Short and long-term effects of kidney donation on mineral and bone metabolism.

Background: Living kidney donors (LKD) experience an abrupt decline in glomerular filtration rate (GFR) resulting in abnormalities of mineral and bone metabolism (MBD), and this may have implications for skeletal health. We prospectively studied acute and long term MBD adaptation of LKD from two kidney transplant centers (São Paulo, Brazil and Miami, USA).

Methods: Renal function and MBD parameters longitudinally after kidney donation (baseline - D0, day 1, 14, 180 and 360 post-operatively) were measured in 74 patients (40 y, 73% female, 54% Brazilian).

Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients.

Background: Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles.

Methods: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2).

Toward an Integrated View of Operational Tolerance in Human Renal Transplantation: A Systems Biology Perspective.

Operational tolerance (OT) is the phenomenon occurring in human renal and liver transplantation in which the body does not reject the organ after discontinuing immunosuppression for at least a year. We revisited the data generated by The Brazilian Multicenter Study on Operational Tolerance involving different conceptual fields - antigen-specific cytokine response, immune cell numbers and repertoire, signaling pathways, and epigenetics. We integrated our data to pave the way to systems biology thinking and harness debate on potential mechanisms in OT.

Regulatory/inflammatory cellular response discrimination in operational tolerance.

Background: Antigen-specific cellular response is essential in immune tolerance. We tested whether antigen-specific cellular response is differentially modulated in operational tolerance (OT) in renal transplantation with respect to critical antigenic challenges in allotransplantation-donor antigens, pathogenic antigens and self-antigens.

Methods: We analysed the profile of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines for the antigen-specific response directed to these three antigen groups, by Luminex.

Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival.

Operational tolerance (OT) is a state of graft functional stability that occurs after at least 1 year of immunosuppressant withdrawal. MicroRNAs () are small non-coding RNAs that downregulate messenger RNA/protein expression of innumerous molecules and are critical for homeostasis. We investigated whether OT in kidney transplantation displays a differential microRNA profile, which would suggest that microRNAs participate in Operational Tolerance mechanisms, and may reveal potential molecular pathways.

Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population.

There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging.

Chikungunya in kidney transplant recipients: A series of cases.

Chikungunya (CHIK) is a mosquito-borne virus (CHIKV) infection that recently appeared in the Americas and thousands of confirmed cases have been reported in Brazil since the first autochthonous cases were reported in September 2014. We reported four cases of CHIK in kidney transplant recipients. The diagnosis was confirmed by positive CHIKV real-time polymerase chain reaction in two cases and positive CHIKV-IgM serology in two patients.

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

Background: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients.

Longitudinal Pharmacokinetics of Everolimus When Combined With Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

Background: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients.

Methods: We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL).

Evaluation of MDRD4, CKD-EPI, BIS-1, and modified Cockcroft-Gault equations to estimate glomerular filtration rate in the elderly renal-transplanted recipients.

Equations to estimate glomerular filtration rate (eGFR) were developed in patients using the variables age, body weight, and serum creatinine, which may be different in the elderly. Elderly renal transplant patients (EG; n=70; mean age 65 ± 4 y) who measured plasma Cr-EDTA-Clearance (mGFR) had mGFR compared to eGFR obtained by the Cockcroft-Gault corrected by body surface area (CG-BSA), the modification of diet in renal disease (MDRD-4), the Berlin Initiative Study (BIS-1), and the chronic kidney disease epidemiology collaboration (CKD-EPI). Results were validated using a cohort of 43, of the 70 elderly recipients, who performed a second Cr-EDTA-Clearance.

[Vasculopathy in the kidney allograft at time of transplantation delays recovery of graft function after deceased-donor kidney transplantation].

Objective: The purpose of this study was to evaluate the impact of donor and recipient characteristics on duration of delayed graft function (DGF) and 1-year serum creatinine (SCr), as a surrogate endpoint for allograft survival.

Methods: We reviewed 120 first cadaver kidney transplants carried out consecutively at our center to examine the effect on 1-year SCr of the presence and duration of DGF.

Results: DGF rate was 68%, with a median duration of 12 days (range, 1-61).

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy.

Objective: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage.

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study.

Objective: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes.

Methods: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009.

Preserving the B-cell compartment favors operational tolerance in human renal transplantation.

Transplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-cell compartment in renal transplantation.

[Ten-year follow-up of kidney transplantation with living unrelated donor].

Introduction: In the current era of scarcity of kidneys available for transplantation, and chronic anti-HLA-mediated rejection as a main cause of graft loss, continuous demonstration of the long-term survival of grafts from living unrelated kidney donors (LURD) is paramount.

Objective: Analyze long-term kidney graft and patient outcomes using LURD, and compare them with living related donors (LRD).

Methods: We analyzed the 389 first renal transplantations performed with a living donor (281 LRD and 108 LURD), in a single center, from January 1998 through December 2007.

GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation.

Some organ-transplanted patients achieve a state of "operational tolerance" (OT) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, IL10, TGFB1, TGFBR1/ TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups.

Home blood pressure (BP) monitoring in kidney transplant recipients is more adequate to monitor BP than office BP.

Background: Hypertension is highly prevalent among kidney transplantation recipients and considered as an important cardiovascular risk factor influencing patient survival and kidney graft survival. Aim. Compare the blood pressure (BP) control in kidney transplant patients through the use of home blood pressure monitoring (HBPM) is more comparable with the results of ambulatory blood pressure monitoring compared to the measurement of office blood pressure.

Differential monocyte STAT6 activation and CD4(+)CD25(+)Foxp3(+) T cells in kidney operational tolerance transplanted individuals.

In organ transplantation, the immunosuppression withdrawal leads, in most cases, to rejection. Nonetheless, a special group of patients maintain stable graft function after complete withdrawal of immunosuppression, achieving a state called "operational tolerance." The study of such patients may be important to understand the mechanisms involved in human transplantation tolerance.

Validation of plasma clearance of 51Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance.

Plasma clearance of (51)Cr-EDTA ((51)Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between (51)Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of (51)Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled.

C4d-positive chronic rejection: a frequent entity with a poor outcome.

Background: Chronic rejection (CR) is an important cause of kidney graft loss. Some studies have suggested the role of antibodies mediating chronic graft dysfunction. In this context, C4d identification is an important tool to evaluate antibody-mediated rejection.

The dynamics of glucose metabolism under calcineurin inhibitors in the first year after renal transplantation in nonobese patients.

Background: The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant.

Methods: Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids.

The beneficial effects of recipient-derived vascular endothelial growth factor on graft survival after kidney transplantation.

Background: Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and contributes to cytoprotection of the graft after kidney transplantation.

Methods: The authors investigated the influence of VEGF single-nucleotide polymorphism (SNP) on graft survival after renal transplantation. The SNP at positions -2578, -1154, and, -7 were analyzed in 306 donors and 387 recipients of renal transplants.

Fundamental role for HO-1 in the self-protection of renal allografts.

Tissue attenuates to injury by the effects of heme oxygenase (HO)-1. The induction of HO-1 expression is modulated by a (GT)(n) dinucleotide polymorphism in the promoter of the gene, of which increased activity is associated with short (S) ( View Article and Find Full Text PDF

Differential expression of heme oxygenase-1 and vascular endothelial growth factor in cadaveric and living donor kidneys after ischemia-reperfusion.

The extent of graft damage after ischemia-reperfusion reflects the balance between deleterious events and protective factors. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) may contribute to cytoprotection by their anti-inflammatory and antiapoptotic properties. For investigating whether HO-1 and VEGF play a role in the adaptive response to ischemia-reperfusion injury after renal transplantation, kidney biopsies were analyzed from living (n = 45) and cadaveric (n = 16) donors, obtained at three time points: at the end of cold storage T(-1), after warm ischemia T(0), and after reperfusion T(+1).

Sampling strategy to calculate the cyclosporin-A area under the time-concentration curve.

The complete area under the time-concentration curve (AUC) is considered to be the gold standard for cyclosporin-A (CyA) monitoring. However, complete AUC is time- and cost-consuming. For this reason, we reviewed 259 4-h AUC (AUC0-4) performed in 74 renal transplanted patients in order to construct an equation to calculate AUC0-4.