coenzyme-q10 and Acute-Kidney-Injury

Coenzyme Q10 (CoQ10), an endogenous antioxidant, has been reported frequently to exert an outstanding protective effect on multiple organ injury, including acute kidney injury (AKI). In this study, we aim to summarize all the current evidence of the protective action of CoQ10 against AKI as there are presently no relevant reviews in the literature. After a systematic search, 20 eligible studies, either clinical trials or experimental studies, were included and further reviewed. CoQ10 treatment exhibited a potent renal protective effect on various types of AKI, such as AKI induced by drugs (e.g., ochratoxin A, cisplatin, gentamicin, L-NAME, and nonsteroidal anti-inflammatory drug), extracorporeal shock wave lithotripsy (ESWL), sepsis, contrast media, and ischemia-reperfusion injury. The renal protective role of CoQ10 against AKI might be mediated by the antiperoxidative, anti-apoptotic, and anti-inflammatory potential of CoQ10. The molecular mechanisms for the protective effects of CoQ10 might be attributed to the regulation of multiple essential genes (e.g., caspase-3, p53, and PON1) and signaling cascades (e.g., Nrf2/HO-1 pathway). This review highlights that CoQ10 may be a potential strategy in the treatment of AKI.

Topics: Acute Kidney Injury; Anti-Inflammatory Agents; Antioxidants; Aryldialkylphosphatase; Humans; Kidney; Ubiquinone

Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue.

Topics: Acute Kidney Injury; Alkyl and Aryl Transferases; Animals; DNA, Mitochondrial; Humans; Kearns-Sayre Syndrome; Kidney Diseases; Mitochondria; Mitochondrial Myopathies; Mutation; Oxidative Phosphorylation; Reactive Oxygen Species; Ubiquinone

Contrast-induced nephropathy (CIN) is one of the common hospital-acquired acute renal failures. The purpose of this study was to investigate whether Coenzyme Q10 (CoQ10) and trimetazidine (TMZ) can prevent the occurrence of CIN after elective cardiac catheterization in patients with coronary artery disease complicated with renal dysfunction.. Consecutive coronary artery disease patients with renal insufficiency scheduled for coronary angiography were enrolled in randomized, paralleled, double-blind, controlled trial. The development of CIN was occurrence at the 48 or 72 h after the procedure. The changes of serum creatinine (SCr), eGFR, and Cys-C within 72 h after the procedure were measured and compared. In vivo contrast medium (CM)-induced acute kidney injury (AKI) animal model was established, and CoQ10 plus TMZ was orally administrated to evaluate its renal protective effect.. 150 patients with renal insufficiency were enrolled finally. CIN occurred in 21 (14.00%) of the 150 patients. 72 h after the procedure, the incidence of CIN was significantly lower in CoQ10 plus TMZ group compared with control group (6.67 vs. 21.3%, p = 0.01). No cardiac death occurred in this study. No side effects were observed after administration of CoQ10 and TMZ. In vivo test demonstrated that CoQ10 and TMZ could significantly reduce the concentration of blood urea nitrogen (BUN) and SCR induced by CM i.v. injection, as well as tubular pathological injuries. Meanwhile, CoQ10 and TMZ could significantly reduce the oxidation stress in kidneys from CM-AKI animals.. CoQ10 plus TMZ could decrease the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization, and their effect may be due to its strong anti-oxidation effect.

Topics: Acute Kidney Injury; Aged; Animals; Antioxidants; Cardiac Catheterization; Contrast Media; Coronary Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Trimetazidine; Ubiquinone

We assessed the potential effect of CoQ10 administration for the prevention of contrast induced-acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. One hundred fifty STEMI patients who were candidates for primary PCI, along with intravenous saline hydration, randomly received a placebo or CoQ10. CoQ10 was administrated orally, 400 mg before the procedure and 200 mg twice daily after the procedure for three consecutive days. Serum creatinine concentration and corresponding creatinine clearance (estimated by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation) were measured at baseline and 24, 48, and 72 h after primary PCI. Furthermore, the serum level of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA) was measured before and 72 h after primary PCI.. The mean serum creatinine concentration before contrast administration was similar in the two groups (0.98 ± 0.08 versus 0.99 ± 0.09 mg/dL). While in both study groups, compared to baseline, the mean serum creatinine concentration increased at 48 and 72 h after contrast exposure, the CoQ10 group showed a lower serum creatinine concentration than the placebo group (P-value = 0.017 and 0.004, respectively). However, comparing the mean values of creatinine clearance between the groups at the study time points did not demonstrate a statistically significant difference. CI-AKI, defined as a > 25% or 0.5 mg/dL increase in baseline serum creatinine concentration, occurred in 8.00% of the cases in the CoQ10 group versus 20.00% in the placebo group (P-value = 0.034). Furthermore, at 72 h, the CoQ10-treated group exhibited higher serum levels of SOD and TAC and a lower MDA level than the placebo-treated group.. Our research's findings proposed CoQ10 supplementation as an adjuvant to saline hydration as a preventive approach against CI-AKI.. The trial was registered at Iranian Registry of Clinical Trials ( https://www.irct.ir/trial/60435 , identifier code: IRCT20120215009014N414). Registration date: 2021-12-29.

Topics: Acute Kidney Injury; Contrast Media; Creatinine; Humans; Iran; Percutaneous Coronary Intervention; Renal Insufficiency, Chronic; Risk Factors; ST Elevation Myocardial Infarction

Combined antioxidants effect for prevention of contrast-induced nephropathy (CIN) remains unclear. This study assessed the potential protective effects of coenzyme Q10 (CoQ10) alone or combined with N-acetyl cysteine (NAC) or atorvastatin against CIN in diabetic rats. Animals were randomly divided into five groups, including control and four disease groups with CIN and diabetes. Group 2 included diabetic rats with CIN. Groups 3-5 included diabetic rats that received CoQ10, CoQ10 and NAC, or CoQ10 and atorvastatin, respectively, before CIN induction. Serum, urine, and tissue were collected to evaluate renal protective effects of tested agents. Renal biomarkers, oxidative stress, and histopathological alterations were investigated. Rats with CIN showed significant renal impairment as revealed by the deleterious effects on kidney function and histology. While induction of CIN did not affect the renal levels of catalase, glutathione peroxidase (GPx), and thiobarbituric acid reactive substances, pretreatment of animals with CoQ10/NAC showed significant increase in GPx and catalase levels versus controls. Lastly, pretreatment with CoQ10/atorvastatin showed regenerative effect on distal tubules with mild kidney histology alterations relative to CIN rats. The combined use of CoQ10/atorvastatin could be a potential strategy to prevent CIN. However, future studies are warranted to test different combinations for longer prophylactic periods.

Topics: Acetylcysteine; Acute Kidney Injury; Animals; Atorvastatin; Contrast Media; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Drug Therapy, Combination; Male; Rats; Rats, Sprague-Dawley; Ubiquinone

Primary coenzyme Q(10) (CoQ(10)) deficiency includes a group of rare autosomal recessive disorders primarily characterized by neurological and muscular symptoms. Rarely, glomerular involvement has been reported. The COQ2 gene encodes the para-hydroxybenzoate-polyprenyl-transferase enzyme of the CoQ(10) synthesis pathway. We identified two patients with early-onset glomerular lesions that harbored mutations in the COQ2 gene. The first patient presented with steroid-resistant nephrotic syndrome at the age of 18 months as a result of collapsing glomerulopathy, with no extrarenal symptoms. The second patient presented at five days of life with oliguria, had severe extracapillary proliferation on renal biopsy, rapidly developed end-stage renal disease, and died at the age of 6 months after a course complicated by progressive epileptic encephalopathy. Ultrastructural examination of renal specimens from these cases, as well as from two previously reported patients, showed an increased number of dysmorphic mitochondria in glomerular cells. Biochemical analyses demonstrated decreased activities of respiratory chain complexes [II+III] and decreased CoQ(10) concentrations in skeletal muscle and renal cortex. In conclusion, we suggest that inherited COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. COQ2 nephropathy should be suspected when electron microscopy shows an increased number of abnormal mitochondria in podocytes and other glomerular cells.

Topics: Acute Kidney Injury; Alkyl and Aryl Transferases; Coenzymes; Electron Transport Chain Complex Proteins; Humans; Infant; Kidney; Male; Mitochondrial Diseases; Muscle, Skeletal; Mutation, Missense; Nephrotic Syndrome; Ubiquinone

Ischemic insult has been considered a cause of cellular injuries under certain circumstance, such as the disturbance of energy metabolism, the alternation of calcium homeostasis, the production of oxygen radical and the release of lysosomal protease. The present study was designed to clarify the pathophysiological effects of coenzyme Q10 (CoQ10), diltiazem, superoxide dismutase (SOD) and urinastatin on the development and progression of ischemic acute renal failure (IARF) of the rat. At 24 hours after reflow following 45 minutes ischemia, serum urea nitrogen, creatinine and fractional excretion of sodium were 99.3 mg/dl, 3.14 mg/dl, 5.95% respectively, in non-treated IARF rats. Renal ATP content was reduced to 0.91 micrograms/mg. prot. from 10.59 micrograms/mg. prot. at 10 minutes after ischemic insult, and remained at almost the same level throughout the entire 45 minutes ischemia. Although the subsequent blood reflow resulted in the recovery of ATP content, it was up to 50% of normal level at 24 hours after reflow following 45 minutes ischemia. During the ischemic period, the pathological changes were mild, whereas, after reflow, tissue involvement was mainly localized in the S3 segment of the proximal tubule. Major alteration were the loss of brush border, high amplitude swelling of mitochondria with matrical densities and fragmentation of the epithelial cell. At 24 hours after reflow, it was observed that renal function was superior in IARF rats treated with CoQ10, diltiazem, SOD and urinastatin. The treated rats also had higher ATP contents and showed less pathological changes than non-treated rats. Among these inhibitory agents, diltiazem exerted the most reliable effect. From these results, it was concluded that IARF was obviously caused by such pathophysiological mechanisms as mentioned above. Especially, Ca influx into the cells is one of the most important factors on pathogenesis of IARF.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Calcium; Coenzymes; Diltiazem; Disease Models, Animal; Glycoproteins; Kidney; Male; Rats; Rats, Inbred Strains; Superoxide Dismutase; Trypsin Inhibitors; Ubiquinone