Voucher-Based Kidney Donation and Redemption for Future Transplant.

Importance: Policy makers, transplant professionals, and patient organizations agree that there is a need to increase the number of kidney transplants by facilitating living donation. Vouchers for future transplant provide a means of overcoming the chronological incompatibility that occurs when the ideal time for living donation differs from the time at which the intended recipient actually needs a transplant. However, uncertainty remains regarding the actual change in the number of living kidney donors associated with voucher programs and the capability of voucher redemptions to produce timely transplants. Objective: To examine the consequences of voucher-based kidney donation and the capability of voucher redemptions to provide timely kidney allografts. Design, Setting, and Participants: This multicenter cohort study of 79 transplant centers across the US used data from the National Kidney Registry from January 1, 2014, to January 31, 2021, to identify all family vouchers and patterns in downstream kidney-paired donations. The analysis included living kidney donors and recipients participating in the National Kidney Registry family voucher program. Exposures: A voucher was provided to the intended recipient at the time of donation. Vouchers had no cash value and could not be sold, bartered, or transferred to another person. When a voucher was redeemed, a living donation chain was used to return a kidney to the voucher holder. Main Outcomes and Measures: Deidentified demographic and clinical data from each kidney donation were evaluated, including the downstream patterns in kidney-paired donation. Voucher redemptions were separately evaluated and analyzed. Results: Between 2014 and 2021, 250 family voucher-based donations were facilitated. Each donation precipitated a transplant chain with a mean (SD) length of 2.3 (1.6) downstream kidney transplants, facilitating 573 total transplants. Of those, 111 transplants (19.4%) were performed in highly sensitized recipients. Among 250 voucher donors, the median age was 46 years (range, 19-78 years), and 157 donors (62.8%) were female, 241 (96.4%) were White, and 104 (41.6%) had blood type O. Over a 7-year period, the waiting time for those in the National Kidney Registry exchange pool decreased by more than 3 months. Six vouchers were redeemed, and 3 of those redemptions were among individuals with blood type O. The time from voucher redemption to kidney transplant ranged from 36 to 155 days. Conclusions and Relevance: In this study, the family voucher program appeared to mitigate a major disincentive to living kidney donation, namely the reluctance to donate a kidney in the present that could be redeemed in the future if needed. The program facilitated kidney donations that may not otherwise have occurred. All 6 of the redeemed vouchers produced timely kidney transplants, indicating the capability of the voucher program.

New priorities: Analysis of the New Kidney Allocation System on UCLA patients transplanted from the deceased donor waitlist.

UNOS implemented a new Kidney Allocation System (New KAS) on December 4, 2014 with a primary goal of increasing equity to organ transplant for patients that were immunologically or socially disadvantaged by the previous allocation system (Previous KAS) that prioritized long wait times. We examined the effects of the New KAS on patients transplanted from the UCLA deceased donor waitlist during the first year and compared to the last year of the Previous KAS. The total number of deceased donor kidney transplants was increased in the New KAS as compared to the Previous KAS (178 vs 148). Transplant of regraft patients and of highly sensitized patients with cPRA⩾99% was significantly increased in the New KAS (New KAS vs Previous KAS, 29.8% vs 11.5%, p⩽0.0001, and 26.4% vs 2.7%, p⩽0.0001, respectively). In the New KAS, the percentage of patient's receiving allografts imported from outside our local area was also significantly increased (34.8% vs 15.5%, p<0.0001). In the New KAS, 59.7% and 48.3% of imported organs were allocated to very highly sensitized (⩾99% cPRA) or re-graft patients, respectively, as compared to 8.7% and 8.7% during the Previous KAS (p<0.001). Recipients and donors with age differences exceeding 15years were decreased in the New KAS as compared to the Previous KAS (36.5 vs 48.7%, p⩽0.032). There was a 40.1% reduction in transplant to patients in the 65+ age group in the New KAS (p⩽0.025). The percentage of patients transplanted with preformed donor specific antibody (DSA) was similar in the New as compared to the Previous KAS (19.7% vs 15.5%) and, patients were transplanted with a range of 1-3 preformed DSA of weak to moderate strength. Cold ischemic time was significantly increased over all organs, and in patients transplanted with preformed DSA during the New as compared to the Previous KAS (17.5 vs 19.1h and 17.2 vs 22.2, p<0.04 and p<0.03, respectively). Episodes of delayed graft function and the number of biopsies for cause were similar between the New and the Previous KAS. However, there were more events of biopsy proven antibody mediated rejection in patients transplanted since the start of the New KAS. The data show that the New KAS is working at the center level as designed to better age match recipients and donors and to increase transplantation of very highly sensitized patients through broader sharing.

Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation.

BACKGROUND: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. METHODS: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation. RESULTS: BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. CONCLUSIONS: Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.

Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence.

BACKGROUND: Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies. METHODS: In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined. RESULTS: A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies (p = 0.002) with a DQ predominance and 71 % reported nonadherence (p = 0.05). CONCLUSIONS: In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence.

3.0Tesla magnetic resonance angiography (MRA) for comprehensive renal evaluation of living renal donors: pilot study with computerized tomography angiography (CTA) comparison.

PURPOSE: Most living related donor (LRD) kidneys are harvested laparoscopically. Renal vascular anatomy helps determine donor suitability for laparoscopic nephrectomy. Computed tomography angiography (CTA) is the current gold standard for preoperative imaging; magnetic resonance angiography (MRA) offers advantages including lack of ionizing radiation and lower incidence of contrast reactions. We evaluated 3.0T MRA for assessing renal anatomy of LRDs. MATERIALS AND METHODS: Thirty consecutive LRDs underwent CTA followed by 3.0T MRA. Data points included number and branching of vessels, incidental findings, and urothelial opacification. Studies were individually evaluated by three readers blinded to patient data. Studies were reevaluated in consensus with discrepancies revealed, and final consensus results were labeled "truth". RESULTS: Compared with consensus "truth", both computed tomography (CT) and magnetic resonance imaging were highly accurate for assessment of arterial and venous anatomy, although CT was superior for detection of late venous confluence as well as detection of renal stones. Both modalities were comparable in opacification of lower ureters and bladder; MRA underperformed CTA for opacification of upper urinary tracts. CONCLUSIONS: 3.0T MRA enabled excellent detection of comprehensive renal anatomy compared to CTA in LRDs.

Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection.

BACKGROUND: Current diagnostic methods of renal allograft rejection are neither sensitive nor specific. Needle biopsies are invasive and associated with patient morbidity. Thus, it is desirable to develop noninvasive tests to predict and diagnose rejection. METHODS: Using a case-control approach, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to identify plasma proteins associated with renal allograft rejection. From each rejection patient (n=16), two plasma samples (one near the biopsy date and the other at a time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48) were further analyzed as controls. Antibody-based quantitative enzyme-linked immunosorbent assay was performed to validate candidate biomarker apolipoprotein A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed rejection (n=40) and nonrejection (n=70) patients. RESULTS: Twenty-two proteins/peptides showed significant differences between rejection and postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100% sensitivity and 94% specificity. The 4467 Da peptide was identified as the C-terminal fragment of α-1 antichymotrypsin and a 28 kDa protein was determined as Apo A1. Both protein levels were significantly lower at rejection compared with postrejection. Protein levels of nonrejection patients were similar to the postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for the second cohort) at the time of rejection compared with nonrejection which coincides with the SELDI findings. CONCLUSIONS: Together α-1 antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma molecular profile, and this is associated with acute cellular renal allograft rejection.

Acute care surgery after renal transplantation.

Emergent operation after renal transplantation (RT) has traditionally been associated with substantial morbidity and mortality. We reviewed 2340 adult patients who underwent RT at our tertiary care center and identified 55 patients who required acute care surgical consultation within 1 year of transplantation. Of these, 43 were treated operatively and 12 nonoperatively. Primary diagnoses were intestinal problems in 29 patients (53%), including diverticulitis, ischemia, perforation, obstruction, and bleeding; cholecystitis in 10 (18%); fluid collections in six (11%), appendicitis and hernias in two each (4%); gastritis in one (2%); and no diagnosis in five (9%). Colonic pathology was treated with resection and diversion in 14 of 16 patients who underwent surgery. Acute allograft rejection preceded the surgical problem in five patients. Complications occurred in 13 per cent of patients, and mortality was 9 per cent. Colonic ischemia had a fulminating presentation and particular morbidity. We conclude that acute gastrointestinal emergencies after RT are rare and that early and aggressive intervention using an acute care surgical model yields excellent results.

Selective use of voiding cystourethrography in children undergoing renal transplant evaluation.

PURPOSE: Voiding cystourethrography is a routine component in evaluating children awaiting renal transplantation. We examined whether this assessment is necessary in children with renal failure due to dysplasia/aplasia/hypoplasia syndrome and unknown etiology, which account for up to 25% of those with renal failure requiring renal replacement therapies. MATERIALS AND METHODS: We performed an institutional review board approved, retrospective review of 191 children undergoing transplantation between 2002 and 2007. We reviewed clinical factors associated with positive findings on voiding cystourethrogram. We also reviewed cystography results in children with chronic kidney disease due to renal dysplasia and unknown etiology. RESULTS: We identified 113 boys and 78 girls who underwent renal transplantation during the study period. Pre-transplant voiding cystourethrography was documented in 108 children (57%). Predictors of positive pre-transplant results included history of hydronephrosis, urinary tract infections and renal failure due to urological causes. No pre-transplant cystogram was positive in children with renal failure due to dysplasia or unknown etiology. CONCLUSIONS: We recommend selective use of voiding cystourethrography to evaluate children awaiting renal transplantation. We continue to support performing this test in children with renal failure due to urological causes and those with a history of urinary tract infection, hydronephrosis or voiding dysfunction. In the absence of these findings children with renal failure due to renal dysplasia/aplasia/hypoplasia syndrome or unknown etiology need not undergo pre-transplant voiding cystourethrography.

Long-term comparative outcomes between 2 common ureteroneocystostomy techniques for renal transplantation.

PURPOSE: We compared the incidence of ureteral complications between the classic (Lich-Gregoir) technique and the recently popularized single stitch (Shanfield) technique in renal transplantation. MATERIALS AND METHODS: The charts of 721 consecutive transplant recipients from May 1999 to July 2002 were retrospectively reviewed. Ureteral and nonureteral complications were reviewed at 3 to 5-year followup. RESULTS: Of the 721 recipients evaluated 713 were included in the study. There were 360 recipients in the Lich-Gregoir group and 353 in the Shanfield group. A significantly higher rate of ureteral complications occurred in the Shanfield group compared to the Lich-Gregoir group (15.6% vs 3.9%, p <0.0001). The Shanfield group consisted of 20 patients with ureteral leakage, 21 with hematuria, 11 with strictures and 3 who had ureteral stones. The Lich-Gregoir group had 8 patients with ureteral leakage, 5 with hematuria and 1 with a stricture. In comparison, urinary tract infections, delayed graft function and rejection rates were not significantly different between the 2 groups (p = 0.76, 0.12 and 0.19, respectively). CONCLUSIONS: In contrast to other reports, the Shanfield group had significantly more ureteral complications. In particular the Shanfield technique may predispose patients to higher rates of hematuria and stone formation. Based on this large series and published meta-analyses we believe that the stented Lich-Gregoir anastomosis is the superior ureteroneocystostomy technique in renal transplantation.

Surgically relevant normal and variant renal parenchymal and vascular anatomy in preoperative 16-MDCT evaluation of potential laparoscopic renal donors.

OBJECTIVE: Using 16-MDCT, we describe and quantify the frequency and types of renal anatomic variants and findings relevant for preoperative evaluation and surgical planning for potential laparoscopic renal donors. MATERIALS AND METHODS: On 16-MDCT, 126 consecutive potential donors underwent scanning before contrast administration and after i.v. power injection of nonionic contrast material during the arterial, nephrographic, and excretory phases. On a 3D workstation, CT images were evaluated retrospectively in consensus by three abdominal imagers. The number and branching pattern of bilateral renal arteries and veins, including anomalies of the inferior vena cava and lumbar-gonadal axis, were categorized along with the frequency of incidental findings of the renal parenchyma and collecting system. RESULTS: Major arterial variants including supernumerary and early branching arteries were present in 16% and 21%, respectively, of left kidneys and 22% and 15%, respectively, of right kidneys. Major and minor venous variants were detected in 11% and 58% of left kidneys and 24% and 3% of right kidneys. Late confluence of the venous trunk was identified in 17% of left kidneys and 10% of right kidneys. Incidental parenchymal and urothelial abnormalities, most commonly cysts and calyceal calcifications, were identified in 30% of the kidneys. Other relevant incidental findings included focal infarcts, cortical scars, atrophic scarred kidney, and bilateral papillary necrosis. Urothelial variants included bilateral simple ureteroceles and rightsided complete duplicated collecting system. CONCLUSION: 16-MDCT angiography and urography allow confident detection and classification of a variety of anatomic and incidental anomalies relevant to the preoperative selection of potential laparoscopic renal donors and to surgical planning.

Noninvasive diagnosis of cellular and antibody-mediated rejection by perforin and granzyme B in renal allografts.

A major milestone in transplantation would be the use of biomarkers to monitor rejection. We examined the association between perforin and granzyme-B gene expression detected in the peripheral blood of renal allograft recipients with cellular and antibody-mediated rejection. Furthermore, we judged the appropriateness of assigning negative rejection statuses to persons without a biopsy whose grafts were functioning well clinically. Of the 46 patients who completed the study, recipients with cellular rejection had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.006). Interestingly, recipients with antibody-mediated rejection also had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.04). Patients with high levels of granzyme B had a probability of rejecting that was 26.7 times greater than those patients with low levels of granzyme B. Perforin and granzyme B had sensitivities of 50% and specificities of 95% in predicting rejection (cutoff value = 140). Assigning negative rejection statuses to recipients without a biopsy whose grafts were functioning well did not have a major effect on the direction or significance of covariate values. This study suggests that perforin and granzyme-B gene expressions in peripheral blood are accurate in detecting both cellular and antibody-mediated rejection.

Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay.

BACKGROUND: Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay. METHODS: Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values. RESULTS: A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients. CONCLUSION: These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability.

Incidence of ureteral strictures after laparoscopic donor nephrectomy.

PURPOSE: Previous reports of laparoscopic donor nephrectomy have suggested that preservation of the gonadal vein with the specimen is important for preventing ureteral strictures. To test this hypothesis we examined our series of patients for the incidence of ureteral strictures when the gonadal vein was not preserved with the specimen during laparoscopic donor nephrectomy. MATERIALS AND METHODS: We reviewed the records of 300 consecutive patients at our institution who underwent laparoscopic donor nephrectomy between 2000 and 2005. Mean donor age was 36.7 years (range 18 to 68) in the 167 female and 133 male donors. Mean recipient age was 38.4 years. Average followup was 2 years. During ureteral dissection the gonadal vein was transected just distal to the renal vein and left in situ. The ureter was dissected and transected at the level of the common iliac vessels. Indwelling ureteral stents were used for all recipient ureteral reimplantations and left in place for 1 month. In the postoperative period transplant recipients were followed biweekly for serum creatinine function during month 1 and monthly thereafter. All patients with increased creatinine (greater than 1.3 mg/dl) or an increasing trend were evaluated with transplant renal ultrasound. Clinically significant ureteral stricture was defined as persistent hydronephrosis resulting in impaired renal function and the need for percutaneous nephrostomy tube placement or ureteroscopic management. RESULTS: After laparoscopic living donor transplantation without gonadal vein preservation we found no incidence of clinically significant ureteral stricture. CONCLUSIONS: Gonadal vein preservation with the specimen during laparoscopic donor nephrectomy is not necessary. Preservation of the periureteral blood supply is sufficient to prevent ureteral strictures.

Utility of 16-MDCT angiography for comprehensive preoperative vascular evaluation of laparoscopic renal donors.

OBJECTIVE: Our objective was to determine the efficacy of 16-MDCT angiography in preoperative evaluation of vascular anatomy of laparoscopic renal donors. METHODS AND MATERIALS: Fifty-five consecutive renal donors (25 men and 30 women) underwent 16-MDCT angiography followed by donor nephrectomy. In the arterial and nephrographic phases, images were acquired with 60% overlap and 0.6-mm reconstruction in both phases after 120 mL of iohexol was injected at 4 mL/sec. On a 3D workstation, images were evaluated retrospectively by two abdominal imagers blinded to surgical results with respect to number and branching pattern of renal arteries and major and minor renal veins. These CT angiography results were compared with surgical findings. RESULTS: The surgically confirmed sensitivity of both reviewers (1 and 2) using the MDCT data for detection of renal arteries was 98.5% (65 of 66), and accuracies were 97.0% for reviewer 1 and 95.5% for reviewer 2. Sensitivity and accuracy detection of renal veins was 97% (61 of 63) and 98% (62 of 63) for reviewer 1 and reviewer 2, respectively. Sensitivity and accuracy detection of early arterial bifurcation (< 2 cm from aorta) was 100% (14 of 14), and sensitivity in detection of late venous confluence (< 1.5 cm from aorta) was 100% (8 of 8). All major renal venous variants were identified; reviewer 1 identified 78% (18 of 23) minor venous variants, and reviewer 2 identified 83% (19 of 23) minor venous variants. There were no hemorrhagic complications at surgery. Excellent agreement between reviewers (kappa = 0.92-0.97) was achieved for detection of normal and variant anatomy. CONCLUSION: 16-MDCT angiography enabled excellent preoperative detection of arterial anatomy and venous laparoscopic donor nephrectomy.

Laparoscopic versus open renal procurement for pediatric recipients of living donor renal transplantation.

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.

A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus and sirolimus.

This study presents the first prospective multicenter study assessing sirolimus-based immunosuppression with early (4-day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti-IL-2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/microL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy-seven patients were enrolled: mean age of 49.7 +/- 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 +/- 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 +/- 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus-based immunosuppression in selected, low-risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.

Sirolimus-associated pulmonary toxicity.

BACKGROUND: Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. METHODS: We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. RESULTS: Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. CONCLUSION: The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.

Treatment of renal transplant ureterovesical anastomotic strictures using antegrade balloon dilation with or without holmium:YAG laser endoureterotomy.

OBJECTIVES: To report our results after antegrade endoscopic treatment of ureteral stenosis with balloon dilation with or without holmium laser endoureterotomy. Ureteral stenosis is the most common long-term urologic complication of renal transplantation. METHODS: From July 2000 to October 2002, 9 renal transplant patients with ureteral obstruction diagnosed by an increase in serum creatinine and radiologic evidence presented for endoscopic treatment. All patients were treated with nephrostomy tube drainage followed by antegrade flexible nephroureteroscopy and balloon dilation of the stricture. Three patients required holmium laser endoureterotomy during the same procedure because of fluoroscopic and endoscopic evidence of persistent stricture. All patients were treated with ureteral stents and nephrostomy tubes postoperatively. The median follow-up was 24 months (range 6 to 32). RESULTS: The site of stenosis was at the ureterovesical anastomosis in all patients, and the mean stricture length was 0.28 cm. Two patients had previously undergone ureteroneocystostomy for prior ureteral stenosis. Six patients (66%) required only balloon dilation, and 3 patients (33%) also required holmium laser endoureterotomy. The median ureteral stent and nephrostomy tube duration was 40 and 62 days, respectively. The mean serum creatinine level was 2.3 mg/dL at presentation and 1.7 mg/dL at the last follow-up visit. After a median follow-up of 24 months, the ureteral patency and graft function rates were both 100%. No perioperative complications occurred. CONCLUSIONS: Balloon dilation with or without holmium laser endoureterotomy was successful and safe in this group of renal transplant patients with short ureterovesical anastomotic strictures.

Fibrin sealant sclerotherapy for treatment of lymphoceles following renal transplantation.

PURPOSE: Fibrin sealant is used in various surgical fields for hemostasis and as an adhesive to approximate tissues. Its use was recently reported as a sclerosing agent for percutaneous treatment of lymphoceles following renal transplantation. We report on the use of fibrin glue sclerotherapy at this institution for the management of renal transplant related lymphoceles. MATERIALS AND METHODS: We reviewed the records of 8 patients at a single institution with lymphoceles after renal transplantation treated with percutaneous fibrin glue sclerosis. RESULTS: Treatment success was achieved in 6 patients (75%), with resolution of lymphoceles assessed with clinical and imaging findings. Four patients (50%) required 2 applications of fibrin sealant, with 2 (25%) subsequently requiring surgical management of the lymphoceles. Clinical followup averaged 27.7 months (range 4 to 44). Complications included lymphocele recurrence, clogging of drainage catheters and catheter dislodgement. CONCLUSIONS: The experience of 8 patients suggests that fibrin glue sclerotherapy may be considered a safe and effective method of treating symptomatic lymphoceles when simple percutaneous drainage has failed. The percutaneous approach does not require hospital admission and is less invasive than surgical treatment.