Expanding the Living Donor Pool "Second Act": Laparoscopic Donor Nephrectomy and ABO-Incompatible Kidney Transplantation Improve Donor Recruitment.

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.

Conversion from Prograf to Advagraf in stable kidney transplant recipients: better renal function after 3-year follow-up.

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.

Do patients who participate in a clinic experimental protocol have the same probability of success from that who were not selected or refused to participate? Outcome surveillance, safety, and bioethical considerations in kidney transplant clinical research.

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.

Elderly kidney transplant recipient with intermittent fever: a case report of leishmaniasis with acute kidney injury during liposomal amphotericin B therapy.

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.

Posttransplant encapsulating peritoneal sclerosis, long-term success with everolimus and low-dose CNI: a case report.

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.

Expanding the living donor pool, "Ist Act": analysis of the causes of exclusion of potential kidney donors.

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.

The reduction of left ventricular hypertrophy after renal transplantation is not influenced by the immunosuppressive regimen.

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.

Metabolic syndrome and cardiovascular disease in kidney transplantation.

INTRODUCTION: Metabolic syndrome (MS) is an important cardiovascular risk factor. The aim of this study was to evaluate the incidence of MS in an Italian kidney transplant recipient population and its relationship to the incidence of major adverse cardiovascular events (MACE) after renal transplantation. METHODS: The prevalence of MS was evaluated according to the National Cholesterol Education Program Adult Treatment Panel III criteria among adult recipients who underwent a renal transplant between January 1997 and December 2007. In this period, we prospectively recorded the incidence of MACE to be related to the presence of MS. RESULTS: We included 425 kidney transplant recipients in the study including 62% males and an overall median age 46 years (interquartile range=36-54). The prevalence of MS was 41.2% at 6 months after transplantation and 46.6% at 5 years. During the follow-up (median=5.1 years), 32 patients (7.5%) experienced at least one MACE. The detection of MS at 6 months after transplantation was significantly associated with an increased risk of MACE occurrence (MS IRR=2.2 P=.05). CONCLUSIONS: Our findings indicated that MS was largely present in the transplant population confirming that as in the general population, it was a significant risk factor for the occurrence of severe cardiovascular disease. Early identification and treatment of patients with MS may improve long-term patient survival.

Once-a-day administration of everolimus is safe in de novo renal transplant recipients: 1-year results of a pilot study.

INTRODUCTION: The half-life of everolimus is approximately 28 hours, but everolimus is generally 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 everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation. METHODS: Forty-one de novo renal transplant recipients prospectively assigned to OD (n=21) or BID (n=20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression. RESULTS: At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P=NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P=NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P<.001). DISCUSSION: This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes.

Evolution of causes of mortality in renal transplantation in the last 10 years.

INTRODUCTION: Improvements in immunosuppressive therapy have significantly changed results of organ transplantation. The aim of this study was to review the causes of mortality among our renal transplant population. METHODS: This study population included 750 patients who underwent kidney transplantation between 1970 and 2007. During the follow-up, we recorded all causes of death and major cardiovascular events: stroke, myocardial infarction, angina pectoris, and cardiac death were considered major adverse cardiovascular events (MACE) The occurrence of MACE was related to wellestablished cardiovascular risk factors-age, sex, arterial blood pressure, diabetes, renal function, cardiovascular body mass index, history, or dyslipidemia measured at 6 months, as well as 5 and 10 years after transplantation. At these times we also calculated the INDANA, Framingham, and ltalian Heart Project scores. RESULTS: The median follow-up was 63 months and mean age was 45 +/- 11 years. The median waiting time for transplant was 34 months. During follow up, 22 patients (6.1%) developed MACE, with 2 (0.55%) events within 6 months 10 (3.1%) between 6 months and 5 years, and 10 (6.5%) between 5 and 10 years. The INDANA score at all the time periods was significantly different among patients with vs without MACE (P < .0001), whereas no significant difference was observed using the Framinghan or the Italian Heart Project scores (P < .11). CONCLUSION: Our study indicated that the INDANA scoring system better predicted the risk of MACE as approved to the Framinghan or Italian Heart Project systems. The INDANA score might be used to plan selective cardiovascular screening among recipients.

Induction with basiliximab plus thymoglobulin is effective and safe in old-for-old renal transplantation: six-month results of a prospective clinical study.

Old-for-old renal transplantation is becoming more frequent, but the optimal immunosuppressive regimens for this transplant population are still unclear. The aim of this pilot prospective study was to evaluate the efficacy and safety of the combination of basiliximab with a short course of low-dose thymoglobulin induction therapy among a group of patients receiving kidneys from donors >60 years (OLD), compared with those receiving organs from donors <60 years (YNG). Forty-six consecutive deceased donor kidney transplant patients received induction therapy with a combination of basiliximab (20 mg IV on days 0 and 4) and thymoglobulin (200 mg total dose IV on days 0-3). As maintenance immunosuppression starting on day 4, patients received a low dose of calcineurin inhibitor and steroids. Demographic characteristics at baseline were not significantly different between the 2 groups. At 6 months, patient survival, graft survival, and acute rejection rates were similar between the YNG and OLD groups: 100% and 95%, 96% and 95%, and 8% and 0%, respectively. Patients in the OLD group showed higher serum creatinine concentrations (YNG 1.5 +/- 0.3 vs OLD 1.9 +/- 0.3 mg/dL; P = .0002) but not proteinuria (YNG 0.11 +/- 0.11 vs OLD 0.15 +/- 0.14 g/24 h; P = ns). No significant difference was evident between the 2 groups regarding infectious, hematologic, or posttransplantation lymphoproliferative disorder complications. This study showed that a combination of basiliximab and a short course of low-dose thymoglobulin provided effective and safe immunosuppression, in old-for-old renal transplantation, with good renal function without an increased risk of posttransplantation infectious or hematologic complications.

Once daily everolimus is safe and effective in de novo renal transplant recipients: six-month results of a pilot study.

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.

Prospective clinical trial comparing two immunosuppressive regimens, tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine, in de novo renal transplant recipients: results at 6 months follow-up.

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.

Cardiovascular risk profile in kidney transplant recipients treated with two immunosuppressive regimens: tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine.

OBJECTIVE: The aim of this prospective study was to compare the cardiovascular risk (CVR) profile in patients treated with 2 different immunosuppressive regimens: tacrolimus and mycophenolate mofetil (TAC) compared with everolimus and low-dose cyclosporine (EVL). PATIENTS AND METHODS: Sixty consecutive renal transplant recipients prospectively assigned to TAC (n = 30) or to EVL (n = 30) were followed for 6 months. TAC group immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroid. EVL group immunosuppression consisted of basiliximab, everolimus, and low doses of cyclosporine and steroid. Main CVR factors analyzed were: hypertension, dyslipidemia, posttransplant diabetes mellitus, and weight gain. RESULTS: Six months posttransplantation, patients in the EVL group showed significantly higher mean serum cholesterol (P < .003) and serum triglyceride levels (P < .027), as well as a greater number of patients were receiving statin treatment (P < .05). Mean systolic blood pressure, mean diastolic blood pressure, number of patients treated for hypertension, number of antihypertensive medications prescribed per patient, posttransplant weight gain, and posttransplant diabetes mellitus were not significantly different among the EVL and TAC groups after 1, 3, and 6 months posttransplantation. CONCLUSIONS: This study showed that at 6 months posttransplantation, patients on EVL displayed significantly greater dyslipidemia with respect to the TAC group. A longer follow-up will be necessary to discover whether the presence of everolimus in the immunosuppressive regimen provides significant benefits for the CVR of renal transplant recipients.

Long-term clinical impact of vesicoureteral reflux in kidney transplantation.

INTRODUCTION: It is unclear whether the presence of vesicoureteral reflux (VUR) after renal transplantation compromises long-term graft function. The aim of this study in renal allograft recipients with a history of late recurrent urinary tract infections (UTI) was to determine whether the presence of VUR conferred an increased risk of long-term graft dysfunction. METHODS: We included 37 renal allograft recipients, who were at least 2 years after transplantation and had a history of at least 1 recurrent UTI per year underwent voiding cystourethrograms (VCUG). The presence and severity of VUR were graded with severity scores ranging from G1 to G5. RESULTS: Of the 37 patients, 15 (41%) showed low grades of reflux (G1-3) on VCUG. Patient and graft survivals were not significantly different in the VUR group (n = 15) compared with the no VUR group (n = 22) at 1, 3, or 5 years. Renal function assessment by means of serum creatinine (Cr) concentration also demonstrated similar results in both groups at 1, 3, and 5 years: 5 y mean Cr: VUR 1.5 +/- 0.6 mg/dL versus no VUR 1.8 +/- 1.1 mg/dL (P = NS). No difference was also observed in the 2 groups in the number of UTI episodes for each patient per year. CONCLUSIONS: In patients with late UTIs, the presence of low-grade VUR did not affect long-term graft function. There was no indication for a operative repair of low-grade VUR.

Risk of Kaposi sarcoma after solid-organ transplantation: multicenter study in 4,767 recipients in Italy, 1970-2006.

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.

Higher incidence of acute rejection in renal transplant recipients with low everolimus exposure.

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.

Incidence of posttransplant diabetes mellitus in kidney transplant recipients immunosuppressed with sirolimus in combination with cyclosporine.

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.

[Evaluation of the in vitro activity of aztreonam on 1990 gram-negative bacterial strains recently isolated in Campania hospitals]. / Valutazione dell'attività in vitro dell'aztreonam su 1990 ceppi batterici gram-negativi di recente isolamento ospedaliero in Campania.

The in vitro activity of aztreonam, leader of a new class of antibiotics, the monobactams, has been investigated. The effectiveness of the new molecule on 1990 strains of Gram-negative clinical isolates has been compared to that of some other drugs widely utilized for the treatment of nosocomial infections. Aztreonam has shown the highest activity against all the tested strains, with a geometrical mean of MICs (MG) of 0.37 and a MIC 90 of 8 micrograms/ml.