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PubMed1997

Clinical correlates to chronic renal allograft rejection.

Chronic rejection is a clinical syndrome characterized by a progressive decline in renal allograft function and nonspecific histologic findings of interstitial fibrosis, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries. Most late allograft failure that is not due to death with a functioning allograft is caused by chronic rejection. Although the pathogenesis and treatment of chronic rejection are unknown, a number of epidemiological studies have examined clinical correlates for possible clues to its pathogenesis. Clinical correlates for chronic renal allograft rejection can be classified in two broad categories: immune (alloantigen-dependent) and non-immune (alloantigen-independent). The strongest evidence that chronic rejection is immune mediated comes from its association with acute rejection and the degree of histocompatibility mismatching. However, not all acute rejection leads to chronic rejection, and there is little evidence that newer immunosuppression regimens which effectively prevent acute rejection have reduced the incidence and severity of chronic rejection. Therefore, many clinical investigators have also looked for potential non-immune causes of chronic rejection. Putative non-immune risk factors include donor source (living-related vs. cadaveric), cold ischemia time, delayed graft function, size mismatching, donor age, donor and recipient gender, recipient race, hyperlipidemia, and hypertension. Although there is little evidence supporting a cause and effect relationship between any immune or non-immune risk factor and chronic rejection, these clinical associations suggest a number of potentially important areas for further study.

Chronic Disease↗

PubMed2005

Chronic kidney disease in renal transplant recipients.

UNLABELLED: The aim of the present study was to investigate the utility in renal transplant patients of the guidelines for the diagnosis and classification of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (GFR) elaborated by the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation. PATIENTS AND METHODS: Four hundred forty-seven cadaveric kidney transplants performed between 1980 and 1994 with graft function at 12 months were included in the study. The GFR was calculated according to the MDRD equation. RESULTS: The mean GFR at 12 months was 54.5 +/- 20.3 mL/min/1.73 m(2): 23 patients (5.1%) had a GFR > or =90 mL/min/1.73 m(2); 136 patients (30.6%), 60-89; 246 (54.7%), 30-59; 35 patients (7.8%), 15-29; and 7 patients (1.6%), GFR <15. Similar distribution of CKD stages was observed at 5 and 10 years. Unadjusted graft survival at 10 years was better among patients with a higher GFR at 12 months: 87% in patients with GFR >90 mL/min/1.73 m(2); 83% of GFR 60-89 mL/min/1.73 m(2); 63%, GFR 30-59 mL/min/1.73 m(2); and 23%, GFR <30 mL/min/1.73 m(2) (P < .001). The association between GFR and graft survival persisted when adjusted by the age and gender of the recipients and donors, time on dialysis, body mass index, immunosuppression, delayed graft function, rejection, and HLA mismatches. The prevalence of complications, such as anemia, hypertension, dyslipidemias, and number of drugs increased as GFR declined. CONCLUSIONS: More than 60% of recipients presented chronic kidney disease. GFR was a predictive factor for graft survival at 10 years. The classification of renal transplant patients by CKD stages may help to identify patients with increased risk of graft loss and also to design strategies to improve outcomes.

Body Mass Index↗

PubMed1996

Double adult renal allografts: a technique for expansion of the cadaveric kidney donor pool.

BACKGROUND: A major impediment to kidney transplantation is the current shortage of donor organs. Currently approximately 22,500 candidates are awaiting kidney transplantation, while the number of donors remains stable at approximately 3500 each year in the United States. Alternative approaches to traditional organ donor selection are necessary. In this setting we hypothesized that kidneys with reduced nephron mass from adult donors may provide satisfactory renal function if both donor kidneys are placed into a single recipient. METHODS: Eighteen paired adult renal allografts were transplanted into nine adult recipients (DUAL). Recipient graft outcome variables were examined and compared with outcomes from single kidneys transplanted from randomly selected "ideal" donors younger than 50 years of age (CONT < 50) and "expanded" donors older than 60 years of age (CONT > 60) who underwent transplantation at our center. RESULTS: Six-month serum creatinine levels in the three groups, DUAL (n = 9), CONT < 50 (n = 20), and CONT > 60 (n = 12), were 1.6 +/- 0.3, 2.3 +/- 0.3, and 4.1 +/- 0.9 mg/dl, respectively, (p < 0.0001) between CONT > 60 and the other two groups. Mean estimated creatinine clearance (ml/min/1.73 m2) was 43.2 +/- 3.4, 62.5 +/- 5.4, and 24.5 +/- 5.3 (p < 0.02). Graft and patient survival at last follow-up in DUAL was 100% compared with 95% in CONT < 50 and 75% graft and 83% patient survival in CONT > 60. Delayed graft function occurred in one of nine patients (11%) in DUAL group compared with 4 of 20 (20%) in CONT < 50 group and 6 of 12 (50%) in CONT > 60 group. Mean follow-up of patients in DUAL group was 6.6 months (range, 2 to 14 months). CONCLUSIONS: Double adult kidney transplants (DUAL) are associated with acceptable short-term graft function, graft survival, and patient survival when compared with transplanted kidneys from an ideal donor group (CONT < 50). Double renal allografts are a preferred use for donor kidneys with suboptimal nephron mass. Long-term follow-up is required to validate further the proposed approach.

Adult↗

PubMed2006

Improved renal function after conversion from tacrolimus/sirolimus to tacrolimus/mycophenolate mofetil in kidney transplant recipients.

BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.

Drug Therapy, Combination↗

PubMed2003

Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies.

BACKGROUND: With a continuing demand for donor kidneys for organ transplantation, it is important to understand the significance of pathologic findings in the donor organ before transplantation. Microvascular thrombosis is sometimes encountered in association with disseminated intravascular coagulation in the donor, and it is unclear whether this finding may affect immediate allograft function and long-term graft survival. To further elucidate this question, we examined our experience with microvascular thrombosis in donor biopsies in the kidney transplant program at our institution. METHODS: Donor kidney biopsies showing microvascular thrombosis were identified from consecutive donor biopsies in the Duke University Medical Center transplant file database between January 1, 1995 and December 31, 2000. These biopsies and all other kidney biopsies and specimens from the recipients of these kidneys thus identified were reviewed. Sections were stained using a variety of methods, including hematoxylin-eosin, periodic acid-Schiff, methenamine silver, and Masson trichrome methods. Clinical records of the transplant recipients of these kidneys were also reviewed to assess allograft performance and survival. RESULTS: From 230 consecutive donor kidney biopsies, we identified eight cases exhibiting donor-microvascular thrombosis. Mean follow-up times were 27.5 months for the thrombi group and 35 months for the non-thrombi group. Recipients of grafts with donor thrombi were more likely to exhibit delayed graft function, but graft function at 1 and 2 years and graft survival were similar between the two groups. Subsequent posttransplantation biopsies in five of eight cases showed no evidence of residual thrombosis. CONCLUSIONS: These data suggest that the presence of donor microvascular thrombosis does not portend poor outcome in renal transplantation.

Adolescent↗

PubMed2001

Eurotransplant Senior Program 'old for old': results from 10 patients.

More frequently there is the need for renal transplantation of older patients. Against the background of an increasing number of old donors and recipients, Eurotransplant Leiden started the Eurotransplant Senior Program (ESP) 'old for old' in 1999. The ESP works with donors and recipients both over 65 yr. The kidneys are transplanted with short cold ischaemia time regardless of the human leukocyte antigen (HLA) compatibility. Compatibility of blood groups, negative crossmatch and less than 5% cytotoxic antibodies are required. First experiences from 10 patients at Heinrich Heine University hospital are reported here. The course of 10 transplanted patients is described from January 1999 until November 1999 (28.4+/-15.8 wk). Age of donor and recipient, cause of dialysis and concomitant diseases from recipients, function of the transplanted kidney and complications are analysed. Immunosuppression consisted initially of cyclosporin A, mycophenolic acid and steroids. The results of these 10 patients were compared to 14 patients who were transplanted according to the ordinary Eurotransplant criteria (Eurotransplant Kidney Allocation System) in the same period of time. Kidneys from six donors (70.5+/-3.3 yr) were transplanted to 10 different recipients (66.9+/-2.2 yr). The control group consisted of 14 patients (47.6+/-14.4 yr) who received kidneys from 14 donors (48.3+/-10.1 yr). One double kidney transplantation was performed in the senior group, i.e. two kidneys from a marginal donor were transplanted to one recipient ('two in one'). In the ESP group, cold ischaemia time was reduced by 5 h and mean of HLA mismatches was more than doubled. Mean length of hospitalisation of ESP and control groups was 47.2+/-28.2 and 34.2+/-11.6 d, respectively. Intraoperatively, no complications were seen, post-operative care was performed on a normal ward. ESP patients suffered more often from delayed graft function, which led to further need for haemodialysis for 11.2 d. Finally, 9 of 10 patients acquired a satisfactory renal graft function. A total of 13 biopsies were performed in eight cases. Altogether seven acute rejections in 6 patients were found (four interstitial, one vascular, one interstitial+vascular, one clinical). The 9 patients with sufficient renal graft function were discharged with a mean serum creatinine level of 2.3+/-0.5 mg/dL (control: 1.9+/-0.8 mg/dL). Comparing these 10 recipients to a control group consisting of 14 patients, the results are comparable and encouraging. In conclusion, the short-term results of the ESP are promising. Nevertheless, the post-operative care requires more attention due to several complications. Though the HLA compatibility was not considered, all rejections were coped with effectively. Quality of life was improved.

Age Factors↗

PubMed1994

Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study.

In a prospective, randomized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients. The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l. All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively. After that, diltiazem or placebo was given orally for 3 months. Donors were not treated. Immunosuppressive therapy consisted of prednisone, azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics, HLA-mismatching, and ischaemic time. Thrombosis leading to graft loss occurred in 3 recipients (diltiazem:2, placebo:1) and one graft was lost due to septicaemia (diltiazem). For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function, the rate of rejections, time to first rejection, whole blood CsA concentration, or graft function. The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group. In conclusion, our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation, except a reduction of costs because of a significant reduction of the CsA dosage.

Adult↗

PubMed1999

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.

Adult↗

PubMed2000

The UNOS Scientific Renal Transplant Registry--2000.

During the 46 years since the first successful kidney was performed, more than 200,000 kidney transplants at United States transplant centers have been reported to the UCLA and UNOS Transplant Registries. After more than 25 years of follow-up, only 4% of cadaver donor transplants and 22% of living donor transplants performed before 1975 are still functioning. When compared with the 30% and 58% 5-year cadaveric and living donor graft survival rates, respectively, reported for kidney transplants 25 years ago, today's results of 66% and 78% are remarkably improved. Between 1995-1999, the 5-year graft survival rates for living donor transplant recipients were 80% for whites, 64% for American blacks and 84% for Asians and others. Among recipients of cadaver kidneys the results for the same racial groups were 70%, 55% and 76%, respectively. HLA-identical sibling transplants provided the best results in whites and blacks with 5-year graft survival rates of 90% and 88% respectively, and superior graft half-lives of 42 and 27 years. No substantial survival differences were noted among whites who received an HLA-mismatched living donor graft (5-year graft survival ranged from 76-81%). Among blacks who received HLA-mismatched living donor kidneys, 69% of sibling grafts survived 5 years compared with 60-62% of all others (p = 0.035). The racial distribution at the 25 largest US transplant centers varied from 6-64% black recipients. Graft survival rates for both blacks and whites were comparable at centers that transplanted more than 33% blacks or less than 20% blacks, suggesting that a larger experience with minority patients does not confer an advantage manifested in graft survival. Blacks consistently had higher rates of early rejection (34% vs. 28% in the first year) and delayed graft function (31% vs. 23%) than whites. Rejection prior to discharge resulted in a decreased one-year graft survival rate from 89% to 76% for both racial groups. DGF also reduced one-year graft survival from 82% to 76% for both racial groups. However, long-term graft survival rates were 15% lower for blacks than whites when there was no rejection or when there was no DGF. Sensitization patterns were similar comparing blacks and whites stratified according to sex, pregnancies, pretransplant transfusions, and previous transplants. There was no indication among patients transplanted between 1995-1999 for higher rates of sensitization among blacks. Recipients over age 60 had the lowest graft survival rate among whites (60% vs. 71% for those aged 19-45; p < 0.001). Among blacks, older recipients had the highest graft survival rate (57% vs. 55% for those aged 19-45; p = ns). Blacks aged 6-18 had the poorest 5-year survival rate (44%). The donor's age was an important determinant of long-term survival in both whites and blacks. The 5-year graft survival rates fell from 74-57% when the donor age was over 60 among whites. However, the difference was more pronounced among blacks, with a 5-year survival rate of 64% when the donor was aged 19-30, 47% when the donor was aged 46-60 and 35% when the donor was over 60 (p < 0.001). Increasing numbers of HLA mismatches resulted in a significantly increased incidence of rejection episodes in both blacks and whites. More than 19% of whites received an HLA-matched graft during 1995-1999 compared with 6% of blacks. HLA matching improved 3-year graft survival by 7-8% for both whites and blacks. Causes of graft failure were similar for blacks and whites during the first posttransplant year, however, after one year, blacks were more likely than whites to have an immunological graft loss whereas whites more often died with a functioning graft. The causes of patient death were also similar between blacks and whites during the first year, but after one year, blacks were more likely than whites to die from infection whereas whites more often died from cardiovascular disease and from malignancies. The racial disparity in renal allograft survival rates has diminished. The graft survival difference between whites and blacks at one year is now less than 2%. The long-term survival rates have also improved for blacks but the rate of late graft loss remains nearly double that for whites.

Adolescent↗

PubMed1999

Renoprotective effects of trimetazidine against ischemia-reperfusion injury and cold storage preservation: a preliminary study.

BACKGROUND: Initial ischemia-reperfusion injury is associated with organ retrieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction. We have recently shown that the protective agent trimetazidine (TMZ) added to preservation solutions: Euro-collins (EC) and University of Wisconsin (UW) was efficient to protect kidneys from ischemia-reperfusion injury in an isolated perfused kidney model. We extended these observations to investigate the role of this drug in the development and progression of organ dysfunction in the autotransplant pig kidney model. METHODS: Five experimental groups were studied. After 48-hr cold preservation, autotransplantation and immediate controlateral nephrectomy was then performed in group EC (EC+placebo (n=8), EC+TMZ (n=8), UW+placebo (n=7), and (UW+TMZ) (n=7) and compared with control group (uninephrectomized, n=4) during 14 days. Blood and urine samples were collected for the measurement of creatinine and blood urea nitrogen on postoperative days 1, 3, 5, 7, 11, and 14. Histological analysis was performed after reperfusion and at day 14. RESULTS: Survivals were 100% in group B and D versus 42% in group A and 57% in group C. Urine production occurred earlier after autotransplantation from TMZ preserved kidneys than in placebo preserved groups. Peak creat and blood urea nitrogen was significantly greater in groups B and D than in groups A and C. TMZ was also efficient both to reduce ischemia-reperfusion injury and to decrease cellular infiltration. CONCLUSION: These results support the beneficial effect of TMZ against ischemia-reperfusion injury and its early effects on grafts in the form of delayed graft function and decreased graft survival. In addition, TMZ reduces inflammatory cellular infiltration in the renal parenchyma.

Adenosine↗

PubMed2001

Effect of cold ischemic time and HLA matching in kidneys coming from "young" and "old" donors: do not leave for tomorrow what you can do tonight.

BACKGROUND: Kidneys from older donors are likely to have a lower nephron mass. Nevertheless they constitute a valuable source of kidney allografts. Long cold ischemic time (CIT), with or without delayed graft function (DGF), has been associated with reduced graft survival. The aim of this study was to review the experience of a single UK center to assess the interaction of cold storage time, donor age, organ exchange, and HLA-DR mismatching on short- and long-term survival. METHODS: We analyzed 788 first cadaver kidney transplants that were performed in our center from 1990 to 1997 and had complete data available. A donor age of 55 years was the cutoff age for "old" and "young" donor kidneys. The primary outcome measured was graft failure from any cause. RESULTS: There were 132 grafts from donors 55 years or older (16.7%), with 76.8% of the kidneys implanted after >20 hr of CIT. Kidney grafts from donors older than 55 years had worse graft survival than grafts from donors younger than 55 (87% vs. 78% at 1 year and 80% vs. 58% at 5 years after transplant, P=0.0001). A CIT of >20 hr significantly reduced graft survival (91% vs.74.3% at 5 years after transplant, P=0.0002) in the young donor group and was associated with an overall graft survival in the old donor group of 57.5% at 5 years. In the same group, ignoring the HLA-DR mismatching to achieve shorter CIT, the predicted initial cost on graft survival at 1 year would have been 3.7% but would have increased to 9% 5 years after transplant. For young donors a CIT of >20 hr had a cost of approximately 18% at 5-year graft survival, far higher than a single DR mismatch. Occurrence of DGF decreased survival in both short (P=0.001) and long (P=0.00001) CIT groups. CONCLUSION: Forming local alliances (common recipient lists) and minimizing delays within the hospital might reduce CIT and DGF while achieving excellent HLA matching. This should improve significantly the outcome of both old and young donor kidney grafts.

Aging↗

PubMed2000

Prolonged cold ischemia time obviates the benefits of 0 HLA mismatches in renal transplantation.

HYPOTHESIS: Recipients of 0 HLA mismatch kidneys with prolonged cold ischemia times of longer than 36 hours do not have superior outcomes compared with recipients of kidneys with 1 or more mismatches. DESIGN: Retrospective review. SETTING: Transplanation centers. PATIENTS AND METHODS: A total of 63,688 recipients who underwent transplantation between January 1, 1990, and July 31, 1998. MAIN OUTCOME MEASURES: Delayed graft function, serum creatinine level, and patient and renal graft survival. RESULTS: Recipients of 0 HLA mismatch kidneys with fewer than 36 hours of cold ischemia time had better 5-year graft survival (75%) when compared with recipients with 1 or more mismatches (67%) (P<.001). However, recipients of 0 HLA mismatch kidneys with longer than 36 hours of cold ischemia time did not have any graft survival advantage (71% in 0 HLA mismatch kidneys vs 72% in 1 or more mismatches, P =.24). CONCLUSIONS: Cold ischemia times of longer than 36 hours obviate the benefits of better graft survival conferred by better matching.

Blood Grouping and Crossmatching↗

PubMed2000

A 100% 2-year graft survival can be attained in high-risk 15-kg or smaller infant recipients of kidney allografts.

BACKGROUND: Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection. HYPOTHESIS: Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status. DESIGN: Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team. RESULTS: Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation. CONCLUSION: One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.

Body Weight↗

PubMed1987

Duodenopancreatectomy for transplantation.

Forty duodenopancreatectomies for transplantation were performed. The technique focused on the maintenance of the cardiovascular hemodynamics of the donor during the procedure, the meticulous dissection and preservation of all vascular supplies to the duodenum and the pancreas, and the suppression of warm ischemia by in situ cooling. Recipient euglycemia was established within two hours of the revascularization in 37 of 38 pancreata transplanted. Only six of the 78 renal transplant recipients receiving more than one organ from the same donor required postoperative dialysis, for a 7.7% incidence of delayed graft function. Immediate function was observed in all six cardiac allograft recipients.

Duodenum↗

PubMed2006

Severe graft rejection, increased immunosuppression, and active CMV infection in renal transplantation.

Associations between active cytomegalovirus (CMV) infection, graft rejection, rejection therapy, and clinical signs and symptoms have been shown repeatedly. However, the causes and the sequence of events remain an area of debate. Two hundred twenty five patients with cadaveric renal transplant were included in the present study. Clinical signs and symptoms, and the development of active CMV infections were recorded during the first 3 months after renal transplantation. CMV monitoring by pp65-antigenemia was performed followed by preemptive antiviral therapy. Delayed graft function and severe graft rejection followed by anti T-cell antibody therapy was associated with the development of active CMV infection. In contrast, the induction therapy with anti-T-cell antibodies was not associated with more active CMV infections. Post-transplant morbidity determined by fever, pneumonia, and duration of hospital stay was increased significantly in patients with active CMV infection. However, in times of preemptive antiviral therapy an increased morbidity occurred in association with severe graft rejection and not with active CMV infection alone. In patients with renal transplantation and preemptive antiviral therapy, the morbidity was no more influenced by the CMV serostatus although the prevalence of active CMV infection was obviously different between CMV exposed (D+/R+,D+/R-, D-/R+) and unexposed (D-/R-) patients. Severe graft rejection and increased immunosuppression could stimulate cooperatively active CMV infections whereas immunosuppression alone may not be as effective. Prevention of severe graft rejection may be important to decrease early post-transplant morbidity and also the development of active CMV infections after renal transplantation.

Adult↗

PubMed2005

The hepatic regeneration power of mild steatotic grafts is not impaired in living-donor liver transplantation.

The aim of this study was to assess histologic changes in steatotic grafts, regenerative capacity, and the outcome of steatotic grafts in living-donor liver transplantation (LDLT). Between September 2002 and February 2004, 55 cases of LDLT with a liver biopsy performed on the 10th postoperative day were enrolled. Patients were grouped according to the intraoperative histologic degree of macrovesicular steatosis (MaS) as follows: Group 1, <5% (n = 24); Group 2, 5 to 15% (n = 24); and Group 3, 15 to 30% (n = 7). The intraoperative microscopic findings and the findings on the 10th postoperative day were compared. Immunohistochemistry was performed using antibody of proliferating cell nuclear antigen (PCNA) and Ki-67 to assess the regeneration power of grafts on the 10th postoperative day. The histologic degree of MaS on postoperative day 10 decreased from 5.22 +/- 1.04% (mean +/- standard deviation) to 2.17 +/- 1.90 in Group 2 (P < .001) and from 21.4 +/- 8.02 to 4.43 +/- 2.70 in Group 3 (P = .003). The number of positively stained hepatocytes in 10 high power fields was 48.0 +/- 17.1, 53.8 +/- 14.4, and 51.5 +/- 4.1 in each group by PCNA (P = .681), and 24.0 +/- 14.0, 25.5 +/- 11.8, and 21.6 +/- 6.8 by Ki-67 (P = .825), respectively. No primary graft nonfunction (PNF) or delayed graft function (DGF) occurred. Major complications were comparable among groups. In conclusion, in LDLT, steatosis disappeared immediately after transplantation and hepatic regeneration power was not impaired in grafts with less than 30% of MaS. Furthermore, a mildly steatotic graft did not increase the risk of graft dysfunction or morbidity in LDLT.

Adult↗

PubMed1993

Cytoprotective effect of glycine in cold stored canine renal tubules.

Reperfusion injury has been suggested to cause delayed graft function in renal transplantation. Methods to reduce reperfusion injury could lead to improved clinical renal transplantation. Glycine has been shown to suppress reperfusion injury in rabbit renal tubules and rat hepatocytes. In this study we have determined the effects of glycine on viability of isolated canine renal tubules. Renal tubules were cold stored at 4 degrees C under hypoxic conditions for up to 96 h in the UW solution and rewarmed to 37 degrees C for up to 2 h under oxygenated conditions to simulate reperfusion of an organ after cold static storage. Short-term storage (24 to 48 h) did not cause membrane injury (leakage of lactate dehydrogenase (LDH)) on rewarming. However, after 72 and 96 h cold storage reperfusion injury was evident and LDH leakage increased from about 25% to 59 +/- 3% and 71 +/- 2% at 72 and 96 h cold storage, respectively. The presence of 3 mM glycine in the reperfusion medium suppressed injury to cold-stored renal tubules. After cold storage for 72 and 96 h LDH leakage was reduced to control concentrations (31 +/- 3% and 29 +/- 1%, respectively). After cold storage for 72 h there was a reduction in ATP concentration in rewarmed renal tubules (3 nmol/mg protein at 48 h to 1.25 nmol/mg protein at 72 h). Also, there was a loss of mitochondrial functions including decreased stimulation of oxygen consumption by uncoupling of oxidative phosphorylation. Although glycine suppressed LDH leakage in renal tubules cold stored for 72 h it had no effect on the regeneration of ATP or mitochondrial functions, which remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed2000

Influence of retrieval conditions on renal medulla injury: evaluation by proton NMR spectroscopy in an isolated perfused pig kidney model.

BACKGROUND: Delayed graft function (DGF) has remained an important complication after renal transplantation. The exact causes of DGF remain to be clarified, particularly the impact of retrieval conditions and preservation factors. In the present investigation, (1)HNMR spectroscopy of urine was assessed in order to detect the influence of retrieval condition on renal medulla damage. METHODS: The isolated perfused pig kidney (IPK) was used to assess initial renal function from multiorgan donors (MOD) or single organ donors (SOD) after in situ cold flush and 24-h cold storage (CS) preservation with two standard preservation solutions: Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys flushed with cold heparinized saline and immediately perfused were used as the control group. Kidneys were perfused for 90 min at 37.5 degrees C for functional evaluation. During reperfusion, renal perfusion flow rate (PF) was measured. Glomerular filtration rate (GFR), tubular reabsorption of Na(+), and lactate dehydrogenase (LDH) and N-acetyl-beta-d-glucosaminidase (NAG) excretions were determined. Ischemia-reperfusion impairment was also determined by histological techniques and (1)HNMR spectroscopy. RESULTS: PF, GFR, and tubular reabsorption of Na(+) were significantly decreased in experimental groups when compared to the control group but there was no significant difference between experimental SOD groups. GFR was significantly greater in UW-MOD than in EC-MOD and tubular reabsorption of Na(+) was significantly greater in UW-MOD than in EC-MOD after 45 min of reperfusion. The release of LDH in the effluent and the urinary excretion of NAG were not significantly different after 24-h CS in the various experimental groups. The most relevant resonances determined by (1)HNMR spectroscopy were citrate, trimethylamine-N-oxide, lactate, acetate, and amino acids. Excretion of these markers was significantly different when compared to biochemical markers. A resonance (P) detected particularly in EC-MOD after 24-h CS was identified and well correlated to renal dysfunction. Histological study showed that ultrastructural damage and mitochondrial injury were more pronounced in the EC-MOD group. CONCLUSION: These results show that retrieval condition influences renal medullary damage. NMR spectroscopy, which is a noninvasive and nondestructive technique, is more efficient in assessing renal damage than conventional histology and biochemical analysis.

Acetylglucosaminidase↗