ABSTRACT
BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection. METHODS: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up. RESULTS: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed. CONCLUSIONS: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.
Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Enzyme-Linked Immunospot Assay , Kidney Transplantation , Adult , Antibodies, Viral/blood , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Female , Humans , Leukocytes, Mononuclear , Male , Middle Aged , Prospective Studies , T-Lymphocytes/immunology , Viral Load , Viremia/drug therapyABSTRACT
OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties.
Subject(s)
Acetylcysteine/pharmacology , Atorvastatin/pharmacology , Free Radical Scavengers/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Kidney Diseases/drug therapy , Oxidative Stress/drug effects , Reperfusion Injury/drug therapy , Animals , Atorvastatin/administration & dosage , Catalase/metabolism , Female , Glutathione Peroxidase/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Kidney/blood supply , Kidney/injuries , Kidney/pathology , Kidney Diseases/metabolism , Oxidation-Reduction , Peroxidase/metabolism , Rats , Reperfusion Injury/metabolism , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: To safely expand our living donor pool, we recently decided to work on 3 areas: analysis of causes of exclusion of potential donors, the results of which we recently published, introduction of laparoscopic donor nephrectomy (LDN), and ABO-incompatible (ABOi) transplantation. We sought to determine the impact of the new strategy on living donor recruitment and transplantation during over a 10-year period at a single institution. METHODS: From January 2005 to September 2014, we evaluated 131 living donors. Of these, 80 (61%) were genetically related, 51 (39%) unrelated, 119 (91%) ABO compatible (ABOc), 12 ABOi (9%). The analysis was divided into 2 eras: era 1, 2005-2010 (n = 53) included the use of open lumbotomy and acceptance of ABOc only; and era 2, 2011-2014 (n = 78), which saw the introduction of LDN and ABOi transplantation. RESULTS: Forty-five (34%) potential candidates successfully donated, 67 (51%) were excluded, and 19 (15%) were actively undergoing evaluation. Overall, 53 potential donors were evaluated in era 1 (8.8 donors/year), 78 in era 2 (19.5 donors/year). There were fewer excluded donors in era 2 vs era 1 (62% era 1 vs 44% era 2), and living donor kidney transplantation (LDKT) significantly increased in era 2 vs era 1 (3.3/year era 1 vs 7.1/year era 2). The establishment of an ABOi LDKT program led to a 15% increase of evaluations in era 2 (12/78 donors). CONCLUSIONS: LDN along with ABOi LDKT allowed for an improvement in recruitment of living donors and corresponding LDKT.
Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Living Donors/supply & distribution , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adult , Aged , Female , Humans , Kidney Transplantation , Laparoscopy , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: The complexity of treatment after solid organ transplantation has been related to non-adherence to therapy prescriptions and to reduced graft survival. The aim of this study was to evaluate the middle-term effects of the conversion from Prograf (TAC), to extended-release tacrolimus (Advagraf) (ADV) in stable kidney transplant recipients. METHODS: Conversion from TAC to ADV (dose, 1:1 mg/mg) was planned in 78 kidney transplant patients with stable renal function 71±48 months after renal transplantation. Before conversion, 1 week after conversion, and every 6 months up to 3 years, patients were evaluated clinically and by means of the usual blood chemistry and pharmacologic parameters. RESULTS: Twenty patients (26%) refused to change their pre-existing immunosuppressive therapy; therefore, 58 patients entered the study and 45 (77%) completed the 3-year follow-up. Patient survival was 98% and allograft survival was 96%. Significant reduction in serum creatinine levels and increased glomerular filtration rate were observed after conversion (3-year creatinine: before TAC 1.67±0.47 mg/dL vs after ADV 1.47±0.62 mg/dL, P<.001; glomerular filtration rate, MDRD abbreviated: before TAC 49±15 mL/min vs after ADV 59±24 mL/min, P<.001). The daily dose and C0 blood levels of tacrolimus were stable before and after conversion (dose before vs 3 years after conversion: TAC 3.79±1.81 mg/day vs ADV 3.54±1.86 mg/day, P=ns; C0 tacrolimus blood levels, before vs 3 years after conversion: TAC 6.03±1.75 ng/mL vs ADV: 5.58±1.38 ng/mL, P = NS). One patient in the ADV group had an episode of acute rejection (2%). CONCLUSIONS: Our data support the safety and efficacy of converting from Prograf to Advagraf in stable kidney transplant patients in the middle term. We suggest that the observed improvement in renal function after conversion to ADV is related to the reduction of the 24-hour tacrolimus area under the curve exposure.
Subject(s)
Delayed-Action Preparations/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Tacrolimus/therapeutic use , Creatinine/blood , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: Safety in conducting a clinical trial is a prerequisite for patients who will be enrolled into that study. The aim of the present study was to evaluate retrospectively if patient and graft survival were similar among patients who participated in clinical trials versus those who did not. PATIENTS AND METHODS: We evaluated pretransplant and posttransplant characteristics of 245 kidney transplant (KT) patients who were selected to participate in at least one Phase II/Phase III clinical trial. We compared them with 361 KT patients who were not enrolled or refused to participate in those clinical trials; all studies were conducted at a single transplant center. Inclusion/exclusion criteria were as noted for each individual protocol. Only studies with enrollment at time of graft implant were considered. RESULTS: Selection of patients participating in clinical trials in general exclude high-risk patients. In our experience, only 36% of transplanted patients were selected for a multicenter, prospective, randomized, international study that included changes to the strategies in the administration of immunosuppressive drugs already on the market or development of a new immunosuppressant. After 5 years, graft and patient survival rates were similar between those who participated and those who did not participate in a clinical study. Although our data were collected retrospectively, an alternative design to achieve these conclusions would be a noninferiority study. CONCLUSIONS: Our results demonstrated similar rates of graft and patient survival among enrolled patients versus nonenrolled patients. Outcome surveillance offers safety in participating in clinical trials that involve changes in standard immunosuppression therapy and are part of the research necessary to develop patient-centered medical interventions.
Subject(s)
Kidney Transplantation , Research Subjects , Adult , Cause of Death , Clinical Trials as Topic , Female , Follow-Up Studies , Graft Rejection/etiology , Humans , Italy/epidemiology , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Middle Aged , Patient SelectionABSTRACT
We present a case report of visceral leishmaniasis in an elderly kidney transplant recipient (age, 73 years) with high intermittent fever in the 2 months before admission. Symptoms started 16 years after transplant. The patient received appropriate treatment with liposomal amphotericin and experienced transient increases in serum creatinine levels. Progression to dialysis was avoided with short duration of therapy (5 consecutive days, plus 1 more dose 1 week apart, a schedule alternative to 15-21 days [supported by the literature]) and a temporary reduction in tacrolimus exposure. After 4 months, recurrence of symptoms without other explanation required a second bone marrow aspirate; it revealed the persistence of amastigote forms. Visceral leishmaniasis is a potentially life-threatening infection; to the best of our knowledge, this is the oldest transplanted patient with a case of leishmaniasis described in the literature.
Subject(s)
Acute Kidney Injury/complications , Amphotericin B/therapeutic use , Antiprotozoal Agents/administration & dosage , Kidney Transplantation , Leishmaniasis, Visceral/complications , Leishmaniasis, Visceral/parasitology , Aged , Antiprotozoal Agents/therapeutic use , Creatinine/blood , Female , Fever/etiology , Humans , Liposomes , Male , Recurrence , Renal Dialysis/adverse effects , Tacrolimus/therapeutic use , Transplant RecipientsABSTRACT
Encapsulating peritoneal sclerosis is a serious complication of peritoneal dialysis and can occur even after transplant. The gut is partially or totally enveloped by a thick fibrous membrane that leads to the formation of multiple sections containing intestinal loops contracted and reduced in volume. Exacerbation after renal transplantation is a very rare but sometimes dramatic condition. We report a patient who developed intestinal obstruction due to encapsulating peritoneal sclerosis 1 year after a deceased-donor kidney transplant. Treatment included laparotomy, small-bowel lengthening by release of adhesions, and high doses of corticosteroids. The patient received immunosuppressive therapy with a combination of low-dose cyclosporine, everolimus, and prednisone, unchanged except for a temporary steroid increase in the postoperative period. We report success with this combined surgical plus medical therapy, with no recurrence after 81 months of follow-up.
Subject(s)
Calcineurin Inhibitors/administration & dosage , Cyclosporine/administration & dosage , Glucocorticoids/administration & dosage , Immunosuppressive Agents/therapeutic use , Peritoneal Fibrosis/drug therapy , Sirolimus/analogs & derivatives , Adult , Drug Therapy, Combination , Everolimus , Female , Humans , Intestinal Obstruction/etiology , Kidney Transplantation , Peritoneal Dialysis , Peritoneal Fibrosis/complications , Prednisone/administration & dosage , Sirolimus/therapeutic useABSTRACT
BACKGROUND: The evaluation of a potential living kidney donor (LKD) leads to exclusion of at least 50% of candidates. The aim of this study was to analyze the reasons for exclusion of potential LKDs referred to our center. METHODS: We retrospectively analyzed historic and clinical data of all potential LKDs who were evaluated over 7 years from January 2005 to March 2012. Data were obtained by review of an electronic database. RESULTS: Among 79 (50 female, 29 male) candidates, 24 (30.3%) successfully donated, comprising 22 related and 2 unrelated donors. We excluded 45 (56.9%), and 10 (12.6%) are actively undergoing evaluation. Reasons for exclusion were medical (n = 14; 31%), nonmedical (n = 18; 40%), positive cross-match (n = l7.7%), pregnancy (n = 2; 4.4%), and other reasons (n = 3; 6.6%). Of the 14 donors excluded for medical reasons, 75.8% were due to diabetes, cardiovascular disease, hypertension, or obesity and 21.5% to inadequate renal function, malignancy, or liver disease. Of the 18 (40%) excluded for nonmedical reasons, 6 (33.3%) were because the intended recipient received a deceased-donor transplantation before the evaluation could be completed, 5 (27.7%) because the recipient was no longer a candidate for transplantation, 5 (27.7%) because of donor withdrawal, and 2 (11.1%) for other reasons. CONCLUSIONS: Positive cross-match and deceased-donor transplantation during the evaluation process were the 2 most common reasons for LKD exclusion. Evaluation of potential LKDs is time consuming, requiring a remarkable amount of human and material resources. A dedicated pathway for the diagnostic work-up of LKDs may speed- the evaluation process and improve its efficiency, use of ABO-incompatible or paired-exchange donations may increase the yield of donor organs.
Subject(s)
Kidney Transplantation , Living Donors/supply & distribution , Adult , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Cardiovascular (CV) disease is the first cause of death after kidney transplantation. Left ventricular hypertrophy (LVH) is one of the main CV risk factors. It has been reported that the antiproliferative properties of everolimus (EVE) treatment may decrease left ventricular mass. The aim of this study was to evaluate the evolution of LVH in two groups of kidney transplant recipients receiving immunosuppressive treatment with low-dose calcineurin inhibitor (CNI) + EVE or CNI + mycophenolate mofetil (MMF). METHODS: We evaluated 104 patients of mean age 47.5 ± 13.1 years who underwent kidney transplantation between January 2006 and December 2009 pretransplant by echocardiography, which was repeated every year for 3 years during which all patients continued the initial therapy. Over the 3-year period 76 subjects were treated with MMF, and 28 with EVE. We recorded left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTD), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular end-diastolic volume and end-systolic volume during the follow-up echocardiographic evaluations. RESULTS: No differences in the evolution of the echocardiographic parameters were observed between the two groups-MMF versus EVE group: LVEDD, 50.3 ± 5.1 versus 51.2 ± 6.7 mm; IVSTD, 11.2 ± 1.9 versus 11.3 ± 2 mm; LVPWD, 10.2 ± 1.9 versus 10.5 ± 1.7 mm; relative wall thickness, 0.041 ± 0.08 versus 0.42 ± 0.08; ejection fraction, 63 ± 6% versus 61 ± 5%; and left ventricular mass index, 113 ± 28.9 versus 121.9 ± 39.4 g/m(2), respectively. Compared with pretransplant echocardiographic evaluations, similar reductions in left ventricular mass index were noted in both groups after transplantation. CONCLUSIONS: We observed that after renal transplantation there was a reduction of the LVH respect to the pretransplant dialytic status. The two immunosuppressive regimen did not influence the evolution of post-transplant LVH.
Subject(s)
Hypertrophy, Left Ventricular/therapy , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Adult , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Psoriasis, one of the most common immune-mediated inflammatory diseases of the skin is mediated by activated effector T cells. CASE REPORT: We report a case of a 56-year-old white man with a 22-year history of severe psoriasis vulgaris with plaque and joint involvement, who experienced a complete clinical remission after renal transplantation. The patient had been on hemodialysis for 6 years because of chronic renal failure caused by an undetermined chronic nephropathy. Psoriasis, which worsened over the years, was symmetrically distributed as erythematous scaly plaques that had increased until they covered about 50% of the body surface, involving mainly the abdomen, legs, back, and arms. The patient also complained of severe itching an responsive to drugs. He had been treated with topical and systemic corticosteroids and phototherapy several times without benefit. After renal transplantation he underwent immunosuppressive therapy with corticosteroids, mycophenolate mofetil (MMF), and tacrolimus (Advagraf, beginning starting dose 1 mg/kg/day, C0 10 ng/mL). RESULTS: From the early days post-surgery the patient reported a fast improvement in the itching with progressive reduction of the skin lesions. After 4 months follow-up the psoriasis had completely regressed, presumably due to the immunosuppressive regimen. CONCLUSION: This finding suggests that systemic immunosuppressive drugs may be useful for psoriasis an responsive to conventional therapy.
Subject(s)
Kidney Transplantation , Psoriasis/therapy , Humans , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Male , Middle Aged , Psoriasis/complications , Psoriasis/physiopathology , Remission InductionABSTRACT
OBJECTIVE: This study investigated whether switching from the twice-daily (Prograf; TAC) to the once-daily formulation of tacrolimus with extended release (Advagraf; XL) affected quality of life, anxiety, and transplant benefit perception after allogeneic kidney transplantation. METHODS: After local Institutional Review Board approval, 78 adult patients prescribed twice-daily tacrolimus for ≥1 year after kidney transplantation were asked to participate in this study. All patients were evaluated at T0 (before the switch), and the 49 who accepted the change were reassessed after 6 months (T1). The following tests were used: (State and Trait Anxiety Inventories Y1 and Y2, (Psychologic General Well-Being Index), and modified Transplant Effect Questionnaire for posttransplantation symptoms. Blood samples for laboratory profiles and determinations of drug concentrations were obtained throughout the study period. RESULTS: There were no significant differences between the psychologic variables at T0 among patients who switched from TAC to XL (n=49) versus those who did not participate (n=29). Eight of the 49 patients who accepted the drug conversion were reswitched to TAC because of adverse events. At T1, the remaining switched patients (n=41) showed an increase in the disclosure of having undergone transplantation (P<.05) versus nonswitched patients; whereas reswitched patients (n=8) showed less positivity and well-being (P<.05) compared with those who remained in the switched regimen. CONCLUSION: The findings suggested increased disclosure of having undergone transplantation among patients who decided to switch from TAC to XL.
Subject(s)
Anxiety/etiology , Graft Rejection/prevention & control , Health Knowledge, Attitudes, Practice , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Perception , Quality of Life , Tacrolimus/administration & dosage , Adult , Aged , Analysis of Variance , Delayed-Action Preparations , Drug Administration Schedule , Drug Monitoring , Female , Graft Rejection/immunology , Graft Rejection/psychology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/blood , Italy , Kidney Transplantation/immunology , Kidney Transplantation/psychology , Male , Middle Aged , Psychiatric Status Rating Scales , Surveys and Questionnaires , Tacrolimus/adverse effects , Tacrolimus/blood , Time Factors , Treatment Outcome , Truth DisclosureABSTRACT
INTRODUCTION: The extremely good results of renal transplantation have favored the use of pre-emptive procedures for treatment of patients with end-stage renal disease before entering dialysis, but still some concerns exist about patient survival. The aim of this study was to analyze the evolution of death rates and the causes of mortality among recipients of procedures performed between 1970 and 2007. METHODS: We examined the outcomes at 1, 5, 10, and 15 years follow-up of 793 adults who underwent primary or repeat renal transplantation from living or deceased donors between January 1, 1970 and December 31, 2007. To evaluate the impact of immunosuppressive regimens on patient survivals, we considered 3 time intervals: the precyclosporine era, the cyclosporine era, and the postcyclosporine era. RESULTS: During follow-up 115/793 (14.5%) renal transplant recipients died. There was a significant decrease in the overall mortality rate over the years. Patients who underwent transplantation more recently in the postcyclosporine era (1997-2007) showed a mortality rate of 1.8% (7/394) at 1 year and 3.3% (13/394) at 5 years, significantly lower than in previous periods. There was no significant change in the most frequent causes of death: cardiovascular diseases and sepsis. CONCLUSION: Our data indicated a significant improvement in patient survival after renal transplantation over the last decade. These data are significantly better than those reported for dialysis treatment thus supporting the strategy of pre-emptive transplantation for end-stage renal disease.
Subject(s)
Kidney Transplantation , Survival Rate , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , ReoperationABSTRACT
The optimal regimen for perioperative antibiotic prophylaxis after renal transplantation remains to be determined. Worldwide, it seems there is a trend toward decreased use of prophylaxis from the first 48 hours to several days after surgery. However, bacterial strains resistant to common antibiotic agents arise even if only a single dose of a molecule is administered at any time. Inasmuch as infections currently are the primary cause of hospitalization after renal transplantation, it is desirable to not favor selection of resistant strains that may not be treated appropriately in the event of onset of infection. Therefore, antibiotic therapy, whether for therapeutic or prophylactic purposes, should be administered based exclusively on clinical evidence. Because systemic antibiotic prophylaxis is not effective against infections of the urinary tract, the objective of perioperative antibiotic prophylaxis should be to prevent infection of the surgical wound. In this case, administration of a single dose of an antibiotic agent (1-shot regimen) at the induction of anesthesia is effective and safe. For these reasons, it is urgent that new guidelines be defined for perioperative antibiotic prophylaxis. Multicenter prospective randomized trials comparing 1-shot vs multiple-dose regimens should be performed to establish the optimal regimen.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Kidney Transplantation/physiology , Surgical Wound Infection/prevention & control , Anti-Bacterial Agents/adverse effects , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , SafetyABSTRACT
INTRODUCTION: The half-life of everolimus is approximately 28 hours, but everolimus is normally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day (OD) everolimus regimen versus the standard twice a day regimen (BID) for immunosuppressive therapy in renal transplantation. METHODS: Forty de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 19) were followed for 6 months. In the OD group, everolimus was given orally once a day to target a trough blood level of 2-6 ng/mL. In the BID, group everolimus was given twice a day to target a trough blood level of 3-12 ng/mL. All patients also received induction treatment with basiliximab and low-dose calcineurin inhibitors. RESULTS: At 6 months follow-up, patient and graft survivals were 100%; renal function and acute rejection rates were similar between the 2 regimens. Patients in the OD group showed significantly lower cholesterol and triglyceride levels compared with those in the BID group, namely, total cholesterol level, OD 212 +/- 54 versus BID 249 +/- 59 mg/dL (P < .05), and serum triglycerides, OD 162 +/- 72 versus BID 245 +/- 133 mg/dL (P < .02). DISCUSSION: This study showed that OD administration of everolimus provided excellent patient and graft survivals and good renal function without an increased incidence of acute rejection episodes. The lipid profile was significantly better among patients receiving everolimus OD. These findings suggested that everolimus can be safely administered once a day.
Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Sirolimus/analogs & derivatives , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Basiliximab , Cholesterol/blood , Drug Administration Schedule , Drug Therapy, Combination , Everolimus , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/physiology , Male , Middle Aged , Pilot Projects , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Safety , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Time Factors , Tissue Donors/statistics & numerical data , Triglycerides/bloodABSTRACT
OBJECTIVE: The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus. PATIENTS AND METHODS: Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids. RESULTS: At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 +/- 38 vs EVL 250 +/- 55 mg/dL; P < .003). CONCLUSIONS: This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.
Subject(s)
Graft Rejection/mortality , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Adult , Cyclosporine/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Everolimus , Female , Follow-Up Studies , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Kidney Function Tests , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Prospective Studies , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Tacrolimus/administration & dosage , Transplant Recipients , Treatment OutcomeABSTRACT
Everolimus (EVL) has shown a potential to reduce nephrotoxicity associated with cyclosporine (CsA) while providing similar protection against rejection. We analyzed the incidence of acute rejection episodes (ARE) among 20 cadaveric renal transplant recipients treated with the combination of EVL + CsA. Immunosuppression consisted of basiliximab induction given pretransplant and on day 4 posttransplant; EVL at a starting dose of 1.5 mg/day followed by concentration control to trough levels of 3 to 8 ng/mL by day 7; CsA at a starting dose of 4 mg/kg per day and then concentration controlled with C2 monitoring (C2 500-700 ng/mL); and steroids in a tapering regimen to reach 5 mg by day 30. The overall incidence of ARE was 25%. On postoperative day 7, patients with ARE showed significantly lower mean EVL trough concentrations compared with those not experiencing ARE (NO ARE: 2.2 +/- 2.1 ng/mL vs 4.8 +/- 2.4 ng/mL) (P = .05). The CsA C2 values were close to the lower end of the target range on day 3 (583 +/- 334 ng/mL). All rejecting grafts were functioning at 3 months posttransplantations, but mean serum creatinine was higher in the ARE group (ARE 2.2 +/- 0.7 mg/dL vs 1.1 +/- 0.2 NO ARE; P = .04). In conclusion, whenever EVL is used in combination with CsA to protect kidney transplant patients against the risk of acute rejection, a threshold of 3 ng/mL must be reached in the first week posttransplantation. We suggest careful monitoring of EVL exposure and increased EVL starting doses.
Subject(s)
Graft Rejection/immunology , Kidney Transplantation/immunology , Sirolimus/analogs & derivatives , Antibody Formation , Autoantibodies/blood , Biopsy , Everolimus , Graft Rejection/epidemiology , Graft Rejection/pathology , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Kidney Transplantation/pathology , Sirolimus/therapeutic useABSTRACT
Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.
Subject(s)
Cyclosporine/adverse effects , Diabetes Mellitus/epidemiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Sirolimus/adverse effects , Adult , Drug Therapy, Combination , Female , Humans , Hypoglycemic Agents/therapeutic use , Incidence , Insulin/therapeutic use , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective StudiesABSTRACT
Lymphocele is a complication of renal transplantation, representing a lymphatic collection around the grafted kidney. The use of the immunosuppressive agent sirolimus (SRL) has been associated with a significant increase in lymphocele formation. This complication has been related to the antiproliferative activity of SRL, which delays surgical wound repair and closure of injured lymphatic vessels. The aim of this study was to relate the incidence of lymphocele with immunosuppression among 158 renal transplant patients operated with routine closure of all the visible lymphatic vessels around the iliac vessels and at the renal hilum. The incidence of lymphocele was not significantly different among the various immunosuppressive regimens.
Subject(s)
Kidney Diseases/surgery , Kidney Transplantation/adverse effects , Lymphocele/etiology , Drainage , Humans , Immunosuppressive Agents/adverse effects , Incidence , Lymphocele/epidemiology , Postoperative Complications/epidemiology , Renal Replacement Therapy , Sirolimus/adverse effectsABSTRACT
The hockey-stick surgical incision is becoming more popular than the oblique incision for kidney transplantations. Both incisions are convenient and comfortable. Both have some drawbacks, such as muscle denervation for the former, or section of lateral muscles for the latter. In this retrospective study, we compared these incisions with regard to the incidence of long-term complications, such as postincisional hernia, relaxation of the abdominal wall, and a poor cosmetic result. One hundred patients (50 of each type) were evaluated at an average of 4.5 years after transplantation (3 months-15 years). Occurrence of incisional hernia was 16% in the former (8 cases) versus 4% in the latter (2 cases: X(2) = 4; P < .05). A major relaxation of the abdominal wall was found in 24% of the former (12 cases) versus 8% of the latter (4 cases) (X(2) = 4.76; P < .05). These complications were not correlated with age, sex, weight, side of transplant, or immunosuppressive drugs. In the former patients with hockey-stick incisions, the overall cosmetic results were poor, because in most cases the incision had been prolonged upward, above the transverse umbilical line, even as high as the costal arch. In 20% of the former patients with hockey-stick incisions, the scar had widened, particularly in the upper vertical branch of the J incision. We conclude that the final outcome of the oblique surgical incision was better than the hockey-stick incision because of the lower incidence of hernia and abdominal wall relaxation and the more favorable cosmetic results.
Subject(s)
Kidney Transplantation/methods , Denervation , Female , Follow-Up Studies , Hernia/epidemiology , Hernia/etiology , Humans , Kidney Transplantation/adverse effects , Male , Muscles/innervation , Postoperative Complications/classification , Retrospective Studies , Time FactorsABSTRACT
BACKGROUND: Abdominal aortic aneurysms (AAA) requiring surgical management are encountered more frequently in renal transplant recipients, presenting an important technical problem during the repair. The aim of the present study was to analyze the epidemiology and natural evolution of AAA among renal allograft recipients. METHODS: Three hundred ninety-four renal transplant recipients were periodically evaluated with abdominal aortic ultrasound tomography for AAA. The indication for surgery was a maximal diameter >5 cm. Renal function, graft, and patient survival were evaluated after a mean follow-up of 51 months. RESULTS: Four AAA were detected in 394 renal transplant recipients, a prevalence of 1.01%. All of the AAA were found in male recipients of mean age 59.2 +/- 5.5 years and mean time posttransplantation of 82.7 +/- 77.3 months. The mean follow-up period between diagnosis and indication for surgery was 14.2 +/- 10.8 months. Two patients underwent open repair with aneurysmectomy and conventional tube graft positioning, and 2 patients refused surgical repair. To preserve renal graft function during the aortic cross-clamping phase, cold perfusion with 4 degrees C Ringer acetate and local hypothermia with sterile ice were used. Renal function did not change after the operation (preoperative serum creatinine levels were 1.2 and 1.3 mg/dL; postoperative 1.3 and 1.5 mg/dL respectively). The 2 patients who underwent surgery are alive with excellent graft functioning after a follow-up of 1.5 and 7 years, respectively. The 2 patients who refused surgical treatment are dead. CONCLUSIONS: Yearly ultrasound screening for AAA must be recommended in renal transplant recipients as part of the routine posttransplantation follow-up. De novo AAA occurs in younger subject in the transplant population and shows a faster evolution.