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.

Reticulated platelets and platelet reactivity in renal transplant recipients receiving antiplatelet therapy.

INTRODUCTION: Renal transplant recipients are at increased risk of cardiovascular morbidity and mortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%) of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who were receiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C). METHODS: Reticulated platelets were measured using a hematology automated analyzer (XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in the total optical platelet count (immature platelet fraction [IPF]), as the percentage of highly fluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessed using optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonic acid, 2 or 10 micromol/L of adenosine diphosphate, or 2 microg/mL of collagen. RESULTS: Group A demonstrated significantly higher values of RP compared with group B or group C. Group B demonstrated a substantially higher percentage of RPs compared with group C, which was significant only for the IPF parameter. Multiple regression analysis demonstrated that IPF and IPF# were significantly and positively related to collagen-induced platelet aggregation. CONCLUSION: We documented the presence of higher concentrations of RPs in transplant recipients compared with a control population, and a significant association between RPs and platelet function.

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.

Renal cell carcinoma of native kidney after renal transplantation: clinical relevance of early detection.

BACKGROUND: Life expectancy after transplantation has improved, and cancer may soon be the leading cause of late death after transplantation. The guidelines of the American and European societies of nephrology and urology have not yet established the optimal frequency for screening for renal cell carcinoma (RCC) of native kidneys in patients who have undergone renal transplantation. OBJECTIVE: To evaluate the prevalence, prognosis, and risk factors of RCC in a series of patients followed up for 16 years in our transplantation unit. MATERIALS AND METHODS: Our study is a follow-up observational cohort study conducted in 694 consecutive renal transplant recipients admitted to our institution from July 1991 through July 2007. At our institution, ultrasound studies of the native kidneys were performed every 6 months after renal transplantation. RESULTS: In the patient cohort studied, 10 patients developed a renal tumor (1.6% incidence). Three patients died of causes other than recurrence of RCC. Seven patients are alive with no evidence of RCC recurrence or metastatic disease after a mean (range) follow-up of 41 (12-96) months. Acquired cystic kidney disease and dialysis duration were positively associated with development of RCC. CONCLUSIONS: The incidence of RCC in the literature varies between 0.3% and 4.8%. The variability depends on the timing of follow-up, with a higher incidence in prospective studies with strict follow-up. We advise ultrasound studies performed by specialized physicians every 6 months after transplantation. More detailed guidelines designed by the major international transplantation societies are necessary.

Renal transplant recipients are at high risk for both symptomatic and asymptomatic deep vein thrombosis.

BACKGROUND: Venous thromboembolism (VTE) is one of the thrombotic complications that can occur in patients receiving renal transplantation (RT). The prevalence of VTE in RT patients is, however, undefined. OBJECTIVES: To evaluate the rate of a first episode of VTE in a series of 538 consecutive RT recipients admitted to our institution, the timing of occurrence of the thromboembolic events after transplantation, and the rate of recurrence after thromboprophylaxis withdrawal. Risk factors for recurrence were also evaluated, particularly in relation to the type of the first event (symptomatic or asymptomatic). RESULTS: During follow-up, 47 of 518 patients (28 males, 19 females; 9.1%) developed a first episode of VTE at a median time of 17 months (range 1-165 months) after kidney transplantation. Cancer was associated with the occurrence of VTE (odds ratio 4.8). Seventeen of 43 patients (39.5%) with deep vein thrombosis were asymptomatic and the diagnosis was made during routine ultrasound examination. Twenty-two patients (46.8%) experienced a recurrence of VTE. A relevant rate of recurrence was documented amongst patients with a first episode of both symptomatic (53%) and asymptomatic (23.5%) VTE. CONCLUSION: This study confirms that RT patients are at high risk of symptomatic and asymptomatic VTE and that this risk persists even after several years. Patients who experience VTE are at high risk of recurrence after thromboprophylaxis withdrawal.

The treatment of fistulae and ureteral stenosis after kidney transplantation.

INTRODUCTION: The incidence of urological complications after kidney transplantation varies from 3% to 14%, with a probable loss of the graft in 10% to 15% of cases and a mortality rate of up to 15%, despite improvements in prevention, diagnosis, and treatment as well as the use of new immunosuppressive therapies. Urinous fistulae, which are considered early complications of transplantation, are due to ischemic damage or necrosis generally occurring in the distal third of the ureter. Preservation of accessory arteries to the lower portion of the kidney is important, as they may constitute the blood supply of this segment of the collecting system or ureter. Their ligation may lead to necrosis and urinary fistulae. Ureteral stenosis, as late complication, is related to a pathology of the ureter itself, to infections, to abscesses, to fibrosis, and to ischemia. An early endoscopic approach permits resolution in 70% of cases. The aim of this retrospective study was to determine incidence and treatment of these complications. MATERIALS AND METHODS: From 1991 to 2004 we performed 453 kidney transplantations both from cadaveric and living donors. In 199 patients we performed a transvesical ureteroneocystostomy (UNCS), and in 260, an extravesical UNCS. RESULTS: The nine patients who showed fistulae (1.9%) underwent surgical treatment. In eight we used a direct ureteral reimplantation, and in one, a Boari flap technique. Nephrectomy was necessary in four patients, including two who died of septic complications. In all 26 cases of ureteral stenosis (5.6%), we used an endourological approach (anterograde or retrograde), with surgical treatment afterward in 11 patients (42%) nine direct reimplants, one anastomosis to the native ureter (transplantation from a living donor), and in one case a Boari flap technique four patients who underwent surgical treatment showed progressive damage to graft function. CONCLUSIONS: In all patients who showed fistulae we suggest surgical review: for patients with ureteral stenosis, we suggest first an endourological approach and only when it is not successful do we consider surgical treatment.

[Malignant neoplasia and kidney transplantation. Retrospective analysis of data on the population having kidney transplantation with de novo neoplasia in the setting of the AIRT]. / Trapianto renale e neoplasie. Analisi retrospettiva dei dati relativi alla popolazione dei trapiantati di rene affetti da neoplasie de novo in ambito AIRT.

BACKGROUND: In transplanted patients undergoing immunossuppressive therapy the incidence of malignant neoplasia is 3-4 times higher than in the general population. Aim of the present study was to evaluate the prevalence of different tumours and the links between modulation of immunosuppressive therapy and patient and graft survival. PATIENTS: We evaluated 2029 kidney-transplanted patients from four Transplant Centres (Bari, Bologna, Modena, Novara) belonging to the Associazione InterRegionale Trapianti (AIRT). RESULTS: The incidence of neoplastic disease after transplantation was 3.9% in our population with a median time between transplantation and clinical onset of 23 months. We demonstrated a significant difference in the geographical distribution of different tumours. We did not observe any correlation with specific immunosuppressive drugs. Finally, dramatic reduction of the immunosuppression levels did not modify either the patients' or the graft's survival. CONCLUSIONS: Several factors can influence the post-transplant onset of neoplastic diseases with immunosuppressive therapy playing a pivotal role. The implementation of a National Registry would be the first step in an attempt to optimise immunosuppression in this particular group of patient's.

High cysteine levels in renal transplant recipients: relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism.

BACKGROUND: Long-term survival of renal transplant recipients seems to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. Preliminary data available in the literature found high levels of cysteine (Cy) as a risk factor for deep venous thrombosis independently of high homocysteine (tHcy) levels, but no data are available about Cy levels in renal transplant recipients. METHODS: To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant recipients and 66 age- and sex-matched normal subjects as controls. RESULTS: Cy, tHcy, and PAI-1 levels were significantly higher in renal transplant recipients with respect to controls (Cy: 254 micromol/L [117-466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1 micromol/L [2.0-24.0], P<0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0-18.0], P<0.00001). High Cy levels were detected in 35.8% of patients. Hyperhomocysteinemia, both in the fasting state and postmethionine loading test, was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the fourth quartile with respect to the other quartiles were markedly increased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0 micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting tHcy levels correlated well with PAI-1 (r=0.65; P<0.0001) but not with Cy levels (r=0.10; P=0.4). The prevalence of the MTHFR 677TT genotype in renal transplant recipients was not significantly higher in patients than in controls (mutant allele frequency: 0.48 in patients and 0.47 in controls) and was associated with significantly higher fasting and postmethionine tHcy levels both in controls and patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 micromol/L [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy levels showed a small decrease that did not reach statistical significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/L [168-300]; P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of decrease of tHcy levels with respect to the other genotypes. CONCLUSION: In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy levels, and the amount of decrease seems to be influenced by the MTHFR genotype.

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.