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Importance: During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements., Objective: To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population., Design, Setting, and Participants: In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022., Exposures: Start of dialysis., Main Outcomes and Measures: The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015)., Results: In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6)., Conclusions and Relevance: In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population.

BACKGROUND Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-g-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. MATERIAL AND METHODS A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. RESULTS Banff scores 't', 'i', 'g', and 'ptc' were significantly related to urinary CXCL10 levels. Multivariate analysis showed that 't' (ß=0.107, P=0.001) and 'ptc' (ß=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799-11.646, P=0.001) after multivariate regression analysis. CONCLUSIONS DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS)., Methods: Cross-sectional study, nested in a prospective population-based cohort. All men (968) aged≥50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed., Results: Mean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303-1.331] for DISH and 1.334 [1.327-1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI., Conclusions: TBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructure., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a large cohort of KT recipients with COVID-19., Methods: Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery., Results: The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery., Conclusions: COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality.

Objective: Hypertension is a major public health problem due to its high prevalence and morbi-mortality. It is associated with a worse health-related quality of life (HRQOL). The aim has been to know the HRQOL of the hypertensive population in a gender-differentiated analysis., Methods: Cross-sectional study. Hypertensive patients attended in Primary Care were enrolled in the study. We evaluated HRQOL (using the EuroQol-5D questionnaire), four covariates related to hypertension (degree of control, duration of disease, use of antihypertensive drugs and target organ damage -TOD-), and sociodemographic, lifestyle and clinical variables. Bivariate analysis was performed and two multivariate models were developed, with the EuroQol-5D index (iEQ) as the dependent variable., Results: We analyzed 198 women (55.7%) and 157 men. Significantly, females had a lower educational level, spent more time alone, consumed more psychotropic medication, their iEQ was lower [0.887 (0.2) vs. 0.914 (0.1); p=0.0001] and scored worse in self-care, usual activities, pain / discomfort and anxiety / depression. In women, no variable related to hypertension presented a significant association with the iEQ after adjusting for confounders, and functional capacity was the most important covariate (β=0.35; p=0.0001). In males, TOD (β=0.18) and duration of the disease (β=0.16) were significantly associated with the iEQ, with the consumption of psychotropic medication being the most relevant covariate in the regression model (β=0.42; p=0.005)., Conclusions: Notable differences in HRQOL of women and men with hypertension have been noted. Detecting these differences allows us to know the frailest states of our patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: We aimed to report our experience in uncontrolled donation after circulatory death (uDCD) kidney transplantation applying a strict donor selection and preservation criteria., Methods: All kidney recipients received a graft from a local uDCD. As controls, we included all renal transplants from local standard criteria donation after brain death (SDBD) donors. Normothermic regional perfusion was the preservation method in all cases., Results: A total of 19 kidneys from uDCD donors were included and 67 controls. Delayed graft function (DGF) was higher in the uDCD group (42.1% vs 17.9%; P = .033), whereas no differences were observed in primary nonfunction (0% cases vs 3% controls; P = .605). The estimated glomerular filtration rate was identical in both groups. No differences were observed in graft survival censored for death between the uDCD and the SDBD groups at 1-year (100% vs 95%) or 5-year follow-up (92% vs 91%). uDCD kidney recipients did not have higher risk of graft loss in the multivariate analysis adjusted by recipient age, cold ischemic time, presence of DGF, and second kidney transplant (HR: 0.4; 95% CI 0.02-6; P = .509)., Conclusions: Obtaining renal grafts from uDCD is feasible in a small city and provides similar outcomes compared to standard DBD donors., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce. We evaluated the phenotype and function of different MDSCs subsets in 38 kidney transplant recipients (KTRs) at different time points. Our data indicate that monocytic MDSCs (Mo-MDSC) increase in KTR at 6 and 12 months posttransplantation. On the contrary, the percentages of polymorphonuclear MDSC (PMN-MDSC) and early-stage MDSC (e-MDSC) are not significantly increased. We evaluated the immunosuppressive activity of Mo-MDSC in KTR and confirmed their ability to increase regulatory T cells (Treg) in vitro . Interestingly, when we compared the ability of Mo-MDSC to suppress T cell proliferation, we observed that tacrolimus, but not rapamycin-treated KTR, was able to inhibit CD4 + T cell proliferation in vitro . This indicates that, although mTOR inhibitors are widely regarded as supportive of regulatory responses, rapamycin may impair Mo-MDSC function, and suggests that the choice of immunosuppressive therapy may determine the tolerogenic pathway and participating immune cells that promote organ transplant acceptance in KTR., (Copyright © 2020 Iglesias-Escudero, Sansegundo-Arribas, Riquelme, Merino-Fernández, Guiral-Foz, Pérez, Valero, Ruiz, Rodrigo, Lamadrid-Perojo, Hutchinson, Ochando and López-Hoyos.)

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum β-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Induction therapy with rabbit antithymocyte globulin is frequently used in kidney transplant recipients and contributes to regulating the humoral alloantibody response. However, the effect of rabbit antithymocyte globulin on B-cell subpopulations, including plasma cells, has not been previously studied in humans in vivo., Materials and Methods: We prospectively studied a cohort of 39 adult kidney transplant recipients. Twenty patients received rabbit antithymocyte globulin as induction therapy. Peripheral blood samples were obtained pretransplant and at 6 and 12 months posttransplant. T and B cells were acquired by flow cytometry., Results: Total lymphocytes and CD3 and CD4 cells significantly decreased at 6 and 12 months only in patients who received rabbit antithymocyte globulin. In contrast, the CD19 population did not change after rabbit antithymocyte globulin induction. One-year circulating plasma cells remained significantly lower than pretransplant levels in patients who received rabbit antithymocyte globulin. We observed sig-nificant differences in plasma cell numbers at 12 months after transplant between patients who received rabbit antithymocyte globulin and those patients who did not receive it (median of 5 and interquartile range of 3-17 vs median of 25 and interquartile range of 12-35; P = .001)., Conclusions: Rabbit antithymocyte globulin induction leads to a late reduction in the number of circulating plasma cells at 1 year after kidney transplant. This effect can contribute to down-regulation of the humoral alloantibody response.

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m 2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m 2 ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012-2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2 ± 14.4 vs. -6.6 ± 12.0 mL/min per 1.73 m 2 , P-value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P-value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To analyze the impact of a specific thoracic donor-treatment protocol (including restrictive fluid balance) on kidney donation and on kidney graft survival., Methods: A cohort study. Lung Donors and kidney recipients from 2003 to 2008 were the pre-protocol cohort, and those from 2009 to 2013 were the protocol cohort. The main outcome variables were graft survival and rate of kidney donation., Results: Kidney donation rates were similar in both periods (86.2 vs. 86.2 %; p > 0.05). Both donors and kidney recipients were older and with more comorbidities in the protocol group and this is the reason there were more cases of delayed graft function (differences not statistically significant) and with higher sequential creatinine levels of kidney recipients during the protocol period. However, graft survival was similar in both groups. The probability of graft survival 5 years after transplantation was 0.75 (95 % confidence interval 0.65-0.85) in the pre-protocol cohort and 0.81 (0.70-0.92) in the protocol cohort., Conclusions: Specific treatment for multi-organ donors including restrictive fluid balance does not affect kidney donation or kidney graft loss, and has no impact on long-term viability. Hemodynamics must be closely monitored by medical personnel with specific training.

Introduction: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs., Objective: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation., Methods: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52)., Results: 22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS)., Conclusions: Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients., Objective: To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients., Methods: We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr)., Results: Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade., Conclusions: A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Since 2004, various criteria have been proposed to define and stage acute kidney injury (AKI). Nevertheless, fixed criteria for assessing severe sepsis-related AKI have not yet been established., Objectives: To assess the ability of the different AKI classification methods to predict mortality in a cohort of patients with sepsis., Methods: A prospective study of patients>18 years with septic shock admitted to the intensive care unit (ICU) of our hospital from April 2008 to September 2010 was conducted. Plasma creatinine levels were measured daily in the ICU. Patients were classified retrospectively according to RIFLE, AKIN, KDIGO and creatinine kinetics (CK) criteria., Results: The AKI rate according to the different criteria was 74.3% for RIFLE, 81.7% for AKIN, 81.7% for KDIGO and 77.5% for CK. AKI staging by RIFLE (OR 1.452, P=.003), AKIN (OR 1.349, P=.028) and KDIGO criteria (OR 1.452, P=.006), but not CK criteria (OR 1.188, P=.148) were independently related to in-hospital mortality., Conclusions: A high rate of patients with severe sepsis developed AKI, which can be classified according to different criteria. Each stage defined by RIFLE, AKIN and KDIGO related to a higher risk of in-hospital mortality. In contrast, the new CK criteria did not relate to higher mortality in patients with severe sepsis and this classification should not be used in these patients without further studies assessing its suitability., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: A low Norton Scale (NS) score predicts pressure ulcer risk and several adverse outcomes in the elderly. On the other hand, health-related quality of life (HRQOL) is an indicator with clinical and predictive utilities. The aim was to assess the relationship between NS and HRQOL, in a gender analysis., Method: Fifty-one women and 39 men, institutionalized and aged≥65 years, were evaluated through personal interview and medical records. The NS, HRQOL -with EuroQol-5D-, age, body mass index, falls, use of psychoactive drugs, cognitive function and Charlson, Barthel and Tinetti indexes, were assessed. Two regression models were developed, with EuroQol-5D as dependent variable., Results: The NS showed the same score in both sexes, with a median (interquartile range) value of 19 (2). Women presented a worse HRQOL, with an EuroQol-5D=0.78, whereas it was 0.87 in men (P=.02). The NS score was correlated with HRQOL in women (r=0.57; P<.001) but not in men (r=0.15; P=.36). After adjusting for confounders, the NS showed a β value of 0.54 (P=.02) in women and β=0.35 (P=.14) in men., Conclusions: The NS has shown to be the strongest factor on HRQOL in women, regardless of age, comorbidity and the rest of covariates. Conversely, the relationship was weaker and non-significant in men., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Background: It is well known the inverse relationship between health-related quality of life (HRQoL) and the use of consultations. However, most studies deal sex as a confounding variable rather than to explicitly investigate sex differences. The study aims to know the influence of HRQoL of the elderly on the use of Primary Care consultations in a sex analysis., Methods: Throughout 2013, 191 women and 155 men aged 65 years or older were enrolled in the study and assessed with interviews and analysis of medical records. We used the EuroQol-5D to assess the HRQoL and several demographic, clinical and social support variables were also analyzed. Two multiple linear regression models were developed., Results: HRQoL showed a negative correlation with the use of consultations (Spearman's rho=-0,22; p=0,0001) and a crude OR value of 1,85 (95% CI:1,2-2,9). The association remained significant after adjusting for demographic [OR=1,99 (95% CI: 1,2-3,2)], clinical [OR=1,79 (95% CI: 1,1-2,9)] or social support covariates [OR=1,83 (95% CI: 1,1-2,9)]. In regression analysis, the values of standardized coefficient (β) related to HRQoL were 0,22 (95% CI:-36,7- -6,9) in females and 0,03 (95% CI:-15,6-23,1) in males., Conclusions: In women ≥ 65 years, HRQoL shows the greatest explanatory power of use of consultations, after adjusting for demographic, clinical and social support covariates. By contrast, its influence on men is negligible.

Background and Objective: Age seems to modify the relationship between hypothyroidism and cardiovascular disease (CVD). Although hypothyroidism in very elderly subjects has been associated with longevity, subclinical hypothyroidism in people ≤ 65 years seems to be related with an increased cardiovascular risk (CVR). The aim of this study was to determine the explanatory power of plasmatic TSH (pTSH) for the CVD, in different strata determined by age (≤ 55, 56-74, ≥ 75 years), sex and CVR factors., Patients and Methods: Six hundred and sixty-four men and women were differentiated into 18 strata and their explanatory models were developed using the multiple linear regression analysis. The dependent variable is the abdominal aortic calcification (AAC) according to the AAC-24 scale. The independent variables are: pTSH, age, smoking, BMI, SBP, DBP, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol and C-reactive protein., Results: Age is the main explanatory factor of AAC. The highest explanatory value of the β-standardized coefficient of the pTSH is observed in males ≤ 55 years (β=0.235, P=.043) and in females ≥ 75 years (β=0.405, P=.042). With increasing age, the prediction power improves in women and decreases in men. In men ≥ 75 years there is a negative correlation between pTSH and AAC (rho-Spearman=-0.213, P=.049)., Conclusions: A positive association is observed between pTSH and CVD in males ≤ 55 years and in women ≥ 75 years. The combination of multiple regression and the stratified analysis shows the complex influence of age in the relation between both variables., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Although cystatin C (Cys) and albuminuria (Alb) are predictors of end-stage renal disease in the general population, there are limited data about the performance of these markers alone or combined with respect to the prediction of the kidney transplant outcome. We assessed the ability of one-yr creatinine (Cr), MDRD equation, Cys, Hoek equation, Alb, the logarithm of albuminuria (LogAlb), and two products of these variables for predicting death-censored graft loss (DCGL) in 127 kidney transplant recipients. Mean follow-up time was 5.6 ± 1.7 yr. During this time, 18 patients developed DCGL. The area under the receiver operating characteristic curve for DCGL ranged from 71.1% to 85.4%, with Cys*LogAlb being the best predictor. Cys-based variables and variables combining LogAlb and renal function estimates have better discrimination ability than Cr-based variables alone. After multivariate analysis, quartiles of all one-yr variables (except of Cr and MDRD) were independent predictors for DCGL. Predictors combining Alb and a Cr- or Cys-based estimate of renal function performed better than those markers alone to predict DCGL. Cys-based predictors performed better than Cr-based predictors. Using a double-marker in kidney transplantation, it is possible to identify the highest risk group in which to prioritize specialty care., (© 2013 John Wiley & Sons A/S.)

ImmuKnow is an in vitro diagnosis method that uses patient samples of whole blood polyclonally stimulated with phytohaemagglutinin. It also measures adenosine triphosphate (ATP) production by CD4+ T cells. The test aims to offer an objective and overall measurement of each individual's cellular immune response. The assay was designed with the idea of individually monitoring the immunosuppression administered to transplant patients. At the same time, it aims to help achieve a balance as a way of avoiding immunosuppression excess and the associated adverse effects (infections, cancer, etc.) or an immunosuppression defect and the subsequent risk of allograft rejection. The majority of studies that have evaluated its clinical usefulness display great diversity in terms of patient recruitment, the immunosuppressant treatment received, the clinical variables analysed and, above all, the time between performing ImmuKnow and the evaluated clinical event. The most consistent data show that this assay on CD4+ T cell functioning is useful for predicting the risk of infection in renal transplant patients. However, its use as a rejection risk indicator is unclear. Lastly, given the great variability of immune response amongst individuals and that of existing publications, it can be deduced that the isolated ImmuKnow value does not have diagnostic capacity and only individual serial monitoring could provide definitive assistance in clinical decision making and immunosuppressant treatment changes. Other aspects of ImmuKnow application in the clinical routine, such as assay cycles, require randomised prospective studies for more comprehensive information.

Immune status monitoring of transplant recipients could identify patients at risk of acute rejection, infection, and cancer, which are important sources of morbidity and mortality in these patients. The ImmuKnow assay provides an objective assessment of the cellular immune function of immunosuppressed patients. Inconclusive results concerning the ability of the ImmuKnow test to predict acute rejection and infection have raised concerns about the predictive value of ImmuKnow in liver transplant recipients. We conducted a systematic literature review to identify studies published up to March 2012 that documented the use of ImmuKnow for monitoring immune function in liver transplant recipients. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 score. We identified 5 studies analyzing ImmuKnow performance for infection and 5 studies analyzing ImmuKnow performance for acute rejection. The pooled sensitivity, specificity, positive likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 83.8% [95% confidence interval (CI) = 78.5%-88.3%], 75.3% (95% CI = 70.9%-79.4%), 3.3 (95% CI = 2.8-4.0), 14.6 (95% CI = 9.6-22.3), and 0.824 ± 0.034, respectively, for infection and 65.6% (95% CI = 55.0%-75.1%), 80.4% (95% CI = 76.4%-83.9%), 3.4 (95% CI = 2.4-4.7), 8.8 (95% CI = 3.1-24.8), and 0.835 ± 0.060, respectively, for acute rejection. Heterogeneity was low for infection studies and high for acute rejection studies. In conclusion, the ImmuKnow test is a valid tool for determining the risk of further infection in adult liver transplant recipients. Significant heterogeneity across studies precludes the conclusion that ImmuKnow identifies liver transplant patients at risk for rejection., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Oncocytosis (oncocytomatosis) is a rare condition characterized by the presence of innumerable oncocytic nodules in one or both kidneys, usually associated with the presence of a dominant nodule. An incidental detection of a renal tumor in a renal biopsy performed for the diagnosis of a medical disease of the kidney is exceptional. We report herein a case of a 58-year-old woman presenting with idiopathic nephrotic syndrome. Histological examination of the percutaneous renal core biopsy revealed a minimal-change glomerular lesion and oncocytosis. A contrast-enhanced abdominal CT scan showed two solid round masses, one in each kidney, measuring 1.5 and 2 cm. The nephrotic syndrome was responsive first to prednisone and finally to cyclosporine. Pathological study of both renal dominant masses confirmed that they were oncocytomas. As far as we are aware, renal oncocytosis incidentally discovered in a biopsy performed for the diagnosis of a medical disease of the kidney has not been reported., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Background: Restrictive management of fluid status has been proposed to increase the rates of lung grafts available for transplant. However, no studies have supported the effect of this negative fluid balance in the kidney graft recipients., Methods: We evaluated the effect of restrictive fluid balance in brain-dead donors and their impact in 404 kidney recipients using Kaplan-Meier curves and Cox regression for long-term effects, and logistic regression for short-term effects. Our primary interest was graft survival and the second was occurrence of delayed graft function (DGF)., Results: A negative or equalized fluid balance with a central venous pressure (CVP) <6 mm Hg affects neither graft survival in kidney recipients (P = 0.983) nor the development of DGF (P = 0.573). A positive fluid balance between brain death and organ retrieval does not reduce either the risk of graft survival or the risk of DGF., Conclusion: We concluded that restrictive management of fluid balance in a multiorgan donor supports adequate perfusion to vital organ systems even with a CVP <6 mm Hg. A strict fluid balance could avoid volume overload and lung neurogenic oedema, increasing the rate of lung grafts available for transplant without impacting either kidney graft survival or DGF development.

Background: The limited supply of deceased donors for renal transplantation led to considering alternative strategies for making more organs available. One of these strategies is the use of donors with renal dysfunction, as this is usually a reversible condition. RIFLE (risk, injury, failure, loss and end-stage renal failure) criteria were developed to standardize the definition and severity of acute kidney injury (AKI) but have not been previously used in brain-deceased donors. We applied the RIFLE classification to evaluate renal function changes in our donor pool, in an attempt to know its influence in transplant outcome., Methods: Data were collected from the renal transplant patient and the intensive care unit brain-dead donors prospectively maintained databases of our hospital. Risk was defined when creatinine increased x1.5, injury when it increased x2 and failure when last creatinine increased x3 with respect to admission-day creatinine., Results: From 176 donors, 10.8% suffered AKI and 7.9% were included in 'risk', 2.3% in 'injury' and 0.6% in 'failure' categories. There were no significant differences between AKI and non-AKI groups in donor and intensive care management variables, except in last-day creatinine. First-day urine volumes were lower (P = 0.043) and delayed graft function rates were higher (P = 0.013) in the AKI group than in the non-AKI group recipients. Graft survival and other outcome variables were not different between AKI and non-AKI recipients., Conclusions: The RIFLE classification system offers us an opportunity to standardize and quantify renal injury in donors. Although >10% of brain-deceased donors can suffer AKI, these grafts can perform adequately. Hence, the development of AKI in donors cannot be an isolated criterion to discard kidney donation.

In the field of organ transplantation, overimmunosuppression is associated with severe side effects, such as infection, drug toxicity, and cancer, whereas underimmunosuppression is associated with acute rejection. Intracellular adenosine triphosphate (iATP) concentration following CD4 cell activation provides an assessment of cellular immune function to help monitor the immune status of immunosuppressed patients. This assay has shown to be the first post-transplant test related not only to the risk of acute rejection but also with the appearance of infection. The aim of our study was to compare the iATP concentrations of CD4 cells between healthy adults and kidney transplant recipients from a European population, analyzing the differences according to transplant clinical status. Samples from 81 kidney transplant patients who were admitted to our hospital over a nine-month period were drawn. T-cell activation was measured by determining the increase of iATP from CD4 cells. Results were compared with patient clinical status (rejection, infection, and stability). Three patients suffered an acute rejection episode and they were not included in the analysis (mean iATP concentration 247 +/- 87 ng/mL). iATP concentrations differed significantly between stable and infected patients (313 +/- 193 vs. 197 +/- 114 ng/mL; p = 0.008). iATP concentration values were not related to the length of admission, age, peak and current panel reactive antibodies, mismatches, leukocytes, weight, creatinine, days after transplantation and blood levels of cyclosporin, tacrolimus, and sirolimus. This assay measures global immune responses of CD4 T cells from a whole-blood sample, allowing for the assessment of the impact of immuno- suppressive drugs and of the patient's underlying clinical conditions. This assay identifies transplant patients at risk for infection or rejection, providing information which can guide immunosuppressive therapy.

Since the immune response in older recipients is weaker they should be less likely to reject a transplanted organ and should need less aggressive immunosuppressive treatment. Our aim was to record the incidence and severity of episodes of acute rejection (AR), estimate the influence of these events on graft survival of elderly recipients (> or = 60) and to compare these with that in younger ones. We performed 363 kidney transplants between 1/94 and 12/98, and recorded clinical and immunological data, incidence-severity of AR and cause of graft loss. Patients were divided into two groups, according to the age at transplantation: A (<60, n = 281/77.4%) and B (> 60, n = 82/22.6%). The percentage of aging recipients and mean age of donors and recipients increased throughout the period. Although the incidence of ATN was higher in the older group (29% vs.19%, p < 0.0001) the number of graft biopsies was equal in both groups. The incidence of AR was similar, 33.4% vs. 26.8%, pNS. The number of AR episodes per patient was 0.44 and 0.41 respectively. The severity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B (48.57) pNS; grade III: A (15.5%)/B (5.7%) pNS. Younger recipients presented a higher level of panel-reactive antibodies (PRA) (4.3% vs. 2.07%, p = 0.01). One-yearpatient survival was 96%/91% (p < 0.05) and graft survival was 81%/78% (pNS) respectively. The age of recipient does not seem to have influenced the incidence-severity of AR or the graft survival. Thus immunosuppression should be individualized for each patient and should not depend on the age at transplantation.

Background: In recent years acceptance of diabetic patients for renal replacement therapy has increased. Renal transplantation for Type I diabetic patients is widely accepted but the appropriate treatment for Type II diabetic patients is still a matter of dispute. Our study was done to determine whether the age of Type II diabetic patients constituted an additional risk factor., Methods: We analyzed the outcome of renal transplantation in 56 diabetic patients, 31 Type I and 25 Type II diabetics (we excluded any who had combined kidney-pancreas transplants). We compared them with 51 non-diabetic patients who were transplanted because of end-stage renal failure due to nephrosclerosis and age-matched to type II diabetic patients. We assessed the one- and three-year patient and graft survival, the quality of renal function, the main complications and causes of mortality., Results: The overall one- and three-year patient survival was 69% and 60% in Type II patients; 73% and 69% in Type I diabetes patients and 88% and 80% in patients with nephrosclerosis. The overall one- and three-year actuarial graft survival was 50% and 38% in patients with Type II disease and 58% and 50% in Type I diabetes, and 76% and 64% in nephrosclerosis. The main cause of graft loss in all groups was death (with functioning kidney) due to infections and cardiovascular complications., Conclusions: Diabetes itself is the most important variable in patients who have poor results after kidney transplantation. Increasing age increases slightly the risk for poor graft and patient survival. Both groups of diabetic patients have poorer results than controls but in this comparison age was an independent factor.