Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury

Factors associating with differences in the incidence of renal replacement therapy among elderly : data from the ERA-EDTA Registry

Background. The incidence of renal replacement therapy (RRT) in the general population >= 75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods. Patients >= 75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results. The mean annual incidence of RRT in the age group >= 75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions. Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low-and high-incidence areas was remarkably similar.Peer reviewe

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014 : a summary

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged >= 65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20-to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.Peer reviewe

Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury

The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients

ABSTRACT Background: Balkan endemic nephropathy (BEN) hemodialysis patients require a higher dose of recombinant human erythropoietin for maintaining target hemoglobin level than patients with other kidney diseases. Objectives: Comparison of the pharmacokinetics of betaerythropoietin given subcutaneously to hemodialysis patients with BEN or other kidney diseases (non-BEN). Methods: Recombinant human erythropoietin (75U/kg) was administered subcutaneously to 10 BEN and 14 non-BEN hemodialysis patients. The predose plasma level of erythropoietin (Epo) was subtracted from all postdose levels. The relevant pharmacokinetic parameters were calculated after noncompartmental pharmacokinetic analysis using Kinetica software (Thermo Scientific, ver.5.0). Results: Although basal plasma Epo concentration was similar in BEN (20.1±10.3U/L) and non-BEN (15.1±8.1U/L; p=.1964) patients, there were significant differences between the groups for elimination rate constant (0.016±0.006 vs 0.026±0.011 hr -1 ; p=.020) and elimination half-life (50.24±19.12 vs 33.79±18.91 hr, p=.048). These differences remained significant after adjustment for patient characteristics (age, sex

Recording blood pressure and eGFR in primary care after the Belgrade screening study

Background: In 2009, Belgrade nephrologists and general practitioners from thirteen health centers carried out screening for chronic kidney disease (CKD). Three years later, medical records of patients from four health centers participating in the screening study were retrospectively analyzed in order to check whether general practitioners had continued to control patients at risk for CKD in accordance with the recommendations provided. Methods: The study included 460 patients who visited their doctor at least once in the three-year period. Data on blood pressure, ACEI use, estimated glomerular filtration rate (eGFR) and comorbidities were taken from patients’ medical records. Results: Blood pressure was not recorded in any of the three years in 42.8% and eGFR in 36.7% of the patients, but blood pressure was registered every year in 7.8% and eGFR in 4.3% of them. Over the three years, the relative number of patients with recorded blood pressure decreased from 41.7% to 17.8%, and with recorded eGFR from 41.7% to 21.5%. Multivariate linear regression found that Health Center, systolic and diastolic blood pressure and presence of hypertension were negatively associated with number of years with recorded blood pressure. Health Center, systolic blood pressure and sum of years with recorded eGFR below 60 ml/min/1.73m2 were associated with number of years with recorded eGFR. Conclusions: Under-recording of blood pressure and eGFR in primary care health centers suggests lack of adherence to current guidelines and insufficient care of CKD patients. This implies the necessity for continuous education of physicians