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PubMed2001

Early and long-term results using older kidneys from cadaver or living donors.

The persisting shortage of organs for transplantation justifies the use of all possible donors. We compared results for 110 patients, who received solitary kidneys from cadaver donors over age 60 years (OCD) with those for 976 patients, who were transplanted with kidneys from 11-49-year-old cadaver donors, whom we defined as "ideal" age. Although the 4% incidence of primary nonfunction and the 24% rate of delayed graft function were significantly higher (p < 0.001) in the OCD group compared with the ideal group (0.8% and 8.0%, respectively), OCD kidneys can offer good results when low-risk recipients are carefully selected and the cold ischemia time is sharply reduced. Moreover, graft survival rates for 14 OCD grafts, implanted in patients under age 45 were 93% at one, 3 and 10 years compared with 79%, 74% and 42% at the same time points for 96 OCD recipients over age 45. The rate of delayed graft function was higher among 19 OCD grafts preserved for more than 20 hours, and these grafts yielded significantly lower survival rates than 91 OCD grafts preserved for less than 20 hours; with rates of 67%, 58% and 44% and 85%, 81% and 51%, respectively, after one, 3 and 10 years. Thirty-five kidneys from living donors over age 60 had comparable overall graft survival rates to living donor kidneys from donors under age 60 (92%, 92% and 92% vs. 92%, 88% and 80% at one, 3 and 10 years, respectively). An original point scoring system, based only on macroscopic evaluation of the graft, avoids the need for a biopsy and does not prolong cold ischemia time. Microvascular bench reconstructions of the renal artery, damaged by atherosclerosis, expand the possibility for safe transplantation of older kidneys without performing a double renal transplant.

Adolescent↗
PubMed1999

A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients.

BACKGROUND: Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. METHODS: The mean recipient age was 50.7+/-13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5+/-21.7 years. The mean cold ischemia time was 30.5+/-9.2 hr. The mean follow-up is 15+/-7 months. RESULTS: The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double-therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6+/-0.8 mg/dl. A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. CONCLUSIONS: This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids.

Adolescent↗
PubMedDate not supplied

The association between length of post-kidney transplant hospitalization and long-term graft and recipient survival.

BACKGROUND: There has been a general trend towards shortened length of post-kidney transplant hospitalization (LOH). The decision regarding patients's discharge from the hospital theoretically may be based on several factors, including, but not limited to, patient well being, insurance status, family situation and other, mostly socio-economic factors, as opposed to hard medical evidence. However, the appropriate LOH in kidney transplant recipients is not well studied regarding long-term outcomes. METHODS: This study retrospectively analysed the association between LOH and graft and recipient survival based on United States Renal Data System dataset. In total, 100,762 patients who underwent transplant during 1995-2002 were included. Kaplan-Meier survival analysis and Cox models were applied to the whole patient cohort and on sub-groups stratified by the presence of delayed graft function, patient comorbidity index and donor type (deceased or living). RESULTS: In recipient survival, both short (<4 d) and long (>5 d) LOH showed a significant adverse effect (p < 0.01) on survival times. In the analysis of graft survival, long LOH (>or=2 wk) also showed significant adverse effects (p < 0.001) on survival times. However, short LOH (<4 d) did not reach statistical significance, although it was still associated with adverse effects on graft survival. These observations were consistent across the whole patient cohort and sub-groups stratified by the presence of delayed graft function, patient comorbidity index and donor type. CONCLUSION: Clinical considerations should be used to make the decision regarding appropriate time of post-kidney transplant recipient discharge. Based on this study, shorter than four d post-kidney transplant hospitalization may potentially be harmful to long-term graft and recipient survival.

Adult↗
PubMed1999

Strategies to expand the donor pool for pancreas transplantation.

BACKGROUND: Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. METHODS: A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. RESULTS: Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. CONCLUSIONS: Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.

Adolescent↗
PubMed1999

Early proteinuria in renal transplant recipients treated with cyclosporin.

PURPOSE: To establish the risk profile for the development of proteinuria in the first months after renal transplantation and to disclose the prognostic significance of this finding. DESIGN: We conducted an observational historic cohort study. SETTING: We conducted the study in a tertiary care hospital renal transplantation unit covering a potential population of approximately 2 million. We made extensive use of suboptimal donors. POPULATION: In our unit, 560 cadaveric renal transplants were performed between January 1988 and June 1997, under Cyclosporine immunosuppression, with a minimum follow up of 1 year. METHOD: The risk profile analysis explored early clinical factors reported to be related to the late course of renal transplantation. The study of the prognostic significance of proteinuria included survival analysis and correlation with late markers of graft dysfunction, taking into consideration the intensity and persistence of early proteinuria. A multivariate approach was used in all cases. RESULTS: Early proteinuria was strongly associated with delayed graft function (odds ratio [OR] 1.03/day of dialysis), acute rejection (OR 1.7 for steroid-sensitive and 6.2 for steroid-resistant rejection), renal transplant to a hypersensitized recipient (OR 2.5), and pediatric (<5 years)(OR 4.1) or older (>60 years)(OR 3.0) donors. The predictive model for persistency of proteinuria was very similar, whereas transient proteinuria could not be adequately modeled. Increasing intensity of proteinuria was strongly associated with poor patient and graft survival. Persistent, but not transient, proteinuria supported this relationship. CONCLUSIONS: Proteinuria appearing early after renal transplantation is strongly associated with delayed graft function, acute rejection, and the use of pediatric or older donors. Whatever its background, proteinuria is a strong predictor of poor patient and graft survival. This effect is directly related to the intensity and persistence of the disorder.

Adolescent↗
PubMed1989

Calcium antagonists and acute renal failure.

PURPOSE: To critically review the question of whether calcium antagonists can prevent or attenuate post-ischemic acute renal failure (ARF). PATIENTS AND METHODS: Using a computer-assisted search, we identified all experimental and clinical studies published in English between 1980 and 1988 in which the main research question addressed the efficacy of verapamil, diltiazem, or nifedipine in the treatment of post-ischemic ARF. Studies were then selected for review based on clearly specified inclusion criteria and evaluated against accepted methodologic guidelines. RESULTS: In experimental studies of warm renal ischemia, calcium antagonists provided significant protection of glomerular filtration rate (GFR) when given before and after ischemic injury; however, isolated pre- or post-ischemic treatment produced equivocal results. In autotransplantation studies on protracted cold ischemia, verapamil produced a modest, although physiologically significant, increase in GFR during warm reperfusion but failed to alter graft survival. Studies of calcium antagonists in humans with ARF have been confined to patients undergoing renal transplantation. Diltiazem given both to donor grafts and to recipients produced a significant reduction in the rate of delayed graft function but failed to improve one-year graft survival. This result may be due to the study of small numbers of low-risk patients. At present, there is no conclusive evidence that one calcium antagonist is more efficacious than another in the treatment of post-ischemic ARF. CONCLUSIONS: Calcium antagonists appear to prevent or reduce the severity of post-ischemic ARF only when given prior to and after the ischemic insult. As a result, these agents will have most utility in the setting of renal transplantation. Although the efficacy of these agents in reducing delayed graft function appears to be established, their failure to improve graft survival is poorly understood and requires further investigation.

Acute Kidney Injury↗
PubMed1998

Two hundred one consecutive living-donor nephrectomies.

OBJECTIVE: To assess donor morbidity, recipient outcome, and changing trends during the past decade in donor nephrectomy for living-donor kidney transplantation. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center. PATIENTS: We reviewed 201 consecutive living-donor kidney transplantations performed between January 1988 and June 1997. INTERVENTION: Donor nephrectomy and living-donor kidney transplantation. MAIN OUTCOME MEASURES: Donor surgical complications, correlation of preoperative imaging of donor vascular anatomy and operative findings, and donor lengths of stay in the hospital were analyzed. Recipient delayed graft function and actuarial 1- and 5-year patient and graft survival rates were also analyzed. RESULTS: Major donor postoperative complications were bleeding (0.5%), pneumothorax requiring a chest tube (1%), wound infection (1%), and pneumonia (1%). Minor postoperative complications were asymptomatic pneumothorax resolving spontaneously (10%), urinary retention (6%), and urinary tract infection (0.5%). Preoperative imaging failed to detect small accessory renal arteries in 12% of donors. The mean donor length of stay in the hospital was 5.0 days but decreased from 6.2 to 4.0 days during the study. Twenty donors (10%) were unrelated (ie, spouse or friend). Three (1.5%) cases of delayed graft function occurred. Overall recipient patient survival at 1 and 5 years was 97% and 90%, and graft survival was 95% and 83%, with no difference between related and unrelated living donors. CONCLUSIONS: Living-donor nephrectomy is associated with low surgical morbidity. Recent trends include shortened lengths of stay in the hospital, the use of computed tomographic angiography instead of digital subtraction angiography for preoperative imaging of donor vascular anatomy, and an expanded use of unrelated living donors.

Actuarial Analysis↗
PubMed2004

The fate of glomerular mesangial IgA deposition in the donated kidney after allograft transplantation.

OBJECTIVE: To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation. METHODOLOGY: Routine pre-transplant cadaveric donor kidney biopsy and repeated renal biopsies were performed at months 1, 3, and 6 after renal transplantation. The patients, 342 in number, were divided into IgA positive deposition kidney group (group A, n = 83) and non-IgA deposition kidney group (group B, n = 259). There were no significant differences between the two groups' sex, age, time of hemodialysis, warm ischemia time, cold ischemia time, complement-dependent cytotoxicity, level of panel-reactive assay, and the distribution of original disease. RESULTS: Recipients in group A received donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition. All of them showed edema, nephrotic range protienuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. Borderline change was higher in group A than in group B, 37.3 and 16.2% (p < 0.001), respectively. Acute allograft rejection was higher in group A than in group B, 31.3 and 19.3% (p < 0.001), respectively. The glomerular mesangial IgA deposits gradually disappeared from the mesangial regions in grafts of acute rejection. Graft survival in both groups was not significant, being 93.8 and 95.6% in 1 yr, and 86.7 and 88.3% in 3 yr. CONCLUSION: Clinical features of the recipients which received from donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition: edema, proteinuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. The presence of IgA deposits on donated kidney, by a possible increase of the immunogenicity of these kidneys, might be a cause of increased rejection. There were no significant differences between the two groups on long-term allograft survival.

Adult↗
PubMed1995

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).

Animals↗
PubMed1997

Outcomes in diabetic patients after simultaneous pancreas-kidney versus kidney alone transplantation.

BACKGROUND: Previous studies have identified more morbidity in simultaneous pancreas-kidney (SPK) transplant recipients compared with kidney alone (KA) recipients. With the development of novel immunosuppressive drugs, studies are needed to determine optimal treatment regimens in specific patient populations. METHODS: We retrospectively compared short-term outcome in diabetic patients receiving either SPK or KA transplantation from December 10, 1991, to July 31, 1996. The SPK recipients received either cyclosporine (CsA) + azathioprine (AZA), FK506+AZA, or FK506 + mycophenolate mofetil (MM). KA group patients received either CsA+AZA or CsA+MM. RESULTS: Recipients of SPK instead of KA transplants were younger, had a longer mean length of stay, had a decreased incidence of delayed graft function, and had more readmissions. There were no significant differences in serum creatinine at 1, 2, and 3 years after transplantation, number of rejection episodes and infections, incidence of kidney graft loss and patient death, and 1- and 3-year actuarial patient and kidney graft survival rates between the two groups. Diabetic SPK patients receiving FK506+MM had a higher mean 3-month creatinine clearance (calculated), compared with recipients of CsA+AZA or FK506+AZA. Diabetic patients after KA transplantation who received CsA+MM demonstrated fewer rejection episodes and graft losses, although differences did not reach statistical significance. CONCLUSIONS: (1) Diabetic SPK recipients have decreased rates of delayed graft function and more readmissions compared with diabetic KA recipients. (2) There is no difference in: serum creatinine levels up to 3 years after transplantation, number of rejection episodes or infections, and 1- and 3-year patient and graft survival rates between SPK and KA recipients. (3) Short-term outcome is improved in diabetic recipients of SPK and KA transplants receiving MM instead of AZA.

Adolescent↗
PubMed2006

Thymoglobulin induction is safe and effective in live-donor renal transplantation: a single center experience.

BACKGROUND: The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. METHODS: Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. RESULTS: Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0+/-1.9 years. The average age of recipients was 44+/-13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P<0.001). CONCLUSIONS: In this analysis, the use of Thymoglobulin in live-donor renal transplantation was associated with an absence of delayed graft function, low acute rejection rates, and high patient and graft survival without increasing the risk of infection or lymphoproliferative disorder.

Adult↗
PubMed1998

Inhibition of intercellular adhesion molecule-1 with antisense deoxynucleotides prolongs renal isograft survival in the rat.

BACKGROUND: Delayed graft function from ischemia-reperfusion injury has a negative impact on long-term renal graft survival. We tested the utility of antisense oligodeoxynucleotide (ODN) against intercellular adhesion molecule-1 (ICAM-1) in the pretransplant treatment of renal isografts in improving long-term graft survival. METHODS: Three groups of 16 inbred Lewis rats each underwent unilateral nephrectomy and were then transplanted with a kidney from a Lewis donor rat, which had received antisense ODN, reverse sense ODN, or saline vehicle six hours prior to nephrectomy. The kidneys were subjected to one hour of warm ischemia and 30 minutes of cold ischemia, which when untreated results in delayed graft function. The remaining native kidney was removed 10 days later. Serum creatinine and urinary protein excretion were measured in surviving rats at weeks 2, 4, 6, 8, 12, 16, and 20 after native nephrectomy. RESULTS: A Kaplan-Meier analysis revealed that by week 6 one half of the animals receiving reverse sense ODN and saline vehicle treatment had died, while all but 2 rats in the antisense ODN-treatment group survived to 20 weeks. Serum creatinine concentrations and urine protein excretion of surviving reverse sense and saline vehicle-treated rats were significantly higher than antisense treated rats at every time point. Histology at week 20 revealed marked interstitial fibrosis, focal glomerular sclerosis, vascular intimal and medial thickening and tubular atrophy in reverse sense and saline vehicle-treated kidneys, while antisense ODN-treated kidneys showed only modest changes. Immunohistochemistry showed macrophage and lymphocyte infiltration, as well as substantial up-regulation of MHC class II, in reverse sense and saline vehicle-treated kidneys compared to antisense ODN-treated kidneys. CONCLUSIONS: These results suggest that by ameliorating acute nonimmunological renal isograft injury, the long-term chronic nonimmunologic processes are improved as well. Furthermore, the data suggest that an antisense ODN strategy directed against ICAM-1 may have utility in human kidney transplantation.

Animals↗
PubMed2005

Use of different immunosuppressive strategies in recipients of kidneys from nonheart-beating donors.

In nonheart-beating donor (NHBD) kidney transplants, immunosuppressive management is difficult mainly because of the high incidence of acute tubular necrosis. This has meant that since the start of our NHBD transplant program, several immunosuppression regimes have been used. The aim of this retrospective study was to evaluate the results obtained over 7 years using different treatment protocols. A total of 172 consecutive NHBD transplants performed between April 1996 and December 2002 were treated as follows: G-I (n = 21), cyclosporine (8 mg/kg/day) plus azathioprine plus steroids; G-II (n = 65), low-dose cyclosporine (5 mg/kg/day) plus mycophenolate plus steroids; G-III (n =17), low-dose tacrolimus (0.1 mg/kg/day) plus mycophenolate plus steroids; and G-IV (n = 69), daclizumab plus low-dose tacrolimus plus mycophenolate plus steroids. Delayed graft function rates were 76.2%, 72.3%, 76.5%, and 42%, respectively, for the four groups (P = 0.000). Rejection-free patient rates were 76.2%, 46.2%, 35.3%, and 71% (P < 0.001). Vascular rejection rates were 19%, 30.8%, 52.9%, and 18.8%, (P = 0.025). Two-year graft survival was 71.4% in group I, 95.4% in group II, 94.1 in group III, and 93.8% in group IV (P =0.004). Patient survival was worse in group I (75.2% in group I, 100% in group II, 100% in group III, and 96.7% in group IV at 2 years; P < 0.001). The use of daclizumab and low-dose tacrolimus could be effective at lowering the incidence of delayed graft function in NHBDT, with no negative repercussions on acute rejection.

Adult↗
PubMed2006

Deceased donor renal transplantation--does side matter?

BACKGROUND: The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. METHODS: A retrospective analysis was undertaken of the left-right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. RESULTS: A total of 201 left-right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 +/- 0.67 vs 3.12 +/- 0.72 h, P = 0.16), warm ischaemic time (0.62 +/- 0.18 vs 0.65 +/- 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 +/- 39.6 vs 51.0 +/- 24.0 ml/min/1.73 m(2), P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67). CONCLUSIONS: Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.

Adult↗
PubMed1990

The impact of steady-state cyclosporine concentrations on renal allograft outcome.

It has been reported that initial cyclosporine levels over 400 ng/ml posttransplantation result in an increased incidence of delayed graft function (DGF). Several studies have shown early graft function to be a major determinant for long-term graft survival. Continuous intravenous infusion (CIVI) has been employed to induce immunosuppression establishing therapeutic drug levels while minimizing toxicity in renal allograft recipients. This study examines the impact of the achieved serum CsA steady-state concentration (Css) levels upon transplant outcome in 228 patients given CsA by CIVI. In spite of administration of a specific drug dose, interindividual variation in elimination rates yields a broad range of Css levels. Six groups were stratified by CsA Css levels: group A 0-75 ng/ml, group B 76-100 ng/ml, group C 101-150 ng/ml, group D 151-200 ng/ml, group E 201-250 ng/ml, and group F greater than 250 ng/ml. Group A showed a significantly lower age and greater incidence of rejection at 0-10 days. Group F had significantly higher incidences of nephrotoxicity, hepatotoxicity, and delayed graft function. The findings suggest that the antirejection Css threshold for CsA may be at least 75 ng/ml, and the toxicity threshold above 250 ng/ml. Controversy exists about whether CsA influences the incidence of DGF, therefore risk factors for DGF were examined among the groups stratified by CsA Css levels. While cold ischemia time for all 228 patients as a group was highly correlated with DGF (P less than 0.001), neither cold ischemia time nor donor age was significantly different among the groups. There does appear to be a synergistic effect between CsA Css and CIT, since the incidence of DGF was significantly higher when the cold ischemia time was 21-24 hr and CsA Css greater than 200 ng/ml. Long-term graft function did not appear to be affected by early CsA Css levels. The Css of 100-250 ng/ml appears to achieve a satisfactory outcome with a 19.5% incidence of rejection within 10 days, 29.7% DGF, and 5.1% nephrotoxicity. Only 118/228 patients (52%) in this study achieved that range despite a fixed low CIVI of CsA. Thus potential renal allograft recipients may benefit from a pretransplant pharmacokinetic study to predict the proper CIVI dose.

Adult↗
PubMed1999

A comparison of OPO pulsatile machine preservation practices and results.

CONTEXT: Kidney preservation has been performed by either ice (static) or machine pulsatile perfusion. Ice storage is simple, with only 1 methodology. Machine perfusion, on the other hand, is accomplished using multiple methodologies. This article delineates the different methodologies of pumping centers throughout the country. OBJECTIVE: Pulsatile machine perfusion is again being viewed as the preservation method of choice for kidneys from non-heart-beating cadaver donors and cadaver kidneys from marginal donors. To develop indices to predict the viability of cadaver kidneys for transplant, a review of the organ procurement organizations, specific perfusion techniques, and a comparison of the delayed graft function and graft survival rates were considered. METHODS: A survey, asking for specifics on perfusion parameters, pulsatile machine perfusion experience, and criteria for perfusion implementation and graft survival results, was mailed to all organ procurement organizations in the United States. RESULTS: Of the 44 centers that responded to the survey, 12 used pulsatile machine perfusion (11 used the Waters perfusion machine), 6 pumped marginal cadaver kidneys, and the remaining 6 pumped all cadaver kidneys. Minimum perfusion criteria, pulse rates, perfusate composition, pressures, renal resistance, and renal pressure and flow were considered. Vasodilators and other machine additives were used to improve flow. The variance in each center's number of cadaver kidneys pumped each year, as well as the differences in pump times, was noted. CONCLUSION: Twelve centers use pulsatile machine perfusion. A variety of techniques are used to perform pulsatile machine perfusion, but 11 of 12 have less delayed graft function than those programs employing ice storage preservation.

Cryopreservation↗
PubMed1998

Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion.

Organs used for transplantation undergo varying degrees of cold ischemia and reperfusion injury after transplantation. In renal transplantation, prolonged cold ischemia is strongly associated with delayed graft function, an event that contributes to inferior graft survival. At present, the pathophysiological changes associated with ischemia/reperfusion injury in clinical renal transplantation are poorly understood. We have performed an immunohistochemical analysis of pre- and postreperfusion biopsies obtained from cadaver (n = 55) and living/related donor (LRD) (n = 11) renal allografts using antibodies to adhesion molecules and leukocyte markers to investigate the intragraft changes after cold preservation and reperfusion. Neutrophil infiltration and P-selectin expression were detected after reperfusion in 29 of 55 (53%) and 24 of 55 (44%) cadaver renal allografts, respectively. In marked contrast, neutrophil infiltration was not observed in LRD allografts, and only 1 of 11 (9%) had an increased level of P-selectin after reperfusion. Immunofluorescent double-staining demonstrated that P-selectin expression resulted from platelet deposition and not from endothelial activation. No statistically significant association was observed between neutrophil infiltration and P-selectin expression in the glomeruli or intertubular capillaries despite the large number of cadaver renal allografts with postreperfusion changes. Neutrophil infiltration into the glomeruli was significantly associated with long cold ischemia times and delayed graft function. Elevated serum creatinine levels at 3 and 6 months after transplantation were also associated with the presence of neutrophils and platelets after reperfusion. Our results suggest that graft function may be influenced by early inflammatory events after reperfusion, which can be targeted for future therapeutic intervention.

Adult↗
PubMed2006

Risk factors that can influence kidney transplant outcome.

The survival and function of a kidney transplant are influenced by numerous immunological and nonimmunological factors. The aim of this study was to evaluate the role of a number of cadaveric donor parameters on transplanted kidney function, and in particular on the occurrence of delayed graft function (DGF) since DGF is one of the most important factors in long-term organ survival. This study looked at 143 patients who underwent kidney transplant of whom 32 displayed DGF. The creatinine levels in organ recipients, which were evaluated during a follow-up that ranged between 6 months and 4 years, were significantly higher among recipients who developed DGF after transplant (1.8 +/- 0.7 vs 1.4 +/- 0.4; P = .02). The following donor parameters were taken into consideration: history of diabetes and hypertension; creatinine levels; inotropie therapy; problems relating to hemodynamics (hypotension and/or cardiac arrest); and cold ischemia time. We observed that a donor history of hypertension (46.8% DGF vs 23.27% no DGF; P = .01) and high levels of donor creatinine prior to organ removal (1.9 +/- 1.2 mg/dL DGF vs 1.2 +/- 0.9 mg/dL no DGF; P = .007) were significant risk factors for DGF among kidney recipients. No significant differences were found for others factors between recipients with versus without DGF.

Cadaver↗