tacrolimus and Delayed-Graft-Function

The study was designed to compare the outcomes of sirolimus (SRL) combined with tacrolimus (TAC) and mycophenolate mofetil (MMF) combined with TAC in kidney transplantation recipients.. A literature search of PubMed, Embase, and Web of Science was performed to identify relevant studies, and the last update was on February 1, 2018. All studies with appropriate data comparing the SRL group with the MMF group were included. SRL and MMF were used in sufficient doses. Relevant information was recorded and analyzed. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the effects of SRL and MMF. Relevant outcomes, including delayed graft function, acute rejection, graft survival, seroma, anemia, lymphocele, and hyperlipidemia, were compared.. Ten studies with a total of 2357 patients (n = 1256 receiving SRL vs n = 1101 receiving MMF) were ultimately included. Our results indicated that the SRL group experienced a higher rate of hyperlipidemia (OR: 1.864; 95% CI, 1.494-2.325) and lymphocele (OR: 2.58; 95% CI, 1.49-4.47). However, no significant differences were detected regarding the rates of delayed graft function, acute rejection, graft survival, infectious complications, anemia, or seroma.. This meta-analysis suggested that SRL combined with TAC and MMF combined with TAC were equally safe and effective for the kidney transplantation recipients. However, the MMF group exhibited a marginally significant advantage of lower incidence of hyperlipidemia and lymphocele.

Topics: Adult; Delayed Graft Function; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Hyperlipidemias; Immunosuppressive Agents; Kidney Transplantation; Lymphocele; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Tacrolimus

The etiology of tako-tsubo cardiomyopathy, defined as a transient left ventricular dysfunction in the absence of significant coronary artery stenosis, still remains unclear. This syndrome mainly occurs in postmenopausal women and is often associated with emotional stress or miscellaneous diagnostic and therapeutic procedures. Estimated prevalence of tako-tsubo cardiomyopathy is found in 1% to 2% of patients presenting with suspected acute coronary syndrome. So far there has been only one case report of tako-tsubo cardiomyopathy in a renal transplant recipient.. We describe the case of a 68-year-old woman with a history of coronary artery disease and coronary artery bypass grafting in whom unspecific transient chest pain and hypotension were observed on the first day after renal transplantation. After transplantation, the patient was anuric with pulmonary congestion and toxic tacrolimus concentrations were observed. Electrocardiogram showed sinus rhythm with left bundle branch block (LBBB) that has not been described before. Plasma cardiac necrosis markers troponin I and creatine kinase MB were mildly elevated. Echocardiography showed severe left ventricular function impairment with characteristic shape of left ventricle. Subsequent cardiac catheterization revealed the absence of angiographic evidence of acute plaque rupture within both coronary arteries and bypass grafts. During the next few days there was marked clinical improvement with resolution of LBBB and full recovery of all biochemical parameters. On discharge, full functional recovery of the left ventricle in echocardiography was observed. Postulated mechanisms of tako-tsubo cardiomyopathy include catecholamine excess, coronary artery spasm, and microvascular dysfunction. On the other hand calcineurin inhibitors are known factors causing coronary epicardial endothelial dysfunction and negatively affecting vasomotor function.. Tako-tsubo cardiomyopathy in patients after renal transplantation may be at least in part a manifestation of calcineurin inhibitor cardiotoxicity.

Topics: Aged; Calcineurin Inhibitors; Chest Pain; Delayed Graft Function; Electrocardiography; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Tacrolimus; Takotsubo Cardiomyopathy; Vasoconstriction; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Cyclosporine; Delayed Graft Function; Endothelium, Vascular; Everolimus; Graft Rejection; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Tolerance; Immunosuppressive Agents; Sirolimus; Tacrolimus; Transplantation Immunology

The incidence of delayed graft function (DGF) among kidney transplant recipients (KTRs) in the United States continues to increase. The effect of immediate-release tacrolimus (tacrolimus) compared with extended-release tacrolimus (Envarsus) among recipients with DGF is unknown.. This was a single-center open-label randomized control trial among KTRs with DGF (ClinicalTrials. gov, NCT03864926). KTRs were randomized either to continue on tacrolimus or switch to Envarsus at a 1:1 ratio. Duration of DGF (study period), number of dialysis treatments, and need for adjustment of calcineurin inhibitor (CNI) doses during the study period were outcomes of interest.. Envarsus patients had less fluctuation in the CNI level, requiring fewer CNI dose adjustments. However, there were no differences in the DGF recovery duration or number of dialysis treatments.

Topics: Calcineurin Inhibitors; Delayed Graft Function; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Renal Dialysis; Tacrolimus; Transplant Recipients

Although cytochromeP450(CYP)3A5 gene polymorphism affects personalized tacrolimus doses, there is no consensus as to whether CYP3A5 genotypes should be determined to adjust the doses. The aims were to compare the therapeutic ranges and clinical outcomes between the conventional and genotype-guided tacrolimus doses.. This randomized controlled study compared 63 cases of the conventional tacrolimus dose group (0.1 mg/kg/day) with 62 cases of the genotype-guided doses group of 0.125, 0.1 and 0.08 mg/kg for CYP3A5*1/*1, *1/*3, and *3/*3 genotypes for the initial 3 days of kidney transplantation. After day 3, dose adjustment occurred in both groups to achieve therapeutic concentrations.. The genotype-guided group had an increased proportion of patients with tacrolimus concentrations in the therapeutic range at the steady state on day 3 (40.3 vs 23.8%, P = .048). A lower proportion of over-therapeutic concentration patients was noted in the genotype-guided group in the CYP3A5*3/*3 genotype (9.7 vs 27%, P = .013). Unexpectedly, more delayed graft functions (DGFs) were in the genotype-guided group (41.9 vs 22.2%, P = .018) especially in the CYP3A5*1/*1 participants who might have had an aggravated DGF by a longer ischaemic time and higher serum donor creatinine levels than in the control group. There were no significant differences of glomerular filtration rates or graft or patient survivals over a median 37-month follow-up period.. Determination of the CYP3A5 genotype improved therapeutic range achievement. CYP3A5*1/*1 patients who have high risks of DGF should be closely monitored because of an increased risk of DGF and reduced glomerular filtration rate with high tacrolimus doses.

Topics: Adult; Allografts; Cytochrome P-450 CYP3A; Delayed Graft Function; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Monitoring; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Polymorphism, Genetic; Tacrolimus

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).

Topics: Aged; Antilymphocyte Serum; Cytomegalovirus Infections; Delayed Graft Function; Donor Selection; Everolimus; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Prospective Studies; Risk Assessment; Risk Factors; Tacrolimus; Treatment Outcome

The premise that lower TAC trough levels are associated with subsequently higher first BPAR risk during the first 12 mo post-transplant was recently questioned. Using our prospectively followed cohort of 528 adult, primary kidney transplant recipients (pooled across four randomized trials) who received reduced TAC dosing plus an IMPDH inhibitor, TAC trough levels measured at seven time points, 7, 14 days, 1, 2, 3, 6 and 9 months post-transplant, were utilized along with Cox's model to determine the multivariable significance of TAC level(t) (a continuous time-dependent covariate equaling the most recently measured TAC level prior to time t) on the hazard rate of developing first BPAR during the first 12 months post-transplant. The percentage developing BPAR during the first 12 months post-transplant was 10.2% (54/528). In univariable analysis, lower TAC level(t) was associated with a significantly higher BPAR rate (P = 0.00006), and its significance was maintained even after controlling for 2 significant baseline predictors (African-American/Hispanic Recipient and Developed DGF) in Cox's model (multivariable P = 0.0003). Use of a cutpoint, TAC level(t) <4.0 vs. ≥4.0 ng/ml, yielded an even greater association with BPAR rate (univariable and multivariable P < 0.000001), with an estimated hazard ratio of 6.33. These results suggest that TAC levels <4.0 ng/ml should be avoided during the first 12 months post-transplant when TAC is used in combination with fixed-dose mycophenolate with or without corticosteroids and induction therapy.

Topics: Acute Disease; Adult; Aged; Delayed Graft Function; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Tacrolimus; Time Factors

Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches.. Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review.. All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P < .05) among desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P < .05). Treatment with PP/IVIG more effectively eliminated preexisting DSAs (67% vs 33%, P < 0.05) than IVIG, but neither regimen prevented de novo formation of DSA (20%, P = not significant). Graft survival was >90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P < .05).. Preemptive perioperative desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone.

Topics: Adult; Antibodies; Antilymphocyte Serum; Cadaver; Cohort Studies; Delayed Graft Function; Desensitization, Immunologic; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Methylprednisolone Hemisuccinate; Middle Aged; Mycophenolic Acid; Perioperative Care; Plasmapheresis; Tacrolimus

The P450 oxidoreductase (POR)*28 variant allele has been associated with altered cytochrome P450 3A enzyme activities. Both CYP3A5 and CYP3A4 are involved in the metabolism of calcineurin inhibitors and recent data show that POR*28 may explain part of the variability observed in tacrolimus (Tac) pharmacokinetics. The aim of this study was to investigate the impact of the POR*28 allele on Tac and cyclosporine A (CsA) immunosuppressive therapies.. Kidney transplant recipients receiving either Tac (n = 184) or CsA (n = 174), participating in a prospective multicenter trial, were genotyped for POR*28, CYP3A4*22, and CYP3A5*3.. CYP3A5 expressers that were carriers of at least 1 POR*28 allele had a 16.9% decrease in dose-adjusted predose concentrations when compared CYP3A5 expressers that carried the POR*1/*1 genotype (P = 0.03), indicating an increased CYP3A5 activity for POR*28 carriers. In CYP3A5, nonexpressers carrying 2 POR*28 alleles, a 24.1% (confidence interval95% = -39.4% to -4.9%; P = 0.02) decrease in dose-adjusted predose concentrations was observed for Tac, suggesting higher CYP3A4 activity. For CsA, POR*28/*28 patients not expressing CYP3A5 and not carrying the CYP3A4*22 decrease-of-function allele showed 15% lower CsA dose-adjusted predose concentrations (P = 0.01), indicating also increased CYP3A4 activity. In both cohorts (ie, Tac and CsA), the POR*28 allele was neither associated with the incidence of delayed graft function nor with biopsy-proven acute rejection. These results were further confirmed in 2 independent cohorts.. Our results show that the POR*28 allele is associated with increased in vivo CYP3A5 activity for Tac in CYP3A5 expressers, whereas POR*28 homozygosity was associated with a significant higher CYP3A4 activity in CYP3A5 nonexpressers for both Tac and CsA.

Topics: Adult; Alleles; Cyclosporine; Cytochrome P-450 CYP3A; Delayed Graft Function; Dose-Response Relationship, Drug; Follow-Up Studies; Genotype; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; NADPH-Ferrihemoprotein Reductase; Polymorphism, Single Nucleotide; Prospective Studies; Tacrolimus

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess.. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids.. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05).. Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

Topics: Adult; Aged; Antilymphocyte Serum; Death; Delayed Graft Function; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; T-Lymphocytes; Tacrolimus; Tissue Donors; Transplantation, Homologous; Young Adult

Mycophenolic acid (MPA) plasma concentrations are highly variable on standard-dose mycophenolate mofetil therapy. At creatinine clearances below 25 mL/min, MPA clearance increases as a result of a higher nonprotein-bound fraction. Patients with delayed graft function (DGF) after renal transplantation are exposed to low total MPA concentrations, when risk of rejection is highest. This study investigated the influence of DGF on MPA exposure and on clinical outcome.. Adult renal transplantation patients treated with mycophenolate mofetil, corticosteroids, and either microemulsified cyclosporine (n = 459) or tacrolimus (n = 371) participated in a randomized controlled trial (the Fixed-Dose Concentration-Controlled [FDCC] Study). Abbreviated MPA areas under the curve (AUCs) were obtained on Day 3, Day 10, Week 4, and Month 3, to calculate MPA AUC₀₋₁₂. Free MPA AUC values were available for a subgroup of patients (n = 269).. The overall incidence of DGF was 187 of 830 (23%) and did not differ between cyclosporine-treated (24%) and tacrolimus- (21%) treated patients. The incidence of biopsy-proven acute rejection at 12 months was significantly higher in patients with DGF (13.8% versus 21.4%). Patients with DGF had significantly lower dose-corrected MPA AUC on Day 3 and Day 10. Free MPA fraction and dose-corrected free MPA AUC were significantly higher in patients with DGF, from Day 3 until Month 3. The total number of patients with at least one opportunistic infection was significantly higher in patients with DGF (33.2%) compared with patients without DGF (25.8%) (P = 0.048). Patients with DGF developing opportunistic infections did not have higher total MPA AUC nor higher free MPA AUC compared with those without opportunistic infections.. Patients with DGF have significantly lower dose-corrected MPA AUC in the first month after renal transplantation, presumably as a result of enhanced MPA clearance on account of the elevated MPA free fraction. Because patients with DGF have a higher rate of acute rejection and lower MPA exposure, higher dosing of mycophenolate mofetil in such patients may improve outcome. However, the already increased incidence of opportunistic infections in patients with DGF is a concern.

Topics: Adrenal Cortex Hormones; Adult; Area Under Curve; Creatinine; Cyclosporine; Delayed Graft Function; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Tacrolimus; Treatment Failure

Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens.. Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels.. The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels.. Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; Cyclosporine; Daclizumab; Delayed Graft Function; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Infections; Kidney Transplantation; Lipid Metabolism; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Sirolimus; Tacrolimus; Treatment Outcome

Erythropoietin promotes nephroprotection in animal models of ischemia-reperfusion injury. Neorecormon and Prevention of Delayed Graft Function (Neo-PDGF) is a French open-label multicenter randomized study to evaluate the effect of high doses of epoetin beta (EPO-beta) during the first 2 weeks of renal transplantation on renal function in patients at risk for delayed graft function (DGF). One hundred and four patients were included in the study. Patients randomized in treatment group (A) received four injections of EPO-beta (30.000 UI each), given before surgery and at 12 h, 7 days and 14 days posttransplantation. Patients randomized in control group (B) did not receive EPO-beta. Immunosuppression included induction with basiliximab and maintenance therapy with steroids, mycophenolate mofetil and tacrolimus. At 1 month posttransplant, the estimated glomerular filtration rate (MDRD formula) was 42.5 +/- 19.0 mL/min in the EPO-beta group and 44.0 +/- 16.3 mL/min in the control group (p = ns). The frequency of DGF was similar in both groups (32% vs. 38.8%; p = ns). No difference in the incidence of serious adverse events was observed. (ClinicalTrials.gov number, NCT00815867.).

Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal; Basiliximab; Blood Pressure; Body Mass Index; Creatinine; Delayed Graft Function; Erythropoietin; Female; France; Glomerular Filtration Rate; Graft Rejection; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Platelet-Derived Growth Factor; Recombinant Fusion Proteins; Recombinant Proteins; Renal Dialysis; Safety; Tacrolimus

Tacrolimus, a calcineurin inhibitor with a macrolide lactone structure, is currently used as a cornerstone immunosuppressive drug in solid organ transplantation. It is metabolized by hepatic and intestinal cytochrome P450 (CYP) 3A4/3A5 enzymes and is a substrate for P-glycoprotein (ABCB1). The disposition of tacrolimus might be influenced by severe renal allograft dysfunction (eg, in cases of delayed graft function [DGF]). New-onset diabetes after transplantation (NODAT) is a known adverse effect of tacrolimus therapy and has been associated with DGF.. The impact of DGF on tacrolimus C(min) and dose requirements was evaluated in renal transplant recipients in the first postoperative week. The effects of the CYP3A5*3 A6986G polymorphism on initial mean tacrolimus C(min) and dose requirements in the presence and absence of DGF were assessed. This study also tested the hypothesis that if DGF influences early tacrolimus exposure, this would lead to a higher risk for NODAT (defined as the need for glucose-lowering medication for an uninterrupted period of ≥ 26 weeks).. This prospective, open-label, observational clinical cohort study enrolled renal allograft recipients aged ≥ 18 years. Tacrolimus was administered as an oral loading dose of 0.2 mg/kg/d and adjusted to achieve a target mean daily tacrolimus C(min) between 12 and 15 ng/mL. C(min) values and oral dose requirements in the first postoperative week were compared between patients with and without DGF. Patients were genotyped for the CYP3A4*1B -290A>G, CYP3A5*3 A6986G, ABCB1 Exon26 C3435T, ABCB1 Exon21 G2677T, and ABCB1 Exon21 G2677A single nucleotide polymorphisms. NODAT that occurred within the first 12 weeks after transplantation was confirmed using an oral glucose tolerance test.. A total of 304 patients were enrolled (184 men, 120 women; mean [SD] age, 52.9 [14.1] years). Through day 3 after transplantation, mean (SD) 12-hour tacrolimus C(min) values were significantly higher in recipients experiencing DGF despite identical loading doses of 0.2 mg/kg. Mean tacrolimus dose requirements were significantly lower in patients with DGF during the first week. After recovery of DGF, mean tacrolimus dose requirements were not significantly different between recipients with and without DGF. In homozygous CYP3A5*3 carriers (n = 252), mean (SD) tacrolimus dose requirements remained significantly lower during DGF, while in CYP3A5*1 carriers with DGF (n = 52), lower mean dose requirements were observed only after postoperative day 4. The proportion of patients in whom NODAT developed was significantly greater in patients with DGF and tacrolimus C(min) >15 ng/mL on the first day after transplantation (27.2%) compared with recipients who remained free of DGF and had C(min) ≤15 ng/mL on day 1 (6.5%) (P = 0.016). On logistic regression analysis, greater recipient age (odds ratio [OR] = 1.044; 95% CI, 1.009-1.080), higher tacrolimus C(min) on day 1 (OR = 1.048; 95% CI, 1.017-1.080), and DGF (OR = 2.968; 95% CI, 1.107-7.959) were associated with an increased risk for NODAT.. In this open-label, observational study, DGF was associated with higher initial mean tacrolimus C(min) values and lower daily dose requirements predominantly in CYP3A5 nonexpressers.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 CYP3A; Delayed Graft Function; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Genotype; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Polymorphism, Single Nucleotide; Postoperative Period; Prospective Studies; Tacrolimus

Chronic renal allograft failure (CRAF) is the leading cause of graft loss post-renal transplantation. This study evaluated the efficacy and safety of tacrolimus as secondary intervention in cyclosporine-treated kidney transplantation patients with impaired allograft function as indicated by elevated serum creatinine (SCr) levels.. Patients receiving cyclosporine-based immunosuppression who had an elevated SCr at least 3 months post-renal transplantation were enrolled. Treatment allocation was 2:1 to switch to tacrolimus or continue cyclosporine. This analysis was performed after 2 yr; patients will be followed for an additional 3 yr.. There were 186 enrolled and evaluable patients. On baseline biopsy, 90% of patients had chronic allograft nephropathy. Baseline median SCr was 2.5 mg/dL in both treatment groups. For patients with graft function at month 24, SCr had decreased to 2.3 mg/dL in the tacrolimus-treated patients and increased to 2.6 mg/dL in the cyclosporine-treated patients (p = 0.01). Acute rejection occurred in 4.8% of tacrolimus-treated patients and 5.0% of cyclosporine-treated patients during follow-up. Two-year allograft survival was comparable between groups (tacrolimus 69%, cyclosporine 67%; p = 0.70). Tacrolimus-treated patients had significantly lower cholesterol and low-density lipoprotein levels and also had fewer new-onset infections. Cardiac conditions developed in significantly fewer tacrolimus-treated patients (5.6%) than cyclosporine-treated patients (24.3%; p = 0.004). Glucose levels and the incidences of new-onset diabetes and new-onset hyperglycemia did not differ between treatment groups.. Conversion from cyclosporine to tacrolimus results in improved renal function and lipid profiles, and significantly fewer cardiovascular events with no differences in the incidence of acute rejection or new-onset hyperglycemia.

Topics: Biopsy; Creatinine; Cyclosporine; Delayed Graft Function; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Risk Factors; Severity of Illness Index; Tacrolimus; Treatment Outcome

Wound complication frequently arises after kidney transplantation and its risk factors are well known. In a previous paper we analyzed these factors, and in this new retrospective study we evaluate the influence of lymphocele in the development of wound complications.. From January 2000 to December 2018, 731 consecutive kidney transplants have been performed in our center. We have analyzed the incidence of wound complication and lymphocele and their risk factors.. Out of 731 kidney transplants, we have observed wound complications in 115 patients (15.7%) and lymphocele in 158 patients (21.7%). Of these, 70 patients developed both complications (9.5%), but 6 patients have been excluded because they were in therapy with mammalian target of rapamycin inhibitors. Twenty-nine patients (45.3%) presented a first level and 35 patients (54.7%) showed second level wound complications. Lymphocele was the only present factor in just 3 cases (4.6%). The other patients showed diabetes in 28 cases (43.7%), overweight/obesity in 38 (59.3%), delayed graft function in 17 (26.5%), and 60 years or more in 38 (57.8%). The association has been found in 30 out 64 patients treated with tacrolimus (46.8%) and in 34 with cyclosporine (53.1%); 40 patients did not receive muscular layer's reconstruction (62.5%).. Our experience shows that lymphocele alone is not a predisposing factor for wound dehiscence after kidney transplantation, and they often coexist because they share the same risk factors, the most important being obesity, diabetes and delayed graft function, older age, and surgical techniques. No relation has been observed with calcineurin inhibitor therapy.

Topics: Adult; Aged; Cyclosporine; Delayed Graft Function; Diabetes Complications; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphocele; Male; Middle Aged; Obesity; Retrospective Studies; Risk Factors; Sirolimus; Surgical Wound Dehiscence; Tacrolimus

In nonimmunized patients, similar rejection rates are observed for patients who have undergone thymoglobulin (antithymocyte globulins [ATG]) or basiliximab (BSX) therapy. While ATG may improve delayed graft function, it may also be associated with higher infection rates and malignancy risk. We compared survival and clinical outcomes in elderly recipients with low immunological risk according to their induction therapy.. We conducted a multicentric study on nonimmunized patients ≥65 years of age receiving a first kidney transplant between 2010 and 2017. The principal outcome was patient and graft survival. Secondary outcomes were cumulative probabilities of infection, first acute rejection episode, malignancy, de novo donor specific antibody, posttransplant diabetes (PTD), cardiac complications, estimated glomerular filtration rate, and occurrence of delayed graft function. Cox, logistic, or linear statistical models were used depending on the outcome studied, and models were weighted on the propensity scores.. Two hundred and four patients were included in the BSX group and 179 in the ATG group with the average age of 71.0 and 70.5 years, respectively. Patient and graft survival at 3 years posttransplantation were 74% (95% CI, 65%-84%) and 68% (95% CI, 60%-78%) in ATG and BSX group, respectively, without significant difference. Occurrence of PTD was significatively higher in BSX group (23% versus 15%, P = 0.04) due to higher trough levels of Tacrolimus on month 3 (9.48 versus 7.30 ng/mL, P = 0.023). There was no difference in other evaluated outcomes.. In elderly recipients, ATG does not lead to poorer outcomes compared with BSX and could permit lower trough levels of Tacrolimus, thus reducing occurrence of PTD.

Topics: Age Factors; Aged; Aged, 80 and over; Antilymphocyte Serum; Basiliximab; Delayed Graft Function; Diabetes Mellitus; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Postoperative Complications; Prospective Studies; Tacrolimus; Transplantation Conditioning; Treatment Outcome

This study aimed to determine whether de novo, prolonged-release tacrolimus- (PR-tacro) based immunosuppressive regimen affected graft and patient survival when compared to an immediate-release, twice-daily, tacrolimus- (IR-tacro) based regimen in kidney transplant recipients. We also aimed to determine the difference between the frequency of side effects, including diabetes control, in study groups.. A total of 115 standard risk kidney transplant recipients were enrolled in this single center, retrospective study. Fifty-two patients received PR-tacro and 63 patients received IR-tacro as a calcineurin inhibitor. The primary outcome measures included incidence of graft loss and delayed graft function (DGF), biopsy-proven acute rejection , graft and patient survival, and creatinine clearance. Secondary outcome measures included the incidence of non-adherence, drug-induced tremor; post-transplant diabetes mellitus diagnosis rate; and control of diabetes in pre-transplant diabetic patients.. Baseline characteristics and mean tacrolimus trough levels were comparable between groups. Incidence of graft loss, DGF, and graft and patient survival were similar between groups (P > .05). Mean creatinine clearance level was also similar (P > .05). Mean serum levels of fasting glucose (P < .05) and A1C (P < .05) were lower in PR-tacro group when compared to IR-tacro group. Post-transplant diabetes mellitus diagnosis rate was also lower in PR-tacro group when compared to IR-tacro group (P = .040).. This study suggests that there is no statistically significant difference between PR-tacro and IR-tacro in terms of patient and graft survival, DGF, and biopsy-proven acute rejection rates in kidney transplant recipients. Post-transplant diabetes mellitus frequency is lower in non-diabetic patients, and glucose metabolism control is better in diabetic patients.

Topics: Adult; Calcineurin Inhibitors; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Survival Rate; Tacrolimus

Practically all kidney allograft recipients require immunosuppressive therapy to prevent rejection and loss of the allograft. The aim of this study was to determine the occurrence of biopsy-proven acute rejection in low-immunologic risk kidney transplant recipients according to the type of induction (basiliximab vs low-dose of rabbit antithymocyte globulin [rATG], 3.5 mg/kg).. A total of 125 patients after primary kidney transplant were included in the retrospective analysis with 6-month follow-up. The immunosuppression regimen included tacrolimus, mycophenolic acid, and corticoids.. We did not find any significant difference in the occurrence of acute rejection or difference in the occurrence of infection complications. Patients in the rATG group had a significantly longer period of cold ischemia, more frequently received kidney transplants from expanded criteria donors, and had significantly more mismatches in HLA-DR. Delayed graft function (DGF) was identified as an independent risk factor for biopsy-proven acute rejection (hazard ratio, 3.4859; P = .003). There was comparable incidence of DGF between the 2 groups despite that there were several factors that are more commonly associated with DGF in the rATG group.. Patients with low immunologic risk and high risk of DGF benefit from the rATG induction in dose of 3.5 mg/kg without the increased risk of infection complications with the assumption of good graft function in long-term post-transplant period.

Topics: Adult; Antilymphocyte Serum; Basiliximab; Biopsy; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Induction Chemotherapy; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Tacrolimus

In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post-transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.

Topics: Adult; Age Factors; Aged; Cold Ischemia; Creatinine; Delayed Graft Function; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors

Topics: Adult; Cations; Delayed Graft Function; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Graft Rejection; Humans; Hyperkalemia; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Patient Safety; Polymers; Tacrolimus; Transplant Recipients; Treatment Outcome

A small percentage of peripheral blood mononuclear cells (PBMCs) circulating during the kidney transplantation (KT) period remain in the blood long after transplantation. A part of the PBMCs penetrates the graft.. To examine if the choice of immunosuppression may change TLR4ex and how TLR4ex affects the transplant function in the future.. The study population-143 transplanted patients (pts) (55 females, 88 males), mean age on recruitment day 50.33 ± 12.8 years old, mean BMI 25.04 ± 4.18. 41 pts. experienced delayed graft function (DGF+). 55 pts. were treated with cyclosporine A (CsA) and 88 with tacrolimus (Tac). All were treated with mofetil mycophenolate (MMF). The PBMCs acquisition and starting point of the follow-up (TLR-day) was at least one month after KT.. We investigated averaged mRNA expression of Toll-like receptors 4 (TLR4ex) in non-stimulated peripheral blood mononuclear cells with the use of real-time polymerase chain reaction. The KT pts. (All, Tac, CsA, DGF+) were divided by the respective median of their TLR4ex (lower: L-TLR4ex, higher: H-TLR4ex). Main clinical parameters and transplant biopsy files (if available) were assessed on TLR-day and post follow-up.. We found that TLR4ex was reduced for a long time in patients who experienced delayed graft function. L-TLR4ex had a higher proportion of DGF+ patients, and patients treated with CsA but lower of those treated with Tac than in H-TLR4ex. The amplitude of changes in renal function parameters (ΔEGFR%/ΔsCr/ΔsCr%) was clearly less favorable for L-TLR4ex. Tacrolimus expressed a stabilizing effect. Both the positive vasculitis score and chronic graft nephropathy were more frequent in the L-TLR4ex group. On TLR-day an association of renal function and Tac concentration with TLR4ex was clear only in the tacrolimus population. The TLR4ex was lower in patients with a future deterioration of the graft function.. In kidney transplant recipients the occurrence of DGF results in a long-term reduction of the averaged TLR4ex in PBMC. Tacrolimus exerts a clear, stabilizing, positive and dose-dependent effect on TLR4ex. An improvement in renal transplant function may be expected in KT patients with high TLR4ex. Evaluation of the averaged TLR4ex can be used to assess the efficacy of immunosuppression in the treatment with tacrolimus and to estimate the likelihood of deterioration in renal function.

Topics: Adult; Biomarkers; Cyclosporine; Delayed Graft Function; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukocytes, Mononuclear; Male; Middle Aged; Mycophenolic Acid; Prognosis; Tacrolimus; Toll-Like Receptor 4; Treatment Outcome

Our study compares 2 immunosuppressive strategies to reduce tacrolimus nephrotoxicity and its risk of acute tubular necrosis: delayed introduction of tacrolimus plus thymoglobulin vs initial tacrolimus plus basiliximab on the results of kidney transplant (KT) using type-III donation after circulatory death (III-DCD).. We analyzed all the transplants performed using type-III DCD in our hospital (42 cases). They were distributed in a first stage with delayed tacrolimus (3°-4° day) + thymoglobulin and a second one with initial tacrolimus + basiliximab, with a follow-up of 6 months. The rate of delayed graft function, the evolution of renal function, and the incidence of rejection were compared.. 28 patients received thymoglobulin with delayed tacrolimus, and 13 patients received basiliximab and tacrolimus from day 0 (1 excluded). There were no significant differences in delayed graft function (27% group 1 and 23% group 2) or in rejection (10.7% and 15.4%), respectively. Serum creatinine at day 3, 7, 14, 30, and 180 showed no statistically significant differences. The levels of tacrolimus measured at 10, 30, 90, and 180 days after transplantation were similar, except for the first month: 10.10 ± 2.3 in group 1 and 12 ± 1.7 ng/mL in group 2 (P = .007).. Delayed introduction of tacrolimus does not seem to suppose a benefit in KT using type-III DCD; therefore, the use of thymoglobulin, with its higher profile of adverse effects, seems unjustified in patients with normal immunological risk.

Topics: Adult; Antilymphocyte Serum; Basiliximab; Delayed Graft Function; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Tacrolimus; Tissue Donors

Delayed graft function (DGF) and pretransplant donor-specific HLA-antibodies (DSA) are both regarded as risk factors for rejection and lower graft survival. However, the combined impact of DGF and DSA has not been studied in detail.. We investigated 375 deceased donor kidney transplantations, which had DSA assignment by single-antigen bead technology and which had surveillance biopsies at 3 of 6 months. Median follow-up time was 6.1 years.. DGF occurred in 137 of 375 patients (37%), and DSA were present in 85 of 375 patients (23%). The incidence of DGF was similar in DSA-positive (DSApos)-patients and DSA-negative (DSAneg)-patients (40% versus 36%; P = 0.45). In DSAneg-patients, 5-year graft survival was not different with/without DGF (81% versus 83%; P = 0.48). By contrast, in DSApos-patients, 5-year graft survival was significantly lower with DGF (64% versus 79%; P = 0.01). Moreover, DSApos-patients with DGF had a higher 1-year incidence of subclinical rejection, which were mostly antibody-mediated or mixed rejection phenotypes. Graft loss due to rejection was significantly more frequent in DSApos-patients with DGF (5/34; 15%) compared to DSApos-patients without DGF (2/51; 4%), and DSAneg-patients with/without DGF (3/103; 3% and 4/187; 2%, respectively) (P = 0.005). In a multivariate Cox model, DSA with DGF was an independent predictor for graft (hazard ratio = 2.84 [95% confidence interval, 1.54-5.06]; P = 0.001) and death-censored graft loss (hazard ratio = 4.65 [95% confidence interval, 1.83-11.51]; P = 0.002).. DGF has a much more detrimental impact in DSApos-patients than in DSAneg-patients, which is likely related to a higher incidence of antibody-mediated rejection. If possible, the combined risks of DGF and DSA should be avoided.

Topics: Aged; Delayed Graft Function; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Histocompatibility; HLA Antigens; Humans; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Risk Assessment; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

Tacrolimus is widely used in renal transplantation to help prevent acute and chronic rejection, but the nephrotoxicity of tacrolimus may compromise renal function. This study investigates the safety and efficacy in delayed initiation of tacrolimus after antilymphocyte induction therapy in kidney transplant recipients.. This retrospective cohort analysis involved data from 68 kidney transplant recipients receiving standard induction therapy (basiliximab [Simulect] or thymoglobulin) combined with tacrolimus. The patients were divided into 2 groups according to whether the start time of tacrolimus therapy was before or after 24 hours posttransplantation. Acute rejection, common complications of immunosuppression, and graft survival were compared.. The mean (SD) timing of tacrolimus administered in the Delayed group was 4 (1.9) days after transplantation. The Delayed group patients had a higher percentage of slow graft function and delayed graft function than the No-delay group. Compared with the No-delay group, delayed initiation of tacrolimus did not increase risk of biopsy-proven acute rejection, infection, posttransplant diabetes mellitus, graft survival, and patient survival.. Our study confirmed delayed initiation of tacrolimus after antilymphocyte induction therapy is safe and effective in renal transplant recipients with slow or delayed graft function.

Topics: Adult; Antilymphocyte Serum; Basiliximab; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Tacrolimus; Time Factors

Whether an early, short-term, adequate exposure to mycophenolic acid (MPA) under tacrolimus-based immunosuppression regimen in kidney transplantation from donation after circulatory death (DCD) was effective and safe is yet unknown.. The study was a single-center, retrospective, cohort study of DCD transplantation in China. Intensified and standard dosage regimens of enteric-coated mycophenolate sodium (EC-MPS) were week 1, 2,160 vs. 1,440 mg/day. The incidences of biopsy-proven acute rejection (BPAR), delayed graft function, infection, and patient and graft survival were compared between the 2 groups.. A total of 209 patients (n = 82 in intensified group and n = 127 in standard group) were enrolled from August 2013 to December 2014. The incidence of BPAR at 12 months was significantly lower in the intensified group as compared to that of the standard group. (2.4 vs. 10.2%, p = 0.035). The mean MPA area under curve (AUC) levels at day 7 was significantly higher in the intensified group than that in the standard group (66.18 ± 35.48 vs. 45.30 ± 23.5 mg·h/L, p < 0.001). MPA AUC levels were significantly decreased in patients with BPAR as compared to those with NO-BPAR.. An early, short-term regimen of intensified EC-MPS with tacrolimus increased early MPA exposure and achieved a low rate of BPAR in kidney transplantation from DCD.

Topics: Adult; Area Under Curve; Biopsy; China; Death; Delayed Graft Function; Drug Administration Schedule; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Patient Safety; Retrospective Studies; Tablets, Enteric-Coated; Tacrolimus; Treatment Outcome

Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL).. Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis.. BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis.. GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.

Topics: Adult; Allografts; BK Virus; Calcineurin Inhibitors; Delayed Graft Function; Disease Progression; Female; Glomerular Filtration Rate; Graft Survival; Humans; Immunosuppression Therapy; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Polyomavirus; Polyomavirus Infections; Postoperative Complications; Postoperative Period; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors

There is continued debate whether early steroid withdrawal is safe to use in high-immunologic risk patients, such as blacks. The goal of this study was to use comparative effectiveness methodology to elucidate the safety of early steroid withdrawal in blacks with kidney transplants.. Our cohort study used United Network of Organ Sharing data including all adult black kidney transplant recipients from 2000 to 2009 followed through 2014. Propensity score matching was used to equalize baseline risk between continued steroid and early steroid withdrawal groups. Interaction terms were used to assess if the effect of early steroid withdrawal on outcomes varied by baseline and post-transplant factors. Of 26,582 eligible black patients with kidney transplants (5825 [21.9%] with early steroid withdrawal), 5565 patients with early steroid withdrawal were matched to 5565 blacks on continued steroid use.. Black patients with early steroid withdrawal had similar risk of graft loss (hazard ratio, 0.98; 95% confidence interval, 0.92 to 1.04; P=0.42) and lower risk of death (hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.99; P=0.02), primarily driven by a late mortality advantage (>4 years post-transplant). Delayed graft function, cytolytic induction, tacrolimus, and mycophenolate significantly modified the effect of early steroid withdrawal on outcomes (P<0.05). Acute rejection rates were slightly higher in the continued steroid group (13.0% versus 11.3%, respectively; P<0.01), but this was not associated with graft or patient survival.. Overall, early steroid withdrawal in black kidney transplant recipients was not associated with graft loss but seemed to be associated with better long-term patient survival. Early steroid withdrawal in blacks not receiving cytolytic induction, tacrolimus, and mycophenolate or those with delayed graft function was associated with higher risk of graft loss and death.

Topics: Adult; Black or African American; Comparative Effectiveness Research; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Steroids; Survival Rate; Tacrolimus; Time Factors; United States; Withholding Treatment

Obesity has been reported as risk factor for reduced posttransplant graft and patient survival and increased delayed graft function (DGF).. The purpose of this work is to analyze the effect of body mass index (BMI) on defined transplant outcomes in patients transplanted under defined guidelines in a kidney transplant program.. Review of a prospectively collected database in renal transplant recipients receiving rabbit antithymocyte globulin induction, mycophenolate mofetil, tacrolimus, and early corticosteroid withdrawal between 2001 and 2011.. This review was conducted in a single abdominal transplant program in the United States.. Primary outcome was death-censored graft survival categorized by posttransplant body mass groups. Secondary outcomes included DGF as well as patient survival.. Four hundred sixty seven patients were identified. No difference was observed in graft survival or DGF between BMI groups. One-year, death-censored graft survival and patient survival rates ranged from 97.5% to 100% and 96.6% to 100%, respectively. Delayed graft function was uncommon across all BMI groups, ranging from 5.3% to 9.1%, with the lowest incidence in patients with a BMI ≥ 35 kg/m(2). Biopsy-proven acute rejection rates at 1 year were similar across all groups (10.1%-14%) as were estimated glomerular filtration rates were at 1, 3, and 5 years.. Our results do not show an effect of BMI on posttransplant outcomes, suggesting that relaxation of BMI criteria may be warranted for recipient selection.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antilymphocyte Serum; Body Mass Index; Comorbidity; Databases, Factual; Delayed Graft Function; Female; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Obesity; Overweight; Retrospective Studies; Survival Rate; Tacrolimus; Thinness; Treatment Outcome

Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like receptors (TLR) at supra-pharmacological concentrations. Earlier studies demonstrated that 24 hours after kidney transplantation (KT), the expression of the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft function (DGF+) was lower than in patients without DGF (DGF-). An assessment was made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+.. We investigated mRNA expression of TLR in non-stimulated PBMC. All patients were transplanted more than 1 month before PBMC acquisition. Patients were divided into groups with respect to positive or negative history of delayed graft function (DGF+/-).. The expression of TLR2, TLR3, and TLR9 in patients was lower than that in the control group. We found an association of Tac C0 with expression of TLR4 only and CsA dose per 1 kg body weight with TLR2 or up to 6 months after KT with TLR9. Mofetil mycophenolate (MMF)contributed to the change of TLR4 expression in the CsA group but not in the Tac group. TLR3 and TLR9 were nearly equally sensitive to both Tac and CsA, with a decrease of expression with respect to control. DGF+ was associated with variable degree of reduction of TLR2, TLR3, TLR4, and TLR 9 expression.. We showed the importance of immunosuppression and delayed graft function as factors that modify the overall expression of mRNA-TLR PBMC for a period of time after KT. Patients with a history of DGF have chronically decreased expression of mRNA TLR2, TLR3, TLR4, and TLR9. This fact is associated with poorer graft function. Measuring the expression of the TLR in the upper range of therapeutic doses of calcineurin inhibitors and MMF gives the opportunity to assess the strength, effectiveness, and toxicity of immunosuppression.

Topics: Adult; Allografts; Calcineurin Inhibitors; Cyclosporine; Delayed Graft Function; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Leukocytes, Mononuclear; Male; Middle Aged; Mycophenolic Acid; RNA, Messenger; Tacrolimus; Toll-Like Receptors

Topics: Adult; Biopsy; Delayed Graft Function; Female; Humans; Hypophosphatemia; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Phosphates; Tacrolimus; Treatment Outcome

Although donor-specific antibodies are regarded as a contraindication for kidney transplantation, the data available for combined liver and kidney transplantation (cLKTx) are scarce, and there is no established therapeutic approach for this category of transplant recipients. De novo use of everolimus and a reduced dose of calcineurin inhibitor reportedly provides excellent kidney function compared with a standard regimen containing a calcineurin inhibitor. This strategy, however, has been applied in only some recipient categories. Here we report a case of A highly sensitized male patient who underwent a cLKTx and received everolimus with low-dose tacrolimus (once-daily prolonged-release formulation) as ab initio immunosuppressive treatment. The pretransplant panel-reactive antibody estimate was 97%, and multiple anti-HLA antibodies were detected at the time of transplantation. Thus far, patient and allograft survival have reached 2 years, with the recipient remaining on a regimen of immunosuppression with everolimus and low-dose tacrolimus, with no episodes of rejection.

Topics: Antibodies; Antilymphocyte Serum; Calcineurin Inhibitors; Delayed Graft Function; Drug Therapy, Combination; Everolimus; Graft Rejection; HLA Antigens; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Liver; Liver Transplantation; Male; Middle Aged; Tacrolimus; Tissue Donors; Transplant Recipients; Transplantation Immunology

The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor-specific antibody) was found between the two groups.

Topics: Adult; Aged; Antibodies; Biopsy; Cohort Studies; Delayed Graft Function; Drug Administration Schedule; Drugs, Generic; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Monitoring, Immunologic; Patient Safety; Proteinuria; Reference Values; Retrospective Studies; Tacrolimus; Thrombosis; Tissue Donors; Treatment Outcome

Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.. We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction.. Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio).. NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.

Topics: Acute-Phase Proteins; Aged; Apoptosis; Biomarkers; Cell Hypoxia; Cells, Cultured; Cohort Studies; Delayed Graft Function; Donor Selection; Female; Gene Expression; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Kidney Tubules; Lipocalin-2; Lipocalins; Male; Middle Aged; Prospective Studies; Proto-Oncogene Proteins; Regeneration; Tacrolimus; Tissue Donors

There is a paucity of modern data on the impact of high tacrolimus levels early after kidney transplantation.. This study analyzed the impact of various trough levels of tacrolimus in the first 2 weeks post-transplant on rates of delayed graft function (DGF), length of stay (LoS), hyperkalemia, hyperglycemia, and biopsy-proven acute rejection (BPAR) rates in the first 3 months post-transplant in a retrospective single-center cohort of patients. Patients were divided into 4 groups based on the average of two highest 12-hour trough tacrolimus levels: <10 ng/mL, 10-12 ng/mL, 12-15 ng/mL, >15 ng/mL.. The incidence of DGF was noted to be significantly higher in the <10 ng/mL, >15 ng/mL and the 12-15 ng/mL tacrolimus groups as compared to the 10-12 ng/mL group (49%, 25% and 4%, respectively, p≤0.0001). Mean LoS was also noted to be significantly higher in the >15 ng/mL tacrolimus group as compared to the 10-12 ng/mL group (7.4 days and 6.1 days respectively, p=0.0007). There was no difference in the rates of hyperkalemia, hyperglycemia or BPAR.. This is a modern confirmation of the association between higher tacrolimus levels early after kidney transplantation and increased rate of DGF and increased LoS.

Topics: Acute Disease; Adolescent; Adult; Aged; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Length of Stay; Male; Middle Aged; Retrospective Studies; Risk Factors; Tacrolimus; Treatment Outcome; Young Adult

Despite potential renal and cardiovascular advantages of proliferation signal inhibitors, their de novo use in kidney transplantation (KT) from elderly donors (ED) is poorly documented. We retrospectively analyzed two consecutive cohorts of KT from ED: low-dose extended-release tacrolimus (Tac) was used from 2010 to 2012 and cyclosporine (Csa) was used from 2008 to 2010.. Associated maintenance drugs were everolimus (Eve) and steroids. Outcomes were compared between groups over a 12-month follow-up. Fifty-six patients were analyzed in the Tac-Eve group and 54 in the Csa-Eve group.. There were no significant differences at baseline with the exception of older donors age in the Tac-Eve cohort (74 vs 71 years, P = .002). There were no deaths, primary non functions, or graft losses. Eight (14%) Tac-Eve and 15 (28%) Csa-Eve patients had delayed graft function (P = .10). Renal function was fairly stable over time (median cGFR 36-49 mL/min and 51-55 mL/min in single kidney transplantation and dual kidney transplantation patients, respectively) with no significant differences between groups at month 12. Surgical complications were infrequent and observed mostly in dual kidney transplantation recipients. Thirty-nine (70%) and 30 (56%) patients remained under their initial Tac-Eve or Csa-Eve regimen, respectively.. Induction with Thymoglobuline and maintenance with Eve and low-dose extended-release Tac and steroids is safe and effective in renal transplant from ED.

Topics: Aged; Calcineurin Inhibitors; Cyclosporine; Delayed Graft Function; Everolimus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Sirolimus; Steroids; Tacrolimus; Tissue Donors; Transplant Recipients

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1-19 yr (mean 14 ± 4.1 yr). Time of follow-up was 7-51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post-transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m(2) , respectively. One, two, and three-yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty-four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0-1.8 mg/dL). One graft was lost four yr after transplantation due to medication non-compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short- and mid-term patient and graft survival in low-immunologic risk pediatric renal transplant recipients.

Topics: Adolescent; Alemtuzumab; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Creatinine; Delayed Graft Function; Female; Follow-Up Studies; Glomerular Filtration Rate; Glucocorticoids; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Renal Insufficiency; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

Delayed graft function affects up to 50% of kidney transplant recipients. Some guidelines recommend surveillance biopsies beginning 7 days after engraftment. This may be unnecessary with anti-thymocyte globulin induction.. We conducted a retrospective study of deceased-donor renal transplant recipients with delayed graft function.. One hundred eleven patients met the inclusion criteria. The incidence of rejections during delayed graft function was 2.7%. They were diagnosed between 9 and 11 days after transplant. The subsequent incidence of rejection at 12-month follow-up was 13.5% (n=15). The median time to rejection after transplant was 10 weeks. Fourteen of 15 patients had subtherapeutic immunosuppression. The only risk factor associated with later rejection after delayed graft function was use of donors after cardiac death.. Early rejection during delayed graft function with anti-thymocyte globulin induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids is rare. When later rejection occurs, it is at a median of 10 weeks after a transplant. Two of the 3 early rejections were antibody mediated. Later rejections were associated with subtherapeutic immunosuppression and donors after cardiac death. Biopsies need not be performed during the early postoperative period when anti-thymocyte globulin is used with tacrolimus, mycophenolate mofetil, and steroids.

Topics: Adult; Aged; Antilymphocyte Serum; Biopsy; Delayed Graft Function; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Time Factors; Transplantation, Homologous

This study analysed associations between tacrolimus, mycophenolic acid (MPA) and prednisolone exposures on day 4 and month 1 post kidney transplant and clinical outcomes. Area under the concentration-time curve (AUC) for each drug was estimated using validated multiple regression-derived limited sampling strategies. Multivariate logistic regression was used to associate drug exposure with clinical outcomes. One hundred and twenty subjects were studied. Between-subject variability in dose-adjusted exposure to each medication was high. Both day 4 tacrolimus and MPA exposures were independently predictive of delayed graft function (2.6 change in odds for a standard deviation (SD) increase in tacrolimus AUC(0-12) , P = 0.02; 0.23 change in odds for a SD increase in MPA AUC(0-12) , P = 0.02). Both day 4 MPA and total prednisolone exposures were independently predictive of rejection (0.20 change in odds for a SD increase in MPA AUC(0-12) , P = 0.04; 0.40 change in odds for a SD increase in total prednisolone AUC(0-6) , P = 0.03). Lowest tertile exposure to all three immunosuppressant medications imposed significantly higher odds of rejection [adjusted odds ratio 34.2 (95% CI 4.1, 284.4), P = 0.001]. This study highlights the importance of achieving early target exposure and suggests a potential role for individualized initial dosing or early therapeutic monitoring of all three immunosuppressive agents.

Topics: Adult; Area Under Curve; Delayed Graft Function; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Tacrolimus; Treatment Outcome

The aim of this study was to investigate the incidence of osteonecrosis of the hip and knee among renal allograft recipients treated with cyclosporin- or tacrolimus-based immunosuppressive regimens and its predictors focusing on the first 8 weeks after transplantation. The subjects were 232 renal allograft recipients who had MRI for osteonecrosis of the hip and knee 3 months or longer after transplant. The following potential predictors of osteonecrosis were tested using univariate and multivariate logistic regression analyses: age, gender, body weight, body mass index, duration on dialysis before transplant, number of human leukocyte antigen mismatches, ABO mismatches, type of transplanted kidney, immunosuppressive regimen, cumulative steroid dose and steroid pulses, incidence of acute rejection, and delayed graft function, defined as requiring dialyses in the first week. Evidence of osteonecrosis was visible on the MRI of 11 recipients (4.7%, 95% confidence interval 2.4-8.3). Univariate and multivariate logistic regression analyses indicated that delayed graft function was the most important predictor of osteonecrosis. In conclusion, we found a lower incidence of osteonecrosis of the hip and knee in renal allograft recipients treated with cyclosporin or tacrolimus. In the patients treated with improved immunosuppressive regimens, delayed graft function was a significant early predictor of osteonecrosis.

Topics: ABO Blood-Group System; Adolescent; Adult; Body Mass Index; Child; Cyclosporine; Delayed Graft Function; Female; Graft Rejection; Hip; HLA Antigens; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Knee; Male; Middle Aged; Osteonecrosis; Tacrolimus; Treatment Outcome; Young Adult

Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4-6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air-treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P-selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP-1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia-reoxygenation-induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes.

Topics: Animals; Carbon Monoxide; Cell Death; Cell Proliferation; Delayed Graft Function; Female; Gene Expression Profiling; Graft Rejection; Kidney; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Reperfusion Injury; Swine; Tacrolimus

The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival.. We retrospectively reviewed the charts of 611 renal transplantations between 1996 and 2005. Most patients received a calcineurin inhibitor as maintenance therapy, either cyclosporine (43%) or tacrolimus (52%) and 76% of the patients received an antilymphocyte induction therapy. Study endpoints were DGF, first-year AR, and long-term graft survival. Uni- and multivariate analyses were performed to determine factors that may have influenced the study outcomes.. DGF was observed in 16.2% of patients. Both older donor age and longer CIT were significant risk factors for DGF. DGF rates were similar whether patients received a calcineurin inhibitor before transplantation or not. AR occurred in 16.5% of grafts during the first year. Independent predictors of AR by multivariate analysis were duration of dialysis, CIT, current panel-reactive lymphocytotoxic antibody more than 5%, and the number of human leukocyte antigen-A, B, and DR mismatches. Each hour of cold ischemia increases the risk of rejection by 4%. With respect to death-censored graft survival, three pretransplant parameters emerged as independent predictors of graft loss: younger recipient age, peak panel-reactive lymphocytotoxic antibody more than 5% and longer CIT. The detrimental effect of CIT on graft survival was entirely because of its propensity to trigger AR. When AR was added to the multivariate Cox model, CIT was no longer significant whereas first-year AR became the most important predictor of graft loss (Hazards ratio, 4.6).. Shortening CIT will help to decrease not only DGF rates but also AR incidence and hence graft loss. Patients with prolonged CIT should receive adequate immunosuppression, possibly with antilymphocyte preparations, to prevent AR occurrence.

Topics: Adult; Cohort Studies; Cold Ischemia; Cyclosporine; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Tacrolimus

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13% of the patients. Patients also received azathioprine (2 mg kg(-1) day(-1), N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg(-1) day(-1), N = 148). Mean time on dialysis was 79 +/- 41 months, 12% of the cases were re-transplants, and 21% had panel reactive antibodies > 10%. In 43% of donors the cause of death was cerebrovascular disease and 27% showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60%, respectively. Mean time to last dialysis and to nadir creatinine were 18 +/- 15 and 34 +/- 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 +/- 0.50 mg/dL (DGF 1.68 +/- 0.65 vs SGF 1.67 +/- 0.66 vs immediate graft function (IGF) 1.41 +/- 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22% (DGF 31%, SGF 10%, IGF 8%). One-year patient and graft survival was 92.6 and 78.4%, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0%, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.

Topics: Adult; Azathioprine; Biopsy; Calcineurin Inhibitors; Creatinine; Cyclosporine; Delayed Graft Function; Drug Administration Schedule; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Prednisone; Retrospective Studies; Risk Factors; Severity of Illness Index; Tacrolimus; Treatment Outcome

The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome.

Topics: Adult; Biopsy; Creatinine; Delayed Graft Function; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Sirolimus; Tacrolimus