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Hepatitis C virus (HCV) positive donors are identified in Spain by antibody detection (HCV-Ab) techniques while a HCV nuclear acid-testing (HCV-NAT) is not mandatory. Since it has been shown that HCV-Ab positive HCV-NAT negative donors do not universally transmit the infection, we designed a protocol based on the identification of viremia in HCV-Ab positive donors to start treatment if needed. HCV-Ab-positive donors were identified and we performed HCV-NAT immediately. Donors coinfected with HIV were excluded. Recipients with a low chance to receive a transplant, with no history of liver disease and who were negative for HCV-Ab were selected after informed consent was signed. Kidney recipients from HCV-NAT-positive donors received glecaprevir and pibrentasvir from 6 h before the transplant until 8 weeks after. Recipients from HCV-NAT-negative donors were not treated. Regular monitoring by HCV-NAT was performed to initiate antiviral treatment. We included 11 recipients from six deceased donors Four recipients received grafts from HCV-NAT-positive donors and seven patients received grafts from HCV-NAT-negative donors. None of our recipients exhibited HCV-NAT positivity during the minimum follow-up period of 6 months. Recipients from HCV-NAT-positive donors exhibited sustained virologic response at 12 weeks. One recipient from an HCV-NAT-negative donor lost his graft via a process thought to be unrelated to HCV. The remaining 10 patients had a stable functioning graft at the end of the follow-up period. Our preliminary data suggest that renal transplantation from HCV-Ab- positive donors to HCV-Ab negative recipients is safe when only the recipients of organs from HCV-NAT-positive donors are treated.
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Seleção do Doador/normas , Hepatite C/sangue , Hepatite C/prevenção & controle , Falência Renal Crônica/cirurgia , Transplante de Rim/normas , Doadores Vivos , Adulto , Idoso , Ácidos Aminoisobutíricos , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Ciclopropanos , Feminino , Rejeição de Enxerto , Hepacivirus , Anticorpos Anti-Hepatite C/sangue , Humanos , Falência Renal Crônica/complicações , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Prolina/análogos & derivados , Estudos Prospectivos , Pirrolidinas , Quinoxalinas/administração & dosagem , Espanha/epidemiologia , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
Background: Compared with conventional haemodialysis (HD), online haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins and reduces inflammation, which could favourably affect nutritional status. We evaluate the effect of OL-HDF on body composition and nutritional status in prevalent high-flux HD (HF-HD) patients. Methods: In all, 33 adults with chronic kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post-dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12 months. The primary outcome was the change in lean tissue mass (LTM), intracellular water (ICW) and body cell mass (BCM) assessed by multifrequency bioimpedance spectroscopy (BIS) at baseline and 4, 8 and 12 months. The rate of change in these parameters was estimated with linear mixed-effects models. Results: Compared with OL-HDF, patients assigned to HF-HD experienced a gradual reduction in LTM, ICW and BCM. These differences reached statistical significance at Month 12, with a relative difference of 7.31 kg [95% confidence interval (CI) 2.50-12.11; P = 0.003], 2.32 L (95% CI 0.63-4.01; P = 0.008) and 5.20 kg (95% CI 1.74-8.66; P = 0.004) for LTM, ICW and BCM, respectively. The normalized protein appearance increased in the OL-HDF group compared with the HF-HD group [0.26 g/kg/day (95% CI 0.05-0.47); P = 0.002], with a relative reduction in high-sensitive C-reactive protein [-13.31 mg/dL (95% CI -24.63 to -1.98); P = 0.02] at Month 12. Conclusions: OL-HDF for 1 year compared with HF-HD preserved muscle mass, increased protein intake and reduced the inflammatory state related to uraemia and dialysis, supporting the hypothesis that high convection volume can benefit nutritional status and prevent protein-energy wasting in HD patients.
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Composição Corporal , Hemodiafiltração/métodos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Falência Renal Crônica/terapia , Estado Nutricional , Diálise Renal/métodos , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos ProspectivosRESUMO
BACKGROUND: Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients. METHODS: This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group. RESULTS: Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearson's R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively]. CONCLUSIONS: In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.
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Albuminúria/prevenção & controle , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Insuficiência Renal Crônica/complicações , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/etiologia , Progressão da Doença , Feminino , Humanos , Hiperparatireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Estudos Prospectivos , Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto JovemRESUMO
Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.
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BACKGROUND: The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list have led to an expansion of the acceptance criteria, such as donors after controlled cardiac death (cDCD) and donors after brain death with expanded criteria (DBD-EC). Some concerns and doubts about survival outcomes achieved with these allografts are still present. Our aim was to compare transplant outcomes from cDCD vs DBD-EC. METHODS: A retrospective single-center observational study including all kidney transplant (KT) donors from all cDCD and DBD-EC (>60 years) from January 2015 to January 2022 was performed. We analyzed clinical characteristics, early clinical outcomes, and patient and graft survival rates. RESULTS: 129 cDCD and 166 DBD-EC KT recipients were included. The median follow-up was 30,2 months. DBD-EC were older and had more comorbidities than cDCD. KTs from cDCD and DBD-EC showed similar rates of delayed graft function and primary nonfunction. Patient survival at 1 year was similar (85% DBD-EC vs 90% cDCD, P = .32). Death-censored graft survival at 1 year was similar among young cDCD (18-59 years) and elderly DBD (60-69 years; 97% vs 92.3%, P = .2). Recipient age and expanded criteria in KT from cDCD were related to worse early graft outcomes. The outcomes achieved with KT from cDCD were similar to those observed in older and more comorbid DBD donors. This assumption is worth consideration when choosing the most suitable donor for each recipient.
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Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Idoso , Transplante de Rim/efeitos adversos , Morte Encefálica , Estudos Retrospectivos , Doadores de Tecidos , Sobrevivência de Enxerto , MorteRESUMO
BACKGROUND: Outcomes of kidney transplant (KT) after controlled cardiac death with older donors are under review. We aimed to analyze early and midterm clinical outcomes using older (≥70 years) controlled cardiac death donors (cDCD). METHODS: Retrospective observational single-center study including all KTs from donors ≥70 years from cDCD and donors after brain death (DBD) performed from January 2017 to January 2022. We performed a comparative study between the 2 groups (cDCD and DBD). An analysis of clinical characteristics, early clinical outcomes, and patient and graft survival rates was made. RESULTS: We included 25 cDCD KTs and 63 DBD KTs ≥70 years. The median follow-up was 18.7 months. Recipients from cDCD were more comorbid. Donors from DBD showed higher hypertension and stroke rate. The KTs from older cDCD showed similar delayed graft function rate (cDCD: 34.6% vs DBD extended criteria donor: 35.3%, P = .59) and primary nonfunction (cDCD 16% vs DBD 17.4%, P = .85) compared with older DBD. Medium (3 years) graft death-censored survival was satisfying (cDCD 73% vs DBD 72%) despite a relevant early graft failure rate in both groups (cDCD 16% vs DBD 23%, P = .26). No differences were observed in patient survival at year 1 (cDCD 94% vs DBD 93%, P = .62). CONCLUSIONS: In our series, the outcomes with older cDCD are similar compared with older DBD. Although older donors showed an increase of early graft failure, these kidneys allowed us to maximize the opportunities for candidates that otherwise should remain on dialysis.
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Sobrevivência de Enxerto , Diálise Renal , Humanos , Idoso , Estudos Retrospectivos , Doadores de Tecidos , Morte , Morte EncefálicaRESUMO
Background: The continued emergence of new COVID-19 variants highlights the importance of vaccination in the effort to reduce disease transmission and burden. The objective of this study is to evaluate the processes and outcomes associated with a novel in-home COVID-19 vaccination program aimed at vaccinating high-risk populations in New York, USA. Methods: To evaluate program processes, we described the program itself and reflected on some key lessons learned. To evaluate program outcomes, we analyzed data reported by vaccine recipients. These outcomes included the percentage of vaccine recipients that successfully received the full course of vaccinations, and the demographic and health characteristics of vaccine recipients. We additionally assessed demographic differences in motivations for receiving in-home care, using chi-squared tests to assess statistical significance. Data were collected and reported via dynamic online intake forms. Results: The median age of vaccine recipients was 79 ± SD 9.0 years. The oldest vaccine recipient was 107 years old. Of those with non-missing data, more than half of vaccine recipients were female (63%), identified as part of a racial/ethnic minority (66%), reported an annual income of < $25,000 (58%), and received a high school degree or less (68%). Most vaccine recipients reported having one or more health conditions associated with increased risk of severe COVID-19 disease (72%). Vaccine recipients were most likely to report receiving in-home vaccination because they were home-bound due to disability. Motivations for receiving in-home vaccination differed by demographic subgroup. Conclusion: The population receiving vaccinations from this in-home care delivery program comprised seniors who were mostly female and non-white, indicated socioeconomic vulnerability, and reported one or more COVID-related health conditions; this signified that the program met its goal of vaccinating those most at risk for severe COVID-19 disease.
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COVID-19 , Vacinas , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Etnicidade , Feminino , Humanos , Masculino , Grupos Minoritários , SARS-CoV-2 , Vacinação , Populações VulneráveisRESUMO
Background: In recent years, there has been increasing interest in studying differences in recipient sex in renal disease treatment, access to renal replacement therapy, and subsequent outcomes. Our aim was to find out whether there are differences in outcomes after renal transplantation between female and male kidney transplant recipients in our series, particularly in adults under 60 years of age during long-term follow-up. Methods: This was a retrospective study of our kidney transplant series (n = 1,101) to compare graft survival depending on the sex of the recipient in the entire series and patients < 60 years of age (n = 687) during long-term follow-up. Results: We observed no association between recipient sex and graft survival throughout the series, regardless of recipient sex. However, adult female recipients under 60 years of age had lower graft survival than male recipients (p = 0.040). Pre-transplant sensitization (HR 2.438, p = 0.002) and donor age (HR: 1.021, p = 0.017) were the independent variables associated with graft failure. Conclusion: Female recipients younger than 60 years of age had lower graft survival than male recipients, although there were no gender differences in graft or patient survival in the overall study population. Recipient sex per se was not related to graft failure, but the greater immunological risk in women and more frequent use of expanded criteria donors in female recipients under 60 years of age were the main factors related to their poorer graft survival. Further studies and new strategies are needed to identify these differences and develop the best approach to address them.
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Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spainhave adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.
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Falência Renal Crônica , Transplante de Rim , Sobrevivência de Enxerto , Humanos , Rim , Falência Renal Crônica/cirurgia , Doadores VivosRESUMO
BACKGROUND: The recent introduction of new antidiabetic drugs, analogs of glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 inhibitors, has shown excellent results in the management of patients with diabetes with chronic kidney disease. However, documented results of these medications in the population that has undergone kidney transplant are sparse. We report our institutional experience with them, including occurrence of side effects and possible interactions with immunosuppressive medications. METHODS: A retrospective analysis of 15 patients (10 with diabetes and 5 without diabetes but with obesity) managed with these medications was carried out in the kidney transplant unit of Hospital Doctor Peset during the year 2019. Data acquired at baseline and 3, 6, and 12 months were analyzed. RESULTS: The median hemoglobin A1c at baseline was 6.7 (interquartile range [IQR] = 5.8-8.2) and at 12 months it was 6 (IQR = 5.3-8.1, P = .96). The mean weight difference at 12 months was a loss of 7.2 ± 6 kg; median body mass index at baseline was 31.2 kg/m2 (IQR = 29.7-35.5) and 29.5 kg/m2 (IQR = 27.6-31.6, P = .01) at 12 months. In addition to weight loss, a reduction in insulin and oral antidiabetic drug requirements was observed. No significant changes were detected in serum creatinine or proteinuria values and the immunosuppressant levels remained stable. No acute rejection episodes were observed. CONCLUSION: Based on our experience, the new antidiabetic drugs are safe, with no significant changes in renal function or immunosuppressant levels or clinically important adverse effects.
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Diabetes Mellitus Tipo 2 , Transplante de Rim , Glicemia , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Estudos RetrospectivosRESUMO
The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.
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The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.
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Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.
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INTRODUCTION: Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. METHODS: We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein-cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. RESULTS: The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2-12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8-8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. CONCLUSION: In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.
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AIM: To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population. METHODS: Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed. RESULTS: Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively. CONCLUSION: 25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines.
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Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.