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PubMed2000

Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool.

The aim of this study was to compare the survival and midterm function of kidneys from non-heart beating donors (NHBD) with those of kidneys from heart beating donors (HBD). From 1989 to 1998, 144 kidneys were procured from NHBD at the Hospital Clínico San Carlos in Madrid, of which 95 were transplanted. The kidney grafts were maintained from the moment of the diagnosis of cardiac arrest until the time of procurement by cardiopulmonary bypass. There was no significant difference in renal function and the number of rejection episodes between the NHBD and HBD transplants. The NHBD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (adjusted relative risk 95% confidence interval, 2.82 to 11.62). One- and five-year survival rates for NHBD grafts were 84.6 and 82.7%, respectively, compared with 87.5 and 83.9% for HBD (P = 0.5767). Cox analysis showed that the predictive factors for worse NHBD graft survival were type of NHBD donor and the occurrence of corticoresistant rejection. Ninety of the NHBD organs were procured from subjects suffering irreversible cardiac arrest on the street who were transferred to our center for the sole purpose of donation. Fifty-four of these kidneys were transplanted and all showed primary function. When a strict protocol is adhered to, the outcome of renal transplant from NHBD compares well with that from HBD. It is believed that the high number of organs obtained from subjects undergoing irreversible cardiac arrest on the street might encourage the adoption of new criteria for the management of this type of pathology with the ultimate goal of kidney donation.

Adult↗
PubMed2005

Rapamycin at six years can exhibit normal renal function without proteinuria or neoplasia after renal transplantation. A single-center experience.

Currently, long-term experience with Rapamune (RAPA) after renal transplantation is scarce. We present our experience with RAPA in patients who were included in clinical trials. Between 1996 and 1999, 27 renal transplant patients received RAPA alone or in combination with cyclosporine (CyA). We study 15 of them (9 males, 6 females; mean age 36 years) who are currently functioning with a mean follow-up of 6 years (range, 5.2-8 years). The presence of delayed graft function was 40% and acute rejection 26.6%, all of them controlled with steroids. Notably, no patients experienced an acute rejection episode after the first year. Among 15 patients, 12 received steroids, RAPA and CyA; and 3 received steroids, RAPA, azathioprine (AZA) or mycophenolate mofetil (MMF) for immunosuppression. At the end of follow-up, the situation was the opposite: 12 patients received steroids (2.5-5 mg/d) and RAPA associated with or without AZA/MMF, and 3 were maintained with steroids, RAPA and CyA. Renal function was excellent in the entire group: mean SCr 1.1 mg/dL (range, 0.7-1.8) with mean RAPA blood levels (HPLC) of 11 ng/dL (range 8-16). Hyperlipidemia was universal with all patients (100%) receiving statins maintaining acceptable levels of cholesterol (mean 209 +/- 28 mg/dL) and tryglycerides (mean 154 +/- 76 mg/dL). Arterial hypertension present in 12 of 15 (80%) patients was controlled with a mean of 1.5 drugs. Notably, no patient presented with proteinuria, neoplasia, posttransplant diabetes, or cardiovascular events. In conclusion, these single-center results suggest that Rapamune may be useful in the long-run after renal transplantation. The presence of normal renal function and the absence of proteinuria and neoplasia in these renal transplant patients may have important clinical implications.

Adrenal Cortex Hormones↗
PubMed2003

Cost-effectiveness analysis of basixilimab induction and calcineurin-sparing protocols in "old to old" programs using Markov models.

INTRODUCTION: Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model. HYPOTHESIS: Calcineurin-sparing protocols using anti-IL-2/antibody induction (Simulect) show a beneficial effect on initial kidney function, reducing transplantation costs reception based upon mean length of stay, mean admission cost, and incidences of delayed graft function and complications during the first month after transplant. PATIENTS AND METHODS: A Markov simulation model was established following three different chains. A calcineurin-free regimen with basiliximab induction (chain A), a calcineurin-sparing protocol with basiliximab induction (chain B), and a conventional immunosuppressive regimen (chain C). After designing the Markov chain and cohorts, 31 patients from the "old to old" program were assigned to each chain eight to chain A, (eight to chain B, and 15 to chain C). A month after transplantation a cost-benefit study was performed guided by the three branches of the Markov model. RESULTS: The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a month there was a clear benefit from Calcineurin=free plus basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols. CONCLUSIONS: Markov models are extremely useful when introducing new clinical therapies. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with basixilimab induction.

Antibodies, Monoclonal↗
PubMed1993

Influence of the pretransplant hematocrit level on early graft function in primary cadaveric renal transplantation.

Although use of human recombinant erythropoietin has alleviated symptoms of anemia in renal failure, effects of increased hematocrit (HCT) on early post-transplant renal function are unknown. Of 244 consecutive primary cadaveric kidney recipients transplanted over 74 months, 43% had HCT > or = 30% and 57% had HCT < 30% at transplantation. The incidence of delayed graft function (DGF) was greater in recipients with HCT > or = 30% (61%) than in recipients with HCT < 30% (33%; P = 0.0001). Ten percent of recipients with HCT > or = 30% experienced primary nonfunction (PNF) of the allograft (P = 0.0001). No recipient with HCT < 30% had PNF. Absolute rises in HCT over the 3 months preceding transplantation were greatest in those with PNF (2.5 +/- 2.4) followed by those with DGF (2.0 +/- 3.1) and immediate graft function (IGF) (0.2 +/- 5.2; P = 0.0328). Logistic regression analysis identified HCT > or = 30% (P = 0.0014), cold storage > or = 24 hr (P = 0.0006) and rising HCT (P = 0.0090) as independent predictors of DGF with relative risks of 3.1-, 3.3-, and 2.7-fold, respectively. Recipients with rising pretransplant HCTs who underwent dialytic fluid removal within 24 hr before transplantation had DGF with greater frequency (67%) than nondialyzed recipients with rising HCTs (45%). Primary cadaveric kidney recipients with HCT > or = 30% at transplantation have significantly greater risk for DGF and PNF. Rising pretransplant HCT levels may predispose recipients to DGF; this risk may be heightened in those undergoing hemodialysis shortly before transplantation.

Adult↗
PubMed1992

Preservation.

1. There were no significant differences in 1-year graft survival rates comparing kidneys stored with 3 commonly used cold storage solutions (Collins', EuroCollins, and University of Wisconsin) over the past 12 years, even though preferences have changed sharply. 2. No significant differences in 1-year graft survival rates were noted when comparing kidneys preserved by pump perfusion and those maintained by simple cold storage. The lower incidence of delayed graft function for pump-preserved kidneys was at least partly attributable to a center effect. 3. Prolonged cold ischemia time (CIT) was associated with an increase in delayed onset of function. Of 2,718 kidneys transplanted within 24 hours, 21% did not function well within the first week. The fraction increased to 28% and 33% of kidneys transplanted between 25 and 36 hours (n = 1,858) and after 36 hours (n = 955), respectively (p < 0.01). One-year graft survival rates were 82%, 78%, and 76% for kidneys transplanted within 24 hours, between 25 and 36 hours, and after 36 hours, respectively (p < 0.01, each comparison). 4. HLA matching neutralized the impact of prolonged CIT completely. One-year graft survival was more than 86% in 715 recipients of 0 HLA-mismatched kidneys, regardless of CIT. For recipients of mismatched transplants, survival decreased by 5-6% as CIT increased from less than 24 to more than 36 hours (p < 0.01). Of the mis-matched kidneys with less than 24 hours CIT, up to 83% survived at 1 year compared with 87% of matched kidneys with more than 36 hours CIT (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Serum erythropoietin and reticulocyte maturity index after renal transplantation: a prospective longitudinal study.

Improvement in erythropoiesis following renal transplantation (RT) was assessed in 74 consecutive patients by serial measurements of serum erythropoietin (EPO), hematocrit, absolute reticulocyte count (ARC) and serum creatinine during the first month after RT. The reticulocyte maturity index (RMI) which provides an objective measure of red-cell maturity was assessed in 31 patients by flow cytometry using thiazole orange. In group I (n = 39) with immediate graft function, EPO levels increased rapidly from day 2 and remained elevated at the plateau between two and three times the upper limit of normal during the first 2 months. In group II (n = 29) with delayed graft function, EPO levels increased gradually from day 10 when renal function improved significantly. No particular significant biphasic pattern of secretion was detected in group I or II. In both groups, hematocrit rose to over 35% approximately 3 months after RT. In a third group (n = 6) with immediate postoperative acute blood loss and severe anemia, a hematocrit fall was followed by a steep increase in EPO levels with a negative correlation between hematocrit and EPO levels during the first 4 days. During acute rejection, EPO diminished significantly by more than 50% either on the day of diagnosis or on the following days in 8 patients. RMI increased by 25% over the pretransplantation values by 7 days on average before the ARC rose. Thus the RMI seems to be an early sensitive predictor of erythropoiesis after RT. EPO response after RT depends on graft function, and the early transient increase in EPO observed in patients with acute blood loss may explain the apparent biphasic response previously reported.

Adolescent↗
PubMed2001

Factors in older cadaveric organ donors impacting on renal allograft outcome.

Transplantation of renal allografts (RA) from older donors has become more common, despite conflicting data on outcome between reports from large series versus individual centres. Factors other than donor age per se may contribute to RA outcome. The outcome of RA procured from 114 older donors over 55 yr of age in NSW, between 1990 and 1997, was analysed. Corresponding donor factors, including demographics, medical history, inotrope use, major hypotension and findings at procurement, were also analysed. Of the potential RA, 8% were discarded and the remainder transplanted. Factors significantly associated with renal discard were pre-transplantation donation biopsy abnormality (p < 0.001) and a history of cardiovascular (CV) disease in the donor (p < 0.02). Donor aortorenal atherosclerosis (AS; p < 0.09) and a donor age of 65 yr or older (p < 0.08) were common in the discard group. The never function rate was 7.6% and was associated with a history of a discarded partner kidney (p < 0.05). The delayed graft function rate was 33% and was associated with a history of donor CV disease. At a median follow up of 5 yr, the death censored allograft failure rate was 24%. Allograft failure was associated with a history of donor hypertension (p < 0.05). Donor AS (p < 0.7) tended to have been more common in the allograft failure group. A number of cadaveric organ donor factors documented at procurement may be associated with inferior outcome of RA. These include biopsy abnormality, history of donor CV disease and history of donor hypertension. A donor age of 65 yr or older or significant visible aortorenal AS may also be factors. This retrospective review of kidneys procured from 114 older cadaveric organ donors identifies factors apart from donor age, which may have a negative impact on both allograft utilisation and outcome. Theses factors include renal biopsy abnormality, history of donor CV disease, discard of a partner kidney and donor hypertension. Visible AS in the donor aorta documented at renal procurement may also be a factor.

Aged↗
PubMed2002

Variability of cyclosporine exposure and its relevance to chronic allograft nephropathy: a case-control study.

BACKGROUND: Population data indicate that cyclosporine (CsA)-based immunosuppression has had relatively little effect on late renal allograft loss. For individual patients, however, the degree and variability of CsA exposure may be of prognostic importance. This case-control study has examined the contribution of these and other factors to the development of chronic allograft nephropathy (CAN) in patients receiving follow-up care in our unit. METHODS: The electronic record was interrogated to identify adult, CsA-treated renal transplant recipients with CAN (group A) and CsA-treated controls with stable graft function for a minimum of 4 years posttransplantation and serum creatinine less than 200 micromol/L (group B). Age at transplantation, gender, years posttransplantation, donor source and age, kidney preservation time, human leukocyte antigen match, occurrence of delayed graft function, immunosuppressive regimen, weight-adjusted maintenance CsA dose, and coefficient of variation (CvarC0 ) of dose-adjusted CsA trough blood levels (C0/dose) were recorded (CvarC0 =[SD (C0/dose)/mean (C0/dose)]x100). Statistical analysis included binary logistic regression analysis. RESULTS: Three transplant recipients were excluded because of known noncompliance with immunosuppressive medication, leaving a study population of 102 patients. Recipient age (A B, <0.01) and CsA dose (A>B, <0.02) were significantly different by univariate analysis. Only low recipient age ( P<0.001) and high CvarC0 ( P<0.02) were independent predictors of CAN in the regression model. CONCLUSION: Younger renal transplant recipients and those with highly variable CsA exposure are predisposed to developing CAN. Investigation of such patients may reveal correctable factors such as poor treatment compliance and lead to appropriate interventions.

Adult↗
PubMed1999

Calcium ion concentration of machine perfusate predicts early graft function in expanded criteria donor kidneys.

Pulsatile preservation offers the advantage of pretransplant assessment of donor kidneys. Selected electrolyte concentrations of machine perfusate were measured over time in order to: (1) describe electrolyte changes in perfusate during the pulsatile preservation of expanded-criteria donor (ECD) kidneys, and (2) to assess the prognostic significance of these characteristics to early graft function. One hundred and fifty ECD kidneys were preserved in our laboratory between 1 January 1995 and 11 January 1997. ECD kidneys were defined as those requiring pretransplant biopsy. Kidneys were grouped by the presence or absence of delayed graft function (DGF), and perfusion parameters were measured every hour during pulsatile perfusion. All kidneys were preserved by continuous hypothermic pulsatile perfusion using Belzer II solution. Renal flow is decreased and renal resistance is increased in the presence of DGF in machine-preserved ECD kidneys. In addition, ionized calcium concentration of the machine perfusate is significantly elevated in the DGF group compared with the No DGF group (0.091 vs 0.054, P = 0.0016). The incidence of DGF is significantly lower in the ECD kidney. Among the pretransplant variables of donor characteristics, perfusion parameters and histology, perfusion parameters are highly predictive of early graft function. In addition, we found that ionized calcium concentration in the perfusate is significantly elevated in kidneys exhibiting DGF, which may have implications for assessing the suitability of donor kidneys for transplantation.

Calcium↗
PubMed2002

Post-transplant renal function in the first year predicts long-term kidney transplant survival.

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.

Creatinine↗
PubMed2003

Non-heart-beating donors: renewed source of organs for renal transplantation during the twenty-first century.

The growing demand of organs for renal transplantation makes it necessary to explore alternative routes for kidney donation. Non-heart-beating donors (NHBDs) are a valuable source of cadaveric organs and have been the subject of renewed interest in recent years. In addition to difficulties with legal and ethical acceptability, there are concerns regarding medical safety. The current NHBD program at St. George's Hospital in London was started in March 1995. A total of 41 kidneys from category I to III donors (according to the Maastricht classification) were retrieved from the Accident and Emergency Department and several intensive care units and were subsequently transplanted. Cold in situ perfusion was commenced via femoral access or rapid aortic cannulation in most donors. Of these transplanted kidneys, 35 started functioning within 4 weeks. The permanent nonfunction (PNF) rate was 14.6% (6/41) and the estimated 1-year graft survival 82.9% (34/41). The delayed graft function (DGF) rate (defined as recipients requiring posttransplant dialysis for 3 days or longer) was 80.0% (28/35). The median serum creatinine concentration in patients with a functioning graft at 1 year was 165 micromol/L. NHBD kidneys have contributed about 15% to the regional transplant activity over the last 6 years, even though not all potential NHBDs were used. It was possible to lower the PNF rate with strict donor selection criteria and more recently with pulsatile machine perfusion. NHBDs represent a valuable source for kidneys and can extend the donor pool. More experience is currently needed to continue to lower PNF rates reliably before promoting more widespread use of NHBDs for renal transplantation.

Cadaver↗
PubMed2002

Nursing management of a renal transplant recipient with premature graft loss.

This case study does not illustrate the typical course for the majority of renal transplant recipients. In fact, 89.4% of recipients will still have a functioning cadaveric transplant after a year. Graft function is maintained in 76.3% of cadaveric recipients after 3 years and 64.7% after 5 years (Transplant Patient Data Source, 2000). C.N. had several predisposing factors that have been implicated in premature transplant loss, including donor age greater than 50 years old, delayed graft function, acute rejection episodes, elevated serum lipid levels, and cytomegalovirus infection (Mudge, Carlson, & Brennan, 1998). With the advent of recently approved immunosuppressant medications used in combination, improved outcomes for transplant recipients can be expected in the future. Yet, renal transplantation is not considered a cure for ESRD. Many of the pathophysiologic issues of renal disease are exchanged for the adverse effects of the immunosuppressant medications. However, for patients who have been appropriately screened both medically and psychosocially, renal transplantation generally increases patients' longevity as well as their quality of life (Wolfe et al., 1999).

Graft Rejection↗
PubMed1994

Renal allograft preservation: a comparison of University of Wisconsin solution and of hypothermic continuous pulsatile perfusion.

A study was performed to compare early allograft function in kidneys preserved with University of Wisconsin (UW) solution to kidneys preserved by hypothermic pulsatile perfusion. The study consisted of two sets of data. The first set was a donor-paired study (matched data) of 30 heart-beating, hemodynamically stable donors. After removal from the donor each cooled kidney was individually prepared for preservation. One kidney was flushed with +/- 500 ml of UW solution and stored in UW solution on slushed ice. The other kidney was continuously perfused with cooled (4-6 degrees C) cryoprecipitated plasma. The kidneys were transplanted into suitable recipients in a random sequence. Twelve donors were excluded from the study because one or both kidneys were transplanted into recipients who had previously been transplanted. The remaining 36 kidneys were implanted into two similar groups after a mean of 19 hours in the pulsatile perfusion group and 18 hours in the UW solution group. The second set of data consisted of all the kidneys preserved in UW solution (n = 62) at our institution and of 57 kidneys preserved by hypothermic continuous pulsatile perfusion during the same period (mixed data) and was used to evaluate the effect of prolonged preservation (longer than 24 hours) on delayed graft function. Both of these groups were also comparable. Acute tubular necrosis (ATN) was defined as the need for dialysis during the 1st week after transplantation, and delayed function as the delayed clearance of creatinine during the early post-operative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed2005

Conversion of azathioprine to mycophenolate mofetil and chronic graft failure progression.

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.

Acute Disease↗
PubMed2004

Soluble interleukin 2 receptor (sIL-2R) levels in renal transplant recipients.

BACKGROUND: Allograft rejection is associated with T cell activation. T cell activation leads to secretion of soluble IL-2 receptor and elevated serum soluble IL-2 receptor (sIL-2R) levels. However, the clinical implication of individual elevated sIL-2 receptor levels is unclear. We followed levels of sIL-2R pre- and post-transplantation to determine if sIL-2R levels predict rejection episodes or degree of graft function. MATERIALS AND METHODS: Serum samples of 12 patients who underwent living or cadaveric renal transplant were followed weekly with serial sIL-2R levels. These levels were followed until the serum creatinine reached a baseline. Of the 12 patients, three patients developed delayed graft function. The remaining nine patients were followed for a period of 3 months. Sera of these nine patients in the initial 3 months post-transplant were monitored for sIL-2R levels. For comparison, sIL-2R levels were also measured in 150 healthy volunteers and five dialysis patients. RESULTS: Recipients undergoing severe rejection episodes had higher overall serum levels of sIL-2R (1515 +/- 496 U/mL) as compared with recipients who had stable renal transplants and no episodes of rejection (698 +/- 333 U/mL) (P = 0.034). Comparison of sIL-2R ratios (post-transplant sIL-2R level/pre-transplant sIL-2R level) revealed that ratios of 0.6 or higher were more frequently seen in patients who subsequently underwent severe rejection episodes. Dialysis patients were found to have higher sIL-2R levels (2605 +/- 1312 U/mL) compared with renal transplant patients (1047 +/- 192 U/mL) (P < 0.001) and healthy volunteers (349 +/- 185 U/mL) (P < 0.001). CONCLUSION: Our results suggest that individual levels of sIL-2R are not predictive of rejection in the early post-transplant period, but s-IL2R ratios greater than 0.6 may be predictive of severe rejection episodes.

Graft Rejection↗
PubMedDate not supplied

Comparison of tacrolimus and cyclosporin in renal transplantation by the protocol biopsies.

Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function. The aim of this study was to compare the effects of tacrolimus (Tac) and cyclosporine microemulsion (CsA) based immunosuppressive protocols using protocol biopsies from well-functioning renal allografts. 35 consecutive renal transplant patients were randomized to Tac (n: 17) versus CsA (n: 18) treatment arms. Patient age and sex, donor type and age, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Treatment protocol consisted of prednisolone, azathioprine and Tac or CsA. Biopsies performed on the third, sixth and twelfth months were blindly evaluated by the same pathologist. The incidences of acute rejection (AR) episodes among CsA vs Tac groups were 33% vs 29%, respectively (NS). The Creatinine level was lower in Tac than CsA, although it was not significant (Table). Subclinical AR and subclinical chronic allograft nephropathy were detected on protocol biopsies in 3 (2 CsA, 1 Tac) and 12 (7 CsA, 5 Tac) patients, respectively. Acute lesion score at the third month PBx was significantly lower in the Tac group (p < 0.05). Chronic lesion scores in all biopsies were lower in the Tac group, although not significantly. The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group.

Adult↗
PubMed2005

Impact of mycophenolate mofetil intolerance on early results of kidney transplantation.

From 1992 to 2003, 407 kidney transplantations were performed on 403 patients using cyclosporine (CyA) or tacrolimus (Tac), mycophenolate (MMF), and steroid immunosuppression. Patient records examined for adverse events (AE) and MMF dose reductions or discontinuations during 100 days posttransplant were correlated with data on rejections, graft function, and survival. AEs occurred in 79.1% of transplantations. Gastrointestinal (GI) symptoms, infections, and cytopenias were common. Surprisingly, in 50% of all transplantations serum alanine transferase (ALAT) was elevated, among 21% the change was over three times the upper limit of normal. Patients with delayed graft function showed increased incidences of GI symptoms and thrombocytopenias. There were more ALAT increases and thrombocytopenias in patients on CyA and more GI symptoms in patients on Tac. In 34% of transplantations, the MMF dose was reduced or discontinued. In CyA patients with MMF reduction by day 21, rejection incidence during the subsequent 21 days was 10% versus 0.6% in patients with full-dose MMF until day 21 (P < .002). Among Tac patients no increased rejection frequency was seen after reducing MMF.

Adult↗
PubMed2006

The place of sirolimus in kidney transplantation: can we reduce calcineurin inhibitor renal toxicity?

Sirolimus, a macrocylic lactone, blocks T-cell activation by a mechanism of action distinct from calcineurin inhibitors (CNIs). Therefore, it may be expected that sirolimus would display a safety profile without the vasomotor form of nephrotoxicity characteristic of CNIs. Initial studies in rodent models and in psoriasis patients showed that sirolimus alone did not impair renal function. Subsequently, two pivotal, randomized double dummy, phase III trials in human renal transplantation demonstrated that sirolimus exacerbated the nephrotoxicity of full doses of CNIs. Both pharmacokinetic and pharmacodynamic mechanisms have been implicated in the pathogenesis of this disorder. Subsequent experience has shown that cyclosporin A dose reduction, elimination, or avoidance mitigates these effects, particularly in patients distant from the transplant procedure. However, there is concern about recovery from ischemia-reperfusion injury. Animal models suggesting that sirolimus may delay recovery in this setting have been supported by non-randomized experiences at single centers, which have observed an increased incidence of delayed graft function among sirolimus-treated recipients. In contrast, large single- and multi-center studies have not confirmed this finding; impaired renal recovery has been observed in only occasional instances. Thus, present data indicate that sirolimus does not impair the function of an uninjured kidney, but whether the drug acts alone or potentiates conditions that delay recovery after ischemic injury remains to be established by large randomized trials specifically targeted to recipients at high risk for this complication.

Animals↗