Donor characteristics associated with liver graft survival

BACKGROUND: Organ availability is affecting the development of liver transplantation in its entirety, leading to transplant teams expanding the criteria for accepting organ donors. In these circumstances, analysis of the impact of the donor's characteristics on graft survival becomes mandatory. METHODS: Fifty-two donor variables from 5,150 liver transplants performed in Spain between 1994 and 2001 were analyzed through a univariate analysis. Those with statistically significant impact on graft survival were entered in a Cox regression model with the recipients' characteristics and other factors linked to the graft technique. RESULTS: Several donor factors negatively affect graft survival: donor age, cause of death, body mass index, vasoactive drug administration, prolonged intensive care unit (ICU) stay, increased alkaline phosphatase and liver enzyme levels, low bicarbonate level, and antecedents of hypertension. However, only four can be mentioned as representing a risk for losing the graft when donor variables are controlled with recipient or technique variables in a Cox regression model: donor age, antecedents of hypertension, prolonged ICU stay, and low bicarbonate level. In the same analysis, norepinephrine administration has a relative risk less than 1. CONCLUSIONS: The multivariate analysis of the impact of 52 donor characteristics on liver graft survival showed the negative effect of an elderly donor, with hypertension combined with the presence of metabolic acidosis, or a prolonged ICU donor stay. The administration of norepinephrine alone during donor management showed a protective effect.     

Donor tissue characteristics influence cadaver kidney transplant function and graft survival but not rejection

Acute injury and age are characteristics of transplanted tissue that influence many aspects of the course of a renal allograft. The influence of donor tissue characteristics on outcomes can be analyzed by studying pairing, the extent to which two kidneys retrieved from the same cadaver donor manifest similar outcomes. Pairing studies help to define the relative role of donor-related factors (among pairs) versus non-donor factors (within pairs). This study analyzed graft survival for 220 pairs of cadaveric kidneys for the similarity of parameters reflecting function and rejection. It also examined whether the performance of one kidney was predicted by the course of its "mate," the other kidney from that donor. Parameters reflecting function showed sustained pairing posttransplantation, as did graft survival. In contrast, measures of rejection strongly affected survival but showed no pairing. Surprisingly, the survival of a kidney was predicted by the early performance of its mate, an observation we term the "mate effect." Six-month graft survival and renal function were reduced in grafts for which the mate kidney displayed any criteria for functional impairment (dialysis dependency, low urine output [/= 400 micro mol/L), even for kidneys which themselves lacked those criteria. Rejection measures did not demonstrate the mate effect. In conclusion, kidney transplant function is strongly linked to donor-related factors (age, brain death). In contrast, rejection affects survival and function, but it is not primarily determined by the characteristics of the donor tissue. Graft survival reflects both of these influences.     

Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.     

Impaired kidney graft survival is associated with the TNF-alpha genotype

BACKGROUND: The TNF2 allele at position -308 of the tumor necrosis factor (TNF)-alpha gene is associated with high TNF production. The purpose was to study the association of this gene polymorphism with rejection episodes and graft survival after kidney transplantation. METHODS: A retrospective analysis of transplant outcomes of patients who only had been treated with one single form of immunosuppression consisting of cyclosporine, azathioprine, and prednisolon was performed. RESULTS: We found that 115 (73%) patients had the TNF1/TNF1 genotype, whereas 42 (27%) were TNF2 positive. There was no difference in the overall acute rejection frequency between these two groups (50% in each), but our data showed a non-significant tendency towards a higher frequency of steroid resistant rejections in the TNF2 positive group (57% vs. 40%). There was no significant difference in graft survival between the two genotype groups, although an early tendency towards worse survival was seen in TNF2 recipients. However, the TNF2 positive recipients with rejection episodes had far worse graft survival compared with the TNF1/TNF1 recipients with rejection episodes (P<0.02). No difference was seen between the two genotype groups in patients without rejection episodes. CONCLUSION: Our data propose that potentially high TNF producers with the TNF2 allele do not have an increased risk for rejection episodes, but if rejection episodes occur, they have a significantly increased risk for early graft loss. TNF production may intensify rejection, but is not a primary factor for the induction of such acute immune activation.     

Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list

BACKGROUND: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). AIM: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. PATIENTS AND METHODS: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. RESULTS: The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. CONCLUSION: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.     

Non-heart-beating donors: an excellent choice to increase the donor pool

A specific program was adopted to obtain organs, for transplant purposes from people who die at home or in the street from sudden or unexpected death (type I non-heart-beating donors [NHBD] according to the Maastricht classification). The objective of our program was to increase the donor pool by obtaining organs from well-selected potential donors who die at home, work, or in the street and are maintained on advanced life support (ALS) until hospital arrival. The great number of people who die in a previously healthy situation constitute an excellent source of organs for transplant purposes. Our program includes pre- and in-hospital attendance. Prehospital attendance is based on application of cardiopulmonary resuscitation in situ and ALS until arrival at hospital. In hospital, specific preservation maneuvers must be performed and family assessment and judge permission obtained. In the last 15 years, we developed a kidney transplant program with better results than transplants performed with organs obtained from encephalic death donors (EDD). A specific NHBD subprogram for lung transplant was developed with excellent results as well. We are now improving the liver transplant program. NHBD are an important source of human tissues, including pancreas islets. It is clear that NHBD are a great source of organs and tissues for transplant, and that this kind of program must be established in all countries in which legal regulations allow it.     

Correlation of fetal kidney and testis congenic graft survival with reduced major histocompatibility complex burden

Prolonged survival was enjoyed by fetal and postnatal testis and midgestational renal grafts transplanted beneath the renal capsule of adult congenic mice, confirming previous findings in nonimmunosuppressed outbred rats (3,5). The strategies that enable immature tissues to escape rejection in a graft survival assay were studied by comparing expression of major histocompatibility class I and class II protein and messenger ribonucleic acid (mRNA) in each tissue at different ages. In general, graft survival was best when class I and II expression was low. After transplantation, surviving kidney and testis grafts both showed marked induction of class I and II mRNA measured using donor and recipient-specific oligonucleotide probes. Immunohistochemically detected protein of both classes, however, could not be found in the kidney and was minimal in the testis. Fetal tissues appear to express lower levels of protein and mRNA--and, although invading lymphocytes may induce expression of class I and II mRNA after transplantation, protein was not inducible. The failure of these tissues to express significant levels of transplantation antigens may explain the prolonged survival of these immature grafts.     

The use of contrast media in deceased kidney donors does not affect initial graft function or graft survival

Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival according to the method used to diagnose brain death. Data from 9921 cadaveric kidneys, transplanted between 1 January 1998 and 31 December 2003, were retrieved from the French National Registry for organ donation. We defined RFR as the number of days for the recipient to reach a plasma creatinine less than 250 mumol/l, and/or a 24-h urine output greater than 1000 ml. RFR and 1-year and long-term graft survival were compared between four different donor groups (according to ICMI and diabetes mellitus). A total of 41.5% of deceased donors received ICMI before organ procurement and 1.95% of them were diabetic. History of ICMI or diabetes in the donor did not influence RFR or 1-year graft survival. Long-term graft survival was decreased in the group of patients transplanted with a diabetic graft as compared to patients transplanted with a non-diabetic graft (P=0.001). History of ICMI in the donor did not affect long-term graft survival in the non-diabetic donor group (P=0.2); however, in the diabetic group, ICMI tended to decrease long-term graft survival (P=0.056). ICMI did not affect RFR or graft survival in non-diabetic deceased donors. However, its use in diabetic deceased donors requires further study.     

Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation

Moore J, Tomson CRV, Tessa Savage M, Borrows R, Ferro CJ. Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation.
Clin Transplant 2011: 25: 406–416. © 2010 John Wiley & Sons A/S. Abstract: The impact of disordered mineral and bone metabolism following kidney transplantation is not well defined. We studied the association of serum phosphate and calcium concentrations, and surrogate measures of arterial stiffness (augmentation index: AIx and Timing of the reflected wave: Tr), with long‐term kidney transplant recipient and allograft survival. Prevalent adult renal transplant patients (n = 270) were prospectively studied over a median 88‐month follow‐up. Detailed demographic, clinical and laboratory data, in addition to both peripheral and central non‐invasive blood pressure measurements, were recorded. Higher serum phosphate and calcium levels were associated with increased all‐cause mortality (HR: 1.21; 95% CI 1.09,1.35, p < 0.001 and HR: 1.22; 95% CI 1.01,1.48; p < 0.04, respectively; adjusted Cox model) and death‐uncensored graft loss (p < 0.001 and p = 0.03, respectively). In addition, serum calcium and phosphate were associated with death‐censored graft loss on univariable analysis (p < 0.001 and p = 0.02, respectively), but did not retain significance on multivariable analysis. AIx and Tr were not associated with mortality or graft loss on multivariable analysis. This is the first report to demonstrate that both higher serum phosphate and calcium levels are associated with increased mortality in kidney transplant recipients. It highlights the need for randomized trials assessing current interventions available for improving disordered mineral–bone metabolism post transplantation.     

Parental donors in live-donor kidney transplantation associated with increased rejection rates and reduced glomerular filtration rates

BACKGROUND: Living unrelated and related kidney transplantation has been shown to have similar allograft survival. However, the effect of donor-recipient relatedness in living-related and unrelated kidney transplantation on graft and patient survival remains uncertain. METHODS: Using Australia and New Zealand Dialysis and Transplant Registry, primary living renal transplant recipients in Australia between 1995 and 2004 were studied (n=1989). Donors were categorized according to their relationship with recipients: parent (n=606), child (n=103), spouse (n=358), sibling (n=656), other living-related donors (n=81), and other living-unrelated donors (n=185). Outcomes analyzed included the presence of rejection at 6 months, estimated glomerular filtration rate (eGFR) at 1 and 3 years, graft survival, and patient survival. RESULTS: A greater proportion of renal transplant recipients from parental and spousal donors were transplanted preemptively. Donor groups had no relationship with graft or patient survival. Parental donors were associated with an increased relative odds of acute rejection (odds ratio 1.69, 95% confidence interval 1.13-2.53, P=0.009) and a lower eGFR at both 1 and 3 years (coefficient -2.99 and -5.68, respectively; P<0.0001) compared to other donor groups (reference sibling donor group). CONCLUSIONS: This study has established that donor-recipient relatedness in both related and unrelated living kidney transplantation had no significant effect on graft and patient survival. Parental donors were associated with a higher relative risk of rejection and lower eGFR in the transplant recipients, although these findings did not translate to a worse graft outcome.     

Persistent cytomegalovirus infection in kidney allografts is associated with inferior graft function and survival

The long-term effects of cytomegalovirus (CMV) infections on kidney allografts are unknown. We examined the impact of persistent intragraft CMV infection on long-term kidney allograft function and survival. CMV was diagnosed in 82/172 renal transplant recipients by antigenemia test and viral cultures. Biopsies from 48 of 82 patients taken after CMV infection and from 15 patients with no previous CMV infection detected were available for the immunohistochemical demonstration of CMV antigens and DNA hybridization in situ. Five-year follow-up data from these 63 patients were analysed. In 17 patients, CMV antigens and/or DNA persisted in the biopsy >2 months after the last positive finding in blood or urine. Patients with persistent intragraft CMV had reduced graft survival (P = 0.041) and Cox regression analysis showed persistent CMV as a risk factor for reduced graft survival (RR: 3.5). Recipients with persistent intragraft CMV had reduced creatinine clearance 1 and 2 years after transplantation (P = 0.007) and in multivariate logistic regression analyses including several potential pre- and posttransplant risk factors, persistent CMV was an independent risk factor for lower clearance at 1 and 2 years (OR: 4.4 and 4.9). Our novel findings show that persistent intragraft CMV infection was associated with reduced kidney allograft function and survival.