A randomized trial of everolimus and low-dose cyclosporine in renal transplantation: with or without steroids?

This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroid-free immunosuppression in renal transplant recipients receiving everolimus.

Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting further detailed exercise protocols and to fostering improved posttransplantation health and survival, helping to ensure that physical activity becomes a safe routine medical treatment plan of patient management.

The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

Pretransplant donor biopsy (PTDB)-based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score<4 [median KDPI: 87; interquartile range (IQR): 78-94] and 62 with a score=4 [median KDPI: 87; IQR: 76-93]; 102 dual transplants [median KDPI: 93; IQR: 86-96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18-51). PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year estimated GFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9 and -18.8 mL/min, for dual transplants, single kidneys with PTDB score<4 and =4, respectively; p<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80-1.79; p=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

Renal transplant in patients with polycystic disease: the Italian experience.

We analyzed the results of kidney transplantation in autosomal dominent polycystic kidney disease (ADPKD) patients in Italy, including 14,305 transplantations performed from January 2002 to December 2010, including: 12,859 first single or double kidneys from cadaveric donors (13% polycystic), 172 combined liver-kidney cases (22% polycystic), and 1,303 living-donor organs (7% polycystic). Among the first transplantations (12,008 single, 851 double), with follow-ups ranging from 16 to 120 months, polycystic patients demonstrated better graft survival compared with other kidney diseases (86% vs 82% at 5 years; P < .01); mortality was not different (92% vs 79% at 1 year). A better trend was obtained also among combined liver-kidney transplantations in ADPKD. Regarding pretransplantation management of polycystic patients, we noticed a conservative attitude in 32/35 transplant centers. The main indication for nephrectomy was for the lack of abdominal space. Regarding instrumental studies, 86% of centers asked for second-level investigations computerized tomography for kidney dimensions. Radiologic investigations for vasculocerebral malformations were required in 97% of the centers: 74% as a routine and 23% in the presence of familial history of cerebral hemorrhage. Polycystic patients are good candidates for kidney transplantation with correct management before transplantation.

Incidence of late deep venous thrombosis among renal transplant patients.

BACKGROUND: Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. METHODS: From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. RESULTS: A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. CONCLUSIONS: Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.

Induction therapy with alemtuzumab (campath) in combined liver-kidney transplantation: University of Bologna experience.

BACKGROUND: Combined liver-kidney transplantation (LKT) is considered to be a safe procedure, but the appropriate immunosuppressive regimen is unclear. PATIENTS AND METHODS: Between January 1997 and October 2011, 55 patients were listed for LKT: 45 (82%) were effectively transplanted, 5 (9.2%) died whereon here the waiting list, 3 (5.5%) temporarily out of waiting list, 1 (1.8%) was on waiting list and 1 (1.8%) refused LKT. Five LKTs treated with cyclosporine (CyA) were excluded from the analysis. Mean recipient age was 50.32 ± 10.32 years (14-65), MELD score at time of LKT was 19.22 ± 4.69 (8-29), mean waiting list time was 8.14 ± 9.50 months (0.1-35.76), and follow-up, 4.09 ± 3.02 years (0.01-10.41). Main indications for LKT were policystic disease (n = 15; 37%), hepatitis virus C (HCV)-related cirrhosis (n = 9; 22%) metabolic disease (n = 5; 13%), hepatitis virus B (HBV) cirrhosis (n = 4; 10%), alcoholic cirrhosis (n = 4; 10%), and cholestatic disease (n = 3; 8%). Immunosuppressive regimen was based on tacrolimus and steroids in 40 cases with induction therapy with alemtuzumab (Campath; 0.3 mg/kg) in 13 of 40 instances cases administered on day 0 and day 7. RESULTS: Postoperative mortality was 2.5%. Acute cellular rejection episodes were biopsy-proven in 2 (5%) cases, post-LKT infections developed in 17 cases (42.5%), and de novo cancer developed in 3 (7.5%) cases. Similar 5-year overall survivals were obtained irrespective of the LKT indication: 100% in cholestatic and alcoholic cirrhosis patients, 86% in policystic disease, 75% in metabolic disease and HBV patients, and 66% in HCV cirrhosis. Overall survivals for the alemtuzumab vs without-induction therapy groups at 1, 3, and 5-years were 100%, 85.7%, and 85.7% vs 76%, 76%, and 70%, respectively (P = .04). CONCLUSION: An immunosuppressive regimen based on tacrolimus and steroids with induction therapy with alemtuzumab was safe, with excellent long-term results for combined LKT.

Family recurrence and oligo-anuria predict uremic restless legs syndrome.

OBJECTIVES: To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD). MATERIALS AND METHODS: One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. RESULTS: Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS- patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. CONCLUSION: Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.

Physical performance in kidney transplanted patients: a study on desert trekking.

Physical performance of kidney transplanted patients in challenging environments, such as deserts, has been poorly studied. Six kidney transplanted (T: 5 males, 1 female; 45±6 yrs) and 8 control (C: 5 males, 3 females; 49±13 yrs) subjects participated in a 5-day desert trek. Blood pressure, hydration status (Height2/Rz by bioimpedance), heart rate, energy expenditure (by SenseWear Pro Armband) and walking velocities were recorded during each daily trekking stage (GPS-assisted wearable devices). Systo-diastolic blood pressure did not differ between C (119/77±12/8 mmHg) and T (121/77±10/6 mmHg) groups throughout the study. The hydration status was stable from day 1 (Ht2/Rz: 64±13 cm2/Ohm in T and 59±12 cm2/Ohm in C subjects) to day 5 (66±11 cm2/Ohm in T and 61±13 cm2/Ohm in C subjects) in both groups. Two patients on steroid treatment showed a relative hyperhydration. Mean heart rate did not differ between T (135±10 bpm) and C (136±5 bpm) subjects throughout the study, although a reduction from day 1 to day 5 was observed in T subjects only (p<0.05 vs C group). No differences were found between T and C group in walking velocity (1.7±0.6 km/h in T and 1.7±0.5 km/h in C group); mean intensity of physical activity was 3.4±0.5 METs in T and 3.3±0.6 METs in C group during each trekking stage. Negligible differences were observed in cardiovascular, metabolic and hydration status adaptations to desert trekking between selected T and C individuals. T subjects with creatinine clearance > 55 ml/min showed acceptable physical performance and acclimatization to desert environment, suggesting a good long-term outcome of transplantation.

Analysis of 80 dual-kidney transplantations: a multicenter experience.

INTRODUCTION: The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers. MATERIALS AND METHODS: Between 2001 and 2007, DKT (n = 80) were performed based upon the ECD kidney allocation assessed by biopsy. RESULTS: The average donor ages for the DKT, edSKT, and idSKT groups were 68.8 ± 7.8, 65.3 ± 7.2, and 40.1 ± 13.8 years, respectively (P < .001). The number of human leukocyte antigen mismatches was greater in the DKT group (3.1 ± 1.2, P < .05). Patient and graft 5-year survival rates were similar among DKT, edSKT, and idSKT recipients, namely, 97.5% versus 95.8% versus 96.9% and 93.7% versus 87.4% versus 86.9%, respectively. Mean serum creatinine values at discharge were lower in the DKT and idSKT recipients (1.5 ± 0.9 and 1.6 ± 0.7 mg/dL; P < .05) compared with the edSKT group (1.9 ± 0.7 mg/dL). Correlations between supposed prognostic factors and survival among the DKT group noted worse outcomes in reoperation cases (P < .05). CONCLUSION: We confirmed that DKT produced successful outcomes. An accurate surgical procedure is particularly important to try to avoid reoperations. In our experience, the use of a biopsy as an absolute criterion to allocate ECD kidneys may be too protective.

Incidence of cancer in kidney transplantation waiting list patients: a single center experience.

INTRODUCTION: It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). RESULTS: Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. CONCLUSION: The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

The influence of intraoperative central venous pressure on delayed graft function in renal transplantation: a single-center experience.

INTRODUCTION: Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. METHODS: One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. RESULTS: CVP at awakening of ≤8 mm Hg (odds ratio [OR] = 3.53; 95% confidence interval [CI], 1.63-7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00-4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11-6.68) were the strongest correlates of DGF. CONCLUSIONS: Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.

A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

Native kidney function after renal transplantation combined with other solid organs in preemptive patients.

Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, namely liver-kidney (LKT), or heart-kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 +/- 8.5 years) with chronic kidney failure (creatinine 2.5 +/- 1.0 mg/dL) caused by polycystic kidney disease (n = 4), vascular nephropathy (n = 2), interstitial nephropathy (n = 1), glomerulonephritis (n = 1), or end-stage kidney disease (n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 +/- 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 +/- 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 +/- 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.

Alpine skiing and anaerobic performance in solid organ transplant recipients.

Limited information has been published about sporting activities in solid organ transplant recipients. The aim of this study was to assess "in the field" performance capacities of a group of transplant recipients involved in an alpine skiing competition. We studied 16 transplant recipients (13 men and 3 women) who had undergone transplantations (11 kidney, 4 liver, and 1 heart) at 89 +/- 68 months prior while participating in an alpine skiing race. The patients performed a countermovement jumping test to measure the explosive power of the lower limbs. In all patients blood lactate concentrations (La) were measured at the end of a giant slalom race. The maximum displacement of the center of mass during the jumping test was 22.4 +/- 9.3 cm; the time to complete the giant slalom was 75.5 +/- 16.5 seconds and La was 3.5 +/- 0.8 mmol/L. We observed significant linear relationships between race time and La (R(2) = 0.4733; P < .01) and between race time and performance in the jumping test (R(2) = 0.3655; P < .05). This study indicated that recovery of anaerobic and technical sporting activities is possible in organ transplant recipients. Muscular power and anaerobic performances among a selected group of solid organ transplant recipients were similar to those of the general untrained population.

Importance of renal mass on graft function outcome after 12 months of cadaveric donor kidney transplantation.

BACKGROUND: Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation. METHODS: We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation. RESULTS: The mean kidney weight was 201.4 +/- 10.2 g (200.5 +/- 11.6 g in women and 210.3 +/- 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01). CONCLUSION: The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.

The cardiovascular burden of end-stage renal disease patients.

Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

A case of Paget's disease in hemodialysis.

Paget's disease is the second most common bone disease after osteoporosis and causes an excessive bone turnover. Moreover, chronic kidney failure causes an impairment of bone mineral metabolism and electrolytes and PTH homeostasis. As far as we know, this is the first reported case of Paget's disease in a hemodialysis patient: the patient was also affected by secondary hyperparathyroidism and was successfully treated with clodronate, cinacalcet and paracalcitol. The safety and efficacy of this combined therapy was periodically revised in a 12-month follow-up considering the common markers of bone turnover as well as the dosage of OPG, RANKL, IL-6 and MCSF, involved in the pathophysiology of Paget's disease.

Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

[Factors determining cardiovascular disease progression after kidney transplant]. / I fattori di progressione della malattia cardiovascolare dopo trapianto renale.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

[Clinical evaluation of living donor]. / La valutazione clinica del donatore vivente.

When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation.