Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study.

BACKGROUND: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION: clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org .

From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors.

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-ß1 and other profibrotic markers, as well as CD163, C/EBPß, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-ß1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-ß1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA-CREB axis, inducing the macrophage M2 phenotype, TGF-ß1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

Urinary miR-155-5p and CXCL10 as prognostic and predictive biomarkers of rejection, graft outcome and treatment response in kidney transplantation.

AIMS: MicroRNAs (miRNAs) may be useful biomarkers of rejection and allograft outcome in kidney transplantation. Elevated urinary CXCL10 levels have been associated with acute rejection (AR) and may predict allograft failure. We examined the correlation of miRNA, CXCL10 levels and immunosuppressive drug exposure with AR and graft function in kidney transplant recipients. METHODS: Eighty de novo kidney transplant recipients were recruited from four European centres. All patients received tacrolimus, mycophenolate mofetil, and methylprednisolone. Urinary pellet expression of miR-142-3p, miR-210-3p and miR-155-5p was assessed by quantitative real-time polymerase chain reaction and urinary CXCL10 levels by enzyme-linked immunosorbent assay at the 1st week and the 1st , 2nd , 3rd and 6th months post-transplantation. RESULTS: Eight patients experienced AR. Before and during AR, patients showed a significant increase of urinary miR-142-3p, miR-155-5p and CXCL10 levels and a decrease of miR-210-3p levels. Receiver operating characteristic curve analysis showed that miR-155-5p (area under the curve = 0.875; P = 0.046) and CXCL10 (area under the curve = 0.865; P = 0.029) had excellent capacity to discriminate between rejectors and nonrejectors. The optimal cut-off values for the prognosis of AR were 0.51, with 85% sensitivity and 86% specificity for miR-155-5p and 84.73 pg ml-1 , with 84% sensitivity and 80% specificity for CXCL10. miR-155-5p and CXCL10 levels correlated with glomerular filtration rate. Levels of both biomarkers normalized after recovery of graft function. CONCLUSIONS: The regular early post-transplantation monitoring of urinary miR-155-5p and CXCL10 can help in the prognosis of AR and graft dysfunction. Large prospective randomized multicentre trials are warranted to refine our cut-off values and validate the clinical usefulness of these biomarkers.

Genetic damage in patients moving from hemodialysis to online hemodiafiltration.

End-stage renal failure patients exhibit a high incidence of genetic damage and genomic instability. Part of this genetic damage is assumed to be caused by the hemodialysis (HD) procedure. To reduce these effects, different alternative HD procedures have been proposed, such as the use of high efficiency convective therapies to improve the reactive oxygen species/antioxidant ratio. To determine the efficiency of online hemodiafiltration (HDF) technique on the levels of DNA damage, we have measured the frequency of micronucleus in peripheral blood lymphocytes of 33 individuals moving from low-flux HD to post-dilution online HDF. In addition to basal levels of genetic damage, potential changes in radiosensitivity were measured as indicators of genomic instability. Plasma antioxidant capacity was also determined. Second samples were obtained after 6 months on the HDF protocol. Results indicate that moving to online HDF therapy produce a significant reduction of the basal levels of genetic damage, but does not affect the genomic instability status. In addition, a greater increase in plasma antioxidant capacity was observed. In spite of the lack of correlation between these parameters, our results confirm the usefulness of the online HDF technique as a way to reduce DNA damage in HD patients.

Genomic damage as an independent predictor marker of mortality in hemodialysis patients.

AIM: Hemodialysis (HD) patients present an enhanced mortality. Since oxidative DNA damage can be considered a biomarker of genomic instability our aim was to evaluate the influence of this genetic biomarker in all-cause mortality in a group of HD patients followed for 4 years. MATERIAL AND METHODS: 123 chronic HD patients were included. Overall genomic damage was analyzed using the Comet assay. Oxidative DNA damage was measured using the Comet assay complemented with the use of Endo-III and FPG enzymes. Follow-up was carried out from January 2007 to July 2011. RESULTS: Selected HD patients had a mean age of 62 ± 15 years. During the follow-up 36% of patients died (48% due to cardiovascular disease) and 23% were transplanted. Older patients, with high CRP levels, low levels of cholesterol-HDL and albumin, and higher genetic damage at the beginning of the study showed an increased risk for mortality. Multivariate analysis showed that only genomic damage, age and CRP were independently associated with mortality. CONCLUSIONS: Our study shows for the first time that, in HD patients, the presence of high levels of genomic damage is a strong predictor of all-cause mortality. This association remains significant after adjustment for relevant covariates.

Stilobezzia Kieffer (Diptera: Ceratopogonidae) from the Brazilian Amazon: three new species, redescription of S. (Stilobezzia) maculata Lane and new records.

Three new species of Stilobezzia Kieffer, 1911 are described and illustrated from the Brazilian Amazon, two in the nominotypical subgenus Stilobezzia: S. (Stilobezzia) brasiliensis n. sp. and S. (Stilobezzia) campinaranensis n. sp., and one in the subgenus Acanthohelea: S. (Acanthohelea) medialuna n. sp. We also redescribe and re-illustrate S. (Stilobezzia) maculata Lane based on the examination of type material and additional specimens. In addition, S. (Eukraiohelea) proxima Cazorla & Felippe-Bauer, S. (Eukraiohelea) quasielegantula Cazorla & Felippe-Bauer, S. (Stilobezzia) chaconi Macfie, S. (Stilobezzia) glauca Macfie, and S. (Stilobezzia) maculata are recorded for the first time from the state of Amazonas, northern Brazil. The number of Stilobezzia species in Brazilian Amazon increases from 11 to 19.

Redescription of Stilobezzia (Stilobezzia) albicoxa Lane amp; Forattini, 1956 with new synonymy (Diptera: Ceratopogonidae).

Stilobezzia Kieffer, 1911 is a diverse genus of predaceous Ceratopogonidae (Ceratopogoninae: Ceratopogonini) with 349 species recognized worldwide (Borkent Dominiak 2020). The genus has four subgenera, three occurs in Brazil, where Stilobezzia s. str. is the most speciose, with 23 species registered (Santarém Felippe-Bauer 2019).

Loci associated with genomic damage levels in chronic kidney disease patients and controls.

Chronic kidney disease (CKD) is a multifactorial disorder with an important genetic component, and several studies have demonstrated potential associations with allelic variants. In addition, CKD patients are also characterized by high levels of genomic damage. Nevertheless, no studies have established relationships between DNA damage, or genomic instability present in CKD patients, and gene polymorphisms. To fill in this gap, the potential role of polymorphisms in genes involved in base excision repair (OGG1, rs1052133; MUTYH, rs3219489; XRCC1, rs25487), nucleotide excision repair (ERCC2/XPD, rs1799793, rs171140, rs13181; ERCC4, rs3136166); phase II metabolism (GSTP1, rs749174; GSTO1, rs2164624; GSTO2, rs156697), and antioxidant enzymes (SOD1, rs17880135, rs1041740, rs202446; SOD2, rs4880; CAT, rs1001179; GPX1, rs17080528; GPX3, rs870406: GPX4, rs713041) were inquired. In addition, some genes involved in CKD (AGT, rs5050; GLO1, rs386572987; SHROOM3, rs17319721) were also evaluated. The genomic damage, the genomic instability, and oxidative damage were evaluated by using the micronucleus and the comet assay in 589 donors (415 CKD patients and 174 controls). Our results showed significant associations between genomic damage and genes directly involved in DNA repair pathways (XRCC1, and ERCC2), and with genes encoding for antioxidant enzymes (SOD1 and GPX1). GSTO2, as a gene involved in phase II metabolism, and MUTYH showed also an association with genomic instability. Interestingly, the three genes associated with CKD (AGT, GLO1, and SHROOM3) showed associations with both the high levels of oxidatively damaged DNA and genomic instability. These results support our view that genomic instability can be considered a biomarker of the CKD status.

Genetic Variants Associated with Chronic Kidney Disease in a Spanish Population.

Chronic kidney disease (CKD) patients have many affected physiological pathways. Variations in the genes regulating these pathways might affect the incidence and predisposition to this disease. A total of 722 Spanish adults, including 548 patients and 174 controls, were genotyped to better understand the effects of genetic risk loci on the susceptibility to CKD. We analyzed 38 single nucleotide polymorphisms (SNPs) in candidate genes associated with the inflammatory response (interleukins IL-1A, IL-4, IL-6, IL-10, TNF-α, ICAM-1), fibrogenesis (TGFB1), homocysteine synthesis (MTHFR), DNA repair (OGG1, MUTYH, XRCC1, ERCC2, ERCC4), renin-angiotensin-aldosterone system (CYP11B2, AGT), phase-II metabolism (GSTP1, GSTO1, GSTO2), antioxidant capacity (SOD1, SOD2, CAT, GPX1, GPX3, GPX4), and some other genes previously reported to be associated with CKD (GLO1, SLC7A9, SHROOM3, UMOD, VEGFA, MGP, KL). The results showed associations of GPX1, GSTO1, GSTO2, UMOD, and MGP with CKD. Additionally, associations with CKD related pathologies, such as hypertension (GPX4, CYP11B2, ERCC4), cardiovascular disease, diabetes and cancer predisposition (ERCC2) were also observed. Different genes showed association with biochemical parameters characteristic for CKD, such as creatinine (GPX1, GSTO1, GSTO2, KL, MGP), glomerular filtration rate (GPX1, GSTO1, KL, ICAM-1, MGP), hemoglobin (ERCC2, SHROOM3), resistance index erythropoietin (SOD2, VEGFA, MTHFR, KL), albumin (SOD1, GSTO2, ERCC2, SOD2), phosphorus (IL-4, ERCC4 SOD1, GPX4, GPX1), parathyroid hormone (IL-1A, IL-6, SHROOM3, UMOD, ICAM-1), C-reactive protein (SOD2, TGFB1,GSTP1, XRCC1), and ferritin (SOD2, GSTP1, SLC7A9, GPX4). To our knowledge, this is the second comprehensive study carried out in Spanish patients linking genetic polymorphisms and CKD.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

[Care, self-care and caring for yourself: a paradigmatic understanding thought for nursing care]. / Cuidado, autocuidado e cuidado de si: uma compreensão paradigmática para o cuidado de enfermagem.

This article presents a reflection about care, self-care and caring for oneself and establishes these issues' relations with the paradigms of totality and simultaneity. On the first part of the text, care and its general aspects are contextualized; the second part discusses about care in Martin Heidegger's philosophical perspective; the third part explores self-care on Dorothea Orem's conception; the fourth part considers Michel Foucault's care of oneself. And finally, the fifth part aims to establish the relationship between the concepts of self-care and care of oneself, and the totality and simultaneity paradigms. Self-care and care of oneself are connected to the objectivism of the totality, and to the subjectivism of the simultaneity. These subjects lead nursing to comprehend such paradigmatic inheritance and its implications on the nursing care.

Three cases of monoclonal gammopathy of renal significance after kidney transplantation. De novo C3 glomerulopathy. / Tres casos de gammapatía monoclonal de significado renal postrasplante renal: nefropatía c3 de novo.

Monoclonal gammopathy of renal significance includes all renal disorders caused by a monoclonal immunoglobulin secreted by a non-malignant B-cell clone. Patients with MGRS do not, by definition, meet criteria for multiple myeloma, with haematological disorders generally considered to be monoclonal gammopathy of undetermined significance. Nevertheless, the renal involvement can be serious and require specific treatment. Monoclonal gammopathy of renal significance is associated with a wide spectrum of disorders, including the recently discovered C3 glomerulopathy. Development of C3 glomerulopathy in the context of monoclonal gammopathy of renal significance after kidney transplantation is uncommon and very few cases have been published to date. We report on three cases of C3 glomerulopathy in the context of de novo monoclonal gammopathy after kidney transplantation.

Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study.

BACKGROUND: Tacrolimus-based immunosuppression, the most widely used regimen in kidney transplantation, increases the risk of new onset diabetes after transplantation (NODAT). However, the prevalence, evolution and risk factors of different prediabetic alterations: impaired fasting glucose, impaired glucose tolerance, and provisional diabetes, have not been established. METHODS: In this multicenter and prospective study we evaluated 154 nondiabetic kidney transplant recipients receiving tacrolimus, mycophenolate mofetil and low dose steroids. An oral glucose tolerance test was performed 3 and 12 months after transplantation and prediabetes was defined by American Diabetes Association criteria. RESULTS: Prediabetes was highly prevalent and showed little variation between 3 and 12 months (36% and 33%, respectively). Impaired glucose tolerance was the most frequent abnormality observed (23% and 25%, respectively) observed. In addition, 20% of recipients showed NODAT by 1 year. Multivariate analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.004-1.14), pretransplant body mass index (OR: 1.3, CI: 1.09-1.6) and triglyceride/high density lipoprotein-cholesterol ratio, a marker of insulin resistance, (OR: 1.4, CI: 1.05-1.9) were independent risk factors for prediabetes. CONCLUSION: One in two recipients with tacrolimus-based immunosuppresion showed prediabetes or NODAT by 1 year posttransplantation when properly investigated. Older age and high pretransplant body mass index and triglyceride/high density lipoprotein-cholesterol ratio were risk factors for prediabetes. These findings may help applying early interventions to prevent the disorder.

Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus.

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.

El profesional de enfermería especializado. ¿hace el mejor uso de la tecnología en el cuidado? / Compliance with the recommendations for physical activity set by the WHO by public bicycle users in a Spanish municipality

Introducción: La percepción de la integralidad del cuidado se logra cuando el profesional de enfermería integra con elevado nivel las competencias científicas, sociales, éticas y el uso de herramientas tecnológicas con la finalidad de conservar y recuperar la salud, a la medida de las necesidades y expectativas del ser cuidado. Objetivo: Analizar el desarrollo de evidencias científicas sobre el modo en que el profesional de enfermería especialista hace uso de la tecnología en el proceso de cuidado de la persona. Material y Métodos: Se realizó una búsqueda bibliográfica en las bases de datos Scielo, Lilacs, Medline, Redalyc, Scopus y Google Académico, en español, inglés y portugués. La información se consultó durante el periodo de 2019-2020, se utilizó un total de 25 referencias para su desarrollo. Resultados: El profesional de enfermería especialista utiliza los recursos tecnológicos en el proceso de cuidado y en otros pilares de su ejercicio laboral con ello se logra el cuidado integral al ser humano. Conclusiones: el profesional de enfermería especialista realiza dos grandes usos de los recursos tecnológicos en el proceso de cuidados: durante la asistencia del paciente para restaurar, mantener la salud, conservando la interacción con la familia y en los grandes pilares del ejercicio profesional: la gestión de los procesos de tratamiento y continuidad del cuidado; la docencia que asegura la excelencia de futuros profesionales y la investigación, de esta manera se aproxima a la oferta del cuidado humanizado, que constituye el ideal moral de la profesión(AU)

Introduction: The perception of the integrality of care is achieved when the nursing professional integrates, at a high level, the scientific, social, and ethical competencies and the use of technological tools to preserve and recover health, tailored to the needs and expectations of the being cared for. Objective: To analyze the development of scientific evidence on how the specialized nursing professional makes use of technology in the process of caring for the person. Material and Methods: A bibliographic search was carried out in the Scielo, Lilacs, Medline, Redalyc, Scopus, and Google Scholar databases in Spanish, English, and Portuguese. The information was consulted during the 2019-2020 period; a total of 25 references were used for its development. Results: The specialized nursing professional uses technological resources in the care process and other pillars of the work practice that contribute to providing comprehensive care to human beings. Conclusions: The specialized nursing professional makes two major uses of technological resources in the care process: during patient care itself to restore and maintain health, preserving interaction with the family; and in the great pillars of professional practice: management of treatment processes and continuity of care, teaching that ensures the excellence of future professionals, and research, thus approaching the offer of humanized care which is the moral ideal of the profession(AU)

DNA damage in kidney transplant patients. Role of organ origin.

Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. Environ. Mol. Mutagen. 58:712-718, 2017. © 2017 Wiley Periodicals, Inc.

Vitamin E-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients.

End-stage renal disease patients present oxidative stress status that increases when they are submitted to hemodialysis (HD). This increase in oxidative stress can affect their genetic material, among other targets. The objective of this study was to evaluate the effect of using polysulfone membranes coated with vitamin E, during the HD sessions, on the levels of genetic damage of HD patients. Forty-six patients were followed for 6 months, of whom 29 changed from conventional HD to the use of membranes coated with vitamin E. The level of genetic damage was measured using the micronucleus and the comet assays, both before and after the follow-up period. Serum vitamin E concentration was also checked. The obtained results showed that 24% of our patients presented vitamin E deficiency, and this was normalized in those patients treated with vitamin E-coated membranes. Patients with vitamin E deficiency showed higher levels of oxidative DNA damage. After the use of vitamin E-coated membranes we detected a significant decrease in the levels of oxidative damage. Additionally, hemoglobin values increased significantly with the use of vitamin E-coated membranes. In conclusion, the use of vitamin E-coated membranes supposes a decrease on the levels of oxidative DNA damage, and improves the uremic anemia status. Furthermore, the use of this type of membrane was also effective in correcting vitamin E deficiency.

Levels of DNA damage in peripheral blood lymphocytes of patients undergoing standard hemodialysis vs on-line hemodiafiltration: A comet assay investigation.

Chronic kidney disease (CKD) patients exhibit high levels of genetic damage. Part of this genetic damage is supposed to be caused by the hemodialysis (HD) therapy. Different and more efficient HD procedures could reduce the genetic damage and improve health status of CKD patients. In the present study, we analyzed if changing to online hemodiafiltration (OL-HDF) has a beneficial effect on the levels of genetic damage. The levels of genetic damage (DNA breaks and oxidatively damaged DNA) were analyzed in peripheral blood lymphocytes by using the comet assay. Forty-nine patients submitted to HD, 34 of them changing to OL-HDF and 15 patients continuing in low-flux HD, were included in the study. Plasma antioxidant capacity was also determined. Second sampling period was established after 6 months on the new or traditional HD protocol. A slight decrease in the levels of DNA damage was observed in patients who switched to OL-HDF (P=0.048) in relation to the reference group. This reduction is indicative that OL-HDF shows greater efficiency than low-flux HD in the reduction of basal levels of genetic damage.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Genomic damage as a biomarker of chronic kidney disease status.

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre-dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre-hemodialysis (pre-HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre-HD patients. In addition, a positive relationship was demonstrated between genomic damage and all-cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients.