PubMed HealthSearch

SEARCH · PubMed Health

Results for “delayed graft function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

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

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

Adult

A case study with delayed renal graft function as a consequence of severe secondary hyperparathyroidism.

A 36-year-old Arab man had been treated with hemodialysis for 6 years. During that time he received no treatment with phosphate binders or 1,25-dihydroxy-vitamin D3. He thus developed a severe form of secondary hyperparathyroidism and presented with bone disease, pseudoclubbing of the fingers, and soft-tissue calcification. He was transplanted with a kidney from a living donor, but there was no immediate onset in renal function. A biopsy showed crystal deposition that was thought to be due to his secondary hyperparathyroidism. Four weeks after the renal transplantation with still no evidence of a functioning graft, a parathyroidectomy was performed. A few days later, graft function recovered, and the amount of the crystals in the kidney decreased. There is strong evidence that the severe secondary hyperparathyroidism prevented the onset of renal function. It is concluded that crystal deposition with graft dysfunction should be an absolute indication for parathyroidectomy.

Adult

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era.

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.

Blood Group Incompatibility

Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.

We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.

Antilymphocyte Serum

Renal transplantation: current status, complications and prevention.

Renal transplantation is the ideal mode of renal replacement therapy. One-, 5- and 10-year graft survival rates are currently > 85%, 60-70% and 40-50%, respectively. Graft loss in the first year is predominantly due to vascular complications, acute rejection, and death with a functioning graft. Other significant causes of early graft dysfunction are urological complications, delayed graft function and drug-induced nephrotoxicity. Subsequently, graft loss is due to chronic rejection or death with a functioning graft secondary to cardiovascular disease, malignancy and infection. Renal artery stenosis, chronic cyclosporin nephrotoxicity and recurrent disease also contribute to late graft dysfunction. The immunosuppressed renal transplant recipient is at long term risk of infection and neoplasia.

Animals

Risk factors for second renal allografts immunosuppressed with cyclosporine.

Second renal allograft survival rates are lower than those of primary allografts. For recipients immunosuppressed with azathioprine, prednisone, and Minnesota ALG (conventional immunosuppression), risk factors associated with decreased second graft survival have been identified: age greater than 40, cadaver donor, less than 6 months between primary graft loss and retransplantation, duration of primary graft function (6 months or 1 year, depending on the study), high peak panel-reactive antibody, number of human leukocyte antigen mismatches, and delayed graft function. In this study, we used a multivariate analysis to identify risk factors associated with decreased second graft survival in patients who did or did not receive cyclosporine. Results were compared with primary graft survival rates. Risk factors for patients receiving conventional immunosuppression were: (a) primary graft loss caused by rejection greater than or equal to 6 months (P = 0.01 vs. either rejection less than 6 months or nonimmunologic loss); (b) cadaver donor (P = 0.005 vs. living related); and (c) interval between primary graft loss and retransplantation of greater than or equal to 6 months (P = 0.05 vs. less than 6 months). For CsA, risk factors that most decreased second graft survival were: (a) primary graft loss caused by rejection less than 6 months (P = 0.11 vs. nonimmunologic loss); (b) conventional immunosuppression for the primary graft (P = 0.08 vs. CsA immunosuppression); and (c) a peak PRA of greater than or equal to 21 (P = 0.14 vs. peak PRA of 1-20). For second graft recipients immunosuppressed with CsA, primary graft loss to either rejection greater than 6 months posttransplant or nonimmunologic causes was not a risk factor for second graft survival. These data extend the recent reports of other investigators by identifying risk factors for retransplant recipients treated with CsA and by demonstrating that subgroups of patients in the retransplant population can be retransplanted without additional risk (i.e., their second graft survival rates are similar to primary graft survival rates). This may become more important if, in the future, organ distribution is based on graft survival data. If so, our data would support retransplantation in patients who are immunosuppressed with CsA, especially those who lost their primary graft to either rejection greater than or equal to 6 months posttransplant or nonimmunologic causes; who receive living related grafts; and who have a peak PRA of 1-20.

Adult

Nonheart-beating donors: the Maastricht experience.

The growing gap between the number of organs available for transplantation and patients on waiting lists demands additional donor sources. Nonheart-beating (NHB)-donor programs are known to increase the number of kidneys available. The group of potential NHB donors is very diverse and therefore 4 categories have been identified. At the University Hospital Maastricht, a NHB-donor program was implemented in 1980 to harvest kidneys after an in situ perfusion technique. In order to evaluate the function of kidney grafts from NHB donors, a retrospective multicenter study on the NHB-donor kidneys transplanted until 1992 was performed, using a control group of kidneys from heart-beating (HB) donors. The short-term results showed more delayed function (DF) in the NHB-donor group accompanied by higher serum creatinine levels at one-month posttransplant. The long-term outcome, however, was equal in both groups showing similar graft and patient survival rates up to 5 years. Apart from the type of donor, HB or NHB, only the number of HLA-DR mismatches could be identified as a potential risk factor for delayed graft function. NHB donors contribute considerably to reducing the gap between offer and demand in kidney transplantation and transplant centers should include NHB donors in their procurement programs. Meanwhile, efforts should be made to improve the short-term posttransplant graft function. Together with reducing DF, searching for valuable tools in viability assessment should also be an objective. Past viability tests never found broad clinical use but might be important in the optimal and safe usage of the potential NHB donor pool.

Adolescent

Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3.

The antiglobulin crossmatch (AGXM) is a sensitive technique employed by many transplant centers to enhance detection of preformed antibody to donor antigens that may cause hyperacute rejection. However, positive AGXM may detect irrelevant or very low titers of anti-HLA antibody precluding transplantation in suitable recipients. To investigate the significance of a positive AGXM, cadaveric renal transplantation was carried out despite a weakly positive AGXM (defined as cell killing above background but not greater than 20%) in 48 recipients. In an initial group (n = 10), maintained on triple therapy (cyclosporine, azathioprine, and prednisone), accelerated acute rejection occurred in 4 recipients and 3 grafts were lost. A subsequent group (n = 38) was treated with a prophylactic course of OKT3 then triple therapy. There were no episodes of accelerated acute rejection (P less than 0.01) although clinical hyperacute rejection claimed one graft and the incidence of delayed graft function was high (75%). The prophylactic OKT3 group had a reduced incidence of acute rejection (0.5 versus 1.0) per recipient and the onset of first episodes was delayed (mean onset: 13 versus 35 days after transplantation). One year actuarial primary graft survival was 88% in the prophylactic OKT3 group as compared with only 50% in the initial group. The outcome in the positive AGXM group was similar to a concurrent group (n = 32) with a negative AGXM and immediate graft function. On the other hand, the subset of positive AGXM regraft recipients treated with prophylactic OKT3 fared poorly, with a 36% (4/11) incidence of primary nonfunction. In summary, a positive AGXM, as defined in this report, is not a contraindication to primary renal transplantation--in fact, the use of the AGXM will identify recipients that would benefit from prophylactic OKT3.

Adult

The use of "marginal" donors for organ transplantation. The influence of donor age on outcome.

The influence of donor age on outcome was studied in the recipients of 12,131 cadaveric renal allografts, 3026 heart allografts, and 2913 liver allografts with followup information in the UNOS data base for transplants performed between 10/1/87 and 12/31/89. For recipients of kidney transplants, donors of ages 6-15 had significantly better 1-year graft survival than donors of ages 56-65, but the difference was only 7.0%. Donors of age greater than 65 actually did better than donors ages 56-65, but donors less than or equal to 5 were less satisfactory. Kidneys from older donors survived as well as kidneys from younger donors in patients with repeat transplants, diabetes, black race, age over 45, O HLA or 5 and 6 HLA matches, delayed graft function, shared kidneys and PRA greater than 50. For kidney recipients, multifactorial analysis by Cox regression showed that donor age was less important than the use of ALG, donor race, diabetes or peak PRA in ages 16-45, delayed function, repeat transplant, and HLA match. Recipients of heart transplants from donors ages 45-55 had 1-year graft survival that was 8.4% less than recipients of hearts from donors age 16-45. However, 32.7% of heart patients died during the first 12 months after listing without benefit of a transplant. Liver transplant recipients of donor ages 16-45 had 10.8% better 1-year graft survival than recipients of donors greater than 45, but a greater percentage of older donors were transplanted to high risk and older recipients. Tragically, 24.3% of patients listed for liver transplantation died within 12 months without a transplant. This analysis shows that satisfactory graft survival can be achieved using older donors and that age in itself should not be a barrier to organ donation, providing that organ function is normal and that specific disease of the organ is absent.

Adolescent

Assessment of plasma neopterin in clinical kidney transplantation.

Serial plasma samples of 172 kidney transplant recipients and 42 chronic dialysis patients were evaluated retrospectively in a radioimmunoassay to determine the clinical relevance of plasma neopterin levels. Dialysis patients had a higher neopterin level 196 +/- 82 nmol/L (mean +/- SD) than 70 healthy controls (7 +/- 4 nmol/L). In 45 patients with a completely uneventful postoperative course, elevated pretransplant neopterin levels dropped rapidly within a week to a mean of 30 nmol/L and remained stable thereafter. In 22 outpatients with stable graft function there was a highly significant correlation between 170 paired serum creatinine and plasma neopterin values (r = 0.94). A group of 13 patients had experienced delayed graft function (ATN) without rejection. Their one-week mean neopterin level was 100 nmol/L and continued to drop in parallel with the serum creatinine. Another 15 patients rejected their kidneys irreversibly within 3 weeks-6 of them had extremely high neopterin levels during the rejection process (range 500-1000 nmol/L) that were not seen in other patients. A total of 169 rejection episodes in 43 patients were treated with bolus-dose cortisone. On the day of bolus therapy, both serum creatinine (P less than 0.002) and neopterin (P less than 0.005) were elevated. At 24 hours prior to bolus cortisone therapy, creatinine levels were not significantly elevated, whereas there was a significant rise in plasma neopterin (P less than 0.01). The overall sensitivity of neopterin increase was 86% with a 17% probability of false positives, and the sensitivity was 95% in biopsy-proved rejections. Plasma neopterin appears to be a useful marker for early detection of rejection and for identifying severe rejections that are not responsive to treatment.

Biopterins

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

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

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

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

Plasma fibronectin levels during acute rejection and acute tubular necrosis in renal transplant patients.

Fibronectin (Fn), an acute phase glycoprotein synthesized by the liver, has an important immunomodulatory role. We have investigated the changes in plasma Fn in patients after renal transplantation in order to determine whether these changes predict graft injury or rejection episodes. Besides normal healthy controls, healthy pregnant controls, and a trauma control group, we used two groups of chronic renal failure patients as controls: group I, patients with end-stage renal failure (ESRF) on peritoneal dialysis; group II, patients with ESRF on hemodialysis. These were compared with two groups of renal transplant patients: group III, patients 3 months after successful renal transplantation; group IV, patients studied sequentially 10 days immediately posttransplantation. The renal transplant patients were treated with low-dose cyclosporine, azathioprine, and steroids. Citrated plasma samples were collected for Fn assay by a sandwich-type ELISA and for SDS-PAGE analysis and Western blotting. The mean plasma Fn levels were as follows: healthy controls 311.6 SEM, 13.5 micrograms/ml; healthy pregnant controls 357 SEM, 5.9 micrograms/ml; trauma controls 262.3 SEM 31.7, micrograms/ml; group I 169 SEM, 25.1 micrograms/ml; group II 199 SEM, 27.2 micrograms/ml; group III 272 SEM, 21.7 micrograms/ml; group IV 212 SEM, 27.4 micrograms/ml (day 3 postop). There was a significant difference in the plasma Fn levels on day 3 posttransplant between the patients with delayed and immediate renal function (P less than 0.03) (group IV). A significant decrease in plasma Fn levels occurred immediately after steroid therapy was stopped (P less than 0.03) in patients treated for acute rejection. Plasma Fn levels were significantly decreased in the presence of delayed graft function but did not predict rejection.

Fibronectins

Preoperative hospitalization to hydrate living kidney donors can be omitted without sacrificing graft function.

This prospective study was done to determine whether preoperative hospitalization for hydration of living kidney donors could be omitted without sacrificing graft function in the recipient. The study group consisted of 36 consecutive kidney donors who underwent donation on a "to come in" basis. Fluid management consisted of 1 l. lactated ringer's solution per hour beginning 2 hours preoperatively. The control group was hospitalized preoperatively for intravenous hydration of an equivalent amount of saline solution given for 12 to 16 hours. No recipient of the study group donors experienced delayed graft function. Furthermore, in that group immediate and longer term graft function, as defined by immediate graft output, serum creatinine on postoperative day 1 and nadir serum creatinine levels, was equivalent to or better than that in the control group. We conclude that a rapid infusion of saline solution in the immediate preoperative period can replace overnight intravenous hydration of living kidney donors, and that the result will be a significant reduction in overall hospital stay for the donor without compromise in graft function for the recipient.

Adult

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.

Adult

Autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens in renal allograft rejection.

Autoantibodies (AA) detected by indirect immunofluorescence on HEp-2 cells and lymphocyte panel reactive antibodies (PRA) were measured pretransplant and within 2 weeks after transplant nephrectomy in a group of 21 consecutive renal allograft recipients with irreversible graft rejection. No patient had clinical evidence or history of autoimmune disease. Although 43% of patients had AA and 29% had a positive PRA pretransplant, 90% had AA and 100% had a positive PRA post-transplant nephrectomy (P less than 0.0032, 0.00001, respectively). Analysis of AA detected following graft failure revealed that all were of IgG class, and more than half the patients had multiple patterns including speckled nuclear, cytoplasmic, perinuclear, mitotic spindle apparatus, and smooth muscle staining. Of 11 patients retested up to one year later, all showed a persistence of previously detected AA in both pattern and titer, although none of the patients had any other signs or symptoms of autoimmune disease. A control group of 21 transplant recipients with functioning grafts was similarly tested revealing that 35% had AA and 29% had positive PRA pretransplant, but only 14% had AA and 14% positive PRA posttransplant. The presence of post-transplant AA or PRA was not associated with antecedent delayed graft function (ATN), rejection episodes, treatment with antithymocyte globulin, the interval posttransplantation, or subsequent graft outcome. However, pretransplant AA and PRA in both groups were associated with prior graft loss, but not with other variables examined. These findings indicate that serologically detectable sensitization to lymphocyte (HLA) antigens and the presence of persistent, multiple autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens is a frequent occurrence following graft loss. Furthermore, the development of AA following graft rejection appears to be unrelated to the prior presence or subsequent development of clinical autoimmune disease.

Adolescent