5 year comparison of very low-dose cyclosporine and high-dose everolimus vs standard cyclosporine and enteric-coated mycophenolate in renal transplantation patients.

In this retrospective study, we compared the outcome of renal transplanted patients who received everolimus (EVR) (C0: 8-12 ng/mL)+cyclosporine (CsA) (C2: 150-300 ng/mL)+steroids, vs those who received enteric-coated mycophenolate sodium (EC-MPS) (1,440 mg/d)+CsA (C2: 500-700 ng/mL)+steroids. Efficacy was evaluated at 5 years. We found a nonsignificant trend toward a better 5-year graft survival (81.2% vs 68.6%) and better graft function (estimated glomerular filtration rate 71.8±35.7 vs 60.0±26.2 mL/min, P=.114) in favor of the EVR group. In our experience, EVR with a very low dose of CsA was associated with a nonstatistical trend toward better renal function and graft survival compared to a standard regimen of CsA and EC-MPS.

Conversion from calcineurin inhibitors to everolimus with low-dose cyclosporine in renal transplant recipients with squamous cell carcinoma of the skin.

Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in renal transplant recipients. Conversion to mammalian target of rapamycin inhibitors after diagnosis of SCC may reduce the incidence of recurrence of skin cancer. This retrospective study evaluated the outcome of renal transplant recipients followed by the Renal Unit with posttransplant diagnosis of SCC treated with conversion from calcineurin inhibitors (CNIs) to Everolimus (EVR) associated with low-dose cyclosporine. Eleven patients developed SCC at a median time from renal transplantation of 107 months (range 36-264). Five patients with creatinine clearance (CCl) below 40 mL/min before conversion developed end stage renal disease (two cases) or further deterioration of renal function (two cases); only one patient in this group maintained a stable renal function. The remaining six patients with a CC1 greater than 40 mL/min and proteinuria below 0.8 g/24 hours maintained a stable renal function after conversion to EVR at a median follow-up of 22 months (range 15-75). Conversion from CNIs to EVR has been proven safe, effective, and associated with low recurrence of SCC in patients with a CCl >40 mL/min. In the case of preexisting deterioration of renal function or significant proteinuria, conversion to EVR should be carefully evaluated.

Contrast-enhanced ultrasound assessment of complex cystic lesions in renal transplant recipients with acquired cystic kidney disease: preliminary experience.

We prospectively studied the potential value of contrast-enhanced ultrasound (CEUS) to characterize complex acquired cystic kidney disease (ACKD) or suspected solid renal masses, avoiding the risk of inducing acute kidney injury in 138 renal transplant recipients by contrast-enhanced computed tomography (CT). Forty-three cases (31%) had ACKD; 15 ACKD patients (35%) showed suspicious or nondiagnostic ultrasound. The latter subgroup underwent CEUS and, if the suspicion was confirmed, a contrast-enhanced CT. Thirty five lesions were identified in the 15 patients studied by CEUS. According to the Bosniak classification, 27 cysts were type I (BI), four type II (BII), two type III (BIII) with enhancement at the level of thickened septa; we also identified two solid enhancing lesions (BIV). We followed the BI and BII lesions with serial CEUS, while the remaining four cases underwent contrast-enhanced CT showing two solid lesions and two complex cysts with contrast enhancement in the septea. The four patients underwent surgical resection yielding three renal cell carcinomas one papillary carcinoma as the pathological findings. This preliminary study characterized solid nodules and BIII lesions for further evaluation by CT. CEUS seems to correctly characterize BI and BII cysts that are not clearly defined by standard ultrasound.

Renin angiotensin system blockade and activated vitamin D as a means of preventing deep vein thrombosis in renal transplant recipients.

BACKGROUND: Venous thromboembolism (VTE) is one of the thrombotic complications that occur in renal transplant recipients (RTR). The observation that vitamin D receptor activators, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARBs) have a protective effect against protrombotic state suggests that their possible combination could reduce the incidence of VTE in RTR. OBJECTIVES: to evaluate the incidence of VTE in RTR and the timing of occurrence after renal transplantation (Tx); to compare the incidence of VTE in our RTR and RTR on calcitriol, ACEi, ARBs and their combination therapy. Risk factors were also evaluated. RESULTS: During follow-up, 96 of 769 RTRs, 73 males 23 females, developed a first episode of VTE: 23 in the first 3 months after Tx; 15 from 3 to 6 months; 9 from 6 to 12 months; 13 from 12 to 48 months and 36 after more than 48 months. The incidence was significantly lower in RTR on treatment with a combination of calcitriol 0.25 µg/day, an ACEi and an ARB and in RTR on treatment with only calcitriol 0.5 µg/day (9.4% and 9%, respectively, vs. 14.5% (p < 0.05)). However, the most decreased rate (5.6% vs. 14.5% (p < 0.01)) was in patients treated with a combination of calcitriol 0.5 µg/day, an ACEi and an ARB. CONCLUSION: A combination therapy with calcitriol 0.5 µg/day, ACEi, and ARB is associated with a 60% lower rate risk of VTE.

Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients.

BACKGROUND: Skin cancer (SC) is the most frequent malignancy after renal transplantation (RT), especially squamous and basal cell carcinoma. The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of skin cancer. OBJECTIVES: To evaluate the incidence of keratinocyte cancer in RT recipients, the timing of occurrence of the skin events after RT; to compare the incidence of SC in our RT recipients and in RT patients on angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers therapy (ARBs) and their combination. Risk factors were also evaluated. RESULTS: During follow up, 52 of 565 patients (9.2%), 38 males 14 females, developed SC at a median time of 59 months (range 29 - 74) after RT. 12 of 52 patients (23%) with SC were on ACEi, ARBs therapy or their combination. The incidence was significantly lower in user patients compared to non user (5.6% and 11.4% respectively). BCC was the most frequent type of keratinocyte cancer in non users and in users. No association with incidence of BCC or SCC was observed for other classes of antihypertensive drugs (calcium antagonists, beta-blockers, alpha-blockers). CONCLUSION: This study confirms that RT patients are at high risk of SC. The use of ACEi or ARBs is associated with an approximately two-fold reduced risk of Keratinocyte cancers compared to non users in RT recipients. We did not observe an association between the incidence of SC and the use of other classes of antihypertensive drugs. Any chemoprotective effect of these agents may reflect inhibition of the growth factor activity of angiotensin II. Use of ACEi or ARBs, when this is possible, should be considered in RT patients with multiple risk factors.

Preemptive therapy for the prevention of cytomegalovirus disease in renal transplant recipients: our preliminary experience.

BACKGROUND: Cytomegalovirus (CMV) disease represents an important cause of morbidity in renal transplant recipients. We report our preliminary evaluation of the efficacy and security of preemptive therapy to manage renal transplant recipients with evidence of active CMV replication. METHODS: Preemptive therapy with gancyclovir and/or valgancyclovir (VGCV) was recently substituted for CMV antiviral prophylaxis at our institution. Between May 2006 and December 2007, all patients undergoing renal transplantation were included in a CMV infection surveillance program. Blood samples to determine CMV viral load were obtained weekly during the first 4 months. Asymptomatic patients, with a viral load determined using polymerase chain reaction (PCR) with CMV DNA >100,000 copies/mL, were treated with VGCV for 3 months or until resolution of viral replication. Until April 2006, patients undergoing renal transplantation received CMV prophylaxis with oral acyclovir and pp65 antigenemia was the test for CMV infection surveillance. The group on preemptive therapy was compared with a historical group on prophylaxis therapy: 100 renal patients who underwent transplantation between April 2004 and 2006. RESULTS: Among 96 recipients, quantitative determination of viral DNA in blood was elevated in 14 asymptomatic patients, who were treated with oral VGCV for 3 months. The patients were followed up for a median time of 13.3 months. None of the 14 patients who received VGCV developed CMV disease. CONCLUSION: VGCV administered as preemptive therapy was safe and efficacious to prevent CMV disease.

Donor characteristics can influence transplant activities and the access to transplant for some age groups.

In recent years Italy has experienced a remarkable increase in organ donation and transplant rates for kidney transplantation. The organ donation rate has placed Italy among the European leaders, but a careful comparative evaluation of Italian and international registries data demonstrates that renal transplantations have not shared the same significant growth. In a decisive way donor characteristics have influenced not only the number of renal transplantations, but also the access to transplant for some age groups. We investigated the probability of transplantation from different age groups using the Kaplan-Meier method and the log-rank test. The 7-year probability of transplant was 72% for the 15 to 45 age group, 85.7% for the 46 to 55 age group, and 88.5% for the over 55 years group (P = .0029). Ethical considerations suggest new approaches of innovative promotion of living donor transplants and a revision of organ allocation criteria.

Immunosuppression in renal transplantation: viral diseases and chronic allograft nephropathy.

Chronic allograft dysfunction after renal transplantation can be ascribed to different causes, among which are viral infections. The aim of this work was to show the various ways by which different kinds of viruses affect transplant structure and function. Polyoma virus is an example of viruses directly affecting the kidney because of a specific tropism to the uroepitelial cells. Cytomegalovirus (CMV) has been chosen both because of the frequency of this infection and because CMV (as other viruses) can produce transplant vascular sclerosis. Finally, we describe hepatitis C virus (HCV) because of its capacity to induce renal lesions independently from chronic allograft nephropathy. Indeed HCV is likely to determine immunologically mediated nephritis in the transplanted kidney as well in the native one.

Efficacy and safety of Palmaz stent insertion in the treatment of renal artery stenosis in kidney transplantation.

The aim of this study was to verify the safety and long-term efficacy of Palmaz stent insertion in the treatment of transplant renal artery stenosis (TRAS) in kidney transplantation. Nine of our transplanted patients were submitted to Palmaz stent insertion because of recurrence of renal artery stenosis after previous percutaneous transluminal angioplasty or because of severe ostial stenosis. The post-stenting results were excellent in all patients, with a follow-up period ranging from 1 to 3 years. The mean blood pressure (one-third systolic pressure plus two-thirds diastolic pressure) fell from 118.11 +/- 7.44 to 103.21 +/- 9.25 mmHg; P < 0.001. Renal artery peak blood flow velocity as determined by Doppler sonography fell from 352 +/- 73.24 cm/s to 169.8 +/- 23.35 cm/s; P < 0.001. The serum creatinine 1-year after stenting was 1.3 +/- 0.3 mg/dl with a slight reduction with respect to the pre-stenting values (1.5 +/- 0.3 mg/dl; NS). As no complication occurred, we conclude that insertion of the Palmaz stent is a safe and effective way to treat recurrence of artery stenosis or ostial stenosis in renal transplanted patients.

Fate of kidneys from the same donor grafted into different recipients: do they behave similarly and are they influenced by donor-related factors?

BACKGROUND: The fate of paired kidneys might be similar and could therefore reflect the influence of donor-related factors on graft outcome. PATIENTS AND METHODS: To verify whether two kidneys retrieved from a single donor and grafted into different recipients have similar short, and middle-term outcomes we investigated the clinical outcome of 103 pairs of cadaveric kidneys grafted into 206 recipients. We evaluated the influence of donor-related factors such as age, sex and cause of death, and of the storage solution and method of harvesting. The incidence of delayed graft function was considered as the short-term outcome and serum creatinine levels at two years as the middle-term outcome. We evaluated the difference from expected frequencies in the incidence of delayed graft function and the incidence of similar serum creatinine levels in each pair of recipients. Univariate analysis of possible risk factors was made by the t-test, chi2 test and Fisher test, as appropriate. Multivariate analysis was done by logistic regression analysis with a forward stepwise variable selection. RESULTS: Delayed graft function was seen in both recipients from the same donor 2.5 times more than the expected frequency (p<0.001). Serum creatinine levels were similar in both recipients with a higher frequency than expected (p<0.01). Multivariate analysis showed that donor-related factors on graft function were age, cause of death and storage solution. CONCLUSIONS: Paired kidneys have similar performances in both the short and the long term. Major donor-related factors in delayed graft function are age and the storage solution. Major donor-related factors in graft function are age and cause of death.

Mycophenolate mofetil (MMF) in the treatment of chronic renal rejection.

BACKGROUND: Experimental studies suggest the efficacy of MMF in the treatment of chronic renal rejection in rats. Studies on the efficacy of MMF in chronic renal rejection in man are scarce and controversial. AIM: The aim of this study was to verify in a prospective non-randomized study the efficacy of MMF given at the dose of 2 g/day in substitution of azathioprine (AZA) in the chronic rejection of cadaveric kidney transplantation. PATIENTS AND METHODS: Twelve patients with histologically proven chronic renal rejection were enrolled. The patients were 5 males and 7 females. Mean age 38.3 +/- 13.8 years, with a mean duration of transplant of 39 +/- 19 months. Mean serum creatinine values at -6, -3, 0, +3, +6, +12 months were respectively 1.72 +/- 0.33, 1.84 +/- 0.36, 2.15 +/- 0.50, 1.88 +/- 0.54, 1.81 +/- 0.71, 1.73 +/- 0.58 mg/dl. Mean creatinine clearance values were 58.85 +/- 10.06,48.8 +/- 13.3,45.8 +/- 10.2, 54.7 +/- 13.3, 51 +/- 12.7, 57.7 +/- 18.5 ml/min. Mean deltaGFR before MMF was -2.15 ml/month. RESULTS: After MMF introduction, the overall GFR decrease attenuated. In particular in seven patients after MMF administration, we obtained a significant reduction of mean serum creatinine value (1.84 +/- 0.55 vs. 1.38 +/- 0.41mg/dl; p = 0.004). In three patients, we obtained a stabilization in GFR. Two patients were slowly progressing even after MMF introduction. After a switch to MMF in almost all patients, we obtained an improvement of renal function. In three patients, we obtained a stabilization of renal function without regression. In particular, seven patients showed a remarkable improvement of renal function. CONCLUSIONS: In conclusion our data even if concerning a small number of patients, confirm the efficacy of MMF in the treatment of renal allograft chronic dysfunction.

Limits of clinical signs and non-invasive techniques in detecting severe acute rejection.

We describe a cadaveric renal transplant patient with an early post-transplant period characterized by normal urine output, normal clinical and biological signs, and a slow decrease of serum creatinine; repeated ultrasonography, color doppler ultrasonography and renal angioscintigraphy were normal or consistent with a clinical diagnosis of mild acute tubular necrosis. Nevertheless a core renal biopsy revealed severe steroid-resistant acute rejection with diffuse infiltrates of lymphocytes and initial transmural arteritis.