Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

Renal transplant recipient with advanced HIV infection: graft and peripheral cell population analysis.

The scenario of a renal transplant recipient who is diagnosed with HIV infection in the late post transplant period is very uncommon. The viral infection effect on immunologic stability, regulatory cells, and allogeneic response during immune quiescence and graft acceptance provides a fertile ground in organ transplantation research and translational immunology.

Pre-transplant angiotensin II type 1 receptor antibodies: A risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT,Rab) are associated with a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and biopsy proven acute rejection (BPAR) during the first year post-transplant in adult renal transplant recipients (RTR), between 03/2009 and 08/2012. Pre-transplant sera were screened for AT1Rab (via enzyme linked immunosorbent assay) and donor specific anti-human leukocyte antigen antibodies (HLA-DSA, via Luminex). Three groups were analyzed: AT1Rab only (n=13); HLA-DSA only (n=8); and no AT1Rab or HLA-DSA (n=90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. RTR with AT1Rab had a lower median estimated glomerular filtration rate (eGFR=20 ml/min/1.73m2) when compared to RTR with no antibodies at 12 months. A significant difference in eGFR was observed since the first month post-transplant. Multivariate analysis showed four factors independently and significantly associated with eGFR at 12 months post-transplant: BPAR (beta -18.7, 95% CI -28.2 to -9.26, p<0.001), AT,Rab (beta -10.51, 95% CI -20.9 to -0.095 p=0.048), donor age (beta -0.42, 95% CI -0.75 to -0.103, p=0.010), and recipient age (3 -0.36, 95% CI -0.67 to -0.048, p= 0.024). In this study, AT1Rab in pre-transplant sera from RTR was an independent and significant risk factor contributing to a lower eGFR at 12 months posttransplant. This finding deserves to be confirmed in a larger RTR population.

Pre-nephrectomy angiotensin II type 1 receptor antibodies in living kidney donors: A concern?

Angiotensin II type 1 receptor (AT1R) autoantibodies (AT1Rab) have been associated with pre-eclampsia and malignant hypertension. Overactivity of the angiotensin-II/AT1R complex has also been implicated in cardiac, renal, and vascular remodeling, leading to mortality and morbidity from cardiovascular disease. Pre-donation prevalence and possible post-donation effects of AT1Rab in living kidney donors (LKD) are unknown. In this study, sera obtained the day before nephrectomy and kept frozen at -70 degrees C from 113 strictly normotensive and non-obese LKD were tested for AT1Rab by OneLambda detection assay. AT1Rab titers >or=17 international units were considered positive. Pre-donation renal function [estimated glomerular filtration rate (eGFR)] and blood pressure at 1 and 12 months post-donation were recorded in every patient. Ten of 113 (8.8%) LKD yielded a positive AT1Rab result. History of sensitization events was similar in both groups. There was no difference in renal function between LKD with positive and negative AT1Rab results, 1 (mean eGFR 73.8 versus 72.4 mL/min/1.73m2) and 12 months post-donation (mean eGFR 74.1 versus 74.5 mL/min/1.73m2). During follow-up, none of the LKD developed hypertension (defined as blood pressure >130/85), nor did they require antihypertensive drugs. AT1Rab are apparently indolent in healthy adults after short-term follow-up. Longer observation of all LKD will be necessary to draw final conclusions.

Peripheral regulatory cells immunophenotyping in kidney transplant recipients with different clinical profiles: a cross-sectional study.

Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. These subpopulations also might participate in maintaining allograft immunological quiescence in kidney transplant recipients (KTRs) with an excellent long-term graft function under immunosuppression (ELTGF). The aim of the study was to characterize and to enumerate peripheral Tregs, Bregs, and DCregs in KTR with an ELTGF for more than 5 years after transplant. Fourteen KTR with an ELTGF, 9 KTR with chronic graft dysfunction (CGD), and 12 healthy donors (HDs) were included in the study. CD19(+)-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4(+)/CD25(hi), and CD8(+)/CD28(-) Tregs, as well as CCR6(+)/CD123(+)/IDO(+) DCs, were quantitated by flow cytometry. IL-10-producing Bregs (immature/transitional, but not CD19(+)/CD38(hi)/CD24(hi)/CD27(+)B10 cells), CCR6(+)/CD123(+)/IDO(+) DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (P < 0.05). By contrast, number of Tregs, DCregs, and Bregs except for CD27(+)B10 cells from CGD patients had lower levels versus HD and ELTGF patients (P < 0.05). The findings of this exploratory study might suggest that in ELTGF patients, peripheral tolerance mechanisms could be directly involved in the maintenance of a quiescent immunologic state and graft function stability.

Time-zero renal biopsy in living kidney transplantation: a valuable opportunity to correlate predonation clinical data with histological abnormalities.

BACKGROUND: Living kidney donation is increasing as a partial solution for wait-listed patients. Despite properly followed guideline criteria for donor selection, current reports identify unsuspected renal pathology at preimplantation or time-zero biopsy (T0-RBx). METHODS: T0-RBx was evaluated for following: interstitial fibrosis (IF), tubular atrophy (TA), arteriolar hyalinosis (AH), mesangial increase (MI), and glomerulosclerosis (GS). Predonation data were demography, body weight, body mass index (BMI), systolic/diastolic blood pressure (BP), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and proteinuria. RESULTS: Two hundred nineteen T0-RBx were analyzed. Of these 54.4% had abnormal findings, namely, IF in 29%, TA in 13%, MI in 12%, AH in 10%, and GS in 10%. Mean clinical data were as follows: age 35.4+/-10 years, weight 66.27+/-10.14 kg, BMI 25.53+/-2.99, systolic BP 115+/-9 mm Hg, diastolic BP 74+/-7 mm Hg, SCr 0.91+/-0.25 mg/dL, eGFR 96+/-16.65 mL/min, and proteinuria 70.25+/-62.8 mg/24 hr. A total of 56.7% were women. IF correlated to age (r=0.22, P=0.001) and SCr (r=0.19, P=0.005); TA to diastolic BP (r=0.15, P=0.03) and proteinuria (r=0.20, P=0.009); AH to SCr (r=0.15, P=0.02) and eGFR (r=-0.16, P=0.018); MI to BMI (r=0.13, P=0.047). Multivariate analysis failed to sustain the significant associations found on bivariate analysis, most likely due to a low event/parameter relation and sample size. CONCLUSIONS: A significant correlation was established between T0-RBx findings and clinical predonation parameters. Whether these mild histologic findings at the time of kidney donation represent a higher risk for the remaining kidney ought to be evaluated during follow-up. In an era, when living kidney donation is increasing, we advise closer donor surveillance to modify risk factors that participate in kidney damage progression.

Partial nephrectomy for renal tumors using selective parenchymal clamping.

PURPOSE: To describe our experience with partial nephrectomy using selective parenchymal clamping for the treatment of renal tumors. PATIENTS AND METHODS: Between 2003 and 2005, seven patients with solid renal tumors underwent partial nephrectomy with selective parenchymal clamping at our Institution. In five, the tumor was in the right kidney and in two the tumor was in the left. Only one patient had a tumor within a solitary kidney. The tumor was located in the upper pole in 2 patients and in the lower pole in 5. Partial nephrectomy was performed with the DeBakey aortic clamp without occlusion of renal vessels. RESULTS: Mean operative time was 236 min (range 175-298 min). Mean intraoperative blood loss was 485 ml with only one patient requiring blood transfusion. There were no major complications. Mean preoperative serum creatinine level was 0.74 mg/dl (range 0.58-1.26 mg/dl) and mean postoperative serum creatinine level was 0.81 mg/dl (range 0.69-1.21 mg/dl) with no patient requiring dialysis. Mean hospital postoperative stay was 5 days (range 4-7 days). Mean tumor size was 2.9 cm (range 1.3-4.0 cm). Pathologic analysis detected renal cell carcinoma in 5 patients, angiomyolipoma in 1 and fibrosis with chronic hemorrhage in 1, all with negative surgical margins. After a mean follow-up of 18 months (range 3-32 months), all patients are free of disease recurrence. CONCLUSION: Partial nephrectomy with selective parenchymal clamping allows resection of solid masses without damage to normal renal tissue, avoids the risk of renal failure and offers an excellent local cancer control.

El estudio del donador vivo para trasplante renal / Evaluation of the living kidney donor

Currently, due to the deficit of cadaveric tissues available for transplantation and due to the long waiting list for a kidney transplant, there is a clear tendency towards living donor kidney transplantations. Most donors are genetically related. Living donation should be considered a gift of extraordinary value, and should be made easy whenever a suitable donor is available. Worldwide, the number of patients on the waiting lists for a kidney transplantation has increased, in the last decades. Renal transplantation with living donor kidneys, is currently considered the best treatment for patients with end stage renal failure, due to the improved short and long term survival benefits over dialysis treatment. Since considerable difference exist between countries in the evaluation and selection criteria for kidney donors, especially in selected patients such as older donors and those with associated comorbid conditions, it is necessary to discuss and establish minimal selection criteria for this cases. A common trend includes a complete clinical record, laboratory and radiologic evaluation which are described in detail in this paper. We also discuss the increasing acceptance of older kidney donors as well as the acceptance of individuals with comorbidities (such as obesity, hipertensión, hyperglucemia, lithiasis and cancer) that were previously considered as not eligible for kidney donation.

Actualmente, por la falta de órganos para trasplante renal provenientes de cadáveres, y debido al largo tiempo de espera por un riñón, existe una tendencia a realizar trasplantes renales utilizando riñones procedentes de donadores vivos. La mayoría de los donadores son familiares del receptor. La donación de órganos debe considerarse como un regalo con un valor extraordinario y debe facilitarse a los candidatos a donación. En todo el mundo se ha observado un aumento en el número de personas en la lista de espera para un trasplante renal. El trasplante renal de donador vivo se considera actualmente como el mejor método de tratamiento en pacientes con insuficiencia renal terminal, debido a que ofrece la mayor supervivencia a corto y largo plazos. En vista de que existen diferencias significativas en los criterios de selección y evaluación de donadores renales, en especial en un grupo selecto de pacientes añosos o con enfermedades asociadas, es indispensable establecer criterios mínimos de selección. Todos los donadores deberán contar con una historia clínica completa y exámenes de laboratorio y gabinete que permitan su evaluación integral. Estos estudios se describen con detalle en este artículo. También se discuten los criterios para donadores renales con ciertas comorbilidades (obesos, hipertensos, hiperglucémicos, con litiasis y neoplasias) que previamente se descartaban como candidatos para donación.

[Evaluation of the living kidney donor]. / El estudio del donador vivo para trasplante renal.

Currently, due to the deficit of cadaveric tissues available for transplantation and due to the long waiting list for a kidney transplant, there is a clear tendency towards living donor kidney transplantations. Most donors are genetically related. Living donation should be considered a gift of extraordinary value, and should be made easy whenever a suitable donor is available. Worldwide, the number of patients on the waiting lists for a kidney transplantation has increased, in the last decades. Renal transplantation with living donor kidneys, is currently considered the best treatment for patients with end stage renal failure, due to the improved short and long-term survival benefits over dialysis treatment. Since considerable difference exist between countries in the evaluation and selection criteria for kidney donors, especially in selected patients such as older donors and those with associated comorbid conditions, it is necessary to discuss and establish minimal selection criteria for this cases. A common trend includes a complete clinical record, laboratory and radiologic evaluation which are described in detail in this paper. We also discuss the increasing acceptance of older kidney donors as well as the acceptance of individuals with comorbidities (such as obesity, hypertension, hyperglucemia, lithiasis and cancer) that were previously considered as not eligible for kidney donation.

[Risk of invasive breast cancer in Mexican population and patterns of screening and prophylaxis]. / Riesgo de cáncer de mama invasor en población mexicana y patrones de escrutinio y profilaxis.

BACKGROUND: The risk of invasive breast cancer based on the Gail model in Mexican population as well patterns of screening and prophylaxis in high risk patients are unknown. METHODS: Ambulatory adult female patients assisting to the breast clinic in a tertiary referral center in Mexico City were included. Personal history of invasive or non-invasive breast cancer was an exclusion criteria. A questionnaire was applied and the 5-year and lifetime risk of invasive breast cancer based on the Gail model were calculated. Patterns of screening mammography and prophylaxis in high risk patients were identified. RESULTS: One-thousand patients were included from January through June, 2002. Mean patient age was 50 years (20-85). Fifty-six percent of patients were postmenopausal. One hundred and four patients (10.4%) had at least one first-degree relative with breast cancer. From 790 patients older than 40, only 48% reported yearly screening mammogram. According to Gail model the mean calculated risk of invasive breast cancer during the following 5-years was 1.2% for the entire group (range 0-5.7%) and the mean lifetime risk was 9.3% (range 1.4-30.1%). There were 256 patients (25.6%) with a 5-year risk greater than 1.66%, proportion significantly lower than in American population. From this group only 57% reported use of annual mammogram. No patient received prophylaxis with tamoxifen. CONCLUSION: The proportion of high risk patients in this sample of Hispanic population is lower than that reported in American, predominantly white population. Screening and prophylaxis recommendations are not followed by the majority of Hispanic patients. This cohort will be followed prospectively in order to validate the Gail model in this subgroup of patients.