Lluís Guirado

Successful liver and kidney transplantation from cadaveric donors with left-sided bacterial endocarditis.

Bacterial infections are frequent in cadaveric organ donors and can be transmitted to the transplantation recipient, which could have devastating consequences for the recipients if adequate preventive measures are not adopted.

Monocyte implication in renal allograft dysfunction

Macrophages are involved in the development and progression of kidney fibrosis. The aim of this study was to analyse the phenotype of circulating monocytes and their ability to predict kidney allograft dysfunction in living kidney transplant recipients. Whole blood samples from 25 kidney recipients and 17 donors were collected at five time‐points. Monocyte phenotype was analysed by flow cytometry, and interleukin (IL)‐10 and soluble CD163 by enzyme‐linked immunosorbent assay. One week after transplantation, surface CD163 and IL‐10 levels increased significantly from baseline [2·99 ± 1·38 mean fluorescence intensity (MFI) to 5·18 ± 2·42 MFI for CD163; 4·5 ± 1·46 pg/ml to 6·7 ± 2·5 pg/ml for IL‐10]. This CD163 increase correlated with 4‐month creatinine levels (r = 0·4394, P = 0·04). However, soluble CD163 decreased significantly from baseline at 1 week (797·11 ± 340·45 ng/ml to 576·50 ± 293·60 ng/ml). CD14+CD16– monocytes increased at 4 months and correlated positively with creatinine levels at 12 and 24 months (r = 0·6348, P = 0·002 and r = 0·467, P = 0·028, respectively) and negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r = 0·6056, P = 0·003). At 4 months, IL‐10 decreased significantly (P = 0·008) and correlated positively with creatinine at 2 years (r = 0·68, P = 0·010) and with CD14+CD16– monocytes at 4 months (r = 0·732, P = 0·004). At 24 h, levels of human leucocyte antigen D‐related declined from 12·12 ± 5·99 to 5·21 ± 3·84 and CD86 expression decreased from 2·76 ± 1·08 to 1·87 ± 0·95. Both markers recovered progressively until 12 months, when they decreased again. These results indicate that monitoring monocytes could be a promising new prognostic tool of graft dysfunction in renal transplant patients.

Is it appropriate to implant kidneys from elderly donors in young recipients

Background. Kidneys from elderly donors tend to be implanted in recipients who are also elderly. We present the results obtained after 10 years of evolution on transplanting elderly kidneys into young recipients. Methods. Ninety-one consecutive transplants are studied, carried out in our center with kidneys from cadaver donors older than 60 years implanted in recipients younger than 60 years. The control group is made up of 91 transplants, matched with those from the study group, whose donor and recipient were younger than 60 years. Results. There were no differences between groups with regard to recipient age, sex, cause of death and renal function of the donor, hepatitis C and cytomegalovirus serologies, cold ischemia time, tubular necrosis, immediate diuresis, need for dialysis, human leukocyte antigen incompatibilities, hypersensitized patients, acute rejection, waiting time on dialysis, and days of admission. Survival in both groups at 1, 5, and 10 years was 97.6%, 87.2%, and 76.6% vs. 98.8%, 87.5%, and 69.5% for the patient (P=0.642), 92.9%, 81.3%, and 64.2% vs. 93.9%, 76.4%, and 69.5% for the graft (P=0.980), and 94.4%, 92.6%, and 77.4% vs. 94.3%, 86.7%, and 84.4% for the graft with death censured (P=0.747), respectively. Creatininaemias at 1, 5, and 10 years were 172, 175, and 210 vs. 139, 134, and 155 (P<0.05). Conclusions. We conclude that patient and graft survival on transplanting kidneys from elderly donors to young recipients is superimposable on that obtained with young donors. However, renal function is better in the group of young donors.

Tratamiento con angioplastia y stent de la estenosis arterial del injerto renal

Transplant renal artery stenosis is a major complication that requires a therapeutic approach involving surgery or angioplasty. The aim of this study was to analyse the evolution of renal transplant patients with renal allograft artery stenosis treated by angioplasty and stent placement. Thirteen patients were diagnosed with transplant renal artery stenosis. Clinical suspicion was based on deterioration of renal function and/or poorly controlled hypertension with compatible Doppler ultrasound findings. The diagnosis was confirmed by arteriography, performing an angioplasty with stent placement during the same operation. A progressive improvement in renal function was observed during the first 3 months after the angioplasty, and renal function then remained stable over 2 years. In addition, blood pressure improved during the first 2 years, and as a consequence there was no need to increase the average number of anti-hypertensive drugs administered (2.5 drugs per patient). In conclusion, angioplasty with stent placement is a safe and effective procedure for the treatment of transplant renal artery stenosis.

C.E.R.A. administered once monthly corrects and maintains stable hemoglobin levels in chronic kidney disease patients not on dialysis: the observational study MICENAS II

BACKGROUND AND OBJECTIVE C.E.R.A. (continuous erythropoietin receptor activator, pegilated-rHuEPO ß) corrects and maintains stable hemoglobin levels in once-monthly administration in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the management of anemia with C.E.R.A. in CKD patients not on dialysis in the clinical setting. METHODS Two hundred seventy two anemic CKD patients not on dialysis treated with C.E.R.A. were included in this retrospective, observational, multicentric study during 2010. Demographical characteristics, analytical parameters concerning anemia, treatment data and iron status were recorded. RESULTS C.E.R.A. achieved a good control of anemia in both naïve patients (mean Hemoglobin 11.6g/dL) and patients converted from a previous ESA (mean Hemoglobin 11.7g/dL). Most naïve patients received C.E.R.A. once monthly during the correction phase and required a low monthly dose (median dose 75 µg/month). The same median dose was required in patients converted from a previous ESA, and it was lower than recommended in the Summary of Product Characteristics (SPC). Iron status was adequate in 75% of anemic CKD patients, but only 50% of anemic patients with iron deficiency received iron supplementation. CONCLUSIONS C.E.R.A. corrects and maintains stable hemoglobin levels in anemic CKD patients not on dialysis, requiring conversion doses lower than those recommended by the SPC, and achieving target hemoglobin levels with once-monthly dosing frequency both in naïve and converted patients.

Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function.

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium‐ and long‐term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68‐positive cells in DD kidneys, which correlated negatively with long‐term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α–smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium‐ and long‐term renal function in DDs. Multivariate analysis point to transforming growth factor‐β1 as the best predictor of long‐term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor‐β1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.

Biomarkers: New Tool to Detect Subclinical Inflammation?

Introduction Nowadays the gold standard test to detect kidney allograft inflammation is kidney biopsy. Because of subclinical inflammation has a very important roll on long term allograft survival some groups are performing follow-up biopsies to detect this inflammation early and to individualize the immunosuppressive treatment. Inflammation urinary biomarkers can become a new non invasive tool to detect this subclinical inflammation early. The aim of our work is to study the correlation between different subclinical lesions in follow-up biopsies and urinary biomarkers (miRNA-155, miRNA-210 and miRNA-142) Materials and Methods Prospective study where we have included kidney transplant (KT) patients from April 2014 until May 2015. We have determined in urine these biomarkers: miRNA-155, miRNA-210 and miRNA-142 one week after KT and one, two, three and six months after KT. We have performed follow-up biopsies at 4th month after KT and we have analysed the presence of tubulitis, interstitial infiltrate, arteritis and IFTA. Lastly we have correlationed these findings with urinary biomarkers levels. Results We have included 25 recipients from a first KT, all of them with low immunological risk. 60% man. Average age 45 years. 76% recipients from living donor. Average time on dyalisis: 10 months (50% preemptive kT). Induction immunosuppressive treatment: Basiliximab (two doses), tacrolimus, sodic micophenolate and prednisone. Average seric creatinine at 4 month after KT: 100umol/L. Anatomo-pathologic findings: 4% of biopsies with some degree of tubulitis, 63% with some degree of interstitial infiltrate, 9% with some degree of arteritis and 18% with some degree of IFTA. Correlation analysis: miRNA-155 levels are significantly higher in the patients with tubulitis. miRNA-142 levels are significantly higher in the patients with tubulitis, in the patients with arteritis and in the patients with interstitial infiltrate. miRNA-210 levels are significantly lower in the patients with tubulitis and in the patients with arteritis. There isn’t correlation between some biomarker and the presence of IFTA. Conclusion Urinary biomarkers can become in a future a new tool to detect subclinical inflammation early and could replace follow-up kidney biopsies. In this study, mi-RNA 142 would be the most associated with the presence of subclinical inflammation. On the other hand, tubulitis would be the lesion most detected for biomarkers. Are necessary more studies to confirm these results.

Apolipoprotein A-Ib as Biomarker of FSGS Recurrence After Kidney Transplantation: Diagnostic Performance in a Prospective Cohort and Assessment of its Prognostic Value

Grupo Español de actualización en Transplante (GREAT). Background Recurrence of idiopathic FSGS is a serious complication after kidney transplantation. Currently, there are no accurate means to diagnose the relapses or to detect the patients at risk. In a previous study we detected Apolipoprotein A-Ib (ApoA-Ib) specifically in urine of kidney transplanted patients that showed recurrence of FSGS. In the present work we aim to confirm the diagnostic performance of ApoA-Ib to detect FSGS recurrence and assess its possible prognostic value. Methods Between January 2013 and December 2015 a urine sample was obtained in three groups of kidney transplant patients treated at the nephrology department of 16 major Spanish hospitals: FSGS patients that relapsed after kidney transplantation (FSGS-R), FSGS patients that did not show recurrence after kidney transplantation (FSGS-NR) and non-FSGS kidney transplanted patients (No-FSGS). ApoA-Ib was determined in the urine of these patients by immunodetection. To assess the ApoA-Ib predictive ability of detecting patients at risk of relapse, 33 patients with idiopatic FSGS were included before transplantation. Thirteen of them were transplanted and followed up to 1 year after transplantation. In these patients ApoA-Ib was periodically determined. Results In the FSGS-R group 14 out of 15 (93.3 %) were positive for apoA-Ib whereas only 2 out of 22 (9.1 %) in the FSGS-NR group and 3 out of 24 (12.5 %) in the No-FSGS group tested positive for ApoA-Ib (P value < 0.001). ApoA-Ib sensitivity and specificity to detect FSGS recurrence were 94.1% and 90.9% to discriminate non-relapsing FSGS patients or 94.1% and 87.5% to discriminate transplanted patients without FSGS as the primary disease. These results were consistent with the obtained in our previous cohort of FSGS patients. The presence of ApoA-Ib in urine was only related to FSGS recurrence and was independent of proteinuria levels or renal function. ApoA-Ib was present in 37.9 % of the FSGS patients before transplantation which is similar to the FSGS recurrence incidence after transplantation (30-50 %). Four of the 13 followed patients showed FSGS recurrence. ApoA-Ib predated FSGS relapse in 4 out of 5 recurrence episodes observed in 4 patients, while in 9 patients who did not relapse ApoA-Ib was negative in 37 out of 38 samples. Conclusions ApoA-Ib has the potential to be a good complementary diagnostic biomarker of FSGS relapses after transplantation, providing a confident exclusion of relapse even in the presence of high proteinuria. It has also a potential to detect patients at risk of relapse, even before transplantation, which should be further evaluated in a larger cohort. The authors thank Oreto Prat, Estefanía Lozano and Anna Caraben for their technical assistance. Grupo Español de Actualización en Trasplante (GREAT, Spanish Group for New Projects in Transplantation): Carme Cantarell (Hospital Vall d’Hebron, Barcelona), Lluis Guirado (Fundació Puigvert, Barcelona), Francisco Gonzalez Roncero (Hospital Virgen del Rocio, Sevilla), Juan C. Ruiz San Millan (Hospital Marqués de Valdecilla, Santander) Carlos Jiménez (Hospital Universitario La Paz, Madrid), Isabel Beneyto (Hospital La Fe, Valencia), Sofia Zárraga (Hospital de Cruces, Barakaldo), Javier Paul (Hospital Miguel Servet, Zaragoza), Vicenç Torregrosa (Hospital Clínic, Barcelona), Ricardo Lauzurica (Hospital Germans Trias i Pujol, Badalona), Angel Alonso (Hospital de A Coruña, A Coruña), Carmen Díaz (Hospital Central de Asturias, Oviedo), Ana Fernández (Hospital Ramón y Cajal, Madrid), Auxiliadora Mazuecos (Hospital Puerta del Mar, Cadiz), Domingo Hernández (Hospital Carlos Haya, Malaga), Alberto Rodriguez (Hospital Reina Sofia, Cordoba), Antonio Osuna (Hospital Virgen de las Nieves, Granada), Antonio Franco (Hospital General, Alicante), Luisa Jimeno (Hospital Virgen de la Arrixaca, Murcia), Marta Crespo (Hospital del Mar, Barcelona).