Peter Wohlfahrt

Identification of expanded-criteria donor kidney grafts at lower risk of delayed graft function.

Background Organ shortage leads to the increased use of expanded-criteria donor (ECD) kidneys, which contribute to a higher risk of delayed graft function (DGF) after transplantation. The aim of this study was to determine factors that may better predict the risk of DGF. Methods Histologic assessments of donor renal biopsy were used with other clinical variables to predict the risk of DGF after kidney transplantation. The total Banff score equaled the sum of interstitial fibrosis (CI), tubular atrophy, arteriolar hyaline thickening, fibrous intimal thickening (CV), and fraction of sclerotized glomeruli. Results In total, 126 of 344 patients developed DGF after kidney transplantation. The histologic score for CI, tubular atrophy, and CV and the total Banff score were increased in patients with DGF. Only CI and CV were independent predictors of DGF (P<0.01). A CIV score (CI+CV; odds ratio, 2.68; 95% confidence interval, 1.55–4.66; P<0.001) was superior to the combination of the total Banff score (odds ratio, 1.48; 95% confidence interval, 0.85–2.55; P=NS). A CIV score≥1, donor age more than 51 years, and anoxia donor brain injury were associated with the highest risk of DGF. A CIV<1 identified a subgroup of ECDs at a lower risk of DGF comparable with standard-criteria donors (29.3% vs. 28.4%). Conclusions Composite CIV score better identifies ECD kidneys with a lower risk of developing DGF. Morphologic evaluation of ECD kidneys and donor characteristics may improve kidney allocation.

Quality of life predictors in chronic stable post-stroke patients and prognostic value of SF-36 score as a mortality surrogate.

Perceived quality of life (QoL) and psychological well-being represents an important target of secondary prevention practice in post-stroke patients. We aimed to identify the major covariates of impaired QoL in stable post-stroke patients and whether impaired QoL itself represents independent mortality predictor.The study consisted of a cross-sectional and a prospective part. Three hundred forty-one patients [mean age 69.0 (SD 9.1)] were interviewed at least 6xa0months after discharge from hospital for their first-ever ischemic stroke. QoL was objectivized using 36-Item Short-Form Health Survey (SF-36) scoring. Standard health-related questionnaires, including Hospital Anxiety and Depression Scale (HADS), risk factors, and biochemical markers, were assessed. To estimate the 5-year all-cause and cardiovascular mortality, we ascertained the vital status and declared cause of death.Anxiety, depression (HADS score ≥11), brain natriuretic peptide levels ≥100xa0ng/mL, residual motor impairment at interview, Rankin Scale ≥4 at discharge from hospitalization, and raised blood pressure were identified as main determinants of impaired QoL in the cross-sectional part. The 5-year all-cause and cardiovascular mortality rates were 25.8 and 19.9xa0%, respectively. After adjustment for potential covariates, patients with an SF-36 score ≤40 at baseline had more than a twofold higher risk of all-cause and cardiovascular mortality (with HRRs 2.01 (95xa0% CI 1.21–3.32), pu2009<u20090.007 and 2.32 (95xa0% CI 1.32–4.09), pu2009<u20090.003, respectively) during the 5xa0years of follow-up.In conclusion, anxiety, depression, and raised brain natriuretic peptide levels were the most important covariates of impaired QoL in post-stroke patients. Moreover, a decreased SF-36 score (≤40) represents an independent surrogate of increased additive mortality risk.

Comparison of Noninvasive Assessments of Central Blood Pressure Using General Transfer Function and Late Systolic Shoulder of the Radial Pressure Wave

BACKGROUNDnCentral systolic blood pressure (cSBP) can be derived by the general transfer function of the radial pressure wave, as used in the SphygmoCor device, or by regression equation from directly measured late systolic shoulder of the radial pressure wave (pSBP2), as used in the Omron HEM-9000AI device. The aim of this study was to compare the SphygmoCor estimates of cSBP with 2 estimates of cSBP provided by the Omron HEM-9000AI (cSBP, pSBP2) in a large cohort of the white population.nnnMETHODSnIn 391 patients aged 52.3±13.5 years (46% men) from the Czech post-MONICA Study, cSBP was measured using the SphygmoCor and Omron HEM-9000AI devices in random order.nnnRESULTSnOmron cSBP and pSBP2 were perfectly correlated (r = 1.0; P < 0.0001). There was a strong correlation (r = 0.97; P < 0.0001) between Omron and SphygmoCor cSBP estimates, but Omron estimate was 13.1±4.7mm Hg higher than SphygmoCor cSBP. On the other hand, Omron pSBP2 strongly correlated with SphygmoCor cSBP (r = 0.97; P < 0.0001) and was 1.7±4.2mm Hg lower than SphygmoCor cSBP. In multivariable analysis, anthropometric and cardiovascular risk factors explained only 10% of the variance of the cSBP difference between devices while explaining 52% of the systolic blood pressure amplification variance.nnnCONCLUSIONSnEstimation of cSBP based on the late systolic shoulder of the radial wave provides a comparable accuracy with the validated general transfer function. When comparing Omron HEM-9000AI and SphygmoCor estimates of cSBP, Omron pSBP2 should be used. The difference between both devices in cSBP may be explained by differences in calibration.

Changes in Hypertension Prevalence, Awareness, Treatment, and Control in High-, Middle-, and Low-Income Countries: An Update

The aim of this paper was to critically evaluate recent publications on hypertension treatment and control in regions by income. Prevalence of hypertension is increasing worldwide, most prominently in low-income countries. Awareness, treatment, and control are most successful in North America while remaining a challenge in middle- and low-income countries. Easy access to medical care and aggressive use of pharmacotherapy are the key strategies which have proved to be successful in reducing the burden of hypertension on the population level.

Tubular atrophy and low netrin-1 gene expression are associated with delayed kidney allograft function.

Background Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development. Methods Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2−&Dgr;&Dgr;Ct) in delayed (n=9) and primary function allografts (n=26). Results Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81). Conclusions Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.

Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance

BackgroundInduction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects.MethodsThe mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, nu2009=u200924), basiliximab (nu2009=u200917), or without induction (no-induction, nu2009=u200919). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis.ResultsrATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group.ConclusionThe rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression.

Early and late outcomes of hybrid endovascular and open repair procedures in patients with peripheral arterial disease

BACKGROUNDnHybrid endovascular and open reconstructions are used increasingly often for multilevel revascularization for lower limb ischaemia. The aim was to evaluate outcomes after such procedures in a single-center non-randomized retrospective study.nnnPATIENTS AND METHODSnConsecutive patients with multilevel arterial disease who underwent single session hybrid procedures were analyzed depending on the type of ischaemia and the type of revascularization.nnnRESULTSn164 patients were included with a median follow up time of 14 months (range: 0 - 70). Indication was claudication (group 1, 47 %), critical limb ischaemia (group 2, 33 %) and acute limb ischaemia (group 3, 20 %). Technical success rate was 99.3 %, perioperative mortality 2 %. Primary, assisted-primary and secondary patency rates at one year were 60 %, 61 % and 64 %, respectively. Primary, primary assisted and secondary patency were lower in group 2 and 3 compared to group 1 (all p < 0.05). Results were better when endovascular repairs were performed above compared to below the open repair site (all p < 0.05). Limb salvage at 1 year in groups 1 - 3 were 98 %, 92 % and 90 %, respectively. The risk of major amputation was highest in group 3 compared to group 1 (p = 0.001) or group 2 (p < 0.04).nnnCONCLUSIONSnThe results depend on the type of ischaemia and the localization of endovascular procedures.

Differential effect of metabolic syndrome on various parameters of arterial stiffness

Abstract Metabolic syndrome (MetSy) is associated with a high risk of cardiovascular complications. Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study investigated the effect of individual MetSy risk factors on central and peripheral parameters of aortic stiffness. In the Czech post-MONICA study, we measured aortic pulse-wave velocity (aPWV), lower extremity pulse-wave velocity (lePWV), augmentation index (AIx) and central augmentation pressure (cAP) in 936 subjects. Based on the definition of MetSy, we divided subjects according to number of risk factors. We used univariate and multivariate linear regression analysis to assess the association between number of risk factors and aPWV, lePWV, AIx and cAP. In analyses adjusted for age, gender, heart rate and mean arterial pressure, aPWV was higher in subjects with MetSy (MetSy+ group) than in those without (MetSy + group) (8.3 vs 7.7 m/s; p < 0.0001), but lePWV was not significantly different between the groups (11.0 vs 11.2 m/s; p = 0.2037). After adjustment for covariates, AIx in MetSy+ was lower than in MetSy− respondents (143.2 vs 146.8; p = 0.014). In adjusted analysis, aPWV rose with increasing number of MetSy risk factors (7.3 ± 0.1 vs 9.0 ± 0.1 m/s; p for trend < 0.0001). The number of MetSy risk factors did not affect lePWV (p = 0.11). AIx decreased with higher number of MetSy risk factors (148.3 vs 141.5; p = 0.020). This finding confirms the fact that PWV and AIx may have different associations with risk factors and AIx should not be used as an isolated parameter of arterial stiffness. The individual MetSy risk factors have only a small effect on lower extremity arterial stiffness.

Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: Consecutive survivors and population-based controls

OBJECTIVEnDue to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking.nnnMETHODSnWe conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism.nnnRESULTSnAge- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; pxa0=xa00.004). There was strong evidence of rs1799963xa0×xa0smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; pxa0=xa00.005). There was no association of rs6025 with IS in general, or with any subtype.nnnCONCLUSIONSnIn our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.

Reply to ‘Cardiac remodeling after reduction of high-flow arteriovenous fistulas in end-stage renal disease: methodological issues’

Reply to ‘Cardiac remodeling after reduction of high-flow arteriovenous fistulas in end-stage renal disease: methodological issues’