Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group

BACKGROUND: Delayed graft function (DGF) remains an important complication in renal transplantation. In this multicenter study, we investigated the influence of donor and recipient factors on the occurrence of DGF and DGF's effect on long-term graft survival. METHODS: A total of 547 transplanted kidney allografts, retrieved from multi-organ donors, were analyzed, and results were compared with literature on kidney-only donors. RESULTS: Median follow-up of patients without graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF. In univariate analysis, the following factors significantly increased the incidence of DGF: (a) among the donor factors, mean creatinine level >120 micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient factors, previous transplant(s), no intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or oliguria. After stepwise logistic regression, donor age, CIT, recipient's number of previous transplants, and intraoperative diuresis proved to be of independent prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%, and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In case of DGF, graft survival was approximately 10% lower when compared with cases with immediate graft function (P<0.001). No difference in incidence of DGF was found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS: DGF results in an approximately 10% higher rate of graft failure. DGF incidence can be reduced by the administration of mannitol during transplantation, which minimizes CIT and optimizes donor management. Grafts from multi-organ donors and kidney-only donors appear to be of equal quality.     

Automated information system for controlling the sociopsychological adaptation of junior grade schoolchildren during learning activities

Acute graft rejection and delayed function are considered to be the major risk factors of short-term as well as long-term graft survival. We studied the impact of these factors on graft outcome among 109 renal transplant recipients. All recipients were treated with triple drug protocol. The recipients were divided into two groups: I group included 57 patients with delayed graft function (DGF), II group included 52 patients with immediate graft function (IGF). We studied graft survival, incidence of acute rejection, serum creatinine levels and the cause of graft loss for patients in both groups. Acute rejection episodes occurred in 49% of patients from DGF group and 45% of patients from IGF group. Graft survival in IGF group was better than in DGF group. Actuarial graft survival at 1, 2, 3 and 4 years in examined groups was 84%, 82%, 72%, 65% vs. 92%, 86%, 84%, 84%, respectively. One-year graft survival in patients with acute rejection from DGF group and IGF group was significantly lower than in patients who remained rejection free (69%, 74% vs. 94%, 96%). We concluded that delayed graft function decreases long-term graft survival, while immediate graft function has an excellent impact on graft outcome. Acute graft rejection is the strongest risk factor of graft loss.     

Transplantation of pediatric en bloc cadaver kidneys into adult recipients

BACKGROUND: To maximize the renal donor pool, cadaveric pediatric en bloc kidneys have been transplanted as a dual unit by some transplant centers. We compared the short- and long-term outcomes of adult recipients of cadaveric pediatric en bloc renal transplants versus those of matched recipients of cadaveric adult kidneys. METHODS: Thirty-three adults who received pediatric en bloc kidney transplants between April 1990 and September 1997 were retrospectively identified and were compared with 33 matched adults who received adult cadaveric kidney transplants. The groups were identical for transplantation era, immunosuppression, recipient sex, race, cause of renal failure, mean weight, and follow-up duration (37.8 vs. 37.5 months). The mean recipient age study versus control was lower (36.3 vs. 48.9 years, P=0.0003). Results. There was no difference between the en bloc and adult donor groups in the 3-year patient survival rates (95% vs. 87%, P=0.16) or the 3-year graft survival rates (87.3% vs. 84.2%, P=0.35). Further, there was no difference in en bloc patient or en bloc graft survival time stratified by recipient age (14-44 vs. >45 years, P=0.11), en bloc donor age (<24 vs. >24 months, P=0.39), or recipient weight (<60, 61-75, >75 kg; P=0.60). Differences in serum creatinine (mg/dl) for the en bloc versus the control group at the time of discharge (3.0 vs. 7.8 mg/dl, P=0.06), at 1 year (1.4 vs. 2.0 mg/dl, P=0.06), and at 2 years (1.1 vs. 1.6 mg/dl, P=0.14) had dissipated by the time of the 5-year follow-up examination (1.1 vs. 1.6 mg/dl, P=0.14). Vascular complications were more prevalent in the en bloc group: renal vein thrombosis (one case), thrombosis of donor aorta (two cases), arterial thrombosis of one renal moiety (two cases), and renal artery stenosis (two cases). There were no differences between groups in delayed graft function, acute or chronic rejection, posttransplant hypertension, posttransplant protein-uria, or long-term graft function. CONCLUSIONS: Collectively, these data indicate that transplanting pediatric en bloc kidneys into adult recipients results in equivalent patient and graft survival compared with adult cadaveric kidneys. Further, the data also suggest that pediatric en bloc kidneys need not be strictly allocated based on recipient weight or age criteria.     

Primary immunosuppression with mycophenolate mofetil and antithymocyte globulin for kidney transplant recipients of a suboptimal graft

BACKGROUND: In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immunosuppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function. METHODS: Patients with preformed reactive antibodies < 500% receiving a first graft from a suboptimal donor (age > or = 40 years, non-heart-beating, acute renal failure, arterial hypertension) or at risk of delayed graft function (cold ischaemia time > or = 24 h) were eligible for this open single-arm pilot trial. From September 1996 to March 1997 we recruited 17 patients. They were treated with MMF 2 g p.o. preoperatively, and after transplantation at 3 g/day; rabbit ATG i.v. at 2 mg/kg preoperatively, and 1.5 mg/kg/day the first day after transplantation, followed by four doses of 1 mg/kg on alternate days; prednisone was given at 0.25 mg/kg/day and reduced progressively to 0.1 mg/kg/day at 3 months. Primary outcomes were incidence of biopsy-proven acute rejection, delayed graft function, opportunistic infections, graft and patient survival, and the need for introduction of CsA treatment. RESULTS: delayed graft function occurred in two cases (12%). Four of 17 patients (24%) had a biopsy-proven acute rejection (2 grade I and 2 grade II) within the first 3 months after transplantation. CsA was added in two cases with grade II biopsy-proven acute rejection, and in one with grade I biopsy-proven acute rejection. In one patient MMF was replaced by CsA because of gastrointestinal intolerance. Mean serum creatinine 6 months after transplantation was 159+/-59 micromol/1. Cytomegalovirus tissue invasive disease occurred in one patient (6%). At 6 months follow-up all patients are alive with functioning allografts. CONCLUSIONS: These preliminary results suggest that in low-immunological-risk patients who receive a suboptimal renal allograft or at risk of delayed graft function, the combination of MMF, ATG, and steroids is an efficient immunosuppressive regime that may avoid the use of CsA in 70% of the recipients.     

Determinants of graft survival after renal transplantation

We studied multiple determinants of graft survival at a single center and the effects of nonimmunologic graft loss on transplant survival. This retrospective study examined the results of 589 cadaver donor transplants performed between 1986 and 1992. Graft survival rates were calculated using Kaplan-Meier estimates for both overall graft survival (all causes of graft loss) and immunologic graft survival (function lost due to acute or chronic rejection and noncompliance). Cadaver graft survival was significantly poorer with an increasing degree of DR mismatch (P=0.02). An analysis of pretransplant variables showed graft loss risk was highest with greater DR mismatches, two B-antigen mismatch, higher donor serum creatinine, and younger recipient age. After transplantation, acute rejection was the most significant factor associated with long-term graft survival. Our data demonstrate a significant advantage for zero DR and one DR mismatch cadaver donor transplants, with excellent immunologic graft survival. This study suggests that a combination of immediate graft function, prevention of acute rejection by appropriate early immunosuppressive therapy, and acceptable DR match enhances cadaveric graft survival.     

Acute intracranial complications of temporal bone trauma

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.     

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.     

Abnormal nocturnal blood pressure fall in normotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement

BACKGROUND: A single-center study of 655 nonsensitized recipients of primary cadaveric kidney grafts is presented. RESULTS: Graft survival in serologically HLA-DR 1-10 antigen-matched grafts to nonsensitized recipients at 1 year was 90%, compared with 82% (P=0.004) and 73% (P=0.001) in one and two DR antigen-mismatched grafts. The corresponding figures at 5 years were 76%, 62%, and 56%, respectively. Matching for the DR antigens 11-14, or for some DR alleles only detectable by genomic typing, further improved graft survival, but the differences did not reach statistical significance. Matching also for the serologically defined HLA-A and -B antigens did not significantly further improve overall graft survival, but some effects for grafts surviving at least 1 year were observed. Among recipients of grafts mismatched for zero, one, or two HLA-DR antigens, acute rejection episodes were experienced in 48%, 64% (P<0.001), and 82% (P<0.001), respectively, within the first 3 months. HLA-A and -B mismatches showed no significant correlation to acute rejection episodes. CONCLUSION: Matching for the DR antigens 1-10 significantly secures and prolongs the survival of first cadaveric renal grafts. Our results also show that DR 1-10 antigen-matched combinations can often be obtained even in rather small recipient pools, when actively sought for.     

The great success of Asian kidney transplant recipients

BACKGROUND: Little has been written about allograft survival in non-African-American minority groups. We examine the success of kidney transplantation in 1900 Asian recipients. METHODS: Data from 42,252 cadaveric and 16,115 live donor kidney transplant recipients were monitored from the United Network for Organ Sharing Scientific Renal Transplant Registry from 1991 through 1996. RESULTS: Asian recipients exhibited the highest cadaveric allograft survival rates (89% 1-year and 83% 3-year survival) and the longest mean allograft half-life (18 years). Asian women had the highest mean graft half-life (23 years). Asians were less likely to be broadly sensitized and had a high incidence of IgA nephropathy causing end-stage renal disease. Although it has been suggested that their low body weights may help explain the excellent allograft outcome, Asians exhibited superior graft survival rates even when compared with low body weight recipients of other races. CONCLUSION: Asian renal allograft recipients, particularly Asian females, have the highest allograft survival rates of all racial groups.     

A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group

BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. METHODS: A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. RESULTS: One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. CONCLUSIONS: Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.     

Pretransplantation immunoadsorption therapy in patients immunized with human lymphocyte antigen: effect of treatment and three years' clinical follow-up of grafts

Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post-transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation.     

Living unrelated renal donation: the University of Wisconsin experience

BACKGROUND: Living unrelated renal donation (LURD) has the potential to reduce the current waiting list significantly for kidney transplantation. The purpose of this study was to examine the long-term results of 150 LURDs performed at our center during a 16-year period. METHODS: From Dec 23, 1981, to Feb 13, 1998, 150 LURDs, 219 human leukocyte antigen (HLA)-identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates between groups were compared. RESULTS: Fourteen surgical complications including lymphocele (n = 7), ureteral stricture (n = 4), and ureteral leak (n = 3) were seen. Seventy-eight patients (52%) had 123 rejection episodes and 66 patients (44%) had 1 or more infections. Thirty-six allografts were lost and 25 deaths occurred. Patient survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaveric transplant procedures were 86%, 82%, 63%, and 64%, respectively. Allograft survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. CONCLUSIONS: Long-term LURD allograft survival rates are lower than those for HLA-identical but equivalent to those of haploidentical and better than those of cadaveric kidney transplantations. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.     

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

Improving results of pediatric renal transplantation

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.     

Factors related to the donor organ are major determinants of renal allograft function and survival

In this study, we analyzed the relative impact of donor and recipient variables on cadaveric renal allograft function and survival. The unique feature of the study population is that each pair of recipients received their allografts from a single donor. The study includes 378 adult patients. In 129 pairs both recipients were Caucasian, and in 60 pairs one recipient was Caucasian and the other was African-American. All transplants were done in one center, thus minimizing differences in preservation time and providing uniform posttransplant management. The initial analysis showed a relationship between the function of the allograft 6 months after transplantation (serum creatinine [SCr]6 mo) and donor variables (P = 0.0004, analysis of variance). Furthermore, it was calculated that 64% of the variability in the SCr 6mo among patients was due to donor factors and 36% was due to recipient factors. An elevated SCr 6 mo was significantly associated with older donors, male recipients, and patients with acute rejection episodes. Furthermore, other unidentified donor factors may have an impact on allograft function. Reflecting the importance of donor factors, there was a significant relationship between SCr 6mo in paired recipients (P < 0.0008 by Spearman). Analysis of racially dissimilar pairs showed that the SCr 6mo and graft survival 6 months after transplantation were not significantly different between Caucasians and African-Americans. However, beyond 6 months, graft survival was worse in African-Americans (P < 0.0001 by Cox). Compared with Caucasians, graft survival was significantly worse in African-Americans with poorly controlled blood pressure (mean arterial pressure > 105 mmHg) (P = 0.002, Cox), but not in those patients with mean arterial pressure < 105 mmHg. In conclusion, donor factors are major determinants of renal allograft function. However, those factors may not be easily identifiable or quantifiable. Donor factors do not contribute to racial differences in allograft survival. However, poorly controlled hypertension correlates with poor renal graft survival in African-Americans.     

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.     

Renal transplantation in children less than two years old

Twenty-one infants, 2 years old or younger, received 21 renal transplants between 1983 and 1995. Six of the transplantations were performed from 1983 to 1989, and the remaining 15 were performed from 1990 to 1995. The median age at transplantation was 16.0 months and the median body weight was 9.0 kg. Living-related donor kidneys were used in 15 cases, an adult cadaveric donor kidney was used in one case, and pediatric cadaveric donor kidneys were used in five cases. All grafts were placed intra-abdominally. The immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisolone. No prophylactic antithymocyte globulins were used. Five infants have died, one with a functioning graft and four after loss of graft function. All graft losses and deaths occurred during the first 6 months after transplantation. The 5-year patient survival and graft survival rates were 87% for recipients of living donor grafts and 44% for recipients of cadaveric grafts. The median height SD score increased from -3.7 before operation to -1.9 at 1 year, -0.7 at 3 years, and -1.1 at 5 years. The glomerular filtration rate in absolute values remained stable in all infants, whereas a reduction in glomerular filtration rate related to body surface area was seen at follow-up, 5 years after transplantation. We conclude that renal transplantation can be performed with good long-term results in children less than 2 years old.     

Determinants of late allograft nephrectomy

When loss of graft function occurs more than six months after transplantation, allograft nephrectomy is not routinely performed at the time of graft failure. It is usually performed only on those patients who subsequently develop specific complications. However, little is known about the characteristics that make patients more likely to require allograft nephrectomy. The purpose of our study was to identify risk factors for the subsequent need for allograft nephrectomy in patients with graft failure occurring more than 6 months after transplantation. Forty-one patients were studied. Inclusion criteria were: loss of graft function > or = 6 months after transplantation, resumption of dialysis and initiation of weaning from immunosuppression. Thirty patients were treated with cyclosporine + prednisone +/- azathioprine and 11 with azathioprine + prednisone. Mean follow-up time was 17.8 months, ranging from 6 months to 6.1 years. Recipient age, sex and race, original renal disease, donor, donor source (cadaveric vs living related), HLA compatibility, levels of panel reactive antibodies, occurrence of initial delayed graft function, causes of graft failure and tapering of immunosuppression were similar in patients with and without allograft nephrectomy. Using univariate analysis, allograft nephrectomy was found to be significantly more frequent in patients with a history of 2 or more episodes of acute rejection than in patients with no rejection episode: 83% vs 30% (p = 0.03). In addition, allograft nephrectomy was found to be significantly more frequent if the immunosuppressive regimen included cyclosporine (62% vs 27.3%; p = 0.04). Using multivariate analysis however, the number of previous episodes of rejection was found to be the only significant predictor for allograft nephrectomy. None of the other variables considered in the multivariate analysis, including the type of immunosuppressive therapy, was identified as a significant predictor for the need to perform allograft nephrectomy. In summary, the need for late allograft nephrectomy was correlated with the number of previous episodes of acute rejection. Patients with a history of numerous rejection episodes should thus be considered more likely to require allograft nephrectomy once immunosuppression is withdrawn. Possible interventions to reduce or prevent the need for nephrectomy include more gradual tapering of immunosuppression at the time of graft failure or indefinite low-dose immunosuppressive therapy.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Increase in Ca(2+)-permeability of the plasma membrane during radiation-induced apoptosis of thymocytes]

BACKGROUND: We previously reported excellent outcome at 6 months after transplantation in recipients of expanded criteria donor kidneys that other local centers had declined, kidneys that nobody wanted (KNW), versus controls. We now report follow-up after 23 months. METHODS: We retrospectively reviewed 27 donor and 24 recipient characteristics in 126 adult recipients of transplants from January 1, 1995, to November 25, 1996. RESULTS: Donors of control kidneys versus KNW were younger and had significantly higher minimum 4-hr urine output. Recipients of control kidneys versus KNW had significantly more HLA matches and lower 3-month posttransplant serum creatinine levels. Patient and graft survival rates were similar between the control kidneys versus the KNW. We also compared the control kidneys and KNW with regard to prompt function or delayed graft function and satisfactory versus unsatisfactory function (unsatisfactory: serum creatinine > or =2.5 ml/dl or graft loss at 6 months) to identify donor and recipient characteristics associated with delayed graft function and unsatisfactory outcome. The incidence of rejection was significantly lower in control kidneys and KNW with satisfactory function versus control kidneys and KNW with unsatisfactory function. CONCLUSIONS: These data demonstrate: (1) similar graft survival at 12 months, (2) lower donor age, (3) higher minimum 4-hr urine output, and (4) more HLA matches in recipients of control kidneys versus KNW. Optimal outcome was achieved in recipients of control kidneys and KNW with prompt function and satisfactory function based upon serum creatinine in the first 6 months and in recipients with lower rates of rejection. Although outcome is dependent upon many donor and recipient variables, we believe that with careful donor and recipient selection, excellent outcome can be achieved using expanded criteria donor kidneys.