Cadaveric Donor Renal Transplantation Research Articles

Combined Liver-Kidney Transplantation and Follow-Up in Primary Hyperoxaluria Treatment: Report of Three Cases

Introduction Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disorder caused by impaired activity of the hepatic peroxisomal alanine-glyoxilate aminotransferase, which leads to end-stage renal disease (ESRD) and requires combined liver-kidney transplantation (CLKT). Herein, we have reported 3 children diagnosed with PH1 who received CLKT. Case 1 A 4.5-year-old boy with an elder brother diagnosed with PH1 was diagnosed during family screening when the sonography showed multiple calculi. Within 5 years he experienced flank pain, hematuria attacks, and anuric phases due to obstruction and received hemodialysis (HD) when ESRD appeared. CLKT was performed from his full-match sister at the age of 9.5. He is doing well at 5.5 years. Case 2 A 7-year-old boy was admitted with polyuria, polydypsia, and stomach pain with renal stones on sonography. PD was instituted when serum creatinine and BUN levels were measured as high values. At the age of 10, CKLT was performed from his mother. His liver and renal function tests are well at 14 months after CKLT. Case 3 A 2.5-year-old girl had attacks of dark urine without any pain; renal stones were imaged on sonography. She was diagnosed with PH1 and operated on several times due to obstruction. She received peritoneal dialysis and a cadaveric CLKT was performed when she was 9 years old. At the age of 16, she experienced chronic allograft nephropathy requiring HD and subsequent cadaveric donor renal transplantation at 1.5 years after inititation of HD. Conclusion Herein, we have presented the favorable clinical outcomes of patients with CKLT to indicate the validity of this treatment choice for PH1.

Failure of Anti-CD20 Monoclonal Antibody Therapy to Prevent Antibody-Mediated Rejection in Three Crossmatch-Positive Renal Transplant Recipients

There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m 2) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occured in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m 2 at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients.

Selective, Concurrent Bilateral Nephrectomies at Renal Transplantation for Autosomal Dominant Polycystic Kidney Disease

An algorithm was developed for performing bilateral nephrectomies for specific indications before or at renal transplantation in patients with autosomal dominant polycystic kidney disease. Outcomes for the living donor arm of the algorithm are reported. Patients with autosomal dominant polycystic kidney disease and end stage renal disease were evaluated for transplantation. Patients with recurrent pyelonephritis, hemorrhage, pain, early satiety or kidneys that extended into the true pelvis underwent bilateral nephrectomies. Bilateral nephrectomies with concurrent renal transplantation were performed if a living renal donor was identified. If no living donor was identified, pre-transplantation bilateral nephrectomies were done and the patients were listed for cadaveric donor renal transplantation. The living renal donor arm of the algorithm was evaluated by comparing certain parameters for 15 and 17 patients with autosomal dominant polycystic kidney disease who underwent pre-transplantation and concurrent bilateral nephrectomies, respectively, including patient and graft survival, delayed graft function, graft function, length of stay for each surgery, transfusions and complications. No deaths, graft failures or delayed graft function occurred. In the delayed renal transplant group median time from nephrectomy to living donor transplantation was 124 days. Serum creatinine at discharge home and 1 year after transplantation for the pre-transplantation nephrectomy cohort was 2.0 and 1.3 mg/dl, respectively. Seven of the 17 patients with concurrent nephrectomy underwent transplantation before starting renal replacement therapy. A longer mean total hospital stay in the pre-transplantation nephrectomy cohort was the only statistically significance outcome variable. Selective bilateral nephrectomies at living donor renal transplantation results in decreased total length of stay without compromising patient or graft outcomes and it allows preemptive renal transplantation. Concurrent nephrectomy is safe and it further validates the algorithm for selective, concurrent bilateral nephrectomies for patients with autosomal dominant polycystic kidney disease who undergo living donor renal transplantation.

Microchimerism and Renal Transplantation: Doubt Still Persists

Objective We sought to study microchimerism in a group of kidney transplant recipients. Materials and Methods In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. Results Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). Conclusion Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.

Living Donor Renal Transplantation in Catalonia: Overall Results and Comparison of Survival With Cadaveric Donor Renal Transplantation

Objectives To describe the general characteristics of living-donor renal transplantation (LRT) in Catalonia, and to compare results with those of the cadaveric donor renal transplant (CRT). Results Four hundred seventy-three LRTs have been performed in Catalonia since 1965. Transplantations carried out between 1980 and 2003, according to the RMRC data, were reviewed. The most frequent degrees of kinship are parents–children (48%), spouses (22%), and siblings (18%). Around 68% of the donors were women. Around 56% of recipients were men. The transplant was advanced in approximately 30% of the cases. The mean cold ischemia was 2 hours. Seven percent showed delayed graft function (DGF). Forty-nine percent of the patients had glomerular filtration >60 mL/min after 1 year. Patient survival at 1, 5, 10, and 20 years were 99%, 97%, 93%, and 82% in LRT; and 96%, 90%, 80%, and 62% in CRT ( P < .00001). Graft survivals over the same periods were 91%, 76%, 58%, and 32% in LRT, and 85%, 69%, 49%, and 23% in CRT ( P = .00008). The graft mean life was 12 years (LRT) and 10 years (CRT). Graft survivals, censoring deaths over the same periods, were 93%, 79%, 62%, and 39% in LRT, and 89%, 77%, 62%, and 37% in CRT ( P = .3). Mean life was 14 years in both cases. The recipients mean age was 31 (LRT), and 44 years (CRT), whereas the donor mean age was 51 (LRT), and 42 years (CRT). Conclusions LRT results were excellent both regarding DGF and patient and graft survivals. They were not comparable to CRT due to the different characteristics of the recipients. LRT is a good solution to reduce waiting lists.

Evolution of the Renal Function is a Better Predictor of Long-Term Survival Than Serum Creatinine

Background In recent years acute rejection has decreased to 10% to 20%. Therefore it is necessary to look for new endpoints in renal transplantation. Serum creatinine and changes in creatinine have been reported to be powerful predictors of long-term kidney transplant survival. Chronic renal allograft nephropathy is the primary cause of long-term graft failure but may appear at any stage in the evolution. Methods Data from 315 patients receiving cadaver donor renal transplants between February 1987 and March 2001 that functioned for 1 year were examined for the influence of demographic characteristics and transplant variables. Creatinine clearance was estimated using the Cockroft-Gault formula. Survival was assessed with the actuarial method. The multivariate analyses were performed using Cox proportional hazard models. Results The 10-year graft survival showed a relative risk of 2.5 in the univariate analysis when there was more than 10% decrease in renal function at 3 months compared with nadir values. When the decrease was more than 25% of creatinine clearance at the third month, during the evolution and serum creatinine at 3 months introduced in the multivariate model, the latter was not significant, while the other variables had a RR of 4.4 and 10, respectively. Conclusion The evolution of renal function at 3 months and throughout the evolution were better predictors of graft failure than an isolated serum creatinine value.

The Influence of Mycophenolate Mofetil and Azathioprine on the Same Cadaveric Donor Renal Transplantation

In order to evaluate whether immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine would differently influence the outcome of the renal transplants, we prospectively analyzed the incidence of acute rejection episodes, cytomegalovirus infection within the first 6 months following renal transplantation and 5 yr graft survival rate after minimizing influences of donor factors by grafting the same cadaveric donor kidney. There was no significant difference in sex, HLA mismatch, cold ischemic time, and patients' weight between the two groups. Contrary to the previous studies which demonstrated that MMF could lower the incidence of acute rejection episodes and improved graft survival rate, the two groups showed no significant difference in the incidence of acute rejection episodes and 5-yr graft survival rate as well. This discrepancy in these results might explain that donor factors could be important to cadaveric renal transplantation. Thus, we suggest that the influences of donor factors should be considered in further clinical studies of cadaveric renal transplantation.

Use of EQUORAL&lt;sup&gt;®&lt;/sup&gt; in de novo renal transplant recipients

This paper presents our experience to date with using a cyclosporine formulation Equoral (IVAX Pharmaceuticals) together with mycophenolate mofetil plus a steroid immunosuppressive regimen in the treatment of de novo renal transplant recipients. Ten cadaveric donor renal transplant recipients of mean age 51.6 years (range 37-66) were followed up over 6 months for the development of rejection attacks and side effects. All patients received prednisolone, mycophenolate mofetil (1 g/day during the first 5 days posttransplant and then 20 mg/kg/day) plus cyclosporine (3 mg/kg/day). Biopsy proven acute rejection episodes were observed in 2 out of 10 patients (20%). Six months patient as well as renal graft survival rate was 100%. The development of graft function was immediate after transplantation. The mean serum creatinine levels were gradually decreased. Over the 6-month posttransplant period, the function of the graft was satisfactory and stable. The majority of observed adverse events were those commonly reported with the use of cyclosporine and they resolved with a reduction in cyclosporine dose. Equoral treatment demonstrated an acceptable safety profile with maintenance of adequate renal function without incidence of malignancy/lymphoproliferative disease or serious infections. In conclusion, Equoral plus mycophenolate mofetil immunosuppression seems effective and safe on terms acute rejection rates, patient and renal graft survival rates and side profiles.

Influence of tacrolimus plus mycophenolate mofetil regimens on acute rejection rate and diabetes mellitus development in renal transplant recipients

In this study we investigated the influence of a tacrolimus (TAC) plus mycophenolate mofetil (MMF) immunosuppressive regimen on the acute rejection rate and side effect profile in renal transplant recipients.The study included 80 living-related and 40 cadaveric donor renal transplant recipients (82 men, 38 women) of mean age 35 ± 10 years (range, 16 to 58) who were operated between August 1999 and September 2002. The mean HLA mismatches was 3 ± 1 (range, 0 to 5). All patients received prednisolone, MMF (2 g/d for the first 14 days posttransplant and then 1 g/d) plus TAC (0.2 mg/kg/d). They were followed for the development of rejection attacks and side effects. Diabetes mellitus developed in 13 patients (9 men, 4 women; 10.8%). Initially, patients required insulin therapy but after 6 months, 5 recipients no longer needed insulin therapy and were switched to oral hypoglycermic agents and diet control. Hypertension was diagnosed in 58 patients (48.3%). Neither gender nor donor origin (P = .14; P = .79, respectively) produced a significant difference in diabetes mellitus development.Biopsy proven acute rejection episodes were observed in 16 out of 120 patients (13.3%). Six out of 120 patients lost their grafts throughout the study period including one death because of suicide, one because of cytomegalovirus disease and hemophagocytic syndrome, one due to posttransplant lymphoproliferative disease and two to a cardiac arrhythmia. Only one patient lost his graft due to acute accelerated vascular rejection. Biopsy-proven chronic rejection appeared in one patient.In conclusion, although the incidence of insulin-dependent diabetes mellitus during posttransplant 6 months, seems high it decreased to 1.6% upon reduction of the TAC dosage. TAC plus MMF immunosuppression seems effective and safe in terms of acute rejection rates and side effect profiles.

Study 1: a prospective, randomized, double-blind, multicenter trial of early (7-day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy under tacrolimus and mycophenolate mofetil therapy with antibody induction

M odern corticosteroid therapy for prevention and treatment of rejection continues to be associated with significant morbidity. To date, only 3 randomized, double-blind, placebo-controlled trials of corticosteroid withdrawal (CSWD) have been conducted in renal transplantation. These trials, however, all evaluated withdrawal at 3 months and beyond, and antibody induction therapy was not standardized among centers. The current study is the first randomized, double-blind, placebo-controlled CSWD trial that includes corticosteroid cessation before 3 months after transplantation, as well as standardized antibody induction therapy. The study was designed as a 2-limb study with 1:1 enrollment to either early (7-day) CSWD or longterm corticosteroid maintenance therapy (taper to 5 mg/d by 6 months after transplantation). Inclusion criteria included primary cadaveric and live donor renal transplant patients aged 18 to 70 years. Exclusion criteria included peak panel reactive antibody 50%, current panel reactive antibody 25%, repeat transplant, and multiple organ transplant. The primary end point was treatment failure defined as death, graft loss, or moderate acute rejection (by Banff criteria and treatment) at 6 months and years 1 to 5. Secondary end points included Framingham cardiac risk estimates at 6 months and years 1 to 5, acute rejection, study drug discontinuation, posttransplant diabetes, weight, infection, and malignancy. Patients received tacrolimus (target, 10-20 ng/mL on posttransplant days 1-90; 5-15 ng/mL after posttransplant day 90) and mycophenolate mofetil (2 g/d). Induction therapy was varied by center with interleukin 2 receptor (IL-2R) antibody or Thymoglobulin (1.5 mg/kg 4 doses) (IMTIX-SangStat, Lyon, France). Patients with a decrease in creatinine level of 30% by posttransplant day 3 were randomized either to stop corticosteroids on posttransplant day 7 or to receive long-term corticosteroids. Longterm corticosteroids were given at 5 mg/d after posttransplant day 180. To assess long-term graft survival and cardiac risk, blinding is planned for 5 years. The study included 396 patients who were enrolled before October 2002. Data presented are blinded data from 176 patients. Follow-up lengths included 12 months in 67% of patients, 6 months in 10%, and 3 months in 23%. Eight percent of patients withdrew from the study. Mean age was 46 12 years; 70% of patients were male, 65% white, 25% African American, 45% cadaveric recipients, and 25% had diabetes before transplantation. Mean number of human leukocyte antigen mismatches per patient was 3.3; 94% of patients had current panel reactive antibody 10%. Mean cold ischemia time was 18.8 6.6 hours, 59% received Thymoglobulin induction, and 41% received IL-2R antibody. Biopsyproven acute rejection occurred in 8% of patients, From the Division of Transplantation, Cincinnati, OH; and Fujisawa Healthcare, Inc, Deerfield, IL. The Fujisawa Steroid Withdrawal Study Group consists of the following: E. Steve Woodle, William Fitzsimmons, John D. Pirsch, Fuad Shihab, Osama Gaber, Laurence Chun, Mark Stegall, Alan Langnas, Jonathan Bromberg, Okechukwu Ojogho, Kenneth Washburn, Kristene Gugliuzza, Ravi Parasuraman, Oleh G. Pankewycs, Eugene Schweitzer, John Sorenson, Christopher Johnson, George Loss, George Francos, Paul Morrissey, Raphael Mendez, David Shaffer, Sandip Kapur, J.R. Thistlethwaite, Richard Freeman, Nasimul Ahsan, Thomas Johnston, Arthur Matas, Donald Hricik, Sameh Abul-Ezz, and Rita Alloway. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.028

Cadaver-donor renal transplantation of children in Israel (1990-2001): racial disparities in health care delivery?

To evaluate the allocation and outcome of cadaver-donor renal transplantation (CDRTx) among Jewish and Arab children in Israel. Data on CDRTxs in patients who had end-stage renal failure (ESRF), were younger than 18 years, and were on dialysis treatment were obtained for the 11-year period of January 1990 to December 2000 from the Israeli Dialysis and Transplant Registry, supplemented by 10 years of follow-up (January 1991-December 2000) from our own center. The Israeli Dialysis and Transplant Registry data show that 64 of 130 available cadaver-donor kidneys (CDKs) were allocated to Jewish patients (49.2%) and 66 of 130 were allocated to Arab children (50.8%): Moslem, Druze, or Christian. The Jew/Arab patient ratio for a waiting time of <1 year was 0.97 and for 1 to 2 years was 1.45, whereas that ratio was 0.6 for 2 to 4 years and 2.0 for >4 years. The mean renal transplant score (RTx score), reflecting the urgency of the need for RTx of an ESRF patient, was identical for Jew and Arab: 4.93 and 4.96. Our own center data refer to 69 dialysis (47 Arabs and 22 Jews) and 4 predialysis patients younger than 18 years who underwent 78 RTxs. Eighteen Arab and 14 Jewish children from our center received 20 and 15 CDRTxs in Israel, with a mean waiting time of 29.6 and 25.4 months for Jew and Arab, respectively (ratio: 1.16). In our center, the outcome (after 7 years) of graft survival and function was not different between Jewish and Arab RTx recipients. Allocation of CDRTxs between young Jewish and Arab ESRF patients on dialysis did not differ and was associated with comparable waiting times, identical RTx scores, and similar long-term outcome. This is a remarkable finding, certainly in the face of the unequal race allocation of RTxs in the United States as well as the long unstable local (Middle East) political situation.

Does cadaveric donor renal transplantation ever provide better outcomes than live-donor renal transplantation?

Live donor renal transplantation (LRT) now comprises more than 40% of all kidney transplants performed in the United States. Many patients on the cadaveric waiting list have a prospective live kidney donor. This study determines whether cadaveric donor renal transplantation (CRT) can demonstrate better outcomes than LRT. From the United States Renal Data System registry, 31,909 adult recipients of a first-time kidney transplant from 1995 to 1998 were analyzed. Recipients were followed until December 31, 2000. CRT, more human leukocyte antigen (HLA) mismatches, increased donor age, cold ischemia time greater than 24 hr, African American recipient, and a history of diabetic nephropathy all increased the risk of graft failure, return to dialysis, and death. Nevertheless, in specific circumstances, CRT could provide better outcomes than LRT. For example, in recipients aged 18 to 59 years with a hypothetical live kidney donor aged 50 years and four HLA mismatches, the relative risk of graft loss with LRT is comparable or increased compared with CRT if the cadaveric kidney donor is much younger or with fewer HLA mismatches. On the other hand, for recipients aged 60 years or older, CRT never provides better outcomes than LRT. All analyses were adjusted for recipient race, gender, and history of diabetic nephropathy. There were no significant interactions among donor type, HLA mismatches, donor age, and cold ischemia time. The elderly recipient with an imminent LRT should never be offered CRT. A combination of recipient and donor factors can make CRT preferable to LRT in younger patients.

Early experience using calcineurin-free protocol in recipients of high-risk cadaver renal transplants

The use of calcineurin inhibitors (CNI) is associated with significant nephrotoxicity, especially DGF in recipients of marginal allografts. Acute nephrotoxicity, which occurs in the early period after transplantation, leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually result in graft loss. Avoidance of CNI for a prolonged period de novo after cadaver donor (CD) renal transplantation may facilitate recovery from DGF. Sirolimus (SRL) and mycophenolate mofetil (MMF) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. To study the efficacy and tolerability of using a CNI-free induction protocol, a SRL-MMF combination plus interleukin-2R: (IL2R) antibody (basiliximab-Simulect) induction was administered to 24 consecutive adult recipients of marginal CD transplants (ie, donor age over 60 years, history of longstanding hypertension or diabetes mellitus, or cold ischemia time over 36 hours).

Renal transplantation during the twentieth century: a review.

To provide an overview of the various advancements and problems associated with both live and cadaver donor renal allograft transplantation during the twentieth century. Major published reviews on renal transplantation during the the last five decades of the twentieth century were reviewed using Medline internet search and the Index Medicus. The developments in immunosuppressive therapy associated with renal transplantation, the problem of the shortage of both live and cadaveric organ donors and post-transplant complications were examined. The future of renal transplantation including cross species transplantation (xenotransplantation) is discussed. Renal transplantation has evolved over the years to become a very successful and routine procedure. However, the transplant waiting lists have remained long due to a continuously shrinking kidney donor pool which is due to improved results of neurosurgical procedures, better emergency and intensive care services and the failure to adequately prevent and treat post transplant chronic renal failure.

Type I membranoproliferative glomerulonephritis in a renal allograft: A recurrence induced by a cytomegalovirus infection?

A 40-year-old white woman with end-stage renal disease from idiopathic type I membranoproliferative glomerulonephritis (MPGN) developed proteinuria and renal dysfunction 7 weeks after cadaveric donor renal transplantation. At the same time, a primary cytomegalovirus (CMV) infection was diagnosed. Complement levels were low. A renal biopsy disclosed an acute exudative proliferative glomerulonephritis with influx of polymorphonuclear granulocytes (PMNs), with granular deposits of C3, C1q, IgG, and IgM. The immunofluorescence (IF) and electron microscopy (EM) findings were compatible with an early stage of a type I MPGN. CMV could not be detected in the glomeruli nor elsewhere in the kidney by IF or EM. The patient was treated with ganciclovir. In a renal biopsy 3 weeks later, the exudative lesions had disappeared, and some glomeruli now showed the characteristic lesions of a type I MPGN with an increase of mesangial cells and matrix, and reduplication of the glomerular basement membrane. Over the following period, repeated biopsies were performed. The activity of the glomerular inflammation and immune complex deposits paralleled the waxing and waning of the CMV viral load. After 10.5 months, the graft was removed because of a life-threatening systemic fungal infection. At that time, the CMV infection had cleared, and in the transplantectomy material, the membranoproliferative pattern of injury had disappeared, and in the glomeruli hardly any deposits were found. These data strongly suggest that a primary CMV virus infection can induce an apparent recurrence of type I MPGN.

Deleterious Effects of Delayed Graft Function in Cadaveric Renal Transplant Recipients Independent of Acute Rejection

Background. In cadaveric renal transplantation, delayed graft function (DGF) correlates with poor long-term graft survival; however, whether its effects are independent of acute rejection is controversial. We wished to study the effect of DGF on graft survival, controlling for acute rejection, discharge creatinine, and human leukocyte antigen match. Methods. We analyzed 27,096 first cadaveric donor renal transplants reported to the UNOS Scientific Renal Transplant Registry between January 1994 and November 1997. DGF was defined as dialysis need in the first week. Acute rejection was recorded for initial hospitalization and within 6 months. Kaplan Meier survival curves were analyzed with the log rank test. Results. DGF increased the incidence of acute rejection before discharge (8% without DGF; 25% with DGF, P<0.01) and any acute rejections by 6 months (25% without DGF, 42% with DGF, P<0.01). Without early rejection, DGF reduced 1-year graft survival from 91 to 75% (P<0.0001) and graft half-life from 12.9 to 8.0 years. In kidneys with acute rejection within 6 months, DGF decreased 3-year graft survival from 77 to 60% and graft half-life from 9.4 to 6.2 years (P<0.001). With a discharge creatinine of less than 2.5 mg/dl, the difference in graft half-life between no DGF and no rejection (13.4 years) and DGF with rejection (9.8 years) was significant (P<0.001). Increased donor age and cold ischemia time additionally decreased graft survival, whereas a good human leukocyte antigen match could not overcome the deleterious effects of DGF or acute rejection. Conclusions. DGF is an important independent predictor of poor graft survival. Newer immunosuppressive strategies must minimize nonimmune and immune renal injury if long-term graft survival is to improve.

Prolonged hypertension (>10 years) is a significant risk factor in older cadaver donor renal transplants

L’objectif de ce travail était d’apprécier la fréquence et la prise en charge des différentes complications vasculaires lors de l’activité de transplantation rénale.Étude rétrospective des patients transplantés rénaux de 2001 à 2006 dans notre centre hospitalo-universitaire. Nous avons recensé les caractéristiques de la population de donneurs et receveurs, du déroulement du prélèvement multi-organes (PMO) et de la transplantation, afin d’étudier les complications vasculaires et leurs conséquences. Les donneurs vivants ont été exclus.Cent soixante-dix-neuf dossiers ont été analysés avec un suivi moyen de 40 mois. Soixante-douze patients transplantés avaient eu au moins une complication vasculaire, dont 32 cas de sténose de l’artère du transplant, 28 cas d’hématome dont sept drainés chirurgicalement, quatre cas de thrombose artérielle, deux cas de thrombose veineuse et une dissection artérielle. L’analyse de notre série a mis en évidence que le tabagisme (p = 0,043) était un facteur de risque des donneurs et la néphropathie glomérulaire (p = 0,0185), les coagulopathies (p = 0,0165) et l’hémodialyse (p = 0,02) étaient des facteurs de risques vasculaires pour le receveur. Les transplants présentant des artères multiples (p = 0,03) et un patch aortique calcifié (p = 0,0274) seraient plus à risque de complications postopératoires. Nos résultats démontraient que le remplissage postopératoire (p = 0,011), l’héparinothérapie (p = 0,0085), l’immunosuppression (p = 0,0478), voire l’utilisation d’amines vasopressives en peropératoire (p = 0,086) seraient également impliqués dans l’incidence des complications vasculaires.La sélection des donneurs était indispensable pour la qualité des transplants, sans négliger la préservation de l’état artériel et le dépistage des coagulopathies des receveurs afin de diminuer la morbidité de la transplantation rénale. La coordination des équipes médicales impliquées était nécessaire pour optimiser les temps d’ischémie, minimiser les risques de complications vasculaires et améliorer la survie du transplant et du patient.The aim of this study was to evaluate frequency and management of vascular complications in renal allograft.We performed retrospective analysis of patients who underwent renal allograft from 2001 to 2006 at our university hospital center. In order to access peri- and postoperative vascular complications, data were also obtained from donors and receivers, as well as organ procurement and renal transplant procedure.One hundred and seventy-nine files were analyzed with a median follow-up of 40 months, mean age of donors was 40.4 ± 11.2 years and 46.01 ± 10.6 years for receivers. Seventy-two allograft patients had at least one vascular complication, with 32 cases of renal arterial stenosis, 28 cases of hematoma with surgical exploration required in seven cases, four cases of arterial thrombosis, two cases of venous thrombosis and one arterial dissection. Our series underlines that tobacco abuse in donors is a risk factor for vascular complication (p = 0.043), as well as glomerular nephropathy (p = 0.0185), coagulopathy (p = 0.0165) and hemodialysis (p = 0.02) are risk factors for receivers. Multiple arteries in renal allograft (p = 0.03) and calcification on aortic patch (p = 0.0274) would present a greater risk of postoperative complications. Our results demonstrate that the following parameters i.e., postoperative transfusion (p = 0.011), heparin therapy (p = 0.0085), immunosuppression (p = 0.0478), and peri-operative aminovasopressive drugs (p = 0.086) could also be implicated in vascular complication occurrence.A careful selection of donors remains a major factor for renal allograft quality, however arterial evaluation and coagulopathy detection in receivers must also be performed prior to transplantation procedure. A multidisciplinary approach (nephrologist, urologist, anesthesist) will optimize vascular ischemia delay and also reduce early and late vascular complications, which could have possible consequences on renal allograft and patient survival.

Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection.

In cadaveric renal transplantation, delayed graft function (DGF) correlates with poor long-term graft survival; however, whether its effects are independent of acute rejection is controversial. We wished to study the effect of DGF on graft survival, controlling for acute rejection, discharge creatinine, and human leukocyte antigen match. We analyzed 27,096 first cadaveric donor renal transplants reported to the UNOS Scientific Renal Transplant Registry between January 1994 and November 1997. DGF was defined as dialysis need in the first week. Acute rejection was recorded for initial hospitalization and within 6 months. Kaplan Meier survival curves were analyzed with the log rank test. DGF increased the incidence of acute rejection before discharge (8% without DGF; 25% with DGF, P<0.01) and any acute rejections by 6 months (25% without DGF, 42% with DGF, P<0.01). Without early rejection, DGF reduced 1-year graft survival from 91 to 75% (P<0.0001) and graft half-life from 12.9 to 8.0 years. In kidneys with acute rejection within 6 months, DGF decreased 3-year graft survival from 77 to 60% and graft half-life from 9.4 to 6.2 years (P<0.001). With a discharge creatinine of less than 2.5 mg/dl, the difference in graft half-life between no DGF and no rejection (13.4 years) and DGF with rejection (9.8 years) was significant (P<0.001). Increased donor age and cold ischemia time additionally decreased graft survival, whereas a good human leukocyte antigen match could not overcome the deleterious effects of DGF or acute rejection. DGF is an important independent predictor of poor graft survival. Newer immunosuppressive strategies must minimize nonimmune and immune renal injury if long-term graft survival is to improve.

Positional Obstructive Uropathy Secondary to Ureteroneocystostomy Herniation in Renal Transplant Recipient

A 59-year-old man with end stage renal disease of unknown etiology underwent cadaveric donor renal transplantation. The donor kidney (right side) was placed in the right iliac fossa after revascularization of the renal to external iliac artery and the renal to external iliac vein. Ureteroneocystostomy was performed in an extravesical fashion. Induction immunosuppression consisted of 9 days of Minnesota antilymphocyte globulin, methylprednisolone, azathioprine and cyclosporine. Convalescence was uneventful and at discharge home serum creatinine was 1.7 mg./dl. (normal 0.6 to 1.4). Two rejection episodes occurred in the first 3 months of which 1 was empirically treated with intravenous methylprednisolone and 1 with OKT3 for biopsy proved rejection. Subsequently, multiple hospital admissions were related to an increase in creatinine to 2.6 mg./dl. At each admission renal transplant ultrasound and nuclear renal scanning were unremarkable,

Real-time monitoring of renal function during ischemic injury in the rhesus monkey.

The presence of delayed graft function (DGF) following cadaver donor renal transplantation is associated with inferior graft survival as well as decreased patient survival. Delay in onset of function eliminates a valuable indicator of allograft viability, which is not easily replaced by standard diagnostic procedures. The purpose of this study was to demonstrate that a new clearance technique could be used to measure renal function minute to minute and under conditions similar to those observed in humans in the immediate posttransplantation period. A monkey model was used to provide controlled conditions. Increasing levels of ischemic injury were produced in 12 Rhesus monkeys by renal hilum cross-clamping. Real-time measurements of glomerular filtration rate (GFR) were obtained from the rate of clearance of the extracellular fluid of the GFR agent 99mTc-DTPA, as measured with a specially designed external radioactivity counting device called the ambulatory renal monitor, or ARM. GRF was measured every 2-5 min as the slope (k) of the log of activity measured minute to minute versus time. GFR measurements were correlated with blood urea nitrogen (BUN), plasma creatinine (Cr), routine light microscopy, and measurement of proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Large changes in renal function due to ischemia or ureteral obstruction were observed within minutes. In addition, the rate constant on Day 1 was predictive of peak serum Cr(R =--0.86, R2=.74, p = .0001). Acute tubular necrosis (ATN) resolution was reflected more quickly when using the rate constant (Day 1) than when using either BUN or plasma Cr (Day 3-4). Because of renal functional reserve, BUN and plasma Cr were relatively insensitive indicators of mild to moderate reductions in GFR as compared with the rate constant. We conclude that ARM is a simple method which provide an accurate, near real-time GFR readout with potential applications not only for the clinical management of patients with DGF, but also as a research tool in acute renal failure (ARF).