Pretransplant Single Antigen Bead-Detected HLA Antibodies in Kidney Transplant Long-term Outcome: A Single-Center Cohort Experience.

Single-antigen bead (SAB) platform permits the identification of antibodies not detectable by complement-dependent lymphocytotoxicity test, but their clinical significance is not completely understood. The aim of this study was to evaluate whether the presence of pretransplant SAB-detected antibodies is associated with the development of allograft failure. This is a single-center cohort study with 10-year follow-up in which 573 kidney recipients with negative pretransplant complement-dependent lymphocytotoxicity crossmatch who received transplants at the Kidney Transplant Center of Policlinico, Milan, from deceased donors between 1996 and 2005 were evaluated. Pretransplant plasma samples were retrospectively analyzed by SAB assay. Survival analyses were performed to assess the risk of allograft failures by SAB-detected antibodies. Pretransplant antibodies were found in 160 (28.0%) recipients, of whom 42 subsequently developed an allograft failure for a survival rate of 70.9% (95% confidence interval [CI), 63.5-78.4). Among those without antibodies, 58 (14.0%) returned to dialysis with a survival rate of 84.7% (95% CI, 81.0-88.4). In Cox regression analyses, patients with SAB-positivity had 2-fold higher risk of allograft failure than those who were SAB-negative (hazard ratio, 2.07; 95% CI, 1.39-2.79). Results did not change after adjustment for putative confounders. In conclusion, in this single-center cohort, 10-year allograft survival rate was significantly influenced by the presence of SAB-detected antibodies.

Intra-operative Postperfusion Micronephrolithotomy for Renal Allograft Lithiasis: A Case Report.

Increasing demand drives the expansion of criteria for kidney donation, and nephrolithiasis is now considered a relative contraindication. We report for the first time a case of intra-operative, postperfusion kidney allograft micronephrolithotomy. A 64-year-old man with end-stage renal disease secondary to Alport syndrome underwent primary deceased donor kidney transplantation at our center. Pre-operative ultrasound of the donor identified a 7-mm calculus in the anterior, lower pole calyx. The kidney was extra-peritoneally implanted in the right iliac fossa and reperfused homogenously. Stone retrieval with a flexible ureteroscope failed due to the narrow calyceal infundibulum. Instead, the calculus was removed using the micropercutaneous nephrolithotomy system under ultrasonographic guidance. The calyx was punctured using a 4.85 Fr needle and the stone was fragmented to dust using a Holmium laser. No bleeding was observed. The post-operative course was uneventful. Outpatient follow up demonstrated good function of the graft which was stone free on ultrasound. Postperfusion micropercutaneous nephrolithotomy for kidney allograft calculi offers a safe and feasible option when pre-operative or intra-operative retrograde intrarenal surgery fails.

Enzyme-Linked Immunospot Assay as a Complementary Method to Assess and Monitor Cytomegalovirus Infection in Kidney Transplant Recipients on Pre-emptive Antiviral Therapy: A Single-Center Experience.

BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection. METHODS: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up. RESULTS: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed. CONCLUSIONS: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.

Search for genomic sequences of microbial agents in atherosclerotic plaques.

Atherosclerosis is a complex, multifactorial disease. Several studies have reported a possible association between infection with microbial agents and atherogenesis. Chlamydia pneumoniae (C. pneumoniae), Herpes Simplex Virus 1 (HSV1), Human Cytomegalovirus (HCMV), and Epstein Barr Virus (EBV) have been widely investigated for their possible role in atherosclerosis development, but the results obtained to date are contradictory. The aim of our study is to search DNA of the aforementioned infectious agents by means of Quantitative Real Time PCR in atherosclerotic plaques from carotid arteries obtained from 17 patients. Genomic sequences of C. pneumoniae, HSV1, HCMV were not found in any atherosclerotic lesion. Therefore, our results do not support the hypothesis of an association between these infectious agents and atherosclerosis. Conversely, three patients were found to be positive for EBV DNA, thus indicating that, at least in a limited number of patients, EBV could play a role in atherogenesis.

Pediatric kidney transplantation: a snapshot 10 years later.

Herein we report the outcomes of pediatric kidney recipients who underwent transplantation at least 10 years prior. A cohort of 36 patients (mean age, 26.4+/-6 years) with a mean follow-up time of 14.2+/-4 years was selected for the study. Immunosuppression consisted of cyclosporine and steroids. Actuarial patient and graft survivals 15 years after the transplantation were 97% and 86%, respectively. Only 1 patient died due to a complicated sclerosant peritonitis. Graft function was good with a mean serum creatinine of this selected cohort of 1.5+/-0.6 mg/dL. Eighteen percent were class 1, 33% class 2, and 49% chronic kidney disease. Hypertension was treated in almost 80% of the patients. The majority of patients were smaller than the average population with a final height (between 0 and -2) standard deviation score (HSDS) but only 27% had a severe growth impairment (HSDS>-2). Regarding nutritional status, fewer than 30% were overweight and only 1 patient was obese with a body mass index (BMI) >30. The majority of patients, except 2 mentally retarded individuals, are or have been attending normal school and achieved full-time employment. In conclusion, long-term survivors of a kidney transplant received during childhood reached a high degree of rehabilitation despite a long period of immunosuppression.

Value of intraoperative resistive index in kidney transplant.

The value of the resistive index (RI) obtained by echo color doppler evaluation of the transplanted kidney is still not well established. Many authors consider the RI to be nonspecific sign of rejection, acute tubular necrosis, or urinary tract obstruction, but its specificity remains low. In this paper, we report our experience with RI determinations in 34 consecutive kidney transplants at different times namely: perioperatively, at 24 hours, at 3 days, at 6 and at 9 days posttransplant. In all patients intraoperative RI was normal. RI increased significantly after transplantation in 10 patients who eventually developed a complication: delayed function, acute rejection, and spontaneous kidney ruptures. This increment from the baseline value was already significant at 24 hours after the kidney transplant, indicating a possible posttransplant complication (0.62 +/- 0.07 vs 0.76 +/- 0.04; P = .0004). We conclude that the value of RI in the early posttransplant phase should be considered an important aid for the early diagnosis of posttransplant complications.

Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience.

Posttransplant bacterial infections are important because of their influence on patient and graft outcomes. Therefore, prevention of infection as well as prompt diagnosis and appropriate treatment are crucial. In this retrospective analysis, we reviewed all posttransplant bacterial infections occurring during the admission of kidney transplant patients from January 2000 to May 2004. Of our patients, 25% had at least one episode of infection. Patients with immunosuppression based on an mTOR inhibitor showed the highest rate of wound infections compared to those receiving a calcineurin inhibitor (odds ratio 5.6, P < .001). Patients with renal failure caused by a urologic disease revealed a increased risk of a urinary tract infections (odds ratio 5.9, P < .001). Although infection complications are an important cause of morbidity in renal transplantation, the extensive use of antibiotics should be avoided in favor of a strict policy for infection prevention and control.

Mycophenolate mofetil pharmacokinetic monitoring in pediatric kidney transplant recipients.

This open-label, longitudinal, long-term study of de novo pediatric renal transplant recipients was designed to investigate the pharmacokinetics (PK) of mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA). Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and mycophenolate mofetil (MMF, 300-400 mg/m2 twice daily) were investigated at 6, 30, 180, and 360 days after transplantation. Considerable interindividual variability in the areas under the concentration curve (AUC(0-12)) of MPA was observed during the follow-up, although the dose of MMF remained the same over the same time. Predose levels (C0) increased significantly during the first 6 months after transplantation: C0 at 6 and 180 days after transplantation was 0.8 +/- 0.6 and 1.9 +/- 1.1 microg/mL (P < .0001). A significant time-dependent increase in the AUC of MPA was also observed during the first 6 posttransplant months: AUC(0-12) at 6 and 180 days after transplantation was 23.3 +/- 10.8 and 40 +/- 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake were the individual time points that best correlated with the full MPA AUC (r = 0.8 and 0.79; P < .001). The abbreviated MPA AUC (0-4 hours) correlated reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant reduction in CsA dose during the first 6 posttransplant months (P < .001) matched the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the interaction of the 2 immunosuppressive drugs. These observations suggest the need for therapeutic drug monitoring when adjusting the dose of MMF in children.

C2 is an age-independent parameter for optimal cyclosporine exposure in long-term kidney transplant recipients.

The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 +/- 455 ng/mL; vs Stable, 1236 +/- 347 ng/mL, P = .0001; and adult CRAD, 781 +/- 518 ng/mL; vs Stable, 1088 +/- 452 ng/mL, P = .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients.

Conversion from tacrolimus to cyclosporine for a non-dose-dependent tacrolimus-induced toxicity, a pediatric kidney transplant recipient case report.

Tacrolimus-induced toxicity is considered a dose-related side effect largely due to a direct action of this potent calcineurin inhibitor on its targets including the kidney and the pancreas. This paper describes a case of tacrolimus systemic toxicity that appeared in a pediatric kidney transplant recipient who received a low drug dose. The kidney biopsy was a crucial aid toward the correct diagnosis, which reversed upon conversion to cyclosporine-based immunosuppression. A review of the literature suggests a chance of systemic toxicity even when the patient is maintained on therapeutic levels of tacrolimus. Because idiosyncratic reactions to the drug have not yet been postulated, we conclude that this suspicion may be addressed by a safe conversion to cyclosporine in pediatric patients.

Cyclosporine monitoring in stable, long-term, pediatric kidney transplant recipients: the value of C2 determination.

Although a generalized consensus has been reached for therapeutic drug monitoring of cyclosporine microemulsion in adult transplant patients, clear guidelines are recently not available for the pediatric population. In this retrospective analysis of pharmacokinetic data obtained from stable, long-term, pediatric kidney transplant recipients, we sought to define a possible approach to manage cyclosporine therapy in a pediatric setting. The 2-hour postdose cyclosporine blood concentration, C(2), rather than trough levels, was the best single time point predictor of the area under the concentration curve. We concluded that therapeutic drug monitoring of cyclosporine-based immunosuppressive regimens should be tailored based on C(2) determinations for pediatric kidney transplant recipients.

One-year experience with a new expanded polytetrafluoroethylene vascular graft for hemodialysis.

Hemodialysis access achieved through a prosthetic vascular graft has become more popular, especially in diabetic and older patients and those who have had several unsuccessful surgical accesses. From January to December 1996, we implanted a newly available expanded polytetrafluoroethylene (ePTFE) graft (DIASTAT Vascular Access Graft) that allows early cannulation in 18 patients (11 men and 7 women; mean age +/- SD, 63.7 +/- 11 years). Thirteen of these patients had at least one failed vascular access. All grafts were cannulated for dialysis within 7 days of implantation, with flow rates > or = 300 ml/min. The time to hemostasis after the first cannulation ranged from 2 to 4 min. The primary patency rate at one year was 56%. Four grafts developed thrombosis requiring surgical intervention; three were salvaged and one was removed. The one-year assisted or cumulative patency rate was 72%. One patient had persistent bleeding requiring graft revision immediately after surgery. The bleeding stopped and its origin was not determined. There were no graft infections or hematomas. Because of the early cannulation possible with the DIASTAT graft, as well as the lesser time to hemostasis than that generally achieved with standard ePTFE grafts, this prosthesis is a good alternative to autogenous access construction.