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Results for “delayed graft function”

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At least 253 records · Page 14Linked to original sources

PubMed2006

Rabbit antithymocyte globulin versus basiliximab in renal transplantation.

BACKGROUND: Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation. A rabbit antithymocyte polyclonal antibody or basiliximab, an interleukin-2 receptor monoclonal antibody, is most commonly used for induction. METHODS: In this prospective, randomized, international study, we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor. Patients taking cyclosporine, mycophenolate mofetil, and prednisone were randomly assigned to receive either rabbit antithymocyte globulin (1.5 mg per kilogram of body weight daily, 141 patients) during transplantation (day 0) and on days 1 through 4 or basiliximab (20 mg, 137 patients) on days 0 and 4. The primary end point was a composite of acute rejection, delayed graft function, graft loss, and death. RESULTS: At 12 months, the incidence of the composite end point was similar in the two groups (P=0.34). The antithymocyte globulin group, as compared with the basiliximab group, had lower incidences of acute rejection (15.6% vs. 25.5%, P=0.02) and of acute rejection that required treatment with antibody (1.4% vs. 8.0%, P=0.005). The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss (9.2% and 10.2%, respectively), delayed graft function (40.4% and 44.5%), and death (4.3% and 4.4%). Though the incidences of all adverse events, serious adverse events, and cancers were also similar between the two groups, patients receiving antithymocyte globulin had a greater incidence of infection (85.8% vs. 75.2%, P=0.03) but a lower incidence of cytomegalovirus disease (7.8% vs. 17.5%, P=0.02). CONCLUSIONS: Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor, induction therapy consisting of a 5-day course of antithymocyte globulin, as compared with basiliximab, reduced the incidence and severity of acute rejection but not the incidence of delayed graft function. Patient and graft survival were similar in the two groups. (ClinicalTrials.gov number, NCT00235300 [ClinicalTrials.gov].).

Acute Disease↗

PubMed2003

Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion.

BACKGROUND: MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here. METHODS: MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 microg/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies. RESULTS: At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 micromol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 microg/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11). CONCLUSIONS: Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.

Adult↗

PubMed2005

Impact of pretransplant dialysis on early graft function in pediatric kidney recipients.

Delayed graft function (DGF) is a frequent complication of kidney transplantation (KT) that may affect both short- and long-term graft outcome. It has been reported that pretransplantation peritoneal dialysis was correlated with a better recovery of graft function than hemodialysis in adult kidney recipients. However, the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the early outcome of KT in pediatric recipients. In this study, the potential impact of PDM on early graft function was evaluated in 174 pediatric patients who underwent KT by using cadaveric donors. The primary outcome parameter was the time to reach a serum creatinine (SCr) level 50% of the pretransplantation value [T(1/2(SCr))], while DGF was defined as a T(1/2(SCr)) >3 days after KT (n = 40). By stratifying kidney recipients for normal function graft or DGF, this latter group showed a significantly higher body weight (BW) on the day of KT (P = 0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P = 0.022), early SCr on the day 1 after KT (P < 0.001), and T(1/2(SCr)) (P < 0.001), whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001) and fluid load (P < 0.001) occurred. Univariate exponential correlation that was carried out between T(1/2(SCr)) and all the other variables had shown a better value than the linear correlation for BW (R(2) = 0.28 vs. R(2) = 0.04), BSA (R(2) = 0.29 vs. R(2) = 0.03), and SCr (R(2) = 0.51 vs. R(2) = 0.28). In a multivariate regression analysis performed by entering T(1/2(SCr)) as dependent variable and following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not PDM (P = 0.195) reached significance. In a Cox regression analysis carried out with T(1/2(SCr)) as dependent variable, neither CIT nor PDM gained significance. This study suggests that PDM does not affect early graft function in pediatric kidney recipients.

Adolescent↗

PubMed1997

Clinical aspects of sensitization.

1. The incidence of broad sensitization has decreased significantly over the past 8 years, probably due to a decrease in pretransplant blood transfusions. Graft survival rates among broadly sensitized patients have improved over this time period (76% graft survival at 2 years posttransplant for patients transplanted in 1995-1996 compared with 66% for patients transplanted in 1989-1990). This is probably due to an improvement in immunosuppression and a related decrease in the incidence of acute rejection episodes. 2. As has been shown before, blood transfusions, previous pregnancies and failed allografts independently increased the incidence of sensitization. It is clear that certain subgroups of patients are more likely to become sensitized, given antigenic stimulation, as evidenced, for example, by the fact that 52% of patients receiving more than 10 units of blood prior to transplant were relatively unsensitized. Males seem to be less apt than nulliparous females to become broadly sensitized, although this may be due to the lower age of nulliparous females. Asians are the least likely race to become broadly sensitized. Among multiparous Asians who received more than 5 units of blood, 27% were broadly sensitized compared with 35% of comparable Whites and African Americans. 3. The incidence of acute rejection episodes increased with increasing degrees of sensitization. About 46% of first cadaveric allograft recipients with PRA levels greater than 50% had at least one acute rejection episode within 6 months after transplantation compared with 38% of unsensitized individuals. In addition, sensitized individuals were more likely to have an episode of early acute rejection before discharge from the hospital. 4. Induction with antilymphocyte antibody preparation was more commonly used in broadly sensitized patients. However, this therapeutic modality did not reduce the incidence of rejection episodes measured at 6 months posttransplant. In addition, the use of induction therapy for broadly sensitized patients has decreased with the advent of newer immunosuppressive protocols that include Neoral, MMF and FK506. 5. There was an association between the incidence of broad sensitization and delayed graft function. Induction therapy was more commonly used in patients with both delayed graft function and broad sensitization, although the decision to use this therapeutic modality seems to be made based on the presence of broad sensitization rather than the presence of delayed graft function. 6. Choosing the optimal immunosuppressive drug regimen is an important decision in broadly sensitized individuals because of the increase in acute rejections and decrease in overall graft survival in this group. Classic teaching suggests that this group of patients should be administered induction therapy with antilymphocyte antibody preparations. Early data suggests, however, that the combination of Neoral, mycophenolate and prednisone may be the optimal regimen for these individuals with respect to graft survival and that the addition of antibody induction therapy to any of the other commonly used regimens does not improve graft survival (at least up to 3 years after transplantation).

Blood Transfusion↗

PubMed2004

Sirolimus in kidney transplantation from marginal donors.

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.

Biopsy↗

PubMed1999

The morbidity of prolonged wound drainage after kidney transplantation.

PURPOSE: The consequences of prolonged wound drainage, defined as extravasation of more than 50 ml. fluid daily for more than 1 week through a drain or wound after renal transplantation, have not been well described in the literature. We examine the association of prolonged wound drainage with other clinical events, and its impact on hospitalization, and patient and graft survival. MATERIALS AND METHODS: We prospectively documented prolonged wound drainage in 392 recipients of cadaver and live renal transplants from July 1993 to December 1997. Potential risk factors, associated outcomes within the first 6 months and effect on length of hospital stay due to prolonged wound drainage were determined. RESULTS: Prolonged wound drainage was significantly associated with pre-transplantation weight, weight gain by post-transplantation day 3, delayed graft function and continuous ambulatory peritoneal dialysis on univariate analysis but only with delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7 additional days during the first hospitalization and overall 11.3 additional days during the first 6 months after transplantation independent of other co-morbid events, such as delayed graft function, rejection or cytomegalovirus disease. CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation event that impacts patient outcomes and hospital resource use. Efforts to prevent this complication should be considered.

Adult↗

PubMed2005

Laparoscopic versus open renal procurement for pediatric recipients of living donor renal transplantation.

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.

Adolescent↗

PubMed1996

Delayed endocrine pancreas graft function after simultaneous pancreas-kidney transplantation. Incidence, risk factors, and impact on long-term outcome.

BACKGROUND: The incidence of delayed endocrine pancreas graft function and its impact on long-term outcome after simultaneous pancreas-kidney transplantation are unknown. METHODS: We studied 54 technically successful adult type I insulin-dependent diabetic recipients of cadaver, whole organ, bladder-drained simultaneous pancreas-kidney transplants (mean age, 37.6 years; 65% male, 35% female; 9% pancreas retransplants; 63% on chronic pretransplant dialysis; mean duration of diabetes, 25.1 years). Insulin was administered during the first 2 weeks after transplantation, as needed, to keep blood glucose < 150 mg/dl. Delayed endocrine pancreas graft function was defined as total, cumulative insulin requirement of > 30 U between day 5 and day 10, and/or > 15 U between day 11 and 15. Quadruple immunosuppression was used for all recipients. RESULTS: The incidence of delayed endocrine pancreas graft function was 69%. By univariate analysis, delayed endocrine graft function was associated with pretransplant recipient weight > 80 kg (P = 0.04), donor age > 45 years (P = 0.02), and cardiocerebrovascular (P = 0.06) and nontraumatic causes of donor death (P = 0.02). The incidence of acute pancreas rejection episodes was similar for recipients without and with delayed endocrine pancreas graft function. Pancreas graft survival at 1 and 3 years was 94% and 82% without versus 76% and 59% with delayed endocrine graft function (P = 0.03). CONCLUSIONS: Increased pancreas graft failure after delayed endocrine function was a consequence of insufficient functional reserve (e.g., older donors) rather than increased immunogenicity. Pretransplant reduction of recipient weight and careful donor selection are therefore crucial in order to decrease the incidence of delayed endocrine pancreas graft function and its negative impact on long-term outcome.

Adult↗

PubMed1996

Living related kidney donors over 60 years old.

The lack of available cadaveric organs for transplantation has resulted in an increased number of kidney transplants from living donors. During a period of 6 years, 149 kidney transplantations were performed from living related donors in our institute, 33.5% of whom were older than 60 years of age. In this study we examined the survival of patients and grafts as well as the graft function in 50 patients with transplants from donors over 60 years (mean age 65 years) as compared with those of 99 patients with transplants from donors younger than 60 years (mean age 47 years). There were no significant differences in the course of donor nephrectomy, postoperative complications, or remnant kidney function. However, delayed graft function occurred more frequently in recipients of transplants from older donors. Improvement in graft function was also slower in recipients of kidneys from older donors, with significant differences in serum creatinine levels observed during the first 12 months after transplantation. More frequent acute complications and more progressive chronic graft failure, irrespective of the causes, occurred during the 1st post-transplant year in recipients with grafts from older donors. Five-year patient survival (77% vs 92%) and kidney graft survival differed significantly for the same period with worse results for patients receiving grafts from older donors. It may be concluded that kidney grafts from donors older than 60 years -- and especially those older than 70 years -- may be used for living related kidney transplantation, but with precautions.

Adult↗

PubMed1996

Effect of rHuEpo therapy in dialysis patients on endogenous erythropoietin synthesis after renal transplantation.

UNLABELLED: We have undertaken a prospective study to examine the effect of recombinant human erythropoietin (rHuEpo) therapy during dialysis on Epo levels after renal transplantation and to evaluate the impact of this therapy on the immediate graft function. Between December 1991 and December 1993, 91 renal transplant recipients were studied. There were 34 females and 57 males and the mean age was 38 years. Forty-two patients were treated during dialysis with rHuEpo due to anemia and 49 patients did not receive it. Endogenous Epo (eEpo), hemoglobin concentration, hematocrit level and serum creatinine were determined on days 0, 2, 4, 8, 15, 30, 60 and 180 after transplantation. Ferritin level was determined pretransplant and on day 60. RESULTS: Patients not treated with rHuEpo during dialysis experienced a transient increase in endogenous Epo after renal transplant that was not observed in treated patients (26 +/- 3.3 vs. 9 +/- 1.5 mU/ml, p < 0.001). The eEpo peak was similar in patients with early or delayed graft function (23 +/- 4.3 vs. 32 +/- 5.4 mU/ml, NS). The recovery of the anemia after a successful renal transplant took place in patients treated as well as those not treated with rHuEpo without significant differences. In the treated group, the pretransplant hematocrit level was similar in patients with early or delayed graft function (31 +/- 3.5% vs. 32 +/- 4.8%), but in the untreated group, the hematocrit level was lower in patients with early renal function (28.5 +/- 4% vs. 32 +/- 3%, p < 0.05). However, these patients also had a significantly shorter warm ischemia time (53 +/- 13.8 vs. 64 +/- 14.5 min). Fifty-two percent of the rHuEpo-treated patients and 36% of the untreated patients had delayed graft function. In conclusion, different courses of eEpo levels after renal transplant were observed depending on whether or not patients had been treated with rHuEpo during dialysis. Untreated patients experienced a transient increase which was not observed in the treated group. Immediate or delayed graft function did not modify eEpo levels. No association was found between rHuEpo therapy during dialysis and delayed graft function.

Adolescent↗

PubMed2003

Immediate tracheal extubation of pediatric liver transplant recipients in the operating room.

Keeping patients on mechanical ventilation after orthotopic liver transplantation (OLT) has been a standard anesthetic approach since the first utilization of liver transplantation. Advances in anesthetic management, surgical techniques and patient preparation, in addition to improved postoperative care and the reported advantages of early postoperative tracheal extubation of liver recipients. encouraged us to extubate most recipients at the end of the operation. The aim of the present study is to evaluate the pediatric liver recipients who were extubated immediately at the end of transplantation, in terms of respiratory complications and allograft function during their stay in the ICU. We retrospectively reviewed the records of 40 pediatric recipients who had undergone OLT at the Ege University Organ Transplantation Center between December 1997 and July 2002. Twelve out of 40 patients who had consecutively undergone OLT were extubated immediately at the end of the operation and were included this study. Mean Child Pugh scores of the patients were 9 +/- 2.3 (range 6-12) and the mean PELD score was 23.1 +/- 12.3 (range 7-41). The mean age of the patients was 8.4 +/- 5.2 (range 0.8-16.8 yr). Five of the 12 extubated patients received a cadaveric and seven a living donor liver graft. The mean ICU stay of the patients was 49.1 +/- 24.2 h (6-120 h). No patients required reintubation or mechanical ventilation in the ICU. Respiratory complications diagnosed in the 12 extubated patients were hypercapnia without hypoxemia in three, atelectasis in one and pleural effusion in two. No primary non-function or delayed graft function was detected. The aspartate transaminase (AST), alanine transaminase (ALT) and protrombin time (PT) were normalized within a week. We believe that immediate tracheal extubation in the operating room is a safe procedure for selected cadaveric and living-related liver transplant recipients and will facilitate the patients' recovery and mobilization leading to reduction in complications and a reduced ICU stay.

Adolescent↗

PubMed2004

Daclizumab induction in solid organ transplantation.

Antibody induction therapy is used in solid organ transplantation to prevent rejection in the early postoperative period. It is especially useful in high-risk groups such as retransplants, patients with delayed graft function to delay the initiation of nephrotoxic calcineurin inhibitors (tacrolimus, cyclosporin), highly sensitised recipients and African-American recipients. Historically, antibody induction has been associated with a high incidence of adverse effects and a complicated administration regimen. Daclizumab is a monoclonal antibody that exerts its effect by binding to the alpha subunit (CD25) of the human interleukin (IL)-2 receptor on the surface of activated lymphocytes, thus preventing the binding of IL-2. It is used for induction therapy and is well-tolerated with easy administration. Although originally studied as a five-dose regimen, there is a growing accumulation of data that fewer doses (two or three) are efficacious and less costly for preventing rejection.

Animals↗

PubMedDate not supplied

Fate of kidneys from the same donor grafted into different recipients: do they behave similarly and are they influenced by donor-related factors?

BACKGROUND: The fate of paired kidneys might be similar and could therefore reflect the influence of donor-related factors on graft outcome. PATIENTS AND METHODS: To verify whether two kidneys retrieved from a single donor and grafted into different recipients have similar short, and middle-term outcomes we investigated the clinical outcome of 103 pairs of cadaveric kidneys grafted into 206 recipients. We evaluated the influence of donor-related factors such as age, sex and cause of death, and of the storage solution and method of harvesting. The incidence of delayed graft function was considered as the short-term outcome and serum creatinine levels at two years as the middle-term outcome. We evaluated the difference from expected frequencies in the incidence of delayed graft function and the incidence of similar serum creatinine levels in each pair of recipients. Univariate analysis of possible risk factors was made by the t-test, chi2 test and Fisher test, as appropriate. Multivariate analysis was done by logistic regression analysis with a forward stepwise variable selection. RESULTS: Delayed graft function was seen in both recipients from the same donor 2.5 times more than the expected frequency (p<0.001). Serum creatinine levels were similar in both recipients with a higher frequency than expected (p<0.01). Multivariate analysis showed that donor-related factors on graft function were age, cause of death and storage solution. CONCLUSIONS: Paired kidneys have similar performances in both the short and the long term. Major donor-related factors in delayed graft function are age and the storage solution. Major donor-related factors in graft function are age and cause of death.

Female↗

PubMedDate not supplied

Organs transplanted from intoxicated donors.

PURPOSE: The purpose of our study was to evaluate short- and long-term results of transplants from cadaver donors who have died of poisoning by various substances. MATERIALS AND METHODS: The actuarial survival rate of organs from intoxicated donors was calculated using the Kaplan-Meier method. RESULTS: Among the 507 donors between January 1998 and December 2002, 5 (0.98%) had a cause of brain death of poisoning, namely, organo-phosphates (n = 2), methanol (n = 1), cyanide (n = 1) and acetylsalicilic acid(n = 1), from whom were procured 10 kidneys, 1 liver, 2 corneas, and 1 set of bones. The follow up for patients receiving solid organs was 15.2 months (range, 0-48 months). At 3 months, 90% of kidneys had normal function. No delayed graft function rejection episodes or major complications were reported in any recipient. None showed evidence of acute or chronic poisoning. Two died, 1 early mortality was due to anesthetic complications and the other at 17 months to an unknown cause. Actuarial kidney survival rates were 90% and 80% at 12 and 24 months, respectively. The liver recipient was well at the end of follow up. CONCLUSION: Using organs of poisoned donors is feasible with comparable graft survival rates to other recipient.

Adolescent↗

PubMed2006

Detection of donor-specific antibodies using HLA-coated microspheres: another tool for kidney transplant risk stratification.

BACKGROUND: Sensitive techniques are able to detect low levels of circulating antibodies. For many newer techniques, the clinical consequences of these antibodies are unknown. We hoped to determine the significance of antibodies detected through the use of Luminex microsphere-based assay. METHODS: Patients who received kidney transplants between March 2003 and May 2004 with negative anti-human globulin-augmented complement-dependent cytotoxicity (AHG-CDC) crossmatches were retested for pre-transplant panel reactive antibodies (PRA) using Luminex microspheres and stored sera. Patients were considered to have circulating antibodies if either class I or class II Luminex PRA was >or=15%. These patients were then analysed for pre-transplant donor-specific antibodies (DSA). Clinical outcomes were compared in patients with and without DSAs. RESULTS: Out of 136 patients who underwent transplantation, 55 had Luminex PRA >or=15%. Of these 55 patients, only 16 had a standard PRA >or=30% and 75% had a history of a sensitizing event. Twenty out of 55 patients were DSA+. Patients with DSA detected by Luminex had higher rates of primary non-function (PNF), delayed graft function, biopsy-proven acute rejection, and lower rates of graft survival at 6 months. A combined endpoint of immunological and clinical events was far more common in patients with DSA. CONCLUSION: The detection of DSAs by Luminex microspheres was associated with significantly higher rates of graft dysfunction and immunological events. Conversely, the presence of antibodies but no DSA by Luminex was associated with excellent outcomes. In patients with negative AHG-CDC crossmatches, the occurrence of low-level DSA by Luminex could assist in identifying patients that require more aggressive immune monitoring or immunosuppressive strategies.

Acute Disease↗

PubMed2004

Rarefaction of peritubular capillaries following ischemic acute renal failure: a potential factor predisposing to progressive nephropathy.

PURPOSE OF REVIEW: Long-term renal complications of acute renal failure have generally not been expected in patients that recover from acute renal failure. However, as the incidence of acute renal failure is rising, the incidence of long-term complications is likely to increase. As a corollary to ischemic acute renal failure, ischemic injury in the setting of transplant is a leading cause of delayed graft function. Unlike acute renal failure in native kidneys, delayed graft function is highly predictive of chronic nephropathy and organ failure. It is generally well accepted that acute reversible injuries mediated by ischemia render grafts susceptible toward future demise. The nature of the susceptibility that is conveyed to grafts following ischemic injury is not well understood. RECENT FINDINGS: Evidence from animal models suggests that acute injury results in microvascular damage and vessel loss in the kidney, which, as opposed to tubular damage, is largely persistent. In addition, various studies of biopsies of renal transplants suggest that ischemia imposes an early and sustained loss in peritubular capillaries in the transplanted graft. The loss of peritubular capillaries has been associated with nephropathies of diverse etiologies and may represent a single, common pathway towards progressive damage. SUMMARY: It is hypothesized that rarefaction of peritubular capillaries represents a critical event, following ischemic injury, that permanently alters renal function and predisposes patients to the development of chronic renal insufficiency. Factors that affect vascular reactivity or the structural dynamics of the kidney vascular system following injury may represent future treatment modalities following renal injury.

Acute Kidney Injury↗

PubMed2003

Intra-renal resistance reflects warm ischaemic damage, and is further increased by static cold storage: a model of non-heart-beating donor kidneys.

BACKGROUND: Non-heart beating donor kidneys increase transplant activity, but their use is associated with a higher rate of both primary non-function and delayed graft function than cadaveric kidneys, due to a period of cold ischaemic damage superimposed on a period of warm ischaemia. We aimed to measure intra-renal resistance in machine perfused porcine kidneys subjected to different periods of warm ischaemic injury, with additional, varying, cold ischaemic times, in an attempt to mimic the injury suffered by NHBD kidneys and test the predictive power of viability testing. MATERIAL/METHODS: Landrace pigs were killed by lethal injection, and the kidneys were subjected to varying WITs of 10-90 minutes prior to explantation. Kidneys were subsequently stored for varying cold times of 2 to 48 hours. IRR (pressure/flow) was calculated during 6 hours cold pulsatile machine perfusion. RESULTS: For all WITs, IRR was higher at the start than at the end of machine perfusion (P<0.001). There was a strong correlation between IRR on MP, and WIT, but no correlation after 6 hours MP. Intra-renal resistance increased as kidneys were exposed to longer CITs; this effect was most marked for the longer WITs (P<0.004), However, the slope gradient was similar for the different WITs. CONCLUSIONS: Early IRR accurately reflects kidney in-situ WIT, and machine perfusion reduces IRR whilst cold ischaemia imposed on periods of warm ischaemia increases IRR and attenuates the beneficial effect of MP. Machine perfusion may partially ameliorate the effects of WIT in terms of IRR, and may prove useful in pre-transplant viability assessment of NHBD kidneys.

Animals↗

PubMed2004

Kidney transplantation from organ donors following cardiopulmonary death using extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) has the ability to provide normal organ perfusion and oxygenation in the absence of cardiac function and thus has the potential to improve viability of subsequently transplanted kidneys. In addition, ECMO support allows the donation following cardiopulmonary death (DCD) process to occur in a controlled manner that is acceptable to staff unfamiliar with DCD. In 1999 our center implemented a controlled DCD program that incorporates post-mortem ECMO support of the organs. Arterial and venous cannulae are placed following consent to donate, but prior to withdrawal of support. ECMO circulation is initiated immediately following declaration of death. Following a brief period where the donor family is allowed to grieve, the donor is moved to the operating room where organ recovery occurs. We reviewed the results of 20 kidney transplants from 13 ECMO supported donors that occurred between October 2000 and August 2003. One renal allograft was lost due to surgical complications, all 19 remaining grafts functioned. An 11% (2/19) delayed graft function rate was observed. Kidneys donated from "controlled" ECMO supported CPD donors are a viable source of organs for renal transplantation. This recovery method warrants further investigation.

Cadaver↗