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PubMed2001

Daclizumab: a review of its use in the management of organ transplantation.

UNLABELLED: The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. When added to standard triple immunosuppression regimens, daclizumab significantly reduces the rate of acute rejection at 1 year in renal transplantation by 36% and there are indications that it may be effective in other solid organ transplantations. Three-year outcomes of two phase III clinical trials in renal transplantation indicate similar values for graft and patient survival between daclizumab and placebo when given in addition to triple immunosuppression; however, these pivotal trials were not designed with sufficient power to demonstrate any statistical significance. The addition of daclizumab induction shows potential in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without increasing the rate of acute graft rejection or adverse effects in renal and liver transplantation. Preliminary reports indicate that daclizumab may also be a useful agent in delayed graft function and graft versus host disease (GVHD). Further investigation of its efficacy in these groups and in children is needed. Data from clinical trials show daclizumab to be well tolerated in solid organ transplantation. It does not increase the incidence of infection, including cytomegalovirus infection, when compared with placebo or no induction groups. Preliminary comparative data with muromonab CD3 indicate that daclizumab may be associated with a lower rate of infectious complications and similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been proven to reduce acute rejection in renal transplant recipients when given in addition to traditional baseline immunosuppression. It has shown potential to reduce acute rejection in other solid organ transplants; however, well designed, randomised studies are required to confirm this. Clinical experience from trials to date indicate that daclizumab has a tolerability profile similar to placebo with no significant effect on the incidence of infection. The relative efficacy and tolerability of daclizumab compared with other induction agents has yet to be defined. Available data suggest that daclizumab may allow the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may have potential in the treatment of GVHD.

Animals↗
PubMed1997

Posttransplant acute renal failure.

Acute renal failure posttransplant is a multifactorial syndrome in the early phases of transplantation. Delayed graft function is common and confers an adverse prognosis for both short- and long-term survival of the renal allograft. Later out from transplantation, the differential diagnosis of acute renal failure is usually between acute renal failure secondary to rejection or cyclosporine nephrotoxicity. Transplant biopsies are often needed to distinguish these possibilities.

Acute Kidney Injury↗
PubMed2003

The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of machine perfusion (MP) compared to cold storage (CS), as a means of preserving kidneys prior to transplantation. Transplantation of kidneys from both heart-beating donors (HBDs) and non-heart-beating donors (NHBDs) is considered. Finally to review whether the use of MP can allow valid testing of kidney viability prior to transplantation. DATA SOURCES: Fifteen electronic bibliographic databases were searched. The reference lists of relevant articles and sponsor submissions were hand searched and various health service research-related resources were consulted via the Internet. REVIEW METHODS: A literature search was undertaken to identify relevant studies and a meta-analysis performed on the studies that had appropriate comparator groups and reported sufficient data. A structured review examined tests of viability of kidneys on MP. Economic modelling was used to determine the cost-effectiveness and cost-utility of MP. RESULTS: The meta-analysis suggested that the use of MP, as compared with CS, is associated with a relative risk of delayed graft function (DGF) of 0.804 (95% confidence limits 0.672 to 0.961). There was no evidence to suggest that this effect is different in kidneys taken from HBDs as opposed to NHBDs. Meta-analysis of 1-year graft survival data showed no significant effect, but the studies, even when aggregated, were severely underpowered with respect to the likely impact on graft survival. The size of effects demonstrated were in line with those predicted by an indirect model of graft survival based on the association of DGF with graft loss. The economic assessment indicated that it is unlikely that in the UK health setting complete cost recovery will be obtained from a reduction in the incidence of DGF. The probability that MP is cheaper and more effective than CS in the long term was estimated at around 80% for NHBD recipients and 50-60% for HBD recipients. Flow characteristics of the perfusate of kidneys undergoing MP may be an indicator of kidney viability, but data were inadequate to calculate the sensitivity and specificity of any test based on this. The concentration of alpha-glutathione-S-transferase (a marker of cell damage) in the perfusate may be the basis of a valid test. A threshold of 2800 micrograms/100 g gave a sensitivity of 93% and specificity of 33% (and hence a likelihood ratio of 1.41). CONCLUSIONS: The baseline analysis indicated that in the long-term MP would be expected to be cheaper and more effective than CS for both HBD and NHBD recipients. A definitive study of the clinical benefit of MP in order to establish its effect on DGF and longer term graft survival would be valuable, together with an economic evaluation of the benefits. While direct evidence relating to improvements in graft survival would be preferable, the small predicted improvement indicates that a very large sample size would be required. In addition to seeking direct evidence of the impact on DGF, research quantifying the impact of DGF on graft survival in this technology is required. Research is also needed to establish whether a valid test (or combination of tests) of kidney viability can be developed.

Cell Survival↗
PubMed2026

Urine-Derived Cells in Kidney Transplantation: Linking Cellular Phenotypes, Secretome Signatures and Multi-Omic Technologies.

Kidney transplant monitoring and early identification of graft dysfunction are central needs for long-term graft survival. Although kidney biopsy represents the gold standard in diagnostic procedures, its invasiveness may limit frequent longitudinal evaluation, highlighting the necessity of non-invasive diagnostic tools. Urine has emerged over the years as an easily obtainable source of cellular and molecular components derived from transplanted kidneys. Particularly, exfoliated cells and extracellular vesicles (EVs) represent complementary and interconnected markers able to reflect tissue injury, inflammatory signals, immune cell infiltration, and regenerative processes occurring in the graft. Also, recent advances in transcriptomics, proteomics, metabolomics, and single-cell technologies have expanded the diagnostic and mechanistic value of urinary liquid biopsy, enabling the identification of disease-specific molecular signatures associated with rejection, delayed graft function, fibrosis, and graft loss. This review discusses the emerging concept of an integrated urinary cell-EV ecosystem and highlights how integrated multi-omic approaches may transform non-invasive graft surveillance and advance precision medicine in kidney transplantation.

Humans↗
PubMed2002

Pathophysiological contributions of fucosyltransferases in renal ischemia reperfusion injury.

Ischemia reperfusion injury (IRI) is a major cause of delayed graft function. Recent studies have shown that selectins play an important role in IRI. Selectins bind to sialylated and fucosylated sLe(x) receptors, and two enzymes, fucosyltransferase IV (FucT-IV) and VII (FucT-VII), are important in the function of these receptors. We hypothesized that fucosyltransferase (FucT) enzymes were important pathophysiologic mediators of renal IRI. We therefore evaluated renal IRI in mice deficient in FucT-IV, FucT-VII, and both FucT-IV and FucT-VII and compared their renal function, tubular injury, selectin ligand expression, and neutrophil infiltration to those in wild-type control mice. Bilateral 30-min renal IRI was performed, and the results demonstrated that mice deficient in both FucT-IV/FucT-VII were significantly protected from renal IRI at 24 and 48 h compared with wild-type control mice. FucT-IV-deficient mice showed only modest protection from renal injury at 24 h. However, FucT-VII-deficient mice had similar injury as wild-type mice. Histological analysis of kidney tissue postischemia revealed that mice deficient in both FucT-IV and FucT-VII had significantly reduced tubular injury compared with wild-type mice. Selectin ligand expression increased postischemia in wild-type, but not FucT-IV/FucT-VII-deficient, mice. Neutrophil infiltration in postischemic kidneys of FucT-IV/FucT-VII-deficient mice was also attenuated. These data demonstrate that fucosyltransferases are important in the pathogenesis of renal IRI and are potential therapeutic targets.

Animals↗
PubMed2002

Early progressive interstitial fibrosis in human renal allografts.

BACKGROUND: Early fibrosis has been described in renal allografts and implicated in the progression of chronic allograft nephropathy (CAN). The precise factors implicated in the initiation and progression of early allograft fibrosis remain uncertain. PATIENTS AND METHODS: We studied retrospectively 23 cadaveric renal allograft recipients over a 3-year period, who had paired renal biopsies (Bx) (at implantation and as clinically indicated) within 3 months of transplantation (Tx). Eight of them have progressed over an average period of 3.16 +/- 0.83 years to CAN. Histological evaluation of interstitial fibrosis (IF) relied on point count analysis of Masson's trichrome (MT) staining as well as immunostainable collagens III (iCol III) and IV (iCol IV). The severity of the IF scores was correlated with the clinical, biochemical and histological parameters. The nature and severity of the interstitial inflammatory infiltrate were also evaluated by immunofluorescence. In addition, patients were subdivided into those whose fibrosis progressed (> 50% increase in IF/iCol IlI; Group 1) and non-progressors (< 50% increase in fibrosis score; Group 2) in an attempt to determine discriminatory features. RESULTS: In the whole group, there was a significant increase in the IF score, as estimated by MT staining and iCol III, from implantation to follow-up Bx (p = 0.0027 and p = 0.0088, respectively). The changes in iCol IV were not significant. Further, the increase in interstitial inflammatory infiltrate of total T lymphocytes, and not of macrophages, from implantation (modal category = 2) to follow-up (modal category = 0) was significant (p = 0.0121). The predictive value of such increase was significant (R2 = 0.617, p = 0.03). The donor's age (R2 = 0.892, p = < 0.0001), death from cerebrovascular accident (CVA) (R2 = 0.822, p = 0.047), as well as recipient's body weight (R2 = 0.892, p = 0.001), male gender (R2 = 0.687, p = 0.041) and elevated mean arterial pressure (MAP) (R2 = 0.892, p = < 0.0001) were all significant risk factors for early IF. Delayed graft function (DGF) proved to be a significant predictor of early IF (R2 = 0.822, p = 0.003) and became more significant in the presence of superimposed acute rejection (AR) (p = 0.0001). Proteinuria > 1 g/day (R2 = 0.882, p = 0.004) and hypertriglyceridemia > 2.25 mmol/l (R2 = 0.808, p = < 0.0001) were also associated with early IF. Of the implantation histological parameters, iCol III proved to be a highly significant predictor of early IF (R2 = 0.892, p = < 0.0001). Interestingly, the predictive value of iCol III for graft survival in terms of CAN was significant (Cox p = 0.088). Group 1 progressor patients (n = 10) were all males (p = 0.038) and received their kidneys from donors who died from CVAs in 90% of cases (p = 0.011). They had, compared to non-progressors, a lower cyclosporin A level (p = 0.047), a higher incidence of AR episodes (80% versus 54%), a higher serum creatinine at 10 days post-Tx (p = 0.005), a higher proteinuria (2.07 +/- 3.89 g/l vs 0.96 +/- 0.97 g/l, p = 0.041) and a higher serum triglyceride (2.48 +/- 1.37 mmol/l vs 1.69 +/- 0.81 mmol/l, p = 0.039) level. 8% of Group 1 patients had DGF compared to 30% in Group 2 (p = 0.023). Of note, the modal category of cytotoxic: helper T lymphocytes ratio was greater than 1 in Group 1 (2:1) patients and not in Group 2 (1:1). CONCLUSION: Implantation histology, and in particular iCol III, is a predictor of early IF in a subgroup of patients with DGF and AR. Additional risk factors include hypertension, proteinuria and hypertriglyceridemia especially in patients receiving kidneys from older donors who died of CVAs.

Adult↗
PubMed2002

Biocompatible membranes do not promote graft recovery following cadaveric renal transplantation.

BACKGROUND: Controversy surrounds the role of biocompatible membrane dialyzers in treatment of acute renal failure. Studies that have shown a benefit have involved critically ill patients where renal recovery and patient mortality are influenced by other comorbid disease. The aim of the present work is to clarify this issue in a more homogeneous population of patients with acute renal failure following cadaveric renal transplantation. METHODS: All patients with delayed graft function between January 1996 and February 1998 were randomized to receive either a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane) membrane for dialysis until onset of graft function. RESULTS: Forty-one patients were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p = NS) with primary non-function of graft were excluded from analysis, leaving 36 cases of acute tubular necrosis (ATN). Patient and donor characteristics were similar in both groups. The BCM group had significantly longer periods of dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There was a tendency towards higher serum creatinine levels in the short term in the BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at latest visit (p = 0.07)) and a greater number of acute rejection episodes in the BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1). With an intention-to-treat analysis of all 41 patients originally randomized, there was no significant difference in time to graft recovery between the 2 groups (p = 0.18). CONCLUSIONS: In the setting of ARF posttransplantation, we have found no evidence to support the use of biocompatible membranes for dialysis. Rather, our study provides argument against a large benefit for the use of BCM in the recovery of ARF, as suggested by earlier studies.

Acute Kidney Injury↗
PubMed1990

Organ preservation: experience with University of Wisconsin solution and plans for the future.

Transplantation of organs continues to be a primary therapeutic modality for treatment of end-stage organ disease, and 1-year graft survival rates show increasing improvements for most organs. A number of transplant centers show 1-yr graft survival rates approaching 90% or more for the kidney, liver and pancreas. Rejection continues to be the major cause for loss of organs and there is still a major shortage of organs for transplantation. Additionally, many organs showed delayed graft function (or primary nonfunction) which may be related to either donor factors or preservation factors. The University of Wisconsin solution for organ preservation has increased the safe time of preservation for the liver, kidney, and pancreas and helped to increase the quality and number of organs available for transplantation. However, the long-range goal of organ preservation (unlimited preservation) is still far from being reached. In the past, preservation could accurately be categorized as an art and preservation solutions were developed based upon theoretical rationales about the mechanisms of organ injury at hypothermia and what agents would suppress injury. The utility and success of this approach is exemplified by the developments of Collins solution and the UW solution. However, further developments in methods to increase the quality and duration of preservation of all transplantable organs would appear to be dependent upon defining, systematically, how organs are injured and what can be done to suppress the injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Forecasting↗
PubMed1999

Preliminary results of heart-beating and non-heart-beating donor kidney transplants--the Singapore experience.

Renal transplantation is the ideal renal replacement therapy for treatment of end stage kidney failure but its limitation is the constant shortage of cadaveric donors. While the traditional source of cadaveric kidneys is procurement from heart-beating donors, organ procurement from non-heart-beating donors (NHBD) would help in coping with the rising demand for organs. However various important legal, logistic and technical constraints have limited the implementation of such a procurement programme. Nevertheless, prolonged warm ischaemic times in procuring kidneys from NHB donors may affect the viability of these organs and adversely affect overall outcome after transplant. Fifty-three consecutive patients who underwent renal allotransplantation (Tx) between January and December 1994 at the Singapore General Hospital were retrospectively reviewed. Outcomes after renal transplantation among 25 heart-beating donor (HBD) and 28 NHBD were compared. Despite significant differences in donor age (23.7 +/- 11.0 and 34.1 +/- 7.9, P = 0.001), first warm (0 and 22.2 +/- 9.0 minutes) and cold ischaemic times (12.8 +/- 6.7 and 5.2 +/- 5.0 hours, P = 0.001) between the HBD and NHBD groups, the two-year patient and graft survivals were very similar in both groups (100% versus 98% and 98% versus 96%). The incidence of delayed graft function (DF) was also comparable between the HBD (41%) and the NHBD (50%) Tx. These results suggest that NHBD is a viable source for kidney transplants and comparable patient and graft survivals can be achieved if the first warm and cold ischaemic times are kept to the minimum.

Adolescent↗
PubMed1998

The UNOS Scientific Renal Transplant Registry.

Based on analyses of kidney transplants reported to the UNOS Scientific Renal Transplant Registry from 1991-1997: 1. The 5-year patient and graft survival rates were 82% and 63%, respectively, for 50,291 recipients of cadaver donor kidneys and 90% and 77%, respectively, for 20,258 recipients of living donor transplants. 2. Black recipients had 12% lower 5-year graft survival rates than Whites whether the kidney was from a cadaver donor (n = 11,575) or a living donor (n = 2,806). 3. The survival rates of second transplants were only 2% less than first transplants, whether the kidney was from a living or cadaver donor. The one-year regraft survival rates for multiply retransplanted patients were 77% and 87% for cadaver and living donor retransplants, respectively. 4. Graft survival rates were 5-6% lower among broadly sensitized recipients (> 50% PRA) than unsensitized (< 10% PRA) recipients, regardless of the donor source. 5. The average recipient aged between 1991-1997. The mean age increased from 42-46 years for cadaver kidney and from 34-40 years for living donor transplant recipients. 6. The percentage of older donors also increased during 1991-1997. The proportion of cadaver kidneys from donors over age 45 rose from 24% in 1991 to 33% in 1997. The percentage of living donors over age 45 increased from 23% in 1991 to 29% in 1997. 7. There was a 25% difference in 5-year graft survival rates comparing recipients of kidneys from 19-30 year-old cadaver donors with those who received kidneys from donors over age 60. Recipients of kidneys from living donors over age 60 had an 8% lower 5-year graft survival rate than when the donor was aged 19-30. 8. Among recipients of cadaver kidneys, the incidence of delayed graft function increased from 17% when the donor was aged 15-20 to 40% when the donor was over 65. DGF reduced one-year survival rates by 10% and half-lives by 2 years when grafts from 19-30 year old donors and donors older than 55 were analyzed separately. Cold ischemia time also resulted in increased DGF, from 17-39% for CIT up to 49-72 hours. However, when the donor was aged 19-30, DGF ranged from 12-30% and when the donor was over 60, DGF increased from 33-68% with longer CIT. 9. Rejection episodes before the initial hospital discharge resulted in a 10% reduction in 5-year graft survival rates regardless of the donor source. 10. The degree of HLA compatibility between the donor and recipient was associated with a 12% difference in 5-year graft survival rates among recipients of cadaver kidneys. The survival difference was 11% among recipients of living-related donor kidneys, but there was no difference in the survival of one- and 2-haplotype disparate grafts. Similarly kidneys transplanted from distant relatives and from unrelated donors with poor HLA compatibility resulted in survival rates that were not distinguishable from HLA-mismatched related donor kidneys.

Adolescent↗
PubMed1998

The fate of 359 renal allografts harvested from non-heart beating cadaver donors at a single center.

The fates of 359 kidneys harvested from 181 non-heart beating donors (NHBD) at a single center, using a regional in situ cooling technique were retrospectively investigated. 1. Thirty-five kidneys (9.7%) were discarded mainly due to poor arterial perfusion and bacterial contamination. 2. The incidence of primary nonfunction in patients treated with Aza was significantly higher than that in patients receiving CsA or FK (20.5% [8 grafts] vs 6.0% [17 grafts], respectively, p < 0.01). 3. The incidences of immediate and delayed graft function were 16.1% and 77.9%, respectively, among 285 recipients treated with CsA/FK. The average of duration of posttransplant dialysis required in recipients with DGF was 13.7 days and the average lowest serum creatinine level in patients who recovered graft function was 1.58 mg/dl. 4. Patient survival rates in the CsA/FK group were 97.2%, 95.0%, 93.2% and 89.3% at one, 3, 5 and 10 years, respectively, and the graft survival rates at one, 3, 5 and 10 years were 83.3%, 72.0%, 64.7% and 48.6%, respectively. 5. Increasing donor age showed a significant correlation with increased serum creatinine levels as well as with prolonged posttransplant dialysis (p < 0.001 and p < 0.01, respectively). 6. Renal grafts from donors with cerebrovascular disease (CVD) had significantly higher lowest serum creatine levels than grafts from non-CVD donors (p < 0.0001). 7. Renal grafts harvested from NHBD using our in situ cooling technique had excellent renal function when the donor was young or the cause of death was non-CVD. However, when the donor was older (> or = 56 years) and the cause of death was CVD, the grafts were acceptable but the early posttransplant function was often impaired. 8. The current NHBD graft survival rate, the UNOS cadaveric renal graft survival rate and the Japanese living-related donor renal graft survival rate were almost identical at 10 years posttransplant. 9. NHBDs should provide an excellent opportunity to increase organ availability.

Adolescent↗
PubMed2000

Is 3-hour cyclosporine blood level superior to trough level in early post-renal transplantation period?

PURPOSE: Cyclosporine dose is traditionally based on trough blood levels. Cyclosporine trough blood level correlates poorly with acute rejection and cyclosporine nephrotoxicity after renal transplantation. We determined whether cyclosporine blood level at any other time point is superior to cyclosporine trough blood level as a predictor of acute rejection and cyclosporine nephrotoxicity. MATERIALS AND METHODS: Cyclosporine blood level was measured before (trough), and 1, 2, 3 and 4 hours after the dose in 156 initial renal transplant cases 2 to 4 days after the initiation of cyclosporine micro-emulsion formula administration. The cylosporine micro-emulsion dose was based on cyclosporine trough blood level targeting 250 to 400 microg./l. RESULTS: Regression analysis revealed that only delayed graft function (p = 0.007) and cyclosporine blood level after 3 hours (p = 0.008) predicted acute rejection. Mean cyclosporine trough blood level plus or minus standard error was not significantly different in patients with and without acute rejection (293+/-21 versus 294+/-11 microg./l.). Mean cyclosporine blood level after 3 hours was significantly lower in patients with acute rejection (1,156+/-90 versus 1,421+/-50, p = 0.008). Cases were divided into tertiles at levels after 3 hours (1,100 and 1,500 microg./l.). The group in which the level after 3 hours was less than 1,100 microg./l. had the highest acute rejection rate (22 of 50 patients, 44%) and a cyclosporine nephrotoxicity rate of 13% (7 of 52 patients). The group in which the level after 3 hours was 1,100 to 1,500 microg./l. had the lowest acute rejection rate (5 of 46 patients, 11%) without increased cyclosporine nephrotoxicity (7 of 52 patients, 13%). A level after 3 hours of greater than 1,500 microg./l. was associated with a rejection rate of 15% (7 of 47 patients) but significantly higher cyclosporine nephrotoxicity (16 of 52 patients, 30%). CONCLUSIONS: Cyclosporine blood level after 3 hours in the early post-transplantation period is associated with acute rejection and cyclosporine nephrotoxicity. A cyclosporine blood level range after 3 hours of 1,100 to 1,500 microg./l. is associated with an optimal outcome. Our data suggest that cyclosporine blood level after 3 hours may represent a better method of monitoring cyclosporine micro-emulsion dose than cyclosporine trough blood level. This hypothesis must be further studied in randomized trials.

Cyclosporine↗
PubMed2000

Pharmacological limitation of damage to renal medulla after cold storage and transplantation by trimetazidine.

Delayed graft function remains an important complication after renal transplantation. In this study, we investigated the influence of trimetazidine (TMZ), a cytoprotective agent, on renal medullary damage after prolonged preservation and autotransplantation. Pig kidneys were cold-flushed and preserved (48 h at 4 degrees C) with two standard renal preservation solutions Euro-Collins and University of Wisconsin supplemented or not with TMZ (10(-6) M). Analysis of plasma and urine from 48-h-cold-stored and autotransplanted kidneys was performed with biochemical methods and proton NMR spectroscopy. Histological study by light and electron microscopy was performed after reperfusion (30-40 min) and on day 14. The results showed that the preservation in either Euro-Collins or University of Wisconsin solution containing TMZ improved significantly glomerular filtration rate compared with kidneys preserved without TMZ. TMZ significantly reduced renal medullary damage, evidenced by decreased excretion of trimethylamine-N-oxide, dimethylamine, dimethylglycine, and acetate in urine. Proximal tubular injury in TMZ-free groups was assessed by significantly greater Na(+) excretion, amino aciduria, and lactic aciduria than in TMZ-supplemented groups. Urinary concentrating ability was significantly improved in TMZ-preserved groups compared with TMZ-free groups. In TMZ-supplemented groups, there was also a greater excretion of citrate, which is a citric acid cycle metabolite. An extensive reduction in apical brush border of tubular cells, notably those of the proximal tubules, was noted in TMZ-free groups. This study clearly shows that TMZ has a beneficial action on in vivo renal preservation and its major impact is the vulnerable renal medulla.

Animals↗
PubMed2000

Double renal transplants from marginal donors: 2-year results.

PURPOSE: Marginal cadaveric renal transplant donors represent a potential source for expansion of the donor pool but these kidneys have generally demonstrated significantly poorer survival compared to those from conventional donors. A strategy to provide sufficient renal mass for adequate nephron dosing and subsequent improved survival is the use of both kidneys for a single recipient. We present our 2-year experience with double renal transplants from marginal donors. MATERIALS AND METHODS: During an 8-year period 28 patients received double renal transplants (group 1) and 31 received a single transplant (group 2) from marginal donors. Donors were older than 55 years, or had diabetes mellitus, hypertension, greater than 15% glomerulosclerosis on biopsy, increasing creatinine or intrinsic renal parenchymal disease. RESULTS: Both groups were of similar age and the number of rejection episodes per year was similar but followup time differed (22.4+/-14.6 months for group 1 versus 43.7+/-20.5 for group 2). Male-to-female ratio, cold ischemia time, terminal creatinine and pre-transplant biopsy rates were similar for donors in both groups. Average donor age was younger in group 1 (48.9+/-15.8 versus 57.5+/-8.2 years, p = 0.01), and incidence of intrinsic renal disease and increasing donor creatinine was greater (12 versus 2, p = 0.002 and 4 versus 0, p = 0.04, respectively). Incidence of primary nonfunction (1 group 1 versus 5 group 2 patients) and delayed graft function (6 versus 7) was similar. The 1 and 2-year graft survival rates of 96% and 96%, respectively, for group 1 were significantly higher than those for group 2 (77% and 73%, p = 0.02). CONCLUSIONS: Our experience to date with double kidney transplants from marginal donors demonstrates acceptable 1 and 2-year survival rates significantly superior to the outcome using only 1 marginal kidney. This finding has important implications in the decision to use marginal donors in regard to cost-effectiveness and patient survival compared to the alternative of continued hemodialysis until an ideal donor organ becomes available.

Female↗
PubMed1999

The LifeLink Foundation and cadaver kidney transplantation in Tampa.

1. LifeLink Foundation, a not-for-profit organization, has been the driving force and absolutely essential entity for kidney and liver transplantation in Tampa providing all the components (patient, organs and clinicians) save for inpatient hospitalization. It also plays a big role in the heart transplant program. LifeLink has increased the kidney transplant rate from the first 1,000 done in 17 years to the second 1,000 in 7 years and is on a pace for the third 1,000 in 5 1/2 years. 2. Because of its innovative programs, cadaver donor procurement by the Tampa LifeLink OPO has been roughly double the national average for the past 10 years. Because of cadaver kidney availability the median wait time from activation on the wait list to transplantation over the past 5 years was 159 days. The recent transplant rate is 14.7-22.7% higher than the national average, dependent upon the parameter measured. Similar results are seen for Tampa patients awaiting heart and liver transplantation. 3. The overall outcome of 1,184 cadaver kidney transplants performed in the decade 1989-98 was similar to that reported from the UNOS database in this series of publications. a) One- and 2-year graft survival increased 2% per year over the decade with a recent one-year graft survival rate of 96%. The overall T1/2 was 10 years. b) Our disastrous 1994 results were quickly reversed by a more intense pretransplant medical evaluation, the introduction of mycophenolate mofetil, more aggressive and earlier treatment of rejection episodes, and mandatory T- and B-cell flow cytometry crossmatching for all transplants. The incidence of rejection episodes decreased from 40 to 20%, and the first year immunological graft loss decreased from 5%, to 1.9%, to 0.8%, to 1.4% and 0% over the succeeding 4 years. 4. Individual factors affecting allograft survival were strikingly similar to national data, although all did not react statistical significance probably due to the smaller numbers. a) Primary and second grafts had similar survival rates (p = 0.97) whereas the third or subsequent graft survival was 7-32% poorer (p = 0.02). b) Black recipients had survival rates 10-13% lower than Caucasians and other races (p = 0.003). c) Patients with a peak PRA > 50 had survival values 4-13% poorer than those with < 50 PRA (p = 0.14). d) Patients with 2-4 HLA mismatches had graft survival rates 4-10% poorer than those with 0-1 mismatch (p = 0.12), whereas those with 5-6 mismatches had rates 6-17% poorer (p = 0.04). e) Although 22% of our transplants were to patients > 60 years of age, there was no difference (p = 0.81 to 0.90) in graft survival for the age groups 0-40, 41-60 and > 61. However, the proportion of grafts lost due to patient death compared with all allografts lost, was very different at 21% in the youngest group, 43% in those 41-60 years of age, and 63% in recipients > 61 years. 5. The rate of delayed graft function with imported kidneys was higher (27 vs. 16%, p = 0.006) but essentially the same as local kidneys with the same ischemia times. However, 41% of local kidneys were transplanted within 12 hours of procurement. Totally, 78% of local kidneys were transplanted within 18 hours (11% DGF rate) versus 79% of imports being transplanted at > 18 hours (32% DGF rate). Ischemia time, not the kidney source is the key issue since: a) There was no difference in overall graft survival of imported versus local kidneys (p = 0.95) nor in comparing local versus import kidneys with (p = 0.66) or without (p = 0.69) DGF. b) There was, however, a 11-17% overall poorer graft survival over 3 years in kidneys with DGF (p < 0.001) seen with both local (9-18% poorer, p = 0.0002) and imported (12-19% poorer, p = 0.008) kidneys. c) Kidneys displaying DGF came from older donors (40 vs. 34 years, p = 0.023) and had longer ischemia times (21 vs. 15 hours, p < 0.0005). 6. Dual kidney transplants were started in late 1996 with older or marginal donors to provide a better chance of success fo

Adolescent↗
PubMed1999

Renal transplantation in Helsinki: influence on long-term survival of early posttransplant factors.

1. The half-life of kidney grafts performed at Helsinki University Central Hospital has tripled from 6.5 years in 1980-84 to 17.1 years in the 1990's. 2. Delayed graft function constitutes a significant determinant of later kidney graft survival. Five-year graft survival was 81% for patients with early graft function and 71% for those with DGF. 3. High (> 350 mg/L) early (10 +/- 2 days after transplantation) cyclosporine trough levels were associated with inferior long-term graft survival. The 5-year graft survival rate was 74% compared with 86% for patients with trough levels between 250-349 mg/L. 4. Posttransplant conversion of the crossmatch test against the kidney donor, especially in association with DGF, indicates a group with significantly worse prognosis. Among 76 patients who developed antidonor antibody after transplantation, half experienced an acute rejection within 100 days and the 5-year graft survival rate was 68% compared with 83% for non-converters.

Adult↗
PubMed1999

Renal transplantation in cyclosporine-treated recipients at the Singapore General Hospital.

1. The 5-year patient and graft survival rates for live-donor renal transplants undergoing transplantation with CsA-based immunosuppression at the Singapore General Hospital from 1985-1999 were 97.0% and 91.6%, respectively. The 5-year patient and graft survival rates for cadaveric renal transplant recipients from the same institution were significantly lower at 91.6% and 79.4%, respectively. Long-term graft survival as described by half-lives (T1/2) were 28.6 years and 20.4 years for live-donor and cadaveric grafts, respectively. 2. Tissue matching had no impact on graft or patient survivals in either live-donor or cadaveric renal transplants. However, sensitisation was associated with significantly worse graft survival in cadaveric transplant recipients. 3. Primary cadaveric transplant recipients enjoyed significantly better graft survival rates than retransplanted recipients (5-year survival rates of 80.1% and 65.0%, respectively; p = 0.032). 4. Among cadaveric renal transplant recipients, a single acute rejection episode was associated with worse long-term graft survival (T1/2 of 14.6 years and 37.0 years for those with and without rejection, respectively, p = 0.001). Likewise, delayed graft function was associated with worse overall graft survival (5-year graft survival rates of 70.7% vs. 86.8% in patients with and without DGF, respectively, p < 0.001). 5. Among cadaveric transplant recipients with a functioning kidney at 5 years after transplantation, 61.4% had normal renal function with serum creatinine levels < 141 mumol/L while 33.9% had mild renal dysfunction with SCr of 141-250 mumol/L. 6. The high graft and patient survival rates in this Asian population as reported from this single centre study may be attributed to selection of younger patients without overt ischaemic heart disease for transplantation and to good patient compliance to CsA therapy. Thus, recipient selection and ensuring patient compliance to treatment are key strategies in optimizing the use of a scarce resource such as organ transplants.

Adolescent↗
PubMed2000

[Kidney transplantation in Macedonia].

During the last 10 years we performed 92 renal transplantations in our Skopje hospital (Macedonia), using 22 cadaver donors and 70 living donors. We also performed 15 explanations from cadavers and seven kidneys were allocated to former Yugoslavia. Standard surgical procedures were used for both living and cadaver donor explantations and transplantations. For living explantations, donors were matching in 66 cases (94.28%) and in four cases (5.7%) non-matching donors who however were relatives of the patient Explantations and transplantations took place only after all ethical- and legal-related problems had been solved. The minimum acceptable HLA mismatch was 50% with negative present or historical cross-match. A quadruple sequential immunosuppressive treatment was used, including either poly- or monoclonal globulins (thymoglobulin [ATG], lymphoglobulin [ALG], daclizumab, OKT-3) as an induction therapy and prednisolone, azathriopin and cyclosporin A as maintenance therapy. Rejection episodes were treated by pulse MP therapy or OKT-3 and increased doses of MMF if the patients were steroid-resistant. Kaplan-Meier survival curves showed that survival at 12, 36 and 60 month reached 90%, 75% and 60%, respectively. Survival was better after transplantation using a graft from a living donor than after transplantation using a graft from a cadaver donor (survival rates: 92%, 82% and 68% at 12, 36 and 60 months after surgery). Delayed graft functioning (DGF) was observed in 16 patients (17.3%), reaching 46.6% after transplantation of a graft from a cadaver donor and 10% after transplantation of a graft from a living donor. The relatively high percentage of DGF in the living donor program was due to the use of grafts from elderly donors (over 65 years of age). We registered 26 (29%) episodes of acute rejection that were predominantly histologically confirmed and further classified according to the BANFF criteria. Treatment of five steroid-resistant rejections proved to be successful. Neither early nor late surgical and medical complications were different from those reported in the literature. Despite the modest number of kidney transplantations, chronic renal failure has decreased in our region. The authors expect further improvement in this powerful therapeutic procedure thanks to links with regional and European transplant centers allowing better cooperation and organ sharing.

Adolescent↗