Stężenie hormonów płciowych w surowicy u młodych kobiet we wczesnym okresie po zakończonym powodzeniem przeszczepieniu nerki

Background: Hormonal disorders are frequently present in hemodialysed patients with chronic kidney disease (CKD). In women with CKD sex hormones abnormalities may lead to irregular, often anovulatory cycles, sexual dysfunction and infertility. Kidney transplantation done in young women tends to ameliorate most of the aforementioned disorders and improve fertility. The aim of this study was to assess the changes of serum sex hormones concentration in young women before, and after the first 6 months after successful KTx Material and methods: Fourteen chronic hemodialysis women with CKD undergoing kidney transplantation and 46 apparently healthy women in similar age (control group) were enrolled into the study. In all women serum concentration of: FSH, LH, PRL and estradiol determined. Measurements in the transplanted group were done four times: immediately before surgery, in the 14th - and 30th - day and 6 months after the transplantation. The results are presented as means and 95% CI. Results: All of the women that have finished the study presented an excellent function of the transplanted kidney – mean serum creatinine concentration was 92.54 (74.85 – 110.23) µmol/l. After successful KTx a significant decrease in the serum concentrations of FSH and LH was observed. Decrease of serum PRL concentration after KTx did not reach statistical significance in the multiple comparisons analyses, but returned to the values observed in healthy controls. KTx did not significantly influence serum estradiol concentration. Conclusions: Successful kidney transplantation leads to the normalization of serum concentrations of hormones linked to fertility disorders in women with chronic kidney disease. Wstęp: U chorych z przewlekłą chorobą nerek (chronic kidney disease, CKD) poddawanych hemodializie często obserwuje się zaburzenia hormonalne. U kobiet z CKD nieprawidłowe stężenia hormonów płciowych mogą powodować nieregularne, często bezowulacyjne cykle, zaburzenia czynności seksualnych i bezpłodność. Po przeszczepieniu nerki u młodych kobiet zwykle następuje złagodzenie większości z tych zaburzeń i poprawa płodności. Badanie przeprowadzono w celu oceny zmian stężeń hormonów płciowych w surowicy oznaczo­nych przed i po udanym przeszczepieniu nerki. Materiały i metody: Do badania włączono 14 przewlekle hemodializowanych kobiet z CKD, u których planowano przeszczepienie nerki oraz 46 zdrowych kobiet w podobnym wieku (grupa kontrolna). U wszystkich kobiet oznaczono stężenia w surowicy hormonu folikulotropowego (follicle-stimulating hormone, FSH), hormonu luteinizującego (luteinizing hormone, LH), prolaktyny (prolactin, PRL) i estradiolu. W grupie poddanej transplantacji pomiary wykonano 4-krotnie: bezpośrednio przed zabiegiem, w 14. i 30. dobie po zabiegu oraz 6 miesięcy po zabiegu. Wyniki przedstawiono jako średnie i 95-procentowe przedziały ufności. Wyniki: U wszystkich kobiet, które ukończyły badanie stwierdzono bardzo dobrą czynność przeszczepionej nerki — średnie stężenie kreatyniny w surowicy wynosiło 92,54 (74,85–110,23) μmol/l. Po udanym przeszczepieniu nerki zaobserwowano istotne zmniejszenie stężeń w surowicy FSH i LH. Zmniejszenie stężenia PRL w surowicy po przeszczepieniu nerki nie osiągnęło poziomu istotności statystycznej w testach wielokrotnych porównań, ale stężenie tego hormonu wróciło do wartości obserwowanych u zdrowych osób z grupy kontrolnej. Przeszczepienie nerki nie wpłynęło istotnie na stężenie estradiolu w surowicy. Wnioski: Zakończone powodzeniem przeszczepienie nerki powoduje normalizację stężeń w surowicy hormonów związanych z zabu­rzeniami płodności u kobiet z CKD

Exposure of pregnant rats to cigarette-smoke condensate causes glomerular abnormalities in offspring

Background: Higher blood pressure and albuminuria are found in offspring of mothers who smoke during pregnancy. Whether or not kidney development is affected by maternal smoking is unknown. Methods: Sprague-Dawley rats were randomly allocated to twice-daily cigarette-smoke and nicotine condensate (1 mg/kg) or vehicle at day 10 of pregnancy until delivery. Results: Exposed offspring did not differ from control offspring with respect to body weight, kidney weight, albuminuria, and creatinine clearance. Both male and female offspring had higher tail-plethysmographic blood pressures and lower mean glomerular volume, podocyte, mesangial-cell, and endothelial-cell number, compared to control offspring. Conclusions: The data document that prenatal exposure to cigarette-smoke condensate containing nicotine influences normal kidney development and could predispose to higher blood pressures later in life. Copyright (c) 2012 S. Karger AG, Base

Effects of eccentric exercise on anaerobic power, starting speed and anaerobic endurance

The aim of this study was to evaluate the effects of eccentric exercise on anaerobic power, starting speed and anaerobic endurance. The participants performed the maximum cycling sprint test (MCST) prior to eccentric exercise (ECC), 10 minutes after, as well as one hour, 24 hours, 48 hours, and one week after ECC. The peak and mean power, time to attain peak power, time of maintaining peak power and power decrease were measured in the MCST. Before and after ECC, the myoglobin concentration (Mb) in the blood plasma was measured. After ECC, a significant (p<.05) increase in Mb was observed. A significant (p<.05) decrease was noted in peak (-.92±0.42 W.kg-1) as well as in mean power (-.57±0.36 W.kg-1) immediately after ECC. A significant (p<.05) decrement of these indicators lasted for at least 24 hours after ECC. Eccentric exercise did not affect starting speed (time to attain peak power) and anaerobic endurance (time of maintaining peak power and power decrease during MCST)

A prospective cohort study in patients with type 2 diabetes mellitus for validation of biomarkers (PROVALID) –study design and baseline characteristics

Background/Aims: The prevalence of diabetes mellitus type 2 and kidney disease in these patients varies widely between European countries. Methods: In addition to store biosamples the “Prospective cohort study in patients with type 2 diabetes mellitus for validation of biomarkers” collects information on history, physical status, laboratory measurements and medication in 4000 patients with diabetes mellitus type 2, being taken care of at the primary level of healthcare in 5 European countries (Austria, Hungary, Netherlands, Poland and Scotland). Next to comparing the rate of loss of eGFR between the countries, a further objective of the PROVALID study is to determine the 5-year cumulative incidence of renal and cardiovascular outcomes. Results: The mean age of the population recruited is 62.9±10 years, 54.6% are male and the mean BMI is 30.9±5.4 kg/m2 . Metabolic control (median HBA1c 6.8 % (6.2;7.5)) is achieved via administration of metformin in 67.4% of the patients and insulin in 30.3%. Median systolic and diastolic blood pressure at recruitment is 135 (125;146) and 80 (72;85) mmHg, 65.4% of subjects received RAAS blocking agents. Mean eGFR is 80.7±29.2 ml/min/1.73m2 and median baseline albumin/creatinine ratio 8.3 mg (IQR: 3.8 and 25.1). Conclusion: PROVALID will provide information on incidence and progression of renal and cardiovascular disease and therapy in patients with type 2 diabetes mellitus in different European countries. Thus, in contrast to many other cohort studies we will be able to associate national clinical practise pattern with outcome in this highly vulnerable patient population

A journey from microenvironment to macroenvironment: The role of metaflammation and epigenetic changes in cardiorenal disease

Chronic non-communicable diseases have become a pandemic public problem in the 21st century, causing enormous burden on the economy, health and quality of life of societies. The role of a chronic inflammatory state in the pathogenesis of chronic disease has been more comprehensively recognized by recent findings. The new paradigm 'metaflammation' focuses on metabolism-induced (high fat or fructose-based diet or excessive calorie intake) chronic inflammation. There is a close correlation between the increased incidence of chronic kidney disease (CKD) and chronic heart failure with both increased inflammatory marker levels and western-type diet. In this review we describe the concept of metaflammation, its role in the development of CKD and chronic heart disease, the molecular and signalling pathways involved and the therapeutic consequencesResearch by A.O. was funded by FIS ISCIII FEDER funds PI16/02057, ISCIII-RETIC REDinREN RD16/0009, EUTOX, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-C

Effect of renin-angiotensin-aldosterone system blockade in adults with diabetes mellitus and advanced chronic kidney disease not on dialysis : a systematic review and meta-analysis

The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of end-stage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3-5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were allcause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n = 9797 participants with CKD stages 3-5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR] = 0.97 [95% confidence interval (CI) 0.85-1.10]}, cardiovascular mortality [RR = 1.03 (95% CI 0.75-1.41)] and adverse events [RR = 1.05 (95% CI 0.89-1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR = 0.90 (95% CI 0.81-1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR = 0.81 (95% CI 0.70-0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3-5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAAS-blocking agents expedited the need for RRT in patients with CKD stages 3-5

Peginesatide in patients with anemia undergoing hemodialysis

BACKGROUND: Peginesatide, a synthetic peptide-based erythropoiesis- stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease. METHODS: We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point - death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia - with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide once monthly or continued to receive epoetin one to three times a week, with the doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher in the comparison of peginesatide with epoetin. The aim of evaluating the composite safety end point in the pooled cohort was to exclude a hazard ratio with peginesatide relative to the comparator ESA of more than 1.3. RESULTS: In an analysis involving 693 patients from EMERALD 1 and 725 from EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin levels (mean between-group difference, -0.15 g per deciliter; 95% confidence interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, -0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in the EMERALD studies. The proportions of patients with adverse and serious adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort. CONCLUSIONS: Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysisSupported by Affymax and Takeda Pharmaceutica

Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care

Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes

Objective: The decline of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes is variable and early interventions would likely be cost effective. We elucidated the contribution of 17 plasma biomarkers to the prediction of eGFR loss on top of clinical risk factors. Research Design and Methods: We studied participants in PROVALID, a prospective multinational cohort study of patients with type 2 diabetes and a follow up of more than 24 months (n = 2560; baseline median eGFR 84 mL/min/1.73m2, UACR 8.1 mg/g). The 17 biomarkers were measured at baseline in 481 samples using Luminex technology and ELISA. The prediction of eGFR decline was evaluated by linear mixed modeling. Results: In univariable analyses nine of the 17 markers showed significant differences in median concentration between the two groups. A linear mixed model for eGFR obtained by variable selection exhibited an adjusted R2 of 62%. A panel of twelve biomarkers was selected by the procedure and accounted for 34% of the total explained variability, of which 32% were due to five markers. Each biomarker’s individual contribution to the prediction of eGFR decline on top of clinical predictors was generally low. When included into the model, baseline eGFR exhibited the largest explained variability of eGFR decline (R2 of 79%) and the contribution of each biomarker dropped below 1%. Conclusions: In this longitudinal study of patients with type 2 diabetes and maintained eGFR at baseline, 12 of the 17 candidate biomarkers were associated with eGFR decline, but their predictive power was low