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Tailoring tacrolimus-based immunotherapy in renal transplantation.

Tacrolimus is a cornerstone immunosuppressive agent in renal transplantation and compared with cyclosporin, its use is associated with a reduced incidence of acute rejection. Optimizing immunosuppressive management in the early post-transplant period is important for achieving long-term graft function and survival. In attempts to improve the long-term outcomes of renal transplantation further, tacrolimus has been combined with two novel immunosuppressive agents, mycophenolate mofetil (MMF) and sirolimus, with encouraging results in terms of patient and graft survival, acute rejection rates and renal graft function. Tacrolimus in combination with MMF adjunctive therapy showed significantly better graft survival in patients with delayed graft function, fewer episodes of corticosteroid-resistant rejection and better renal function at the 3-year follow-up compared with cyclosporin microemulsion plus MMF immunosuppression. A tacrolimus plus MMF regimen was also effective for renal transplant recipients at our centre in Pennsylvania, resulting in excellent survival and rejection rates at 1 year post-transplantation. The 3-month results of a US multicentre study comparing tacrolimus in combination with either MMF or sirolimus showed these two treatment regimens to be equivalent in terms of patient and graft survival, delayed graft function, the incidence of biopsy-confirmed acute rejection and renal graft function, although differences were apparent in terms of acute tubular necrosis and hyperlipidaemia. In conclusion, the development of a new immunosuppressive regimen in renal transplantation should take account of factors that influence graft function, both in the short and long term, as a way of optimizing individual maintenance therapy.

Clinical Trials as Topic↗

Graft function after kidney transplantation from non-heartbeating donors according to maastricht category.

PURPOSE: Donor shortages have led to some groups using alternative sources such as non-heartbeating donors (NHBDs). Kidneys from NHBDs suffer from warm ischemia at cardiac arrest which is reflected by acute tubular necrosis of the allograft, resulting in a period of delayed graft function. NHBDs are categorized by the circumstances surrounding the agonal events of death which reflect differences in the likelihood of ischemic injury to the kidney. In this study we determined the impact of ischemic injury on the renal function of kidneys procured from different categories of NHBDs. MATERIALS AND METHODS: From 1998 to 2003, 144 kidneys were procured from 72 NHBDs resulting in 93 transplants characterized into Maastricht categories II, III and IV NHBD renal transplants. Renal function after transplant was evaluated from the last dialysis until discharge from hospital, and then at 3 monthly intervals thereafter. RESULTS: Primary warm ischemic time is more prolonged in the uncontrolled donor (category II) than controlled donor (category III greater than IV). Delayed graft function occurs more frequently (Maastricht category II 83.8%, III 67.4% and IV 0%, ANOVA p <0.05) and the return to normal function is more prolonged in uncontrolled donors. This is illustrated by the greater incidence of acute tubular necrosis (Maastricht category II 81.1%, III 65.2% and IV 50.0%, ANOVA p = nonsignificant) in the kidney allograft. There was no difference in year 1 allograft survival (Maastricht category II 83.9%, III 92.5% and IV 100%, ANOVA p = nonsignificant). CONCLUSIONS: Early graft function is poorest in kidneys derived from Maastricht category II donors and best in category IV with III in-between. However, after 3 months the function of kidneys from all donors is the same.

Adult↗

Combined simultaneous kidney/bone marrow transplantation.

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Adolescent↗

The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function.

BACKGROUND: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function. METHODS: We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels. The effect of different variables on the occurrence of delayed graft function (DGF) was analyzed by means of stepwise logistic regression. Improvement in kidney function during the first week after transplantation was compared between groups by means of Kaplan-Meier survival analysis. RESULTS: Intake of an ACE inhibitor or ATII blocker did not influence immediate posttransplantation graft function or the occurrence of DGF. Conversely, serum creatinine levels decreased significantly faster in patients administered an ACE inhibitor/ATII blocker than in those without therapy (P < 0.01). The only variables delaying graft function were number of previous transplantations, cold ischemia time, and male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy had significantly faster graft recovery (P < 0.001). CONCLUSION: Our results suggest that intake of an ACE inhibitor or ATII blocker during the immediate posttransplantation course is safe and does not impair graft function. Additionally, patients with DGF might profit from blockade of the renin-angiotensin-aldosterone system, which possibly shortens the time to graft recovery.

Angiotensin II↗

Impact of automated peritoneal dialysis on initial graft function after renal transplantation.

In this retrospective study, we evaluated the impact of automated peritoneal dialysis (APD) on initial graft function after cadaveric renal transplantation. Each patient on APD was matched for donor age, donor serum creatinine, and cold ischemia time with one control patient on HD. The study sample consisted of 67 cases and 67 controls. The rate of delayed graft function--defined as a need for dialysis within the first week following renal transplantation-was 16% in the APD group and 10% in the HD group [p = nonsignificant (NS)]. The proportion of patients with a creatinine clearance below 10 mL/min 6 days after renal transplantation was 7% in the APD group and 3% in the HD group. Of the 67 APD patients, 12 had slow graft function as compared with 13 of the 67 HD patients (p=NS). Weight changes 3 days after transplantation were +2.1% +/- 3.7% of dry weight in HD patients and -0.1% +/- 4.6% of dry weight in APD patients (p < 0.05). The total amount of fluid infused during the surgical procedure was similar in the two groups (55.8 +/- 14.3 mL/kg vs. 60.7 +/- 14.8 mL/kg). Compared with HD, APD was not associated with a lower rate of delayed graft function.

Adult↗

Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach.

BACKGROUND: Donor glomerulosclerosis, interstitial fibrosis, and fibrous intimal thickening correlate with graft outcome. We evaluate chronic lesions in donor biopsies according to Banff criteria and with a morphometric technique to ascertain their predictive value on graft outcome. METHODS: We evaluated 77 cadaveric donor biopsies according to Banff criteria. Glomerulosclerosis was expressed as the percentage of global sclerotic glomeruli. The following morphometric parameters were obtained: cortical interstitial volume fraction (Vvint/c), cortical glomerular volume fraction (Vvglom/c), mean glomerular volume (Vg), mean and maximal intimal arterial volume fraction (Vvintima/art), and Vvintima/art of the largest artery. We evaluated the correlation of histologic lesions with delayed graft function, 3 months' glomerular filtration rate (GFR), and death-censored graft survival. RESULTS: Multivariate logistic regression showed that delayed graft function was associated with cv score [relative risk (RR) 4.2 and 95% CI 1.1 to 16.0) and glomerulosclerosis (RR 1.06 and 95% CI 1.01 to 1.13). Stepwise regression showed that Vvint/c and glomerulosclerosis were independent predictors of 3 months' GFR (R= 0.62, P= 0.0001). Repeated analysis not considering morphometric parameters showed that glomerulosclerosis, cv score and ci score were independent predictors of 3 months' GFR (R= 0.64, P= 0.0001). A donor chronic damage score was generated considering glomerulosclerosis, cv score and ci score. This score after adjusting for clinical variables was associated with 3 months' GFR (R= 0.71, P < 0.0001) and death-censored graft survival (RR 2.2 and 95% CI 1.3 to 3.7). CONCLUSION: Combined evaluation of donor glomerulosclerosis, chronic vascular and interstitial damage according to Banff criteria allows a precise prediction of graft outcome. Morphometric evaluation of donor biopsies does not improve the predictive value of semiquantitative grading.

Adult↗

Recipient outcome following living donor kidney transplantation using kidneys procured laparoscopically.

BACKGROUND: Laparoscopic live donor nephrectomy is becoming increasingly popular as it has been shown to minimize donor morbidity, length of hospital stay and length of time to return to work. Initial experience suggested that kidneys procured laparoscopically had higher rates of delayed graft function and ureteric complications but with increasing experience, these complications have become less common. METHODS: Retrospective chart review of all patients who underwent living donor kidney transplant using kidneys procured laparoscopically at our centre was performed. From the initiation of the laparoscopic donor nephrectomy programme at our institution in November 1998 until February 2002, we performed 71 living donor kidney transplants (69 kidneys procured laparoscopically and two procured by open donor nephrectomy after failed laparoscopic approach). Donor left kidney was used in all except in one patient. Mean duration of warm ischaemia time was 206 +/- 79 s. RESULTS: The mean age of the recipients was 42 +/- 15 years (range 1-68) including five paediatric recipients (age < 18 years). There were 48 males and 23 females. Nine (13%) were retransplants (seven second transplants and one each of third and fourth transplants). Two patients died with functioning grafts and four patients lost the graft (three thrombosis, one anastomotic rupture). No patient developed ureteric complications. The incidence of delayed graft function (need for dialysis in the first week post-transplant) was 4%. Patient and graft survival rates (actual) were 97% and 91%, respectively. Mean length of hospital stay was 9 +/- 7 days (median 7 days). CONCLUSIONS: Recipient outcome is not compromised and excellent results can be achieved with living donor kidney transplantation using laparoscopically procured kidneys.

Adolescent↗

Early evolution of nutritional status and body composition after kidney transplantation.

BACKGROUND: Previous series have dealt with nutritional status after kidney transplantation. However, few studies have described the outcome of body composition after kidney transplantation. METHODS: A total of 44 cadaver kidney transplant recipients (28 men and 16 women) were followed prospectively during the first post-transplant year. Biochemical nutritional markers, dietary records, anthropometric measurements, and body composition were assessed at kidney transplantation and 3, 6, and 12 months later. RESULTS: By the end of the first year, serum albumin level was not significantly different from initial values. Prealbumin and retinol binding protein decreased from 42.3 +/- 10.2 mg/dL to 30.4 +/- 6.3 mg/dL and from 1.96 +/- 0.61 g/dL to 0.65 +/- 0.2 g/dL (P < 0.0001). Separating patients by gender showed that dietary caloric and protein intake increased in women only. At the end of the follow-up period, mean weight change was +5.4 kg in women (P = 0.009) and -0.9 kg in men (not significant). Body composition analyses showed that in women total fat and lean masses increased (+2.1 kg, P = 0.05, and +2.4 kg, P = 0.006), whereas in men total fat mass decreased (-1.4 kg, P = 0.04), and total lean mass tended to increase (+0.5 kg, not significant). Percentage change in total bone mass was +1.4% in women (not significant) and -2.1% in men (P = 0.05). In multivariate analyses, an independent impact of female gender on weight gain was observed, although increased fat mass was related only to energy intake. Increased total lean mass was related to low steroid doses and the absence of acute rejection and delayed graft function. Bone loss was related to male gender and high steroid doses. CONCLUSION: Changes in body composition during the first year after kidney transplantation are modulated by gender, energy intake, steroid doses, the occurrence of acute rejection, and delayed graft function.

Absorptiometry, Photon↗

Impact of laparoscopic donor nephrectomy on allograft function in pediatric renal transplant recipients: a single-center report.

Laparoscopic donor nephrectomy (LDN) is rapidly becoming the preferred technique for the procurement of living donor kidneys. An association of this technique with delayed graft function and higher risk for rejection has been reported in pediatric recipients. We reviewed our experience of 17 pediatric patients who received a living donor kidney, from 2002 to 2004, procured by LDN, and compared it with a matched group that received living donor kidneys harvested by the open technique. Patient demographics, etiology of renal failure, intra-operative events, length of stay, serum creatinine decline, and graft function were reviewed. Our experience confirmed the findings of earlier reports specifically in small pediatric recipients. The LDN group showed a significantly slower decline in creatinine in the immediate post-operative period and longer intra-operative time. However, there was no difference between the two groups in the length of hospital stay, and creatinine clearances at discharge, six, 12 and 24 months post-operatively. The incidence of acute rejection was similar in both groups. LDN is a safe procurement modality for pediatric patients. The risk for prolonged OR time and delay graft function has to be considered during the evaluation process.

Adolescent↗

[Reduction of the renal transplantation cold ischaemia time by the use of a timesheet].

OBJECTIVE: Reduction of the cold ischaemia time is one of the major objectives designed to improve the quality and cost of renal transplantation. Based on the experience of other centres, we report the impact of using a renal transplantation timesheet on the cold ischaemia time in our centre. MATERIAL AND METHOD: Since March 2004, we have used a renal transplantation timesheet with the collaboration of all personnel involved in transplantation (coordination, nephrologists, clinical pathologists). For each kidney harvested, the name of the personnel and the start and end times of their interventions were recorded. The authors report the results for the first 7 months. Cold ischaemia times and the incidence of delayed graft function were studied. RESULTS: 47 kidneys were harvested between 01/03/2004 and 30/9/2004 in our centre and 46 transplantations were performed. The mean cold ischaemia time was 14 h 51 min, i.e. a reduction of 8 hours 58 minutes compared to that observed in 2003 (23 h 50 min) (p < 0.01). Delayed graft function (DGF) was observed in 10/46 (21.74%) recipients. This DGF rate was significantly lower than that observed in 2003 (DGF 2003 = 30%), while the mean donor serum creatinine was higher (155 +/- 177 micromol/l vs 98 +/- 71 micromol/l in 2003, p < 0.05). The longest delays were those related to availability of an operating room (n=2: 10 h and 14 h). CONCLUSION: The use of a renal transplantation timesheet allowed a significant reduction of the cold ischaemia time and DGF rate. It requires the collaboration of all renal transplantation personnel and is an indicator of motivation. This timesheet allowed the correction of certain habits that can still be improved. These results should lead to an improvement of the results and cost of renal transplantation.

Creatinine↗

The OPTN/UNOS renal transplant registry.

This chapter summarizes analyses of 66,843 kidney-only transplants reported to the OPTN/UNOS Renal Transplant Registry between January 1999-December 2003. The 5- and projected 10-year graft survival rates for 28,260 recipients of living donor (LD) kidneys were 80.5% and 67.0%, respectively, based on a computed halflife of 17.8 years for those grafts that survived one year. Comparable results for 33,118 recipients of standard criteria deceased donor (SCD) and 5,943 recipients of expanded criteria deceased donor (ECD) kidneys were 68.8% and 50.9%, and 51.8% and 32.9%, respectively. The half-lives for SCD and ECD were 10.8 and 6.8 years, respectively. ECD kidneys (from donors aged 60+ or 51-59 with other risk factors) were preferentially transplanted to older patients (median age 58) even though there was no formal requirement to allocate these kidneys to older patients. The oldest recipients of deceased donor (DD) kidneys, 991 aged 71-75 and 254 over age 75 had 5-year graft survival rates of 48.9% and 40.7%, respectively and 40% of graft losses in these groups were due to death with a functioning graft. Among 469 LD kidney recipients over age 70, graft survival rates were 70% or higher with 40% of grafts lost due death with function. About 13% of DD and 5% of LD kidneys were transplanted to broadly sensitized patients during this period. One-fourth and one-fifth of broadly sensitized patients who were transplanted received an HLA-matched DD or LD kidney, respectively. Overall, the proportion of transplants to unsensitized patients has increased in recent years to more than 50% of DD and nearly 70% of LD kidneys. There was no apparent correlation between the sensitivity of crossmatch tests and graft survival of first or repeat DD transplants; however, use of the more sensitive flow cytometry and AHG enhanced crossmatches significantly reduced the incidence of early rejections. Mean cold ischemia times have declined by about 7 hours between 1991- 2003, but the reduction in average cold time has not produced any notable reduction in the incidence of delayed graft function for recipients of SCD or ECD kidneys. Histocompatibility laboratories that waited for donor spleen or lymph node cells to perform final crossmatches added an average of 3 hours of cold ischemia for the kidneys they tested compared with laboratories that performed the tests with peripheral blood lymphocytes. There was no net increase in delayed graft function (DGF) with SCD kidneys tested at labs using spleen or nodes but the incidence of DGF among ECD kidneys was 25% when the lab used PBLs and 35% when the lab used spleen or nodes.

Adolescent↗

Urinary interleukin-18 is a marker of human acute tubular necrosis.

BACKGROUND: Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. METHODS: IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. RESULTS: Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). CONCLUSION: IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

Adult↗

Factors associated with improvement in deceased donor renal allograft function in the 1990s.

The decade of the 1990s saw an improvement in cadaveric renal graft function and dramatic reduction in the acute rejection (AR) rate. The purpose of this study was to determine whether the reduction in rejection rate was the primary cause of the improvement in graft function seen and whether this improved long-term graft survival. All adult patients who received a cadaver renal transplant between 1991 and 2000 and had graft survival of at least 6 mo and complete data for creatinine at 6 mo, HLA mismatch, delayed graft function, and acute rejection (AR) were identified in the United Network for Organ Sharing database. A total of 40,164 cases that met the inclusion criteria were identified. The mean Modification of Diet in Renal Disease GFR at 6 mo improved from 49.94 ml/min per 1.73 m2 in 1991 to 54.59 ml/min per 1.73 m2 in 2000 (P < 0.001). The improvement in GFR was not gradual but occurred over a 4-yr period between 1994 and 1997, coinciding with the introduction of new immunosuppressive agents mycophenolate mofetil and tacrolimus into maintenance immunosuppression regimens. The improvement was seen in all subgroups of patients, even patients without clinical AR or delayed graft function. The magnitude of improvement in patients without clinical AR was similar to that seen in patients with AR. The drop in clinical AR rate accounted for a minority of the improvement in graft function in the 1990s. Other factors, such as reduced drug toxicity and improved control of subclinical rejection, seem to account for the majority of the improvement. This improvement in graft function at 6 mo did not translate into improved long-term graft survival, however.

Acute Disease↗

Long-term renal function in kidneys from non-heart-beating donors: A single-center experience.

BACKGROUND: Cadaveric kidneys from brain-stem-dead donors continue to be limited because the number of donors has reached a plateau. Wide recruitment of non-heart-beating donors (NHBD) could significantly increase the donor pool. NHBD renal transplants are underused because of the concern of poor quality graft function from such donors. In response to this perception, we reviewed 46 NHBD renal transplants performed in our center since 1998. METHODS: All NHBD kidneys were machine-perfused using the Newcastle continuous-hypothermic pulsatile preservation system before transplantation. A control heart-beating-donor (HBD) group was taken as the next consecutive HBD renal transplant to the NHBD transplant. The outcome and quality of function of the groups of renal transplants were analyzed for short-term and long-term performance. RESULTS: The renal transplant patients were matched for donor and recipient factors. Survival rates for allografts and patients were similar for 1 to 3 years. There was an increased incidence of delayed graft function in the NHBD renal transplants in the perioperative period. The creatinine clearance was 22.8+/-2.3 mL/minute for NHBD patients and 44.4+/-2.9 mL/minute for HBD patients at the time of discharge from hospital. This difference equalized after 3 months and the creatinine clearance for NHBD was 44.2+/-2.4 mL/minute and for HBD 49.2+/-3.4 mL/minute. CONCLUSIONS: Our results for NHBD renal transplants confirm that such grafts suffer primary warm ischemic injury, shown by the increased incidence of acute tubular necrosis and consequent delayed graft function. This produced poor renal function at the time of hospital discharge. After 3 months, the renal function of NHBD cases improved to the level seen in HBD patients.

Adult↗

Ten years of training community urologists and general surgeons to do cadaver kidney retrievals.

We trained 82 community hospital cadaver kidney retrieval teams during a 10-year period ending June 30, 1987. During the last 5 years of that period the concept of multiple organ retrieval was introduced into the training sessions and 429 cadaver kidney grafts were retrieved. Of those kidneys 292 were transplanted at our hospital, and the function of 220 cadaver kidney grafts retrieved by the community hospital teams was compared to that of 72 retrieved by the transplant center retrieval team. Of the cadaver kidney transplants 114 were from multiple organ donors. There was no significant difference in 1-month serum creatinine nadir of surviving grafts (2.1 +/- 1.8 versus 1.9 +/- 1.7 mg. per dl.), 6-month serum creatinine level (1.7 +/- 0.8 versus 1.6 +/- 0.6 mg. per dl.), 12-month serum creatinine level (1.8 +/- 0.9 versus 1.6 +/- 0.6 mg. per dl.) and 5-year actuarial graft survival (44.8 +/- 4.1 versus 52.4 +/- 7.5%), with the community hospital data presented first. The delayed graft function rate was significantly higher in the recipients of cadaver kidney grafts retrieved by community hospital teams (54 versus 35%), which was reduced by the in situ flush technique. There was no significant difference in delayed graft function rate (48 versus 40%) for the 114 cadaver kidney transplants retrieved from multiple organ donors by either community hospital or transplant center teams. With continuing education and quality control, community hospital retrieval teams can provide kidneys satisfactory for transplantation, even when working with multiple organ retrieval teams.

Actuarial Analysis↗

The clinical significance of conversion of complement-dependent cytotoxic T cell crossmatch test after renal transplantation.

The purpose of this study was to investigate the clinical relevance of conversion of post-transplant T cell crossmatch between kidney donor and recipient. This study comprises 892 cadaveric renal transplantations performed on 874 adult patients between August 1991 and December 1997. Recipient selection was based on a negative complement-dependent cytotoxic T cell crossmatch test with current (< or = 2 months old) serum. For this study, on day 0 and day 14 after transplantation, serum samples were collected for later crossmatching. On day 14 after transplantation, the crossmatch had converted to positive in 76 transplantations (8.5%). Acute rejection occurred in 50% of the converters and 22% of the non-converters (P < 0.005), and graft survival was significantly poorer (P < 0.025), being 85 vs 94% at 1 and 68 vs 83% at 5 years, respectively. In patients with delayed graft function, 1-year graft survival was 77% in the converters and 91% in the non-converters (P < 0.05). Conversion of T cell crossmatch, especially in connection with delayed graft function, identifies a subgroup of patients at high risk of severe rejection and poor graft survival.

Acute Disease↗

Ascorbic acid against reperfusion injury in human renal transplantation.

The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion. Both these mechanisms are known to cause cell damage, which may impair graft function. Reperfusion injury (RPI) is mediated by reactive oxygen species (ROS). Ascorbic acid (AA) is a potent physiological extracellular scavenger of ROS. We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI. From every donor, the contralateral kidney served as a control. The control grafts were perfused with the same perfusion as those of the AA group, only without the AA substitution. We assessed the effect of AA by recording serum creatinine, creatinine clearance, initial graft function and early rejections. The incidence of delayed graft function (DGF) was 32% in the AA group, and 29% in the control group. Other parameters were also similar in both groups, except for the length of DGF, which showed a trend towards a shorter duration in the AA group. The pre-operative systemic AA concentration was significantly ( P=0.01) lower in the haemodialysis patients than in those on peritoneal dialysis. In conclusion, this clinical study could not demonstrate significant benefits of AA in renal transplantation.

Aged↗

Two doses of daclizumab with delayed introduction of low-dose tacrolimus in elderly recipients of cadaveric renal transplants from donors >55 years of age.

BACKGROUND: Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients. METHODS: This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months. RESULTS: Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection. CONCLUSIONS: Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

Aged↗