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Lloyd E Ratner

Publications and source records attributed to Lloyd E Ratner.

At least 19 recordsLinked to original sources
PubMed2006

Alloantibodies and the outcome of cadaver kidney allografts.

The role of humoral immunity in causing antibody-mediated rejection (AMR) of organ allografts has been extensively documented. For this reason, negative complement-dependent cytotoxicity (CDC) cross-matches between recipient sera and donor T and B lymphocytes have become a mandatory requirement for cadaveric kidney transplantation. However, the significance of donor-specific antibodies (DSAs) detectable only by flow cytometry (FC) or solid phase assays (SPA) but not CDC is still controversial. We have performed a retrospective analysis of FC cross-matching results in 80 consecutive cadaver kidney allograft recipients. Antibodies against HLA class I and class II antigens were measured by CDC and SPA in sequential samples of sera obtained prior to transplantation. The preoperative cross-match was performed by CDC using magnetically sorted T and B cells from donor spleen. Sera obtained from each patient before and at the time of transplantation were included in the final cross-match. The sample of serum obtained at the time of transplantation was cross-matched retrospectively by FC and analyzed for anti-HLA antibody specificity on high resolution SPA. The actuarial kidney allograft survival at one year was 98%. Two of these eighty patients lost the graft, one due to AMR, the other for reasons unrelated to DSAs. Donor-specific antibodies were detected by FC in 17 of 80 patients, yet only 6 of 17 had an early episode of AMR. This episode was successfully reversed by desensitization therapy using intravenous immunoglobin (IVIG) and plasmapheresis. Flow cytomery cross-matching showed 95% specificity but only 35% sensitivity for prediction of AMR (p = 0.002). There was a significant correlation between high panel reactive antibodies (PRA) and positive FC cross-matching (p = 0 .0001), as well as high PRA and AMR (p = 0.0004 by CDC and 0.0011 by Luminex). Reversible AMR occurred 12-30 days post-transplantation in 8 patients. Of these 8 patients, 3 had no detectable DSAs in spite of C4d positivity, 4 had C4d deposition in conjunction with anti-HLA antibodies, and 1 patient had DSAs (anti-MICA) yet no C4d deposition. We conclude that early initiation of desensitization protocols can prevent transplant failure and that retrospective FC cross-matches may facilitate the diagnosis of AMR. Extensive analysis of patients' sera using a comprehensive set of tests may contribute to early treatment and better understanding of the mechanism underlying humoral rejection.

Cadaver↗
PubMed2006

Fatal and nonfatal hemorrhagic complications of living kidney donation.

OBJECTIVE: After anecdotal reports of severe hemorrhage from failure of surgical clips to sustain closure of renal artery stumps in live donor nephrectomies were received, this study was designed to identify specific surgical techniques that are associated with an increased risk of failure to control bleeding and might represent opportunities to improve patient safety. BACKGROUND: Preventing complications for living kidney donors must be paramount in addressing end-stage renal failure through living kidney donation. Major hemorrhage from technical failure, albeit an infrequent occurrence, can cause significant, yet preventable, morbidity or death. Open and laparoscopic approaches to living kidney donation use several vascular control methods, some of which may be more prone to failure and life-endangering hemorrhage than others. METHODS: To define hemorrhagic complications of living kidney donation, a survey was sent to all 893 surgeon-members of the American Society of Transplant Surgeons. Descriptive and bivariate analyses were used to ascertain study participant characteristics, most frequently used vascular control techniques, and incidence of events (death, transfusion, reexploration or conversion to open nephrectomy, or contralateral [remaining kidney] renal failure). Outcomes of hemorrhage and comments by respondents were sought as were data from other sources. RESULTS: In 213 surveys returned (24%), 66 and 39 episodes of arterial and venous hemorrhage were reported, respectively. Among arterial control problems, 2 resulted in donor death and 2 resulted in renal failure; 19 episodes required transfusion. Open conversions in laparoscopic nephrectomy or late reoperations for hemorrhage were reported for 29 cases. Locking and standard clips applied to the renal artery were associated with the greatest risks. CONCLUSIONS: Significant hemorrhagic complications occur with living kidney donation in both open and laparoscopic approaches. Loss of arterial control jeopardizes donor life and health, especially when it occurs in the postoperative period. Vascular transfixion provides the best vascular control of major vessels.

Data Collection↗
PubMed2006

Characterization of rejection episodes in patients following positive crossmatch and ABO-incompatible live donor renal transplantation.

For kidney transplant recipients with donor-specific antibody (DSA) to HLA- (+XM) or ABO-antigens (ABOI), there is a need to improve detection and treatment of antibody-mediated rejection (AMR). The methods included a retrospective review of consecutive patients that received plasmapheresis and immune globulin (PPIVIg) to abrogate +XM or ABOI. Twelve patients were transplanted after PPIVIg (+XM = 9, ABOI = 2, +XM/ABOI = 1). No hyperacute rejections occurred. Rejection occurred in seven patients [four AMR, three acute cellular rejection (ACR)]. In four +XM patients, DSA was detected during graft dysfunction despite lack of histologic and C4d features of AMR. In one patient, DSA preceded the histologic and immunofluorescent features of AMR. In another patient with borderline changes and DSA, graft function improved after PPIVIg, despite lack of histologic or immunofluorescent evidence of AMR. One patient with Banff IIA ACR and DSA treated with antithymocyte antibody but not PPIVIg had recurrent rejections and poor graft function. In +XM and ABOI recipients with graft dysfunction: (i) DSA may represent AMR in the absence of C4d or histologic features of AMR; (ii) DSA can precede C4d or light microscopic features of AMR; (iii) A poor outcome may result if DSA or continued allograft dysfunction is present and not treated despite a negative biopsy.

ABO Blood-Group System↗
PubMed2005

Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation.

CONTEXT: First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. OBJECTIVE: To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. DESIGN, SETTING, AND PATIENTS: Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. INTERVENTION: Kidney paired donation and live donor renal transplantation. MAIN OUTCOME MEASURES: Patient survival, graft survival, serum creatinine levels, rejection episodes. RESULTS: A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). CONCLUSIONS: This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.

Adolescent↗
PubMed2005

Patterns of volunteerism, testing, and exclusion among potential living kidney donors.

We found that in kidney transplantation, more females donate. We analyzed transplant recipients for patterns of potential donor exclusion and found that equal proportions of male and female potential donors existed among first-degree biological relatives. More male recipients were married and therefore had more spousal potential donors. Among friends and non-first-degree relatives, significantly fewer males offered to donate to females. Equal proportions of female and male potential donors were excluded from donating for medical comorbidities, blood type incompatibility, recipient refusal, and potential donor reluctance. We concluded that female transplant candidates had fewer potential donors among spouses and opposite sex volunteers from friends and non-first-degree relatives.

Adult↗
PubMed2005

Pancreatico-renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis.

Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one-third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico-renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.

Adult↗
PubMed2005

Attitudes, psychology, and risk taking of potential live kidney donors: strangers, relatives, and the general public.

It is unclear whether potential living kidney donors and the general public differ in attitudes and psychological characteristics. We performed a case-control study to explore differences in these groups using a standardized questionnaire (analyzed using conditional logistic regression). Strangers (N = 42) were more willing than controls (N = 126) to incur risks: 64% strangers versus 35% controls accepting >50% medical complications (MC) risk; 90% strangers versus 61% controls accepting >8 days hospitalization; 71% strangers versus 43% controls accepting >3 months unpaid; 55% strangers versus 16% controls accepting 100% kidney failure (KF) risk; 70% strangers versus 34% controls accepting < or =10% likelihood of successful transplant (all p < 0.01). Relatives (N = 251) were also more willing than controls (N = 251) to incur risks. Strangers were most willing to incur MC, KF and transplant failure. Groups did not differ in attitudes, depression or anxiety. Potential stranger and related donors are willing to undergo greater risks with donation than the general public, but do not differ in other attitudes, depression or anxiety. This should help reassure transplant centers and the public that both forms of live donation do not necessarily involve increased ethical risks of donor coercion or irrational thought processes. Still, careful attention to communication of all risks of donation is warranted.

Adult↗
PubMed2004

Consensus opinion from the antibody working group on the diagnosis, reporting, and risk assessment for antibody-mediated rejection and desensitization protocols.

During the past few decades, much of the experimental and clinical effort in solid-organ transplantation has been directed toward ameliorating or abrogating T-cell-mediated responses. As a result, universally understood and accepted nomenclature and diagnostic criteria have evolved. Humoral immunity in transplantation has yet to undergo a similar renaissance. Readers of transplant journals regularly find it difficult and often impossible to interpret data on the diagnosis and management of antibody-mediated rejection. The Antibody Working Group was assembled in an attempt to provide guidelines for the standardization of nomenclature, diagnostic criteria, reporting, antibody profiling, and risk assessment.

Graft Rejection↗
PubMed2004

Whole body donation for medical science: a population-based study.

Although cadaveric whole-body donation for the purposes of medical science is extremely important for medical education, the number of persons who choose to donate remains low. We assessed persons' willingness to consider whole body donation in a standardized telephone survey of Maryland households, identified using random digit dialing. In multivariable analyses, we assessed the independent relation of sociodemographics and attitudinal factors to willingness to consider donation, and we determined the amount of variation in willingness to consider donation among the study population that could be explained by these factors. Of 385 participants (84% of randomized homes), 49% reported they would consider whole body donation. In bivariate analysis, younger age, African-American race/ethnicity, less education and income, greater number of dependents, marital status, and attitudes about religion/spirituality, trust in hospitals, and income, gender, and racial/ethnic discrimination in hospitals were statistically significantly associated with 40-70% less odds of willingness to consider donation. After adjustment, persons of African-American race/ethnicity, less education, and those agreeing with the statements, "Rich patients receive better care at hospitals than poor patients," and "White patients receive better care at hospitals than other racial or ethnic groups," had 40-60% less odds of willingness to consider donation when compared to their counterparts. Respondents' race/ethnicity and education contributed most to willingness to consider donation. We conclude that demographic and attitudinal factors are strongly related to willingness to consider whole body donation. Efforts to enhance donation should seek to identify ways in which potential barriers to donation can be addressed by health professionals.

Adolescent↗
PubMed2004

Laparoscopic live donor nephrectomy: trends in donor and recipient morbidity following 381 consecutive cases.

OBJECTIVE: To review a single-institution 6-year experience with laparoscopic live donor nephrectomy detailing the technical modifications, clinical results, as well as the trends in donor and recipient morbidity. SUMMARY BACKGROUND DATA: Since 1995, laparoscopic donor nephrectomy has had a significant impact on the field of renal transplantation, resulting in decreased donor morbidity, without jeopardizing procurement of a high-quality renal allograft. This technique has become the preferred method of allograft procurement for many transplantation centers worldwide but still remains technically challenging with a steep learning curve. METHODS: Records from 381 consecutive laparoscopic donor nephrectomies were reviewed with evaluation of both donor and recipient outcomes. Trends in donor and recipient complications were assessed over time by comparing the outcomes between four equally divided groups. RESULTS: All 381 kidneys were procured and transplanted successfully with only 8 (2.1%) open conversions. Mean operative time was 252.9 +/- 55.7 minutes, estimated blood loss 344.2 +/- 690.3 mL, warm ischemia time 4.9 +/- 3.4 minutes, and donor length of stay was 3.3 +/- 4.5 days. There was a significant decline in total donor complications, allograft loss, and rate of vascular thrombosis with experience. The rate of ureteral complications declined significantly when comparing our early (Group A) versus later (Groups B-D) experience. CONCLUSION: Laparoscopic donor nephrectomy has remained a safe, less invasive, and effective technique for renal allograft procurement. Over our 6-year experience and with specific refinements in surgical technique, we have observed a decline in both donor and recipient morbidity following laparoscopic live donor nephrectomy.

Cohort Studies↗
PubMed2004

Successful living donor renal transplantation despite ABO incompatibility and a positive crossmatch.

Potential live kidney donors have been rejected when the prospective recipients are blood type or crossmatch incompatible. By utilizing plasmapheresis combined with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific antibodies against blood group or human leukocyte antigens (HLA) have been removed, thereby allowing successful renal transplantation. A 26-yr-old male with a panel reactive antibody level of 100% and repeated positive crossmatches against deceased donor kidney offers, including zero HLA mismatched donors, successfully underwent ABO-incompatible kidney transplantation from his HLA-identical but nevertheless crossmatch-incompatible sister. The initial anti-A blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37 degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an individualized PP/IVIg regimen based on donor-specific antibody titer, however, the relevant antibodies were adequately reduced and hyperacute rejection avoided. Subsequent antibody-mediated rejection, likely directed against a minor histocompatibility antigen, was diagnosed on postoperative day 7 and successfully treated. Neither ABO, or crossmatch incompatibility, or both in combination prohibit kidney transplantation.

ABO Blood-Group System↗
PubMed2004

Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers.

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.

ABO Blood-Group System↗
PubMed2003

Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients.

BACKGROUND: Donor-specific antibody (DSA) is the major barrier to success of kidney transplants. Attempts to deal with this problem have used plasmapheresis to remove antibodies or high-dose pooled immunoglobulin (IVIg) to down-regulate DSA. However, elimination of antibodies by these methods has been limited in duration or scope. METHODS: We have confirmed the presence of immunoglobulin (Ig)G antibody to one or more donor HLA antigens in 49 patients treated with alternate-day, single-volume plasmapheresis followed by low-dose cytomegalovirus (CMV) hyperimmune globulin (CMV-Ig) combined with quadruple immunosuppression. We examined the effect of the treatment protocol on antibodies to donor HLA, third-party HLA, and nominal antigens. RESULTS: At the end of treatment, 63% of patients had lost antibody to donor HLA, whereas only 27% had lost antibody to third-party HLA (P<0.001). More strikingly, loss of antibody to donor and third-party HLA antigens occurred in 89% and 19%, respectively, of patients followed for 2 or more months after end of treatment (P<0.0001). No elimination of antiviral antibodies tested was seen. With one exception, elimination of DSA appeared to be independent of antibody titer or specificity, the number of different antibody specificities, or whether or not the target antigen was a repeat mismatch. The effect appears to be long lasting, with no return of DSA observed in patients followed for an average of 13 months. CONCLUSIONS: Plasmapheresis and low-dose CMV-Ig combined with traditional immunosuppression is effective in producing a specific and durable elimination of antibody to donor HLA.

Antibody Formation↗
PubMed2003

Laparoscopic adult donor nephrectomy for pediatric renal transplantation.

To evaluate retrospectively our laparoscopic adult donor nephrectomy experience for pediatric transplantation. Since February 1995, 7 adult donors have undergone laparoscopic donor nephrectomy for pediatric renal transplantation (recipients younger than 18 years and weighing less than 30 kg). The outcomes of these donors and pediatric recipients were evaluated. The 7 laparoscopic renal donors had a median operative time of 306 minutes, median allograft warm ischemia time of 275 seconds, median blood loss of 200 mL, median hospital stay of 3 days, and 14.2% overall complication rate. No graft loss or patient mortality occurred. The pediatric recipients of the laparoscopic live-donor allografts had a median creatinine clearance level of 52.1, 52.1, 44, and 41.1 mL/min at 3, 6, 12, and 18 months, respectively. The overall complication rate was 14.2%. The 1 and 2-year graft survival rates were 100%. No mortality occurred in the pediatric recipients. Laparoscopic donor nephrectomy is well tolerated by the adult donors and appears to provide acceptable recipient and allograft outcomes in the pediatric population.

Adolescent↗
PubMed2003

Impact of renal artery multiplicity on outcomes of renal donors and recipients in laparoscopic donor nephrectomy.

OBJECTIVES: To review our laparoscopic donor nephrectomy experience to determine the impact of multiple renal arteries on renal donor and recipient outcomes. Multiple renal arteries can present a challenge during live laparoscopic donor nephrectomy. METHODS: During a 6-year period, 353 patients underwent laparoscopic donor nephrectomy and an equal number of patients underwent living-related renal transplantation. A retrospective chart review was performed to evaluate the renal donors and recipients associated with the laparoscopic procedure. RESULTS: Laparoscopic donor nephrectomies were associated with one renal artery in 277 cases (78.5%), two renal arteries in 71 cases (20.1%), and three renal arteries in 5 cases (1.4%). A left-sided procedure was most commonly performed in all three groups. The operative and renal allograft warm ischemia times increased with the number of renal arteries, but the differences were not statistically significant. The renal artery anatomy did not have a significant association with intraoperative blood loss, postoperative hospital stay, or complication rate in the donor group. Regarding the transplant recipients, renal artery multiplicity had no significant association with the complication rate, 1-year graft survival, or creatinine clearance levels at 1, 2, or 3 days or at 3, 6, or 12 months postoperatively. CONCLUSIONS: With meticulous procurement and reconstructive transplantation techniques, the presence of multiple renal arteries in laparoscopic donor nephrectomy does not have a significant impact on the outcomes of the renal donors or recipients.

Adolescent↗
PubMed2003

Concomitant surgery with laparoscopic live donor nephrectomy.

Routine live donor evaluations reveal unexpected silent pathologies. Herein, we describe our experience treating such pathologies at the time of laparoscopic donor nephrectomy. We have not encountered any previous reports of such an approach. We prospectively collected data on 321 donors. Concomitant surgeries at the time of procurement included two laparoscopic adrenalectomies, one colposuspension, one laparoscopic cholecystectomy, and one liver biopsy. Mean operative time was 321 min (range 230-380), with a mean blood loss of 280 mL (range 150-500). No blood transfusions were required. The left kidney was procured in four cases. The right kidney was obtained on one occasion. Mean hospital stay was 3 days (median 3, range 2-4). No short- or long-term complications have been identified. Mean follow-up time was 2.63 years (median 2.76, range 2.23-2.99). Four of the five kidney recipients were first-time transplants who had not yet started dialysis. Simultaneous surgical interventions at the time of laparoscopic live kidney donation are safe and can be undertaken in selected cases. This practice is beneficial to both the donor and the recipient, and is likely to become more commonplace with changing practice patterns involving donor evaluation and management.

Adenoma↗