 supplementation may be renoprotective in type 2 diabetes, via preservation of mitochondrial function.

Topics: Adenosine Triphosphate; Albuminuria; Animals; Citrate (si)-Synthase; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Hepatitis A Virus Cellular Receptor 1; Kidney; Kidney Function Tests; Membrane Potential, Mitochondrial; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Oxidation-Reduction; Random Allocation; Reactive Oxygen Species; Ubiquinone

Therapy of mitochondrial respiratory chain diseases is complicated by limited understanding of cellular mechanisms that cause the widely variable clinical findings. Here, we show that focal segmental glomerulopathy-like kidney disease in Pdss2 mutant animals with primary coenzyme Q (CoQ) deficiency is significantly ameliorated by oral treatment with probucol (1% w/w). Preventative effects in missense mutant mice are similar whether fed probucol from weaning or for 3 weeks prior to typical nephritis onset. Furthermore, treating symptomatic animals for 2 weeks with probucol significantly reduces albuminuria. Probucol has a more pronounced health benefit than high-dose CoQ(10) supplementation and uniquely restores CoQ(9) content in mutant kidney. Probucol substantially mitigates transcriptional alterations across many intermediary metabolic domains, including peroxisome proliferator-activated receptor (PPAR) pathway signaling. Probucol's beneficial effects on the renal and metabolic manifestations of Pdss2 disease occur despite modest induction of oxidant stress and appear independent of its hypolipidemic effects. Rather, decreased CoQ(9) content and altered PPAR pathway signaling appear, respectively, to orchestrate the glomerular and global metabolic consequences of primary CoQ deficiency, which are both preventable and treatable with oral probucol therapy.

Topics: Albuminuria; Alkyl and Aryl Transferases; Animals; Anticholesteremic Agents; Antioxidants; Energy Metabolism; Female; Hyperglycemia; Kidney; Kidney Diseases; Male; Mice; Mice, Knockout; Mutation, Missense; Oxidative Stress; Probucol; Signal Transduction; Ubiquinone

Homozygous mice carrying kd (kidney disease) mutations in the gene encoding prenyl diphosphate synthase subunit 2 (Pdss2kd/kd) develop interstitial nephritis and eventually die from end-stage renal disease. The PDSS2 polypeptide in concert with PDSS1 synthesizes the polyisoprenyl tail of coenzyme Q (Q or ubiquinone), a lipid quinone required for mitochondrial respiratory electron transport. We have shown that a deficiency in Q content is evident in Pdss2kd/kd mouse kidney lipid extracts by 40 days of age and thus precedes the onset of proteinuria and kidney disease by several weeks. The presence of the kd (V117M) mutation in PDSS2 does not prevent its association with PDSS1. However, heterologous expression of the kd mutant form of PDSS2 together with PDSS1 in Escherichia coli recapitulates the Q deficiency observed in the Pdss2kd/kd mouse. Dietary supplementation with Q10 provides a dramatic rescue of both proteinuria and interstitial nephritis in the Pdss2kd/kd mutant mice. The results presented suggest that Q may be acting as a potent lipid-soluble antioxidant, rather than by boosting kidney mitochondrial respiration. Such Q10 supplementation may have profound and beneficial effects in treatment of certain forms of focal segmental glomerulosclerosis that mirror the renal disease of the Pdss2kd/kd mouse.

Topics: Albuminuria; Alkyl and Aryl Transferases; Animals; Dietary Supplements; Female; Gene Expression; Glomerulosclerosis, Focal Segmental; Kidney; Liver; Male; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Mice, Transgenic; Mitochondria; Mutation; Nephritis; Protein Binding; Protein Subunits; Transfection; Ubiquinone