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PubMed1990

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↗
PubMed1999

A comparison of OPO pulsatile machine preservation practices and results.

CONTEXT: Kidney preservation has been performed by either ice (static) or machine pulsatile perfusion. Ice storage is simple, with only 1 methodology. Machine perfusion, on the other hand, is accomplished using multiple methodologies. This article delineates the different methodologies of pumping centers throughout the country. OBJECTIVE: Pulsatile machine perfusion is again being viewed as the preservation method of choice for kidneys from non-heart-beating cadaver donors and cadaver kidneys from marginal donors. To develop indices to predict the viability of cadaver kidneys for transplant, a review of the organ procurement organizations, specific perfusion techniques, and a comparison of the delayed graft function and graft survival rates were considered. METHODS: A survey, asking for specifics on perfusion parameters, pulsatile machine perfusion experience, and criteria for perfusion implementation and graft survival results, was mailed to all organ procurement organizations in the United States. RESULTS: Of the 44 centers that responded to the survey, 12 used pulsatile machine perfusion (11 used the Waters perfusion machine), 6 pumped marginal cadaver kidneys, and the remaining 6 pumped all cadaver kidneys. Minimum perfusion criteria, pulse rates, perfusate composition, pressures, renal resistance, and renal pressure and flow were considered. Vasodilators and other machine additives were used to improve flow. The variance in each center's number of cadaver kidneys pumped each year, as well as the differences in pump times, was noted. CONCLUSION: Twelve centers use pulsatile machine perfusion. A variety of techniques are used to perform pulsatile machine perfusion, but 11 of 12 have less delayed graft function than those programs employing ice storage preservation.

Cryopreservation↗
PubMed1998

Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion.

Organs used for transplantation undergo varying degrees of cold ischemia and reperfusion injury after transplantation. In renal transplantation, prolonged cold ischemia is strongly associated with delayed graft function, an event that contributes to inferior graft survival. At present, the pathophysiological changes associated with ischemia/reperfusion injury in clinical renal transplantation are poorly understood. We have performed an immunohistochemical analysis of pre- and postreperfusion biopsies obtained from cadaver (n = 55) and living/related donor (LRD) (n = 11) renal allografts using antibodies to adhesion molecules and leukocyte markers to investigate the intragraft changes after cold preservation and reperfusion. Neutrophil infiltration and P-selectin expression were detected after reperfusion in 29 of 55 (53%) and 24 of 55 (44%) cadaver renal allografts, respectively. In marked contrast, neutrophil infiltration was not observed in LRD allografts, and only 1 of 11 (9%) had an increased level of P-selectin after reperfusion. Immunofluorescent double-staining demonstrated that P-selectin expression resulted from platelet deposition and not from endothelial activation. No statistically significant association was observed between neutrophil infiltration and P-selectin expression in the glomeruli or intertubular capillaries despite the large number of cadaver renal allografts with postreperfusion changes. Neutrophil infiltration into the glomeruli was significantly associated with long cold ischemia times and delayed graft function. Elevated serum creatinine levels at 3 and 6 months after transplantation were also associated with the presence of neutrophils and platelets after reperfusion. Our results suggest that graft function may be influenced by early inflammatory events after reperfusion, which can be targeted for future therapeutic intervention.

Adult↗
PubMed2006

Risk factors that can influence kidney transplant outcome.

The survival and function of a kidney transplant are influenced by numerous immunological and nonimmunological factors. The aim of this study was to evaluate the role of a number of cadaveric donor parameters on transplanted kidney function, and in particular on the occurrence of delayed graft function (DGF) since DGF is one of the most important factors in long-term organ survival. This study looked at 143 patients who underwent kidney transplant of whom 32 displayed DGF. The creatinine levels in organ recipients, which were evaluated during a follow-up that ranged between 6 months and 4 years, were significantly higher among recipients who developed DGF after transplant (1.8 +/- 0.7 vs 1.4 +/- 0.4; P = .02). The following donor parameters were taken into consideration: history of diabetes and hypertension; creatinine levels; inotropie therapy; problems relating to hemodynamics (hypotension and/or cardiac arrest); and cold ischemia time. We observed that a donor history of hypertension (46.8% DGF vs 23.27% no DGF; P = .01) and high levels of donor creatinine prior to organ removal (1.9 +/- 1.2 mg/dL DGF vs 1.2 +/- 0.9 mg/dL no DGF; P = .007) were significant risk factors for DGF among kidney recipients. No significant differences were found for others factors between recipients with versus without DGF.

Cadaver↗
PubMed2004

Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

BACKGROUND: Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. METHODS: We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. RESULTS: The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. CONCLUSIONS: One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.

Adult↗
PubMed2004

Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients.

BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium channel blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library issue 2, 2003) MEDLINE (1966 to January 2003) and EMBASE (1980 - January 2003). The Trials Search Coordinator was contacted to develop the search strategy. SELECTION CRITERIA: Randomised controlled trials comparing calcium channel blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Nine trials were suitable for inclusion. Treatment with calcium channel blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.44, 95% CI 0.28 to 0.69). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. REVIEWER'S CONCLUSIONS: These results suggest that calcium channel blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.

Calcium Channel Blockers↗
PubMed2005

Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients.

BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium channel blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last database and register search: January 2005 SELECTION CRITERIA: Randomised controlled trials comparing calcium channel blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Ten trials were suitable for inclusion. Treatment with calcium channel blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.51, 95% CI 0.36 to 0.72). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. AUTHORS' CONCLUSIONS: These results suggest that calcium channel blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.

Calcium Channel Blockers↗
PubMed2004

Anemia in pediatric renal transplant recipients.

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.

Adolescent↗
PubMed2001

Renin system activation and delayed function of the renal transplant.

Delayed graft function (DGF), defined as persistent renal failure that requires dialysis within the first week after kidney transplantation, occurs commonly after cadaveric renal transplantation (CRT). This has important implications for long-term outcome because the 1-year allograft survival rate is significantly reduced when DGF occurs. The mechanisms contributing to the development of DGF are not well established. However, several lines of evidence indicate that excess renin system activity, in both the cadaver kidney donor and recipient, contributes importantly to the pathogenesis of DGF. If this hypothesis can be verified in clinical studies, then pharmacologic agents that interrupt the renin-angiotensin system (eg, type 1 angiotensin II receptor blockade, angiotensin converting enzyme inhibition, and beta-adrenergic blockade) in the donor and recipient might significantly improve the outcome of cadaveric renal transplants.

Graft Survival↗
PubMed1995

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↗
PubMed1996

Twelve years' experience with non-heart-beating cadaveric donors.

From 1983 to August 1995, the University of Miami Organ Procurement Organization evaluated 41 candidates for non-heart-beating cadaveric donation and determined that 34 patients met the criteria. All patients had irreversible brain injury incompatible with survival. All families gave permission for withdrawal of life support and for tissue and organ donation after cardiac arrest. Thirteen donors died in the operating room, and 9 died in the ICU or emergency department. Four of the 9 patients who died in the ICU had undergone femoral cannulation. The remaining 12 donors were brain-dead but had an unpredicted cardiac arrest before laparotomy. All kidneys were preserved by using machine pulsatile perfusion, and 21 kidneys were transported to other centers. Of the 35 transplanted kidneys, 26 (74%) had immediate function, 6 (17%) had delayed graft function, and 3 (9%) were not used for other reasons. Five of the six transplanted livers had immediate function.

Adolescent↗
PubMed1998

Effect of recipients' peri-operative parameters on the outcome of kidney transplantation.

In this prospectively collected data base multifactorial study, the influence of the peri-operative recipients' parameters on the transplanted kidney function were examined. One hundred and twenty-one patients who underwent first cadaver kidney transplantation in our unit were involved and were followed up for another 2 yr. The recipients were divided into three groups. Group I, patients with non-functioning grafts, group II, with delayed graft function, and group III, with good graft function. All routinely measured parameters were involved in the examination. The pre-operative haematocrit level differed significantly among the three groups. Significant intra-operative differences were found among the three groups in mean arterial pressure, (group I: 81 +/- 31 mmHg, group II: 90 +/- 24 mmHg, vs. group III: 108 +/- 26 mmHg, p < 0.01) at 5 min before revascularisation. The patients who had better post-operative kidney function, had lower pre-operative haematocrit level, and higher blood pressure in the different phase of operation, than those who had post-operative kidney function problems. The second warm ischaemic time in Group III was significantly shorter than in group I. (Group I: 51.5 min vs. group II: 47 min, vs. group III: 46.3 min, p < 0.001). Rejection rate was higher during the first 5 post-operative days in patients with non-functioning grafts. (Group I: 53% and group II: 24% vs. group III: 12% p < 0.001). The other examined parameters had not differed significantly among the three groups. The kidney function differences observed in the early (first 5 d) post-operative period, remained similar at the end of the next 2 yr. According to our results the peri-operative fluid-balance is one of the most important factors which may influence the success of the kidney transplantation.

Adult↗
PubMed1999

Excellent outcome in recipients of dual kidney transplants: a report of the first 50 dual kidney transplants at Stanford University.

HYPOTHESIS: Recipients of dual kidney transplants from older expanded criteria donors (ECDs) have outcomes similar to recipients of single kidneys from younger donors. Dual transplantation is the use of both adult donor kidneys into a single adult recipient. DESIGN: Donor and recipient variables were entered into a database. Analysis was performed in a retrospective fashion. The unpaired t test and chi2 test were used as appropriate. SETTING: A university teaching hospital. PATIENTS: All adult recipients of cadaveric kidney-only transplants from adult donors between November 1991 and January 1999. Patients were grouped based on whether they received a dual or single transplant and whether the donor was an ECD. The control group of patients received non-ECD cadaveric kidneys. RESULTS: Donors for recipients of dual kidneys were older and had a lower creatinine clearance on hospital admission than recipients of single control kidneys. Recipients of dual transplants were older, had fewer rejections, and had similar 3-month and 1-year serum creatinine levels vs controls. Predictors of an elevated serum creatinine level or graft loss at 3 months in recipients of ECD dual and single transplants included kidneys from donors with unstable preprocurement renal function, and recipients who developed delayed graft function. CONCLUSION: Recipients of dual kidney transplants from ECDs have excellent outcomes similar to recipients of single control kidneys.

Adult↗
PubMed2004

Laparoscopic right donor nephrectomy: a large single-center experience.

BACKGROUND: Laparoscopic procurement of right donor kidneys is frequently avoided or performed using hand-assist devices because of concerns regarding donor safety, adequate exposure, and vessel length. The present study describes the authors' large series of right donor nephrectomies performed laparoscopically without the use of hand ports or other manual assist devices. METHODS: The authors retrospectively analyzed all right laparoscopic donor nephrectomies performed at their center from November 1, 1999, to February 20, 2004. Study variables included operative times, blood loss, hospital stay, graft function, and donor and recipient complications. Left donor nephrectomies performed during the same period served as controls. RESULTS: Of 387 laparoscopic kidney procurements, 54 (14 %) were right nephrectomies. Blood loss, extraction times, length of stay, and overall complication rates were similar between right and left donor groups. The mean operative time in the right nephrectomy group was significantly shorter than in the left nephrectomy group (169 +/- 25 and 186 +/- 29 min, respectively; P = 0.003). Graft function 1 month after transplantation and the incidence of delayed graft function were similar in both groups. There was one graft loss caused by thrombosis in the left nephrectomy group; other graft-related complications in the recipients were similar in both groups. CONCLUSIONS: This large single-center experience demonstrates that laparoscopic right donor nephrectomy performed without hand-assist devices is safe and yields kidneys with excellent function. The authors conclude that selection of the appropriate kidney for donation using this approach can be based on the same criteria that have traditionally governed open donor nephrectomy.

Adult↗
PubMed2004

Donor kidney glomerular filtration rate and post-transplant graft function.

This study aimed to estimate the relationship between the single kidney glomerular filtration rate (SKGFR) of a planned kidney transplant and the subsequent graft function and survival of living related kidney recipients (LKRs). Of 180 LKRs with the graft functioning for more than a year, 70 patients without delayed graft function (DGF) or acute rejection (AR) were selected for the study. According to SKGFR, assessed by 99mTcDTPA, the patients were allocated into Group 1, receiving kidney with SKGFR < 50 mL/min (32 patients), and Group 2, with SKGFR > 50 mL/min (38 patients). The database included donor, recipient and transplant variables. No significant difference was found between the patient and graft survival rate, creatinine clearance (CCr) and the rate of CCr change between the groups. Additional evaluation revealed no significant influence of the ratio of SKGFR and the recipient's body weight/size on patient and graft outcome. The analysis of factors of influence on patient and graft survival and function revealed the major influence of nonimmunological factors but not of SKGFR of the transplanted kidney. Our study did not confirm the influence of SKGFR on graft function and survival in the LKRs without DGF and AR but the limited number of patients must not be disregarded.

Female↗