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PubMed1996

Macrophages and chronic renal allograft nephropathy.

In a previous study we demonstrated that macrophage infiltrates stained for thromboxane A synthase (TxAS) correlated inversely with renal function six months after biopsy. We propose that macrophage based inflammation is a cofactor leading to chronic allograft nephropathy. For this study we compared four indices of renal allograft nephropathy with renal survival. The Banff Score of Inflammatory Changes (BSI) is an index of acute inflammation. The Banff Chronic Index (BCI) and Chronic Allograft Damage Index (CADI) are indexes of chronic disease. The Macrophage Index (MI) is the same as the BSI applied only to macrophages. These indices were determined on renal allograft biopsies obtained because of delayed graft function within the first week of transplantation, and for increasing plasma creatinine levels after stable function. All four indices predicted renal survival in the post-biopsy interval. MI predicted renal survival for the entire transplant period. In addition, the presence of TxAS transcripts in the renal allografts was determined using a reverse transcription-polymerase chain reaction-based assay. This confirms previous observations of TxAS in the grafts. This study supports the hypothesis that macrophage derived inflammation is a cofactor for chronic allograft nephropathy.

Biopsy↗
PubMed2005

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

BACKGROUND: We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viability of kidneys transplanted. METHODS: We retrospectively reviewed medical record data for all patients enrolled in our ECMO-supported DCD donor protocol between 10/1/2000 to 2/01/2004. We also reviewed the records for all patients undergoing organ donation after brain-death (DBD) during the study period at our institution. Recipient data were obtained and analyzed for all kidneys procured from both groups. RESULTS: Twenty patients were enrolled in our DCD protocol and underwent attempted organ donation. Fifteen patients completed the protocol; 3 maintained cardiac function throughout the prescribed 60 minutes after withdrawal of life support, and two patients' organs were deemed unsuitable for transplantation. Fourteen (70%) of the DCD donor patients originated on the trauma service and six (30%) were from other clinical services. The DCD program increased the potential donor pool by 33% (61 versus 81 patients) and the number of kidneys transplanted by 24% (100 versus 124). A total of 24 kidney, 5 liver, and 1 pancreas transplants were performed with these organs. Two of 24 (8.3%) DCD kidneys had delayed graft function. There were no perioperative rejection episodes or deaths. CONCLUSION: The implementation of a DCD protocol using extracorporeal perfusion increased the potential organ donor pool at our institution by 33%. This was accomplished without short term adverse effect on organ function compared with kidneys transplanted from DBD donors.

Adolescent↗
PubMed1995

Cold ischemia and outcome in 17,937 cadaveric kidney transplants.

To determine if cold preservation time continues to affect renal transplant outcome, prospectively collected data from 17,937 cadaveric renal transplants performed between 1982 and 1991 were analyzed. Cold preservation intervals of 1-16, 16-32, 32-48, and greater than 48 hr were studied by multi- and univariate methods for two time periods: 1982-1989 (n = 13,800) and 1990-1991 (n = 4137). The functional one-year graft survival for kidneys stored over different intervals was significantly different (P < 0.001) only for the 1982-1989 epoch: one-year allograft survival ranged from 76% (1-16), to 72% (16-32 and 32-48) to 74% (> 48) hr. One-year graft survival ranged from 81 to 83% for the four preservation times in 1990 through 1991 (P = NS). Overall actuarial graft survival was 76% (74% prior to 1990, and 82% after 1990). Factors significantly (P < 0.0001) affecting kidney transplant outcome before and after 1990 were delayed graft function (DGF): n = 4232, 65% one-year graft survival; retransplant status: n = 3029, 67% one-year graft survival; and HLA match at three or more loci: n = 6067, 79% one-year graft survival. While DGF occurred more often with prolonged preservation, kidneys with DGF had similar survival regardless of preservation duration. Before 1990, pretransplant transfusion was associated with better and black recipient race with worse outcome; neither transfusion nor recipient race had any effect after 1990. Patients receiving kidneys preserved for longer periods demonstrate one-year graft survival comparable to kidneys preserved for shorter periods. Prolonged cold ischemic time should no longer be a principal reason for considering organ discard.

Analysis of Variance↗
PubMed2004

Non-heart beating donors.

BACKGROUND: Several groups have demonstrated that non-heart beating donation is a viable source of organs for transplantation. However, the theoretically worse graft function and survival of the kidneys obtained from non-heart beating donors (NHBDs) is still a matter of debate that has led to consider them as marginal donors for kidney transplantation. METHODS: In this report, we compare the outcome and course of 83 kidney transplants from NHBDs with those corresponding to 3177 adult cadaveric heart beating donor (HBD) transplants performed over the same period in our country. Graft and patient survival were estimated by means of Kaplan-Meier analysis. In addition, groups were compared using Cox proportional regression. RESULTS: The delayed graft function (DGF) rate was higher on NHBD transplants than in HBD kidneys (58.8 vs 28.9%, P<0.0001). However, in 1998, where the highest number of NHBD transplants was performed, graft function estimated by serum creatinine levels at 3 months and 1 year, was significantly better in the NHBD transplant group (1.42+/-0.45 vs 1.66+/-0.66 and 1.45+/-0.59 vs 1.62+/-0.64, respectively, P = 0.01 and 0.07). Graft survival at 2 years was 97%, 95% at 4 years and 84% at 6 years for NHBDs and 97, 90 and 84%, respectively, for HBDs. Interestingly, DGF was a risk factor for worse graft survival in HBDs but not on NHBDs. CONCLUSIONS: We conclude that, in our study, both graft function and graft survival of NHBD kidney transplants are at least similar to those from HBD transplants. Therefore, NHBDs should be considered as a viable source of non-marginal kidneys for transplant.

Death↗
PubMed2004

Transplanting kidneys from CMV-seropositive donors to CMV-seronegative recipients is not associated with poorer renal allograft function or survival.

BACKGROUND: Cytomegalovirus (CMV)-seronegative recipients of renal allografts from CMV-seropositive donors (D+/R-) have a higher rate of acute rejection than other renal transplant recipients. A relationship between CMV infection/disease and chronic allograft nephropathy (CAN) has been proposed from animal studies, although human studies have been inconclusive. The objective of this study was to determine if CMV seromatching has an effect on renal allograft function and allograft survival. METHODS: A retrospective single centre study was carried out in 333 first cadaveric transplant recipients from January 1, 1991 to December 31, 1997. The primary end-point was creatinine clearance at 3 years post-transplant in groups based on CMV seromatching. The secondary end-point was renal allograft survival. RESULTS: Mean creatinine clearance 3 years post-transplant was 53.4 ml/min/1.73 m2 of body surface area. There was no significant difference in the mean creatinine clearance for groups formed on the basis of CMV seromatching. Delayed graft function and acute rejection were associated with a lower creatinine clearance at 3 years and reduced overall graft survival [hazard ratios 2.35 (1.56-3.54) (P<0.001) and 1.57 (1.0-2.46) (P = 0.046), respectively]. Considering the end-point of graft loss due to acute rejection (censoring for death with a functioning graft) identified the D+/R- group as having an increased hazard of graft loss due to acute rejection [hazard ratio 3.12 (1.16-8.57) (P = 0.024)]. CONCLUSIONS: The D+/R- group does not appear to have poorer renal allograft function 3 years post-transplant. This group does, however, have an increased risk of early allograft loss due to acute rejection.

Adult↗
PubMed2003

Early versus late acute rejection episodes in renal transplantation.

BACKGROUND: Acute rejection is a major complication after renal transplantation and the most important risk factor for chronic rejection. We investigated whether the timing of the last treated acute rejection episode (ARE) influences long-term outcome and compared the risk profiles of early versus late ARE. METHODS: A cohort of 654 patients who underwent cadaveric renal transplants (1983-1997) that functioned for more than 6 months was studied. In 384 of 654 transplant recipients, one or more treated AREs were documented; the last ARE occurred in 297 of 384 transplant recipients within 3 months and in 87 of 384 after 3 months. Applying multivariate logistic regression analysis, we compared the predictor variables of the two groups with transplants without AREs. RESULTS: Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%, 86%, and 45% for patients without ARE, with early ARE, and with late ARE, respectively. Delayed graft function, odds ratio (OR) 2.37 (1.55-3.62), and major histocompatibility complex (MHC) class II incompatibility, OR 2.28 (1.62-3.20) per human leukocyte antigen (HLA)-DR mismatch, were independent risk factors for early ARE. In contrast, recipient age, OR 0.75 (0.61-0.93) per 10-year increase, donor age, OR 1.28 (1.07-1.53) per 10-year increase, female donor gender, OR 1.74 (1.03-2.94), and MHC class I incompatibility, OR 1.35 (1.07-1.72) per mismatch of cross reactive groups, were associated with late ARE. CONCLUSIONS: Late ARE has a detrimental impact on long-term graft survival and is associated with MHC class I incompatibility, whereas early ARE is correlated with HLA-DR mismatches and has a better prognosis. These data are consistent with the role of direct and indirect allorecognition in the pathophysiology of early and late ARE, respectively.

Acute Disease↗
PubMed2002

Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination.

BACKGROUND: Sirolimus (Rapamune; SRL) in combination with cyclosporine (CsA) reduces the incidence of acute rejection episodes in renal allograft recipients. This study evaluated whether renal function could be improved by elimination of CsA from an SRL-based regimen. METHODS: This phase 2, open-label, controlled, randomized study was conducted at 17 centers in the United States and Europe. Two hundred forty-six first cadaveric renal allograft recipients were enrolled, and 197 were randomized to full-dose CsA (microemulsion) plus fixed-dose SRL (2 mg/day; group A, n=97) or reduced-dose CsA plus concentration-controlled SRL (troughs 10-20 ng/mL; group B, n=100). Most patients with acute tubular necrosis-delayed graft function that resolved later than posttransplantation day 7 were not randomized but were assigned to a third group (nonrandomized, n=49) and received up to 5 mg per day of SRL as part of their individualized treatment regimen. All patients received standard doses of corticosteroids. At the end of posttransplantation month 2, eligible patients (those not treated for rejection within 3 weeks) in group B had CsA tapered and eliminated over the subsequent 4 to 6 weeks. RESULTS: At 12 months after transplantation, renal function was significantly better in the CsA-elimination arm. In patients who were on therapy and who had not experienced an acute rejection episode before month 6, serum creatinine level was significantly lower (1.38 mg/dL vs. 1.82 mg/dL, P < 0.001) and calculated glomerular filtration rate (Nankivell method) was significantly higher (73.5 mL/min vs. 57.1 mL/min, P < 0.001) in group B than in group A. In the intention-to-treat population, rates of biopsy-confirmed acute rejection at 12 months were similar between groups A and B (18.6% vs. 22.0%, respectively; P = 0.598). In addition, graft survival (92.8% and 95.0%) and patient survival (96.9% and 96.0%) rates at 12 months were not significantly different between groups A and B, respectively. Furthermore, there were no significant differences between black and nonblack recipients within treatment groups in terms of rejection rates and graft survival at 12 months. Black recipients in group B had better serum creatinine levels at 12 months compared with black recipients in group A (1.55 mg/dL vs. 2.69 mg/dL, respectively, P = 0.011), as did nonblack recipients in group B compared with nonblack recipients in group A (1.53 mg/dL vs. 1.75 mg/dL, respectively, P = 0.055). Black patients in group A had higher mean serum creatinine levels (2.69 mg/dL) than nonblack patients in group A (1.75 mg/dL, P = 0.028). Hypertension, edema, hypomagnesemia, and dyspnea were reported significantly less frequently in patients randomly assigned to undergo CsA elimination compared with patients in group A (P < 0.05); group B patients had a significantly greater (P < 0.05) incidence of abnormal liver function tests, diarrhea, hypokalemia, and thrombocytopenia. CONCLUSION: Concentration-controlled SRL with early elimination of CsA is safe and results in improved renal function. Reduced exposure to CsA does not result in a clinically significant increase in the incidence of acute rejection episodes. This is true for both black and nonblack recipients. SRL may be used to reduce the exposure of renal allograft recipients to the nephrotoxic effects of CsA.

Adult↗
PubMed1998

31P-magnetic resonance spectroscopy (31P-MRS) of human allografts after renal transplantation.

BACKGROUND: 31P-Magnetic resonance spectroscopy (31P-MRS) can be used as a non-invasive tool for measuring the relative intracellular concentrations of several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. METHODS: We determined the relative concentrations of phosphate-containing metabolites in renal allografts of humans with 31P-MRS (1.5 Tesla) in the first few weeks after transplantation; 18 patients with an uneventful clinical course and 10 patients who required dialysis after transplantation were examined. Six patients with a stable allograft function 2-3 months after transplantation served as controls. RESULTS: In patients with primary allograft function, we found a significant correlation between the phosphomonoester/phosphodiester-ratio (PME/PDE) (r = 0.66, r < 0.01) and the time after transplantation, but no correlation between the nucleoside triphosphate (beta-NTP)-concentration (r = -0.11) and the time course. In the patients with primary or early allograft dysfunction caused by histologically proven rejection (n=5), we found a low beta-NTP compared to patients with an uncomplicated clinical course (0.09+/-0.01 vs 0.15+/-0.03), but no differences in the PME/PDE ratio (0.73+/-0.21 vs 0.80+/-0.21). In contrast, the PME/PDE ratio was lowered in three patients with delayed graft function caused by acute tubular necrosis (0.45+/-0.07 vs 0.80+/-0.21), but the beta-NTP concentration was not reduced (0.15+/-0.003 vs 0.15+/-0.03). The 31P-MR spectrum of two patients with cyclosporin A damage was not altered compared to the controls. CONCLUSIONS: 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the beta-NTP concentration was found in patients with primary allograft function in the first 4 weeks after renal transplantation. Different patterns of 31P-MR spectra were observed depending on the different causes of primary and early transplant dysfunction.

Adult↗
PubMed2000

[Factors influencing the development of chronic renal allograft nephropathy in children].

Chronic renal graft nephropathy (CRGN), with progressive deterioration of graft function and development of chronic graft pathology remains the main cause of late graft loss. Overall 191 patients, at aged 1.5 to 19 years were evaluated, divided in two groups: #1 (n = 103) with pathomorphological CRGN pattern in renal biopsy, and #2 (n = 88) with no chronic changes (22) or no indication to biopsy (66). Several factors were evaluated, including HLA matching, PRA, early graft function, early and late acute rejection, hypertension index, proteinuria, hemoglobin and albumin level, CsA dosing, blood levels and instability, CMV infection, CMV in-situ presence in the graft and correlations with graft survival and time post-transplant when CRGN assessed with Banff and CADI scales, occurred in renal biopsy, were analyzed. Statistical analysis showed, that significantly lower CsA blood level and dosage at 1,2,3 years post-transplant, CsA blood level instability, acute rejection within first year post-transplant, poor control of hypertension, proteinuria, lower hemoglobin level and hypoalbuminemia were major, while delayed graft function, CMV infection and CMV in-situ presence in renal tissue were minor factors affecting development of CRGN.

Adolescent↗
PubMed2003

Influence of delayed initiation of cyclosporine on everolimus pharmacokinetics in de novo renal transplant patients.

We quantified the influence of delayed initiation of cyclosporine on everolimus pharmacokinetics in order to provide dosing guidance for kidney transplant patients. In a randomized multicenter study, 56 de novo kidney transplant patients received everolimus, basiliximab, corticosteroids and either immediate (n = 40) or delayed (n = 16) initiation of cyclosporine based on renal function. Everolimus and cyclosporine predose blood levels (Cmin) were obtained over the first 3 months post-transplant. Everolimus Cmin averaged 9-11 ng/mL in the immediate cyclosporine group over the first 3 months. In the delayed cyclosporine group, average everolimus Cmins were significantly lower by 2.9-fold in the absence vs. presence of cyclosporine: 2.9 +/- 2.8 vs. 8.3 +/- 3.7 ng/mL (p < 0.001). Likewise, the within-patient ratio of everolimus Cmins in the presence/absence of cyclosporine averaged 2.9 (range, 0.7-5.6). Both everolimus and cyclosporine blood concentrations need to be monitored in kidney transplant patients with delayed graft function during the period when cyclosporine is withheld and shortly after its initiation. Dosing of everolimus needs to be adjusted to take into account an average threefold increase in everolimus exposure when cyclosporine is added to the regimen.

Cyclosporine↗
PubMed1999

Transplant renal artery stenosis: potential role of ischemia/reperfusion injury and long-term outcome following angioplasty.

PURPOSE: We assess long-term arterial pressure, renal function, and patient and graft survival in recipients of cadaveric kidney transplant with or without transplant renal artery stenosis. We also evaluate the risk factors for transplant renal artery stenosis. MATERIALS AND METHODS: We reviewed and analyzed baseline clinical, immunological and outcome data for 26 patients with transplant renal artery stenosis before and after angioplasty, and 72 without stenosis on angiography. We also analyzed graft and patient survival in 304 cases in which angiography was not performed. RESULTS: The incidence of transplant renal artery stenosis was 6.6% (26 of 402 patients). Acute rejection episodes (42 versus 22%, p <0.05) and delayed graft function (50 versus 32%, p <0.10) were more frequent, and mean cold ischemia time plus or minus standard error (29.2+/-1.7 versus 24.8+/-1.3 hours, p <0.01) was longer in patients with than without transplant renal artery stenosis. The technical success of angioplasty was 92.3%. Restenosis was documented in 6 of 26 patients (23.1%). Revascularization resulted in a decrease in arterial pressure and better renal function. The 8-year patient (100, 98.6 and 95.7%, respectively) and graft (88.1, 88.9 and 89.3%, respectively) actuarial survival rates were similar among patients with or without transplant renal artery stenosis, and those who did not undergo angiography. CONCLUSIONS: Transplant renal artery stenosis had no detectable influence on long-term arterial pressure control, renal function, and patient and graft survival rates, which were similar to those in patients without stenosis. Long cold ischemia time may have a role in the development of transplant renal artery stenosis through ischemia/reperfusion injury.

Adult↗
PubMed2004

Improved pretransplant assessment of renal quality by means of phosphorus-31 magnetic resonance spectroscopy using chemical shift imaging.

BACKGROUND: Phosphorus-31 (P) magnetic resonance spectroscopy (MRS) has been evaluated in several studies for pretransplant assessment of renal viability. As an indicator of graft quality, the ratio of phosphomonoesters (PME) to an organ's inorganic phosphate (Pio) is the parameter of choice. However, exact calculation of the PME/Pio ratio is disturbed by interference from the signal of phosphorus contained in the preservation solution (Pip). In this article, the authors present an improvement attained by using volume selective P-MRS using chemical shift imaging (CSI) enabling reduction in the disturbing influence of Pip. METHODS: Sixteen renal grafts were investigated using a 2.0-T whole-body scanner and a cross-coil setting with an active decoupled receiver coil. P-CSI was used to measure two-dimensional spectra of a 4-cm slice of the graft in a 12 x 12 matrix. Peaks of each spectrum were fitted with magnetic resonance user interface-MatLab software using VarPro and the mean PME/Pio ratio was calculated. RESULTS: Significant correlation between the PME/ Pio ratio and clinical kidney function was found. In comparison to former trials using PME/Pio ratios calculated from non-volume-selective spectra, the correlation outcome improved significantly. Furthermore, overlay of CSI-spectra matrix and corresponding slice image of the kidney illustrates the origin of different signals in the spectra. CONCLUSIONS: The authors' work demonstrates that the PME/Pio ratio calculated from CSI spectra is a reliable indicator of viability of renal grafts. Early knowledge of graft quality may allow therapy to be adapted to the conditions of the organ, for example, by initial withholding of nephrotoxic calcineurin-inhibitors in kidneys with high risk of delayed graft function.

Adult↗
PubMed2005

Use of Neoral C monitoring: a European consensus.

Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C(2) monitoring significantly reduces the severity and incidence of acute rejection compared with C(0) monitoring, without adverse consequences in terms of renal function or tolerability. Different C(2) targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1-2 weeks post-transplant, and this should be taken into account to avoid overshooting C(2) target range. A patient with a low C(2) value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C(2) monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C(2) monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single-center trials have evaluated Neoral C(2) monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.

Absorption↗
PubMed2004

Acute rejection and late renal transplant failure: risk factors and prognosis.

BACKGROUND: Acute rejection episodes are a major determinant of renal allograft survival, and the improvement of the transplantation results in the last two decades is largely due to a progressive decrease in the incidence of acute rejection. These results are explained by the incorporation of new immunosuppressive agents since the introduction of cyclosporine. Because the detrimental effect of acute rejection on graft survival is not limited to the early post-transplant period, we have focused on the impact of acute rejection episodes on late transplant failure in patients with the graft functioning 1 year after transplantation. METHODS: We have retrospectively analysed in 3365 renal transplants performed in adults in Spain during 1990, 1994 and 1998 the incidence and severity of the acute rejection episodes, their risk factors, and their influence on graft and patient survival. RESULTS: The incidence of rejection episodes in the whole series was 32.5%, decreasing in 1998 (25.1%) compared with the previous years (38%) (P<0.0001). Corticoid-resistant rejection episodes also decreased from 8% in 1990 and 1994 to 3.4% in 1998 (P<0.0001). Multivariate analysis showed that patients < 60 years old (P<0.0001), sensitized recipients (P = 0.038), patients with delayed graft function (P<0.0001), cytomegalovirus infection (P = 0.0060), and those transplanted in 1990 or 1994 (P<0.0001) had an increased incidence of rejection episodes. In the univariate analysis, induction treatment with antilymphocyte globulines or OKT3 (P = 0.0002), and traumatic donor death (P = 0.042) were associated with a lower incidence of acute rejection. In the univariate analysis of the transplants performed in 1998, addressed to evaluate the effect of the new immunosuppressive agents, treatment with mycophenolate mofetil (P<0.0001) or tacrolimus (P = 0.0067), but not with anti-IL2 antibodies reduced the incidence of acute rejection. Patients with rejection episodes had an increased risk of late graft failure (Cox proportional hazards model, P<0.0001), which was homogeneous in the three periods analysed, with no effect on patient survival (P = 0.13). CONCLUSIONS: Despite a decreased incidence and severity of acute rejections in 1998, compared with the previous years, acute rejection still remains a powerful risk factor for late transplant failure.

Acute Disease↗
PubMed2003

Enzyme linked immunosorbent spot (ELISPOT) assay for interferon-gamma independently predicts renal function in kidney transplant recipients.

Post-transplant monitoring of cellular immunity might be useful in predicting long-term outcomes of kidney transplant recipients. We used an enzyme linked immunoabsorbent spot (ELISPOT) assay to serially measure the frequency of peripheral blood lymphocytes producing interferon-gamma in response to stimulator cells from donors or third parties in 55 primary kidney transplant recipients. Mean frequencies measured during the first 6 months after transplantation correlated significantly with the serum creatinine concentration at both 6 and 12 months following transplantation. The mean frequencies were higher in patients with acute rejection than in those without acute rejection. Multiple regression analyses indicated that the correlations between the early ELISPOT measurements of interferon-gamma and serum creatinine were independent of acute rejection, delayed graft function, or the presence of panel reactive antibodies before transplantation. Patients with low mean frequencies of interferon-producing cells in the early post-transplant period were generally free from acute rejection and exhibited excellent renal function at 6 and 12 months post-transplant. In conclusion, using the ELISPOT assay, we show an independent correlation between early cellular alloreactivity and long-term renal function. Increased levels of early alloreactivity measured with this assay may serve as a surrogate for chronic allograft dysfunction.

Adult↗
PubMed2005

Changes in renal transplantation: comparison between two different series.

BACKGROUND: New immunosuppressives have improved the results of renal transplants. However, the features of donors and recipients have changed, producing an increased age in both cases and more donors dying from strokes. We analyzed the impact of donor and recipient profile on survival of graft in recipients treated with new immunosuppressive agents. METHODS: Data from 343 patients receiving cadaveric renal transplants functioning for 1 year on February of 1987 and March of 2001 when cyclosporine was incorporated in the immunosuppressive regimen. Two series were distinguished from the point of view of immunosuppression: an historical series and a current series. Graft survival rates were analyzed using the actuarial method. Multivariate analysis was achieved with Cox proportional hazards model. RESULTS: Actuarial survival at 5 years was lower in the current series, 77%, as opposed to 82% in the historic series. Donor and recipient age, proteinuria, and losses in immediate postoperative period were significantly higher in the current series. However, acute rejection episode dropped from 54% to 21%. Delayed graft function also decreased from 18% to 10% in the current series. When multivariate analysis was performed of grafts functioning at 1 year, the relative risk was 3.12 in the historical series adjusted for other variables. CONCLUSION: The data suggested that new immunosuppressive regimens counteract suboptimal features for donors and recipients.

Age Factors↗
PubMed1998

Long-term renal function in on-heart-beating donor kidney transplantation: a single-center experience.

BACKGROUND: One of the most serious problems facing major transplant programs is the severe shortage of organs. Expansion of the donor pool to include nontraditional donors, such as non-heart-beating donors (NHBDs), would considerably expand the availability of organs. METHODS: Between 1983 and 1996, we performed a total of 125 non-heart-beating cadaveric renal transplantations under cyclosporine-based or tacrolimus-based immunosuppression. Thirty-nine recipients were females and 86 were males. Total ischemic time (TIT) and warm ischemic time (WIT) were an average of 761+/-347 min (322-2027 min) and 7.4+/-13.1 min (0-45 min), respectively. RESULTS: Of the 125 transplanted kidneys from NHBDs, 98 (78.4%) developed delayed graft function (DGF), which lasted a mean of 16+/-21 days (range 3-37 days). One hundred and eight patients (86.4%) were off dialysis by the time of discharge. Of the 125 grafts, 11 (8.8%) were primary nonfunction. The average of the nadir of serum creatinine levels, which was evaluated using 108 patients who were off dialysis by the time of discharge, was 1.4+/-0.5 mg/dl. The lowest creatinine levels (nadir) were under 2.0 mg/dl in 98 (78.4%) of the 125 patients. Acute rejection occurred in 64 (51.2%) of the 125 recipients. Patient survival rates were 90% at 5 years and 88% at 10 years. Graft survival rates were 65% at 5 years and 46% at 10 years. We tried to find the risk factors that affected graft survival. We examined the various possible risk factors, including harvesting condition (controlled versus uncontrolled), HLA-AB mismatches, HLA-DR mismatches, graft weight, donor age and sex, recipient age and sex, posttransplant DGF, acute rejection, WIT, and TIT. However, no significant risk factor was identified except acute rejection. We tried to discover the risk factors that caused primary nonfunction. Possible risk factors, including donor age, TIT, WIT, graft weight, and harvesting condition were compared, but no significant risk factor was identified. Long-term renal function was evaluated by serum creatinine levels. Serum creatinine levels at 1, 5, and 10 years were 1.76+/-0.7 mg/dl, 1.7+/-0.96 mg/dl, and 1.53-/+0.6 mg/dl, respectively. CONCLUSIONS: In conclusion, our data demonstrated that the procurement of kidneys from NHBDs leads to acceptable long-term graft survival and renal function, despite a high incidence of DGF.

Adult↗
PubMed2002

Increased transplanted organs from the use of a standardized donor management protocol.

The organ shortage has resulted in increasing recipient waiting lists and waiting-list deaths. The increased use of expanded donors has been associated with increased discarding of procured organs because of poor organ function. A structured donor management algorithm or critical pathway was tested to determine its effect on the donor management and procurement process. A pilot study examined donors from 88 critical care units in 10 organ procurement organizations managed under the critical pathway and compared them to retrospective data collected at those same pilot sites. The total number of organs both procured and transplanted per 100 donors was significantly greater (p <0.01) in the critical pathway group when compared to the control group. There was no significant difference in 1-year graft survival for any of the organs recovered, and no significant difference in the rate of delayed graft function in the kidneys transplanted. Use of a structured donor management algorithm results in significant increases in organs procured and organs transplanted without any reduction in the quality of the organs being transplanted.

Clinical Protocols↗