Sirolimus-based immunosuppression in kidney transplantation for type 2 diabetic nephropathy.

INTRODUCTION: Kidney transplantation is the best replacement therapy of type 2 diabetic patients and recently similar graft and patient survival between diabetic and nondiabetic recipients has been reported. However, standard immunosuppressive protocols are lacking. We present our experience with sirolimus-based immunosuppression in a population of 24 type 2 diabetic patients who underwent a kidney transplantation. PATIENTS AND METHODS: From January 2001 to December 2006, 396 kidney transplantations were performed. Twenty-four patients had type 2 diabetes mellitus as a cause of end-stage renal disease. They were randomized in two groups: thirteen patients (group A) received an immunosuppressive treatment with sirolimus, low-dose tacrolimus and steroids, while 11 patients (group B) received sirolimus, mycophenolate mofetil and steroids. RESULTS: Clinical characteristics were similar between the two groups. A slightly better kidney functionality was observed in group B patients. There were neither acute rejection episodes nor severe infectious complications in both groups. One patient in each group underwent a foot amputation. Graft and patient survival was 100% for both groups at a median follow-up of 29 months. CONCLUSIONS: Sirolimus-based immunosuppression is safe and efficacious in type 2 diabetic patients who underwent a kidney transplantation, allowing a better glucose metabolism control.

New-onset diabetes mellitus after kidney transplantation: the role of immunosuppression.

BACKGROUND: Complications related to posttransplantation immunosuppressive therapy remain common. New-onset diabetes mellitus after transplantation (PTDM) is a well-recognized complication associated with reduced graft and patient survival. The type of immunosuppression may be responsible for more than two thirds of PTDM. We retrospectively reviewed our experience in a population of 284 kidney transplant recipients, evaluating the incidence of PTDM with regard to the type of immunosuppression. PATIENTS AND METHODS: From January 2001 to December 2005, 284 kidney transplantations were performed using tacrolimus-based (TAC) immunosuppression in 192 patients and a cyclosporine-based (CyA) regimen in 62 patients, whereas 30 patients received sirolimus-based immunosuppression. RESULTS: The overall incidence of PTDM was 4.9%. Among the immunosuppression protocols, 8 patients (4.1%) received TAC and 6 patients (9.6%) received CyA, whereas no patients treated with sirolimus developed PTDM. Graft and patient survival rates were 93% and 100%, respectively. CONCLUSIONS: The overall risk of PTDM with recent immunosuppressive protocols is low, but it is increased among calcineurin inhibitor (CNI)-treated kidney transplant recipients. Sirolimus did not increase the risk of PTDM, allowing potential clinical application in diabetic recipients and in patients affected by PTDM.

Fenoldopam vs dopamine as a nephroprotective strategy during living donor kidney transplantation: preliminary data.

UNLABELLED: Fenoldopam is a selective DA1 agonist with potential nephroprotective capabilities. The aim of this study was to compare the nephroprotective effect of fenoldopam and dopamine during general anesthesia for living donor kidney transplantation. METHODS: Forty donors enrolled in the study received a similar anesthetic and fluid protocol. The patients were randomly divided into group F (receiving 0.1 mg*kg-1*min-1 fenoldopam) versus group D (receiving "renal dose" 3 mg*kg-1*min-1 dopamine). The mean volume of infused fluids, diuresis, and urinary electrolytes (Na, K, Cl) at infusion start and 120 minutes later were studied. RESULTS: Anthropometric parameters, administered anesthetics, mean infused volume, and urine outputs, did not show significant differences between the groups. Statistically significant differences were observed for urinary excretion of sodium, potassium, and chloride after 120 minutes of continuous fenoldopam infusion, with significant variations within groups for sodium only. CONCLUSIONS: Fenoldopam compared with dopamine resulted in better nephroprotective effects. No adverse events were recorded, and side effects were minimal. Further studies are necessary to evaluate these data.

Monolateral dual kidney transplantation from marginal donors.

BACKGROUND: Dual kidney transplantation (DKT) offers a safe way to face the organ shortage with good short-term and medium-term renal function. However, its application is limited by the longer operating time and the risk of surgical complication. This study reviews our results with DKT performed with an ipsilateral technique in terms of graft loss, graft and patient survival rates, and surgical complications. PATIENTS AND METHODS: From January 2002 to March 2006, 23 patients underwent DKT through a monolateral Gibson incision with placement of both kidneys. RESULTS: One primary nonfunction occurred (4%). Delayed graft function was observed in 3 DKT (13.3%). Acute rejection rate was 4.3% (1 patient). All patients are alive at a mean follow-up of 28 months. One-year and 2-year graft survival rates were 100% and 96%, respectively. Mean serum creatinine level at 1-year posttransplantation was 1.3 mg/dL (range, 0.8-2.1 mg/dL). One DKG recipient lost 1 graft, retaining the second normal functioning graft due to ureteral necrosis. The mean hospital stay after transplantation was 15 days (range, 12-34 days). CONCLUSIONS: Monolateral placement in DKT offers the advantage of a single incision, minimizing the surgical risk. Tailored immunosuppression and careful selection of potential recipients, by excluding those with severe cardiopulmonary pathologies, could significantly improve both patient and graft survival in this group of patients.

Voriconazole in the treatment of invasive aspergillosis in kidney transplant recipients.

BACKGROUND: Aspergillosis and other invasive mold infections are severe complications in immunosuppressed patients, and in renal transplant patients it is the most common cause of systemic fungal disease with an incidence ranging from 0.4% to 2.4% with a high mortality of 56% to 100%. We present our experience with voriconazole in a population of kidney transplant recipients with invasive aspergillosis. PATIENTS AND METHODS: From January 2002 to December 2005, 245 kidney transplantations were performed. RESULTS: Four patients (1.6%) presented with clinical and laboratory findings of invasive aspergillosis. Three patients presented with pulmonary aspergillosis, while one patient presented with pulmonary and ocular aspergillosis. All patients underwent a therapy with voriconazole 200 mg twice a day, in combination with caspofungin in one patient. All patients are alive, with no clinical recurrence of aspergillosis at a median follow-up of 13 months. One patient lost her graft due to discontinuation of immunosuppression. CONCLUSIONS: Voriconazole is a potent and well-tolerated antifungal drug that is extremely efficacious in the treatment of invasive aspergillosis in kidney transplant recipients. A careful monitoring of immunosuppressive drugs should be considered to avoid nephrotoxicity.

Kidney transplantation from donors with viral B and C hepatitis.

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our experience in transplanting kidneys from donors with hepatitis B virus (HBV) or hepatitis C virus (HCV) among matched serology-positive recipients. MATERIALS AND METHODS: From January 2002 to November 2005, 44 patients with end-stage renal disease and HCV seropositivity underwent kidney transplantation. In 28 transplants in HCV+ recipients, the donor was HCV+ (DC+/RC+) and in 16 of these cases the donor (one living donor) was HCV- (DC-/RC+). In the same period 14 patients with HBV infection and HbsAg seropositivity underwent kidney transplantation: eight received their graft from a cadaveric HbsAg-positive donor (DB+/RB+), while six patients received their graft from an HbsAg-negative donor. RESULTS: Viral reactivation was higher among DC+/RC+ (21.4%) than DC-/RC+ patients (6%). Graft survivals were 90% and 88% for DC+/RC+ and DC-/RC+, respectively; patient survivals were 100% for DC+/RC+ and 94% for DC-/RC+. Among the group of DB+/RB+, all the patients developed an HBV-DNA positivity in the early postoperative period. Patient and graft survivals were 100% in both groups. CONCLUSIONS: Our results suggest that HBV- and HCV-positive donors can be considered as an alternative donor source, because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.

Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients.

BACKGROUND: Infection is a common cause of morbidity and mortality in kidney transplant recipients. The incidence of esophageal and urogenital candidiasis in kidney and kidney-pancreas transplant recipients has not been well documented. Azoles are safe, effective agents to treat esophageal candidiasis. However, resistance to azoles is now becoming common. This study reports the use of caspofungin for the treatment of azole-resistant esophageal and urogenital candidiasis in kidney transplant recipients. PATIENTS AND METHODS: The incidence of esophageal and urogenital candidiasis was evaluated among 140 kidney transplantations and four combined kidney-pancreas transplants performed over a 2-year period. RESULTS: Twenty-two patients (15.7%) presented with esophageal candidiasis, while seven patients (5%) showed urogenital candidiasis. Thirteen patients with esophageal candidiasis (59%) and four patients (57%) with urogenital candidiasis did not improve after a week of azole treatment. A regimen of caspofungin was started in these patients, who tolerated the treatment. Urogenital candidiasis recurred in two patients 2 and 3 months after the treatment. One patient with esophageal candidiasis did not improve with caspofungin and was switched to amphotericin B therapy. There were no other recurrences of candidiasis among patients treated with caspofungin for a median follow-up of 8 months. CONCLUSIONS: Renal transplant patients remain at high risk for fungal infections. Although the number of patients was limited, the results of this study indicated that caspofungin is an effective, well-tolerated alternative for difficult-to-treat, azole-resistant candida infections in kidney and pancreas transplant recipients. The high costs of the drug limit the use of caspofungin as first-line antifungal therapy, reserving its use to recipients who had undergone unsuccessful azole therapy.

Kidney transplantation from cadaveric donors unsuitable for other centers and older than 60 years of age.

INTRODUCTION: The demand for kidney transplants and the improvement in recipient outcomes over the last years have stimulated surgeons to expand the criteria for usable donor organs, by accepting older patients to expand their donor pool. We herein report our experience with kidney transplants from donors aged older than 60 years, who have been declined by other transplantation centers. PATIENTS AND METHODS: Sixty kidney transplantations were performed with grafts procured from donors aged older than 60 years. Forty-five patients received a single kidney graft (SKG) and 15 received a dual kidney graft (DKG). Mean donor age was 62 years for SKG and 64 years for DKG. Double kidney transplantations were performed with the ipsilateral allocation of both grafts. RESULTS: No primary graft nonfunction occurred. Delayed graft function was observed in 22 SKG (48.8%) and in 7 DKG (46.6%). Acute rejection rates were 9% for SKG and 0% for DKG. One-year patient survival rates were 95% and 100% for SKG and DKG, respectively. Mean serum creatinine levels at 1-year posttransplantation were 1.9 mg/dL for SKG and 1.3 mg/dL for DKG. There were no surgical postoperative complications and mortality. Death censored 1-year graft survival rate was 88% for SKG and 94% for DKG. CONCLUSIONS: Our experience with marginal donors who have been declined by other transplantation centers has demonstrated that such organs, with accurate selection criteria, could be safely allocated to elderly recipients with no increase in postoperative complications, guaranteeing satisfactory results in the short and medium term, allowing a significant improvement in the number of transplants.

Kidney transplantation from hepatitis B surface antigen-positive donors into hepatitis B surface antigen-positive recipients: preliminary findings.

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our initial experience in transplanting kidneys from hepatitis B surface antigen (HbsAg)-positive donors into HbsAg-positive recipients. MATERIAL AND METHODS: From January 2002 to March 2004, 5 patients with end-stage renal disease, hepatitis B virus (HBV) infection, and HbsAg seropositivity underwent a kidney transplantation from a cadaveric HbsAg-positive donor. The median time on the waiting list was 8 months, compared with the median of 3 years on the national waiting list. RESULTS: One patient experienced an acute rejection; 1 patient had an increase in serum level of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) with no signs of recurrence of hepatitis. Graft and patient survival at a median follow-up of 12 months was 100%. CONCLUSIONS: Although the number of patients is small and the follow-up is short, our results suggest that HbsAg-positive donors can be considered as an alternative donor source because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.

Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool?

INTRODUCTION: Because the disparity between the number of patients waiting for kidney transplants and the number of available cadaveric renal allografts continues to increase, there is a clear need to review the inclusion criteria for cadaveric donors. PATIENTS AND METHODS: From January 2001 to March 2004, 24 patients with end-stage renal disease and hepatitis C virus (HCV) seropositivity underwent a kidney transplantation. In 10 transplants in HCV-positive recipients, the donor was HCV-positive (D+/R+) and in 14 cases the donor (1 living donor) was HCV-negative (D-/R+). RESULTS: Two of 3 HCV-RNA-negative recipients who received a HCV-RNA+ kidney became HCV-RNA+ in the posttransplantation period. There was a low rate of acute rejection (8.3%). One D+/R+ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the resurgence of severe infectious disease. The serum creatinine levels at 6 months posttransplantation were similar in both groups. Acute liver dysfunction was observed in 1 patient. There was no death in the entire series. Graft survival was 92% and 90% for D+/R+ and D-/R+, respectively.

Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients.

INTRODUCTION: The rate of hepatitis B virus transmission via organs from with isolated hepatitis B virus core antibody-positive (HBcAb+) donors in kidney transplant recipients seems very low. PATIENTS AND METHODS: Over 4 years, we performed 36 transplants from Ig HBcAb+, hepatitis B surface antigen (HBsAg)-negative donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination (28 patients) and in recipients who were not immunized and received a pretransplant prophylaxis with hepatitis B immunoglobulins. We examined the HBV-related outcomes in these 36 patients in comparison with 40 recipients of allografts from HBcAb- donors. RESULTS: No patient receiving an allograft from an HBcAb+ donor developed clinical HBV infection or HBSAg positivity. The rate of seroconversion was 14.2% in immunized patients, 12.5% in nonimmunized patients, and 0% in the control group. The 17.8% of immunized patients developed elevated transaminases after transplant, in comparison with 25% and 10% in the nonimmunized patients and the control group, respectively. Graft and patient survival was 93% and 93% for immunized patients, 100% and 100% for nonimmunized patients, and 98% and 95% for the control group, respectively. CONCLUSION: The use of anti-HBc antibody-positive kidneys was associated with no risk of transmission of HBV infection, without affecting graft and patient survival, and could be considered a safe way to expand the donor pool. Our preliminary results suggest that such kidneys could be safely transplanted even in not immunized patients who underwent a prophylaxis with hepatitis B immunoglobulins.

Living kidney transplantation: a starting experience.

INTRODUCTION: We present our initial experience with living kidney transplantation. PATIENTS AND METHODS: From January 2001 to December 2002, we performed 27 living kidney transplants using immunosuppression with induction basiliximab, cyclosporine (n = 10 patients), or tacrolimus (n = 17), mycophenolate mofetil, and steroids. RESULTS: Nineteen (70.3%) donors were women and 8 (29.7%) were men of mean age 50.6 years. Four donors were over 65 years of age at the time of living donation. Donor morbidity was 5.5%: namely, one wound infection and one asymptomatic acute pancreatitis. There were no differences between the preoperative and the postoperative mean serum creatinines and systolic blood pressure values. All living donors are in good health with a mean serum creatinine of 0.80 mg/dL at a mean follow-up of 15.2 months. Nineteen (70.3%) recipients were men and 8 (29.7%) were women of mean age 36 years. Acute rejection occurred in 6 (22.2%) recipients. It was more common among spousal donors and among cyclosporine-treated recipients. Patient and graft survivals at a mean follow-up of 15.2 months was 100%. CONCLUSIONS: Our early results showed that accurate selection and preoperative management of potential living donors lead to excellent results in kidney transplantation. The health of the living donors was not impaired by the donation. The rate of early postoperative complications was low. Living donor kidney transplantation, in our geographical area with a low-rate of cadaveric donor transplants, is an alternative to expand the donor pool, which offers better results in term of patient and graft survival.

Kidney transplantation from marginal donors.

AIM: The increasing demand for transplantation and the shortage of available organs limit the success of organ transplant programs. The use of marginal donors to expand the donor pool is receiving increased attention. We reviewed a 28-month experience of kidney transplants from marginal donors to assess the impact on patient and graft survival. PATIENTS AND METHODS: From January 2001 to May 2003, 78 kidney transplants were performed, including 50 grafts from cadaver donors and 28 from living donors with 3 patients receiving a double kidney transplant. The patients were divided into 4 groups: 31 patients received a kidney from an ideal cadaver donor (group 1a); 19 patients received a graft from a marginal cadaver donor (group 1b); 19 patients received an ideal living related kidney (group 2a); and 9 patients received a marginal living kidney graft (group 2b). RESULTS: Twenty-eight grafts from marginal donors were transplanted with an average follow-up of 16 months (range, 1-28 months). The graft survival rates for groups 1a, 1b, 2a, and 2b were 93%, 79%, 100%, and 100% and patient survival rates were 96%, 89%, 100%, and 100%, respectively. CONCLUSION: Despite the observation that use of marginal donors has been associated with a worse outcome compared with ideal donors, we of such grafts resulted in improved quality of life and survival expectancy compared with maintenance dialysis. The marginal kidney donors represent a feasible way to improve the donor pool.

Early de novo malignancies after kidney transplantation.

INTRODUCTION: Immunosuppressed renal transplant patients display a higher incidence of carcinoma than the general population. The chronic use of immunosuppressive therapy to prevent acute rejection increases the long-term risk of cancer. We reviewed our experience to identify factors affecting the development of de novo neoplasms. PATIENTS AND METHODS: Between January 2000 and May 2003, 135 renal and three combined kidney-pancreas transplantations were performed. RESULTS: Sixteen (11.6%) cancers were diagnosed in nine renal transplant recipients (6.5%). Tumors presented at a mean time of 14 months. Three patients displayed in malignancies; three, Kaposi's sarcoma; one, papillary microcarcinoma of the thyroid; one, bladder carcinoma; and one, breast carcinoma. CONCLUSION: Although de novo malignancies occur more frequently many years after kidney transplantation, our experience demonstrates that they can occur early during the posttransplant follow-up. Skin malignancies showed the best prognosis, probably because of early detection and treatment. Patients with Kaposi's sarcoma benefit from reduction or cessation of immunosuppression, but this entails a higher risk of graft loss. Solid organ de novo malignancies are often more aggressive than those in normal population; the life expectancy of these recipients is low.

[Early de novo neoplasia after renal transplantation]. / Neoplasie de novo precoci dopo trapianto renale.

INTRODUCTION: The chronic use of immunosuppressive therapy in transplant recipients to prevent acute rejection increases the long-term risk of cancer. The overall incidence of de novo malignancies (DNM) after kidney transplantation ranges from 6% to 11%. PATIENTS AND METHODS: Between January 2000 and December 2002, 135 renal and 3 combined kidney-pancreas transplantations were performed. RESULTS: Of 138 solid organ transplant recipients, a total of 16 (11.6%) cancers were diagnosed in 10 renal transplant recipients (7.2%). Six patients were male and three female, with a mean age of 47 years (range, 19-63, years). Tumor presented at a mean time of 14 months (range, 2-24, months) after transplantation. There were three patients with skin cancers, three with Kaposis's sarcoma, one with renal cell cancer, one with bladder carcinoma and one with breast cancer. CONCLUSIONS: Although the DNM occurs more frequently many years after a kidney transplantation, our experience demonstrated that they can occur early in the follow-up. Skin malignancies had the best prognosis, probably because of early detection and treatment. Kaposi's sarcoma benefits from reduction or cessation of immuno-suppression, but there is a higher risk of graft loss. Solid organ de novo malignancies are often more aggressive than in normal population, and the life expectancy of these recipients is very low. Careful long-term screening protocols are needed for detection of such malignancies in an early stage.

[Blunt trauma of hepatic ducts: a difficult diagnostic-therapeutic approach]. / I traumi chiusi dei dotti epatici: un difficile inquadramento diagnostico-terapeutico.

Traumatic injuries of left and right hepatic ducts are rare, with about 40 cases reported in literature. Preoperative diagnosis is difficult, so that up to 40% of lesions may be undetected at laparotomy. Prompt diagnosis could preserve by high morbidity rate of such injuries. The extremely widespread and routine use of ERCP as well as intraoperative cholangiography may allow reducing dramatically the diagnostic time lag and the percentage of lesions formerly undetected by laparotomy. Therapeutic options are extremely variable. On the basis of the experiences reported for the treatment of iatrogenic lesions of the biliary tract, reconstruction by jejunal Roux-en-Y loop biliodigestive anastomosis is preferred, whenever lacerations of an hepatic duct appear to be complete or nearly so, on account of the high incidence of stenosis and late complications, detected in case of termino-terminal direct biliary anastomosis. However, in selected cases, when the transection appear neat and simple, an end-to-end anastomosis could be performed with low risk. Mortality after blunt biliary duct injury represents nowadays a rare event at least in patients presenting without severe associated traumatic lesions, so that the clinical attention has been progressively focused on the relatively high rate of postoperative complications. These adverse events are often extremely demanding in terms of prolongation of hospital stay, need for multiple invasive procedures and overall costs of patient's management.