Polyphenols and Novel Insights Into Post-kidney Transplant Complications and Cardiovascular Disease:A Narrative Review

Kidney transplantation is the preferred treatment for end-stage kidney disease. It is, however, not devoid of complications. Delayed graft function related to ischemia-reperfusion injury (IRI), calcineurin inhibitor (CNI) nephrotoxicity, diabetes, and a particularly high-rate cardiovascular disease (CVD) risk, represent important complications following kidney transplantation. Oxidative stress and chronic low-grade inflammation are mechanisms of disease incompletely abrogated in stable kidney transplant recipient (KTR), contributing to the occurrence of these complications. Polyphenols, bioactive compounds with recognized antioxidant and anti-inflammatory properties have been strongly associated with prevention of CVD in the general population and have been shown to decrease IRI and antagonize CNI nephrotoxicity in animal experimental models, therefore they may have a role in prevention of complications in KTR. This narrative review aims to summarize and discuss current evidence on different polyphenols for prevention of complications, particularly prevention of CVD in KTR, pointing toward the need of further studies with potential clinical impact

Antithrombotic Management in Adult Kidney Transplantation: A European survey study

In kidney transplantation (KTx), renal graft thrombosis (RGT) is one of the main reasons for early graft loss. Although evidence-based guidance on prevention of RGT is lacking, thromboprophylaxis is widely used. The aim of this survey was to obtain a European view of the different thromboprophylactic strategies applied in KTx. An online 22-question survey, addressed to KTx professionals, was distributed by email and via platforms of the European Society for Organ Transplantation. Seventy-five responses (21 countries, 51 centers) were received: 75% had over 10 years' clinical experience, 64% were surgeons, 29% nephrologists, and 4% urologists. A written antithrombotic management protocol was available in 75% of centers. In 8 (16%) centers, respondents contradicted each other regarding the availability of a written protocol. Thromboprophylaxis is preferred by 78% of respondents, independent of existing antithrombotic management protocols. Ninety-two percent of respondents indicated that an anticipated bleeding risk is the main reason to discontinue chronic antithrombotic therapy preoperatively. Intraoperatively, 32% of respondents administer unfractionated heparin (400-10,000 international units with a median of 5,000) in selected cases. Despite an overall preference for perioperative thromboprophylaxis in KTx, there is a high variation within Europe regarding type, timing, and dosage, most likely due to the paucity of high-quality studies. Further research is warranted in order to develop better guidelines.</p

The Association between Body Composition Measurements and Surgical Complications after Living Kidney Donation

Obesity is considered a risk factor for peri- and postoperative complications. Little is known about this risk in overweight living kidney donors. The aim of this study was to assess if anthropometric body measures and/or surgical determinants are associated with an increased incidence of peri- and postoperative complications after nephrectomy. We included 776 living kidney donors who donated between 2008 and 2018 at the University Medical Center Groningen. Prenephrectomy measures of body composition were body mass index (BMI), body surface area (BSA), waist circumference, weight, and waist-hip ratio. Incidence and severity of peri- and postoperative complications were assessed using the Comprehensive Complication Index. Mean donor age was 53 +/- 11 years; 382 (49%) were male, and mean BMI at donor screening was 26.2 +/- 3.41 kg/m(2). In total, 77 donors (10%) experienced peri- and postoperative complications following donor nephrectomy. Male sex was significantly associated with fewer surgical complications (OR 0.59, 0.37-0.96 95%CI, p = 0.03) in binomial logistic regression analyses. Older age (OR: 1.03, 1.01-1.05 95%CI, p = 0.02) and a longer duration of surgery (OR: 1.01, 1.00-1.01 95%CI, p = 0.02) were significantly associated with more surgical complications in binomial logistic regression analyses. Multinomial logistic regression analyses did not identify any prenephrectomy measure of body composition associated with a higher risk of surgical complications. This study shows that higher prenephrectomy BMI and other anthropometric measures of body composition are not significantly associated with peri- and postoperative complications following living donor nephrectomy

Pathophysiological Changes in the Hemostatic System and Antithrombotic Management in Kidney Transplant Recipients

Nowadays, the main cause for early graft loss is renal graft thrombosis because kidney transplant outcomes have improved drastically owing to advances in immunological techniques and immunosuppression. However, data regarding the efficacy of antithrombotic therapy in the prevention of renal graft thrombosis are scarce. Adequate antithrombotic management requires a good understanding of the pathophysiological changes in the hemostatic system in patients with end-stage kidney disease (ESKD). Specifically, ESKD and dialysis disrupt the fine balance between pro- and anticoagulation in the body, and further changes in the hemostatic system occur during kidney transplantation. Consequently, kidney transplant recipients paradoxically are at risk for both thrombosis and bleeding. This overview focuses on the pathophysiological changes in hemostasis in ESKD and kidney transplantation and provides a comprehensive summary of the current evidence for antithrombotic management in (adult) kidney transplant recipients.</p

Introduction of the Grayscale Median for Ultrasound Tissue Characterization of the Transplanted Kidney

Ultrasound examination is advised for early post-kidney transplant assessment. Grayscale median (GSM) quantification is novel in the kidney transplant field, with no systematic assessment previously reported. In this prospective cohort study, we measured the post-operative GSM in a large cohort of adult kidney transplant recipients (KTR) who consecutively underwent Doppler ultrasound directly after transplantation (within 24 h), compared it with GSM in nontransplanted patients, and investigated its association with baseline and follow-up characteristics. B-mode images were used to calculate the GSM in KTR and compared with GSM data in nontransplanted patients, as simulated from summary statistics of the literature using a Mersenne twister algorithm. The association of GSM with baseline and 1-year follow-up characteristics were studied by means of linear regression analyses. In 282 KTR (54 ± 15 years old, 60% male), the median (IQR) GSM was 55 (45-69), ranging from 22 to 124 (coefficient of variation = 7.4%), without differences by type of donation (p = 0.28). GSM in KTR was significantly higher than in nontransplanted patients (p < 0.001), and associated with systolic blood pressure, history of cardiovascular disease, and donor age (std. β = 0.12, -0.20, and 0.13, respectively; p < 0.05 for all). Higher early post-kidney transplant GSM was not associated with 1-year post-kidney transplant function parameters (e.g., measured and estimated glomerular filtration rate). The data provided in this study could be used as first step for further research on the application of early postoperative ultrasound in KTR

The evolution of the Čanište epidote-bearing pegmatite, Republic of Macedonia: evidence from mineralogical and geochemical features

The epidote-bearing Čanište pegmatite and adjacent Upper Carboniferous granodiorites cut Precambrian gneises, at the western slopes of the Selečka Mts., the Eastern Pelagonian zone, FYRO Macedonia. The pegmatite exhibits zonal internal structure with the following sub-units: the wall zone (amazonite microcline ± biotite, quartz), the first intermediate zone (epidote + hematite + grossular + muscovite + quartz + almandine ± zircon, beryl, microcline, quartz), the second intermediate zone (albite + quartz ± microcline) and the core (massive quartz). According to the microprobe data epidote belongs to clinozoisite subgroup with formula (Ca1.96-1.99Mn0.02-0.03Fe2+0.00-0.02)(Al2.17-2.46Fe3+0.51-0.82Ti0.00-0.01)(Si2O7)(Si0.99-1.00Al0.00-0.01O4)O(OH). The occurrences of almandine and zircon with low U, Th and REE content, are indicative to weakly evolved granitic/granodioritic rocks. The absence of aplites suggests steady pressure condition during the course of pegmatite crystallization. Microthermometric data combined by the two-feldspar geothermometer gained pressure from 4.8 to 5.6 kbar for the second intermediate zone. The wall zone, composed of amazonite microcline, crystallized at temperature between 650 and 760. Dropping of melt temperature below 550°C, under the oxygen fugacity between 10-22 and 10-19.5 bar, was the principal trigger for deposition of minerals in the first intermediate zone. The residual fluid, depleted in Ca, Fe and K, and enriched in water, Na and Si, caused deposition of the second intermediate zone (albite + quartz) at temperature between 445 and 465°C. The massive quartz core crystallized in the very last stage of the pegmatite evolution (T ≈ 400-480°C) from melt residue enriched in silica, water and CO2 content.</p

A high abdominal aortic calcification score by dual X-ray absorptiometry is associated with cardiovascular events after kidney transplantation

Background: Aortic calcification is associated with an increased risk for cardiovascular events in renal transplant recipients. This study focused on the association of abdominal aortic calcification (AAC) and cardiovascular events assessed using a dual-energy X-ray absorptiometry (DXA) scoring methodology for AAC. Methods: From 2008 to 2014, renal transplant recipients referred for a DXA procedure within 6 months after transplantation were included in a retrospective, single-centre study. The primary endpoint was the occurrence of cardiovascular events, defined as myocardial infarction, cerebrovascular accident or transient ischaemic attack, after transplantation. AAC was quantified using an 8-point scoring system and patients were divided into three groups; a control group (AAC = 0), a low AAC group (AAC = 1-3) and a high AAC group (AAC = 4-8). Results: We evaluated 701 patients, 267 (38.1%) had detectable calcifications (low AAC 190 patients, high AAC 77 patients) and 434 (61.9%) had no calcifications. Cardiovascular events were seen in 37 (8.5%) patients in the control group, in 18 (9.5%) in the low AAC group and in 20 (26.0%) in the high AAC group. Univariate Cox proportional hazards analysis of the high AAC score showed a hazard ratio (HR) of 4.23 [95% confidence interval (CI) 2.44-7.33; P < 0.01] for cardiovascular events, while results were not significant for the low AAC score. Multivariate analysis showed an independent significant association between a high AAC score and cardiovascular events [HR 2.78 (95% CI 1.05-7.64); P = 0.04]. Assessment of the continuous net reclassification index (NRI), comparing the combined clinical variables with a model of both AAC scoring and clinical variables, showed an NRI of 0.76 (95% CI 0.65-0.86; P < 0.01). Conclusions: An independent association between a high AAC score, assessed by DXA, and cardiovascular events was identified and provides an opportunity for early cardiovascular risk stratification in renal transplant recipients

The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied

Neuropsychological intervention in kindergarten children with subtyped risks of reading retardation

Kindergarten children at risk of developing language problems were administered the Florida Kindergarten Screening Battery. A principal components analysis revealed a verbal and a visual-spatial component and subsequent discriminant function analyses a high verbal/low visual-spatial group (LAL: Latent L) and a high visual-spatial/low verbal group (LAP: Latent P). LAL- and LAP-children were considered at risk for developing an L- or P-type of dyslexia, respectively. As is common practice with children suffering from manifest L- or Pdyslexia, the LAL- and LAP-kindergartners received right and left hemisphere stimulation, respectively. The outcomes were compared with those of bilateral hemispheric stimulation and no intervention. Reading tests were administered in primary school Grades 1 and 5/6; teachers' evaluation of reading took place in Grade 5/6. Overall, the LAL- and LAP- groups showed significant backwardness in word and text reading, both at early and late primary school. Types of intervention made a difference though: not significantly backward in early word, late word, and late text reading were the LAL-children who had received right hemisphere stimulation. Nonintervened LAP-children did not show significant backwardness in early word reading and late text reading, nor did LAP-children who had received left hemisphere or bilateral stimulation. Early text reading was not affected by any treatment. Teacher's evaluations were in support of these findings. Copyright © 2005 by The International Dyslexia Association®

Transitions in frailty state after kidney transplantation

Purpose: Frailty is the body’s failure to return to homeostasis after every day or acute stressful events, causing adverse outcomes. To study its dynamics in kidney transplant recipients (KTR), we determined whether the degree of frailty and its domains are affected by kidney transplantation (KT). Methods: Between 2015 and 2017, 176 KTR were included. Frailty scores were measured using the Groningen Frailty Indicator (GFI), assessed preoperatively and during follow-up. Transitions in frailty state and changes in the individual domains were determined. Results: Mean age (±SD) was 51.8 (± 14.1) years, and 63.1% of KTR were male. Thirty patients were considered frail (GFI ≥ 4) at baseline. After a mean follow-up of 22.8 ± 8.3 months, 34 non-frail patients (19.3%) became frail, 125 patients (71.0%) remained the same, and 17 frail patients (9.7%) became non-frail (GFI < 4). In the domain psychosocial functioning, 28.4% of the patients had an increase in GFI score after follow-up. Patients who scored a point in the domain cognition at baseline had a greater chance of becoming frail (OR 4.38, 95% CI 0.59–32.24). Conclusion: In conclusion, almost one-fifth of non-frail KTR transitioned to a frail state after their transplantation. These results could be used to predict the impact of KT on frailty course and help with implementing prehabilitation for patients at risk