Comparing survival after transplantation with survival on dialysis: net benefit or a way to identify healthier patients?
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Humans↗
Biomedical subjects
J Michael Cecka
Publications and source records attributed to J Michael Cecka.
Could more effective use of kidneys recovered from older deceased donors result in more kidney transplants for older patients?
In the face of a severe shortage of kidneys from deceased organ donors that limits access to transplantation for many patients, about one of every seven kidneys (more than 1,500 each year) recovered from deceased donors in the United States are not transplanted. Eurotransplant, which coordinates organ distribution for six countries and a population of about 118 million, discards only one of every 20 kidneys procured for transplantation. We compared kidney procurement, transplants, and discards between January 2000 and June 2003 in the United States and in the Eurotransplant region using the Organ Procurement and Transplantation Network/United Network for Organ Sharing and Eurotransplant databases to examine differences that might account for this wide disparity.
Aged↗
Kidney allocation in the United States: fuzzy on the details?
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Fuzzy Logic↗
Preformed cytotoxic antibodies in potential allograft recipients: recent data.
Presensitization to donor human leukocyte antigen (HLA) remains a major barrier to cell and organ transplantation, thereby contributing to patient mortality. The risks associated with transplantation in the presence of preformed antidonor HLA antibodies range from hyperacute rejection and increased frequency and severity of rejection to no appreciable effect on transplant outcome. Recent evidence has emphasized the importance of immunologic history, anti-HLA antibody class and titer, and differential organ susceptibility to antibody-mediated damage to explain differences in risk for antibody-mediated rejection. Furthermore, in studies of endothelial cells, ligation of class I molecules by subsaturating concentrations of antibodies stimulated expression of cell survival proteins, raising the possibility that, under certain conditions, antibodies promote graft accommodation providing a mechanism for the endothelium to resist immune and inflammatory damage. The discovery of capillary-bound C4d as a robust diagnostic marker for antibody-mediated rejection, coupled with the development of solid-phase assays for the identification of HLA-specific antibodies, has enhanced our ability to detect antibody-mediated rejection and interpret cross-match results. With new diagnostic tools and immunosuppression regimens such as plasmapheresis and intravenous immunoglobulin therapy targeting the humoral immune response, it is time for a concerted effort to reassess the role of alloantibodies in acute and chronic rejection.
HLA Antigens↗
Impact of portal venous pancreas graft drainage on kidney graft outcome in simultaneous pancreas-kidney recipients reported to UNOS.
Clinical data on the potential immunologic impact of portal (PD) vs. systemic (SD) venous pancreas graft drainage on outcome remains controversial. We reviewed the UNOS database to study the effect of PD vs. SD on the incidence of kidney graft rejection and survival in first cadaveric simultaneous pancreas-kidney (SPK) recipients transplanted 1994-2001. We studied three groups: all SPK (n=6629, 13% PD) (group I), SPK on tacrolimus (n=3563, 17% PD) (group II), and SPK on tacrolimus performed at centers with significant PD experience (n=948, 46% PD) (group III). The cumulative kidney graft rejection incidence for PD vs. SD was only significantly different in group I (for PD vs. SD, respectively: at 6 months, 31% vs. 36% [p=0.015]; at 1 year, 37% vs. 43% [p=0.006]). Kidney graft survival was similar in all groups for PD vs. SD. Multivariate analysis of group III showed only transplantation during the earlier era (1994-96), but not SD, to be an independent risk factor for kidney graft rejection. Portal venous pancreas graft drainage does not affect kidney graft rejection and survival in SPK recipients on tacrolimus. Our data suggests that the efficacy of current immunosuppressive protocols and increasing center experience are clinically much more relevant than any potential immunologic advantage of portal venous drainage in SPK recipients.
Adult↗
The OPTN/UNOS renal transplant registry.
This chapter summarizes analyses of 66,843 kidney-only transplants reported to the OPTN/UNOS Renal Transplant Registry between January 1999-December 2003. The 5- and projected 10-year graft survival rates for 28,260 recipients of living donor (LD) kidneys were 80.5% and 67.0%, respectively, based on a computed halflife of 17.8 years for those grafts that survived one year. Comparable results for 33,118 recipients of standard criteria deceased donor (SCD) and 5,943 recipients of expanded criteria deceased donor (ECD) kidneys were 68.8% and 50.9%, and 51.8% and 32.9%, respectively. The half-lives for SCD and ECD were 10.8 and 6.8 years, respectively. ECD kidneys (from donors aged 60+ or 51-59 with other risk factors) were preferentially transplanted to older patients (median age 58) even though there was no formal requirement to allocate these kidneys to older patients. The oldest recipients of deceased donor (DD) kidneys, 991 aged 71-75 and 254 over age 75 had 5-year graft survival rates of 48.9% and 40.7%, respectively and 40% of graft losses in these groups were due to death with a functioning graft. Among 469 LD kidney recipients over age 70, graft survival rates were 70% or higher with 40% of grafts lost due death with function. About 13% of DD and 5% of LD kidneys were transplanted to broadly sensitized patients during this period. One-fourth and one-fifth of broadly sensitized patients who were transplanted received an HLA-matched DD or LD kidney, respectively. Overall, the proportion of transplants to unsensitized patients has increased in recent years to more than 50% of DD and nearly 70% of LD kidneys. There was no apparent correlation between the sensitivity of crossmatch tests and graft survival of first or repeat DD transplants; however, use of the more sensitive flow cytometry and AHG enhanced crossmatches significantly reduced the incidence of early rejections. Mean cold ischemia times have declined by about 7 hours between 1991- 2003, but the reduction in average cold time has not produced any notable reduction in the incidence of delayed graft function for recipients of SCD or ECD kidneys. Histocompatibility laboratories that waited for donor spleen or lymph node cells to perform final crossmatches added an average of 3 hours of cold ischemia for the kidneys they tested compared with laboratories that performed the tests with peripheral blood lymphocytes. There was no net increase in delayed graft function (DGF) with SCD kidneys tested at labs using spleen or nodes but the incidence of DGF among ECD kidneys was 25% when the lab used PBLs and 35% when the lab used spleen or nodes.
Adolescent↗
Allocation of deceased donor kidneys: past, present, and future.
The manner in which deceased donor kidneys are allocated has broad relevance to the care of patients with end-stage renal disease. An algorithm governing the allocation of deceased donor kidneys has been applied in the United States since 1987. Adjustments were made to facilitate the national sharing of highly matched kidneys, but the main components of the algorithm remained largely unchanged. In ensuing years, the number of patients on the waiting list has increased steadily while the supply of kidneys has remained constant. The waiting time for an organ now is measured in years, and the allocation of organs has become unpredictable. As of October 2002, several important changes have been made to the algorithm. These changes are designed to increase the relative number of minority patients who undergo transplantation and the use of extended-criteria donor kidneys. They also have practical implications for the management of patients on the waiting list. The rationale behind these changes is discussed in the context of the ethical underpinnings of kidney allocation.
Algorithms↗
The report of a national conference on the wait list for kidney transplantation.
In March, 2002, over 100 members of the transplant community assembled in Philadelphia for a meeting designed to address problems associated with the growing number of patients seeking kidney transplantation and added to the waiting list each year. The meeting included representatives of nine US organizations with interests in these issues. Participants divided into work groups addressing access to the waiting list, assigning priority on the list, list management, and identifying appropriate candidates for expanded criteria donor kidneys. Each work group outlined problems and potential remedies within each area. This report summarized the issues and recommendations regarding the waiting list for kidney transplantation addressed in the Philadelphia meeting.
Congresses as Topic↗
Kidney allograft and patient survival in type I diabetic recipients of cadaveric kidney alone versus simultaneous pancreas kidney transplants: a multivariate analysis of the UNOS database.
Simultaneous pancreas-kidney transplant (SPK) is now a common treatment for insulin-dependent diabetic patients with end-stage renal disease. Renal graft survival rates after SPK have been less well studied. This study compared the kidney survival results for 3642 SPK and 2374 cadaveric renal transplants (CRT) in type I diabetic patients at 112 US transplant centers reported to UNOS during 1994 through 1997. The analysis included follow-up information through September 2000. The kidney graft survival rates were significantly lower among recipients of CRT compared with SPK recipients (P < 0.001). Patients who received SPK were younger, less often sensitized, transplanted after shorter periods on dialysis, and less often black. The donors of SPK organs were younger, more often died from head trauma, were less often female, and more often black. SPK renal grafts were transplanted with a shorter cold ischemia time to more poorly HLA-matched recipients. After adjustment of these and other factors, whether a patient was recipient of CRT or SPK was not associated with increased risk of kidney graft failure or patient death. SPK recipients experienced half the rate of delayed kidney function (11% versus 23%) but nearly double the rate of rejections during the initial hospitalization (15% versus 9%) compared with CRT recipients. SPK was associated with better renal allograft survival compared with CRT, despite a higher rate of renal allograft rejection. This observation was explained by favorable donor and recipient factors in the SPK group. After controlling for these factors, SPK provided no protective or detrimental effect on short-term renal allograft or patient survival.
Adult↗
The OPTN/UNOS Renal Transplant Registry 2003.
The number of living donor kidney transplants reported to the OPTN/UNOS Registry more than doubled during the decade from 1992-2002, from 2,535 to 6,236, with the largest increases in transplants from offspring to their parents and from spouses and other genetically unrelated donors. Despite the rise in more HLA-incompatible living donors, 5-year graft survival rates among recipients transplanted between 1998-2002 were 78.5% and 77.5% for spouse and other unrelated donor grafts, respectively, and were comparable to that for one-haplotype-matched sibling transplants (80.7%). The number of deceased donor kidneys transplanted has remained static at less than 7,000 per year including about 850 (12%) from expanded criteria donors. The 5-year graft survival rate for ECD kidneys was 52.2% compared with 69.9% for standard criteria donor kidneys transplanted between 1998-2002. More than 1,000 patients aged 70-75 were transplanted during this period with 5-year graft survival rates of 50% or less when they received a deceased donor kidney. Nearly 40% of graft losses in this older group were due to death with a functioning graft, however, 25% reportedly died when their graft failed, suggesting a high rate of problems among older recipients. Early acute rejection episodes reduced both short- (10%+ at one year) and long-term (20-30% reduction in graft half-life) survival among first transplant recipients. However, when the serum creatinine level at discharge was <2.5 mg/dl, the early rejection had little if any effect on short- or long-term outcome. Time on dialysis before transplantation was an important determinant of first graft survival, with 5-year graft survival differences of about 10% comparing those transplanted within the first year with those who were on dialysis 4 or more years, regardless of the type of donor kidney. More than 60% of living donor kidney recipients were transplanted within 2 years of starting dialysis, compared with fewer than 20% of those who received a deceased donor kidney. Efforts to reduce cold ischemia times for ECD kidneys have been modestly successful, even before implementation of the new allocation system in November 2002. The percentage of ECD kidneys transplanted within 12 hours increased from 18% in 2001 to 25% in 2003 and the percentage with more than 24 hours of cold ischemia fell from 28% in 2001 to 20% in 2003. Prolonged ischemia of 42 hours was associated with a 5% lower 4-year survival rate of ECD kidneys compared with those transplanted within 12 hours.
Aged↗
Four causes of cadaveric kidney transplant failure: a competing risk analysis.
Multiple pathological processes are responsible for renal transplant loss. Development of effective prophylactic regimens requires that risks associated with different outcomes be assessed when several processes act together. A multistate competing risk model that derived multiple endpoint probabilities without averaging impacts of covariates over different outcomes or overestimating fractions of survivors was used to estimate the influence of 16 factors simultaneously on four failure types (acute rejection, chronic rejection, death with a functioning graft and all other causes combined). We analyzed 12,413 non-Black and 5,121 Black patients undergoing primary cadaveric kidney transplantation reported to UNOS during 1994-96. Black recipients generally demonstrated higher rates of failure, but the method provided joint probabilities for each failure type and covariate level. To illustrate, a middle-aged Black recipient had probabilities of 6.5%, 5.9%, 2.6% and 6.6% to experience acute rejection failure, chronic rejection failure, death with a functioning graft and other failures, respectively, within 3 years. The corresponding non-Black's chances were 2.9%, 2.5%, 2.7% and 3.6%. The overall 3-year survival equaled 78.4% [100%-(6.5% + 5.9% + 2.6% + 6.6%)] and 88.3% for Blacks and non-Blacks, respectively. The growing complexity of transplantation will benefit from new analytic approaches that accommodate multiple transitions along diverse paths to eventual graft loss or death.
Adult↗
Putting one objection to HLA matching on ice.
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Cadaver↗
The UNOS Renal Transplant Registry.
Based upon data reported to the UNOS Renal Transplant Registry between 1998-2001, the overall one- and projected 10-year graft survival rates for 31,720 cadaveric kidney transplants were 89% and 51%, and for 14,162 living donor transplants they were 95% and 68%, respectively. These results represent improvements of 15% and 13%, respectively, over the 10-year graft survival rates reported for transplants performed during 1987-1989. Repeat kidney transplants accounted for 14% of deceased donor kidney transplants during 1998-2001 and the 3-year graft survival rates were significantly lower for second (77%) and multiply regrafted (73%) than for recipients of a first transplant (79%; p < 0.001). About 1,200 newly defined expanded criteria donor (ECD) kidneys were transplanted each year between 1998-2001. ECD kidneys represented 15% of deceased donor kidneys and yielded a significantly poorer 3-year graft survival rate (68%) and half-life (7.1 years) than kidneys from normal donors over age 5 (81% and 11.9 years; p < 0.001). The graft failure rates (censoring death with a functioning graft) were similar among recipients aged 31-50 and those aged 51-70 comparing both ECD and normal kidneys. The effect of HLA matching on kidney graft survival remains essentially unchanged after 30 years even with remarkable improvements in immunosuppression. Considering transplants performed between 1995-2001, matching for antigens at the HLA-A,-B, and -DR loci resulted in a 16% higher projected 10-year graft survival rate when compared with grafts mismatched for 5-6 HLA antigens (p < 0.001). The 10-year graft survival difference associated with HLA matching in US transplants performed between 1979-1984 and reported to the UCLA Registry before the introduction of cyclosporine was also 16%. The 3-year graft survival rates for zero HLA-DR mismatched normal kidney grafts (excluding ECD kidneys) were 83%, the same as for recipients of 0 HLA-BDR mismatched grafts. Those with one or 2 DR antigens mismatched had significantly poorer outcomes (80% and 77%, p < 0.001). Living donor transplants from offspring to parents and from genetically unrelated donors including spouses increased more than 5-fold since 1994. In 2001 the number of non-spouse unrelated donors surpassed the number of spouses (701 and 616, respectively). Despite the growing number of these HLA-disparate living donor transplants, their 3-year graft survival rates and half-lives remain as high as those for related donors sharing one HLA haplotype with the recipient. Laparoscopic donor nephrectomy now accounts for more than half of living donor surgeries reported to UNOS. There was no difference in graft survival or in early graft function associated with the type of donor surgery for 19,223 living-donor transplants between 1998-2001. Kidney transplants from non-heartbeating donors are beginning to increase and despite a significantly higher incidence of delayed function, 3-year graft survival rate was 79% for transplants between 1998-2001, the same as for conventional brain-dead deceased donor transplants.
Graft Survival↗