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PubMed1999

Histological factors of 1-h biopsy influencing the delayed renal function and outcome in cadaveric renal allografts.

The morphological characteristics of a kidney biopsy specimen taken 1 h after reperfusion of blood into the graft (1-h biopsy) during a cadaveric transplant operation were studied. The aim of the 1-h biopsy is to evaluate the pre-transplant risk factors for the delayed graft function, assess the renal function of the graft, and predict long-term graft survival. The total number of 1-h biopsies was 113, consisting of 86 male and 27 female donors. The mean age of the donors is 39.5 +/- 17.3 yr. Arteriosclerosis (AS) and tubulo-interstitial injury (TI) were both estimated using a semi-quantitative scale. AS score was graded into four categories, according to the severity of the thickening of interlobular artery: 0: none, 1: mild, 2: moderate and 3: severe. No biopsy revealed severe AS of grade 3. The TI score was graded from 0 to 5, according to the morphological injury: 0: none, 1-2 non-specific tubulo-interstitial injury (NSTI), and 3-5 compatible with acute tubular necrosis (ATN) in terms of pathological diagnosis. The mean ages of donors showing as AS of score 0, 1, and 2 were 30.6 +/- 14.6, 49.7 +/- 13.5, and 56.9 +/- 6.30, respectively. The mean donor age of the AS 1 group and AS 2 group was significantly lower than for the AS 0 group. The lowest serum creatinine values after operation (best Cr) of recipients with AS scores of 0, 1, and 2 were 1.31 +/- 0.45, 1.60 +/- 0.70, and 1.84 +/- 0.71 mg/dL, respectively; the best Cr of AS scores of 1 and 2 was significantly higher than in the AS score 0 group. The mean creatinine level at the final point of the AS 0 group was significantly lower than in the combined AS 1 and AS 2 group (serum creatinine 1.44 +/- 1.03 vs 1.87 +/- 1.53 mg/dL: p < 0.01). The duration of severe hypotension less than 50 mmHg or 80 mmHg was significantly shorter in the NSTI group than in the ATN group (less than 50 mmHg was 29.7 +/- 124 vs 72.5 +/- 174, less than 80 mmHg 105 +/- 234 vs 193 +/- 261 min: p < 0.01). The post-operative (po) day expressing diuresis in excess of 1000 mL of urine per d was 8.28 +/- 17.5 and 13.7 +/- 23.3 (p < 0.01) in the NSTI and ATN group, respectively. The po-d of the last hemodialysis and the po-d showing serum creatinine less than 2.0 mg/dL in NSTI and ATN group was 7.74 +/- 17.4 and 13.3 +/- 23.2 (p < 0.01), and 25.0 +/- 30.5 and 38.0 +/- 35.2 (p < 0.01), respectively. We concluded that 1-h renal biopsy is useful for assessing the outcome of renal allograft. AS of a donor kidney is one of the most important risk factors for both short and long-term outcome of the graft. The TI score was useful to predict the outcome of delayed graft function.

Adult↗

PubMed1991

The UNOS Scientific Renal Transplant Registry--1991.

Based upon data reported to the UNOS Scientific Renal Transplant Registry between October 1987 and November 1991: 1. One-year graft survival rates were 79%, 73% and 62% for recipients of first (20,864), second (3,217), and multiple (673) cadaver donor transplants, respectively. 2. One-year graft survival rates were 94%, 89%, and 90% for first transplant recipients of kidneys from HLA-identical siblings (970), parents (1,487), and 1-haplotype-mismatched siblings (1,206), respectively. 3. Half-lives calculated after the first year were 7 years for cadaver donor transplants, 11 years for parent, 12 years for 1-haplotype sibling and, 27 years for HLA-identical sibling-donor first transplants. 4. The 1-year first transplant survival rate has improved from 78% in 1987-88 to 80% in 1990-91 transplants (p = 0.001). There has been an attendant decline in the percentage of broadly sensitized patients transplanted from 15% in 1987 to 8% in 1990 (p less than 0.01), which may have contributed to rising survival rates. 5. There has been a remarkable improvement in the 1-year graft survival of retransplanted patients from less than 70% in 1987-88 to 78% in 1990 (p less than 0.001). This improvement has been most notable in broadly sensitized patients and those with delayed graft function. 6. Diabetics who received a pancreas and kidney transplant (995) had 81% 1-year graft survival compared to 77% for those who received a kidney transplant only (p less than 0.002). 7. One-year graft survival rates decreased significantly in recipients of kidneys from donors aged under 16 or over 45. Survival was less than 70% when the donor was under 5 or over 60 compared to 81% when the donor was aged 16-45 (p less than 0.001) for recipients of first cadaver transplants. Delayed graft function occurred in 40% of cases when the donor was over 60 and 28% of cases when the donor was under 5. When function was delayed, survival was 50% for these marginal kidneys compared to 68% for younger adult kidneys with delayed function (p less than 0.001). Rejection also had a greater impact on survival of kidneys from donors under 5 or over 60. 8. The 1-year graft survival rate for 2,504 first transplant recipients of cadaver kidneys from young male victims of traffic accidents was 85%. The 1-year graft survival of 2,670 patients given kidneys from older female donors who died of cerebrovascular accidents was 73% (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1993

Excellent outcome with a calcium channel blocker-supplemented immunosuppressive regimen in cadaveric renal transplantation. A potential strategy to avoid antibody induction protocols.

Many transplant centers routinely utilize monoclonal antibody or polyclonal antibody based induction protocols in recipients of cadaver renal allografts. Given the potential complications associated with antibody-based immunosuppression regimens (e.g., CMV disease), we tested the hypothesis that a combination of a calcium antagonist and a triple drug protocol (cyclosporine + prednisone + azathioprine) would be an effective substitute for antibody-based induction protocols in ensuring excellent patient and graft survival rates. Our postulate was tested in a prospective study of 52 consecutive recipients of cadaver renal allografts (44 first, 5 second, and 3 third grafts) utilizing nifedipine as the first line calcium antagonist. Nifedipine was selected over verapamil or diltiazem due to its lack of interference with the metabolism of CsA. Some of the significant outcomes of our prospective trial were (A) a cumulative patient survival rate of 98.1% for the 52 recipients at 18 months posttransplantation; (B) a cumulative allograft survival rate of 92.1% for the 52 consecutive cadaver renal allografts at 18 months; (C) a cumulative allograft survival rate of 100% at 18 months for the 24 of 52 renal allografts without delayed graft function following transplantation; and (D) a cumulative allograft survival rate of 86% at 18 months for the 28 of 52 renal allografts with delayed graft function. Of the 4 of 52 who lost their grafts, 2 grafts were removed following discontinuation of immunosuppressive therapy while the remaining 2 had primary nonfunction; and (E) the lack of a requirement for monoclonal or polyclonal antibodies for the treatment of acute rejection episodes in this patient population. These gratifying results compare very favorably with (A) recent reports of the effects of long-term diltiazem therapy and of verapamil used in conjunction with an induction protocol that included Minnesota antilymphocyte globulin in recipients of cadaver renal allografts, and (B) the clinical outcome in many institutions with OKT3/ATG/ALG induction protocols. Whereas the mechanisms involved in the excellent clinical outcome found with the calcium antagonist remain undefined, our results strongly argue for a prospective, randomized and controlled study in which a calcium antagonist-supplemented immunosuppressive regimen is compared with antibody-based induction protocols.

Adult↗

PubMed2002

Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion.

BACKGROUND: Ischemia-reperfusion injury after organ transplantation is a major cause of delayed graft function. Prevention of post-transplant ischemia acute renal failure is still elusive. METHODS: The present study was designed to examine whether propionyl-l-carnitine, an acyl derivative of carnitine involved in fatty acid oxidation pathway and adenosine 5'-triphosphate (ATP) generation of mitochondria, prevented renal function deterioration and structural injury induced by ischemia-reperfusion in an ex vivo rat model of isolated perfused kidney (IPK) preparation and in vivo in a model of syngeneic kidney transplantation. RESULTS: In the model of ischemia (20 or 40 min)/reperfusion (90 or 70 min) in IPK, untreated kidneys showed a marked reduction of glomerular filtration rate (GFR) and renal perfusate flow (RPF) as compared to baseline, when perfusion was established by restoring effective perfusion pressure to 100 mm Hg. Exposure of kidneys to propionyl-l-carnitine before establishing the ischemia insult to tissue, largely prevented renal function impairment. Pre-exposure of ischemic kidneys to propionyl-l-carnitine largely reduced the percent of lactate dehydrogenase (LDH), a cell injury marker, released into the perfusate after reperfusion as compared to untreated ischemic kidneys. Histologic findings showed very mild post-ischemic lesions in kidneys exposed to propionyl-l-carnitine as compared to untreated ischemic kidneys. Immunohistochemical detection of 4-hydroxynonenal protein adduct, a major product of lipid peroxidation, was very low in kidney infused with propionyl-l-carnitine and exposed to ischemia/reperfusion as compared to untreated ischemic kidneys. ATP levels were not affected by propionyl-l-carnitine treatment. Renal function of kidneys exposed for four hours to cold Belzer UW solution added with propionyl-l-carnitine and transplanted to binephrectomized recipients was largely preserved as compared to untreated ischemic grafts. Propionyl-l-carnitine almost completely prevented polymorphonuclear cell graft infiltration and reduced tubular injury at 16 hours post-transplant. CONCLUSIONS: These data indicate that propionyl-l-carnitine is of value in preventing decline of renal function that occurs during ischemia-reperfusion. The beneficial effect of propionyl-l-carnitine possibly relates to lowering lipid peroxidation and free radical generation that eventually results in the preservation of tubular cell structure. The efficacy of propionyl-l-carnitine to modulate ischemia-reperfusion injury in these models opens new perspectives for preventing post-transplant delayed graft function.

Animals↗

PubMed1999

Pre-transplant identification of risk factors that adversely affect length of stay and charges for renal transplantation.

BACKGROUND: In the current era of renal transplantation, increasing attention is being focused on resource utilization. The purpose of this study was to identify demographic, medical and immunologic risk factors that are associated with changes in length of stay (LOS) and charges for renal transplantation. METHOD: The study was a retrospective analysis of 311 consecutive renal transplants performed at a single institution. Univariate and multivariate analyses were used to examine relationships between risk factors, LOS, charges and post-operative complications. RESULTS: The following pre-transplant variables were found to be independently significant in predicting increased LOS and/or charges: African-American race, obesity for women, chronic obstructive pulmonary disease (COPD), presence of cardiac disease or previous stroke, pre-transplant dialysis time > or = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and retransplantation. The analyses were performed with and without adjustment for key outcome variables such as delayed graft function (DGF) and use of induction antibody therapy. Increased LOS or charges for specific risk factors could be attributed to increased complication rates, including delayed graft function seen with various co-morbidities, or increased immunologic risk and more frequent use of induction antibody therapy. CONCLUSION: Analysis of linked financial and clinical databases can reveal demographic, medical and immunologic risk factors that correlate with LOS, charges and complications for renal transplantation. Efforts to establish quantitative relationships for various risk factors relative to resource utilization will become important in managed care and/or capitated healthcare delivery systems.

Adult↗

PubMed1995

Long-term renal preservation and prevention of acute tubular necrosis by inhibition of arachidonate metabolism.

Experimental preservation time for pulsatile perfused dog kidneys was extended from three to five days by phospholipase A2 inhibition suggesting a pathomechanical role of products of phospholipolysis like thromboxane and leukotrienes in the development of acute graft failure after renal transplantation. We therefore investigated the effects of thromboxane- and leukotriene synthase inhibitors on postoperative renal transplant function in a model of pulsatile perfusion preservation as well as a cold storage preservation of dog kidneys. Addition of a thromboxane-synthase-inhibitor to the perfusion medium in pulsatile perfused kidneys and the combined application of a thromboxane-synthase-inhibitor and a leukotriene-synthase-inhibitor to the recipient of a cold storage preserved graft, improved graft function and reduced the incidence of delayed graft function as well as histopathological features of acute tubular necrosis.

Adenosine↗

PubMed1998

[Classification of kidney grafts by renographic parameters].

The aim of this work was to analyze the use of some renographic parameters derived from the 99mTc-MAG3 renogram to classify post-transplantion studies in two groups: Normal functioning grafts (NFG) and delayed grafts function (DGF) which included Acute Tubular Necrosis (ATN) and Acute Rejection (AR). The analysis included data from 38 NFG, 33 ATN and 23 AR. The parameters calculated were: mean transit time (MTT), the Initial Uptake (IU) and the maximum activity (MA) of the renogram. The results obtained from this analysis show that ln(IU) is the best parameter to classify individuals in either group and that the use of MA or the MTT does not improve the results. Using a cutoff point of ln(IU) = 0.28 and a prevalence of 25% for DGF, the estimated predictive values were 92% for DGF and 99% for NFG.

Acute Disease↗

PubMed1993

A phase I trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients.

Several adhesion molecules contribute to the interaction between T cells and antigen presenting cells or target cells. Leukocyte function-associated molecule-1 (LFA-1[CD11a/CD18]) and intercellular adhesion molecule-1 (ICAM-1 [CD54]) are one such critical adhesive receptor-counter-receptor combination. The importance of ICAM-1 dependent adhesion in the rejection response was initially demonstrated in cynomolgus renal allograft recipients treated with the anti-ICAM-1 murine monoclonal antibody BIRR1. BIRR1 also appeared to limit ischemic damage in these animals. A Phase I clinical trial has subsequently been completed in 18 patients who received cadaver donor renal allografts at high risk for delayed graft function (prolonged preservation time, highly-sensitized recipient). An adequate BIRR1 serum level was associated with significantly less delayed graft function (P < .01) and rejection (P < .01). In 1-hr biopsies, mouse IgG was detected along the endothelium of the vessels and glomeruli in the graft. There were no instances of primary non-function (PNF), and current allograft survival (followup: 16-30 months) in these "high-risk" mAb-treated patients is 78%. There were 3 instances of PNF and a graft survival rate of 56% in the recipients of the contralateral kidney allografts treated with conventional immunosuppression. No significant "first-dose" effect was associated with BIRR1 administration. These results establish a dosing schedule and the clinical safety of BIRR1. They also suggest that inhibition of leukocyte adhesion by mAb therapy may be useful in controlling allograft rejection and possibly in limiting reperfusion injury. Thus, these observations support the clinical importance of accessory molecules in T cell function. We hypothesize that anti-CD54 mAb acts by blocking leukocyte adhesion to the endothelium, thereby interfering with sensitization or target cell interaction.

Adolescent↗

PubMed1992

Protective effects of diltiazem and the prostazycline analogue iloprost in human renal transplantation.

To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investigated the effects of diltiazem and those of the prostacycline analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/L in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following 2 days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to 4 years. In the second study, 11 control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iliprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of cyclosporin-A (CyA) nephrotoxicity in diltiazem-treated patients compared to controls, even though these patients also exhibited higher CyA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1992

Protective effects of calcium antagonists in human renal transplantation.

To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investigated the effects of diltiazem and those of the prostacyclin analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/liter in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following two days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to four years. In the second study, 11 control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iloprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of Cyclosporin A (CsA) nephrotoxicity in diltiazem-treated patients compared to controls, even though these patients also exhibited higher CsA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1985

Short-term kidney preservation: to perfuse or not to perfuse with the new Belzer perfusate.

Delayed graft function is ischaemically induced and the consequence of high energy phosphate depletion. A new perfusate, described by Belzer, has been used in 43 kidney preservations, 16 of which had prolonged cold ischaemia. The overall immediate function rate was 37 of 43 kidneys or 86 per cent. Of 18 kidneys cold-stored during the same period, only nine functioned immediately. Twenty-six of these patients received cyclosporine for immunosuppression without an increase in delayed graft function or evidence of increased nephrotoxicity because of ischaemic injury or prolonged preservation.

Adenosine Triphosphate↗

PubMed2002

Creatinine reduction ratio and 24-hour creatinine excretion on posttransplant day two: simple and objective tools to define graft function.

To devise objective criteria for early diagnosis of delayed graft function (DGF), 59 adult living donor kidney transplants with immediate graft function (IGF) and 51 cadaveric kidney transplants were investigated for creatinine reduction ratio (CRR2) from posttransplant day 1 to day 2 and 24-h urine creatinine excretion (UC2) on day 2. The mean CRR2 in living donor transplants was 53% (SD +/- 11); the distribution of CRR2 was gaussian, and all of them had UC2 >1000 mg. Criteria for DGF were developed on the basis of living donor transplant: CRR2 < or =30% (2SD below 53%) +/- UC2 < or =1000 mg. Overall, 24 cadaver transplant recipients (47%) developed DGF (CRR2 < or =30%); 13 patients (25%) had mild DGF (UC2 >1000 mg), and the remaining 11 (22%) had severe DGF (UC2 < or =1000 mg). All the patients with severe DGF had a measured creatinine clearance <25 ml/min on day 7, and 8 of 11 were dialyzed within the first week of transplantation. Patients with IGF and mild DGF had a creatinine clearance of > or =25 ml/min on or before day 7, and none of them were dialyzed. Calcineurin inhibitors were avoided or delayed in five patients with mild DGF and all patients with severe DGF. In conclusion, diagnosing DGF within 48-h after transplantation is simple and may be valuable in the management of these patients.

Adult↗

PubMed1999

Peritoneal dialysis immediately post transplantation.

Many peritoneal dialysis (PD) patients undergo successful renal transplantation. The outcome is similar to that for transplanted hemodialysis (HD) patients. For delayed graft function, dialysis is necessary in the immediate post-transplant period. PD can be undertaken, with a small risk of peritonitis and other PD-related complications. Delayed graft function is less prevalent in patients who were on PD before transplantation than in those who were on HD. The dialysis modality may have an impact on graft survival. The graft thrombosis rate is unaffected by the prior mode of dialysis. Catheter-related problems are infrequent, but there must be a low threshold for catheter removal for any sign of non response to therapy for peritonitis or for exit-site and tunnel infections. PD can be undertaken successfully in the immediate post-transplant period.

Catheters, Indwelling↗

PubMed1993

Post-transplant lymphoceles: a critical look into the risk factors, pathophysiology and management.

To define better the prevalence and pathophysiology of lymphoceles following renal transplantation, we prospectively evaluated 118 consecutive renal transplants performed in 115 patients (96 cadaveric, 22 living-related, 7 secondary and 111 primary). Ultrasonography was performed post-operatively and during rehospitalizations or whenever complications occurred. Perirenal fluid collections were identified in 43 patients (36%). Lymphoceles with a diameter of 5 cm. or greater were identified in 26 of 118 cases (22%). Eight patients (6.8%) had symptomatic lymphoceles requiring therapy. The interval for development of symptomatic lymphoceles was 1 week to 3.7 years (median 10 months). Risk factors for the development of lymphoceles were examined by univariate and multivariate analysis, and included patient age, sex, source of transplants (cadaver versus living-related donor), retransplantation, tissue match (HLA-B/DR), type of preservation, arterial anastomosis, occurrence of acute tubular necrosis-delayed graft function, occurrence of rejection, and use of high dose corticosteroids. Univariate analysis showed a significant risk for the development of lymphoceles in transplants with acute tubular necrosis-delayed graft function (odds ratio 4.5, p = 0.004), rejection (odds ratio 25.1 p < 0.001) and high dose steroids (odds ratio 16.4, p < 0.001). When applying multivariate analyses using stepwise logistic regression, only rejection was associated with a significant risk for lymphoceles (symptomatic lymphoceles--odds ratio 25.08, p = 0.0003, all lymphoceles--odds ratio 75.24, p < 0.0001). When adjusting for rejection, no other risk factor came close to being significant (least p = 0.4). Therapy included laparoscopic peritoneal marsupialization and drainage in 1 patient, incisional peritoneal drainage in 4 and percutaneous external drainage in 3 (infected). All symptomatic lymphoceles were successfully treated without sequelae to grafts or patients. We conclude that allograft rejection is the most significant factor contributing to the development of lymphoceles. Therapy of symptomatic lymphoceles should be individualized according to the presence or absence of infection.

Adolescent↗

PubMed2001

Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation.

BACKGROUND: The adoption of calcineurin inhibitors (CNI) as the mainstay of immunosuppression has resuited in a significant decrease of acute rejection and improvement of short-term graft survival. However, because of the irreversible nephrotoxicity associated with the chronic use of the CNI, the magnitude of the improvement of long-term graft survival has been more modest. Therefore, an effective immunosuppression regimen that does not rely on CNI may result in improvement of long-term outcome and simplification of the management of transplant recipients. METHODS: Ninety-eight patients of primary cadaver or living donor kidneys at low immunologic risk were enrolled in a CNI avoidance study. The immunosuppression regimen consisted of daclizumab, a humanized monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (IL-2Ralpha), administered for a total of five doses at biweekly intervals; 3 gm/day mycophenolate mofetil for the first 6 month and 2 gm thereafter; and conventional corticosteroid therapy. Patients who underwent rejection episodes could be started on CNI. The primary efficacy end-point was biopsy-proven rejection during the first 6 months posttransplant. RESULTS: Biopsy-proven rejection was diagnosed in 48% of patients during the first 6 months after transplantation. The majority of rejection episodes were Banff grade I and IIA and were fully reversed with corticosteroid therapy. The median time to the first biopsy-proven rejection among patients who experienced this event during the first 6 months was 39 days. In 22 patients with delayed graft function, the proportion of patients with biopsy-proven rejection was 50% at 6 months. However in the first 2 weeks posttransplant, only 1 of 22 patients with delayed graft function developed biopsy-proven rejection. At 1 year, patient survival was 97% and graft survival was 96%. Only two grafts were lost secondary to rejection. At 1-year posttransplant, 62% of patients had received CNI for more than 7 days. At 1-year posttransplant, the mean serum creatinine in the nonrejectors with no CNI use was 113 micromol/L (95%, confidence interval [CI], 100.7 to 125.3 micromol/L) and in the rejectors or patients with CNI use (more than 7 days) was 154 micromol/L (95% CI, 135.0 to 173.0 micromol/L). In selected patients with rejection, analysis of circulating and intragraft lymphocytes revealed complete IL-2Ralpha saturation. CONCLUSIONS: This CNI avoidance study in immunologic low-risk patients, while only partially successful in preventing acute rejection, provided benefits to a sizable minority of patients who have not required chronic CNI therapy. However, wide acceptance of a CNI-sparing immunosuppression regimen may require a lower rate of acute rejection, possibly through the addition of a non-nephrotoxic dose of CNI. However, because complete IL-2Ralpha blockade was present during rejection, it can be assumed that alternative pathways, such as IL-15, may be responsible for the rejection; thus, the incorporation of non-nephrotoxic immunosuppressive agents, such as sirolimus, may provide a more strategic approach.

Antibodies, Monoclonal↗

PubMed2003

Tailoring tacrolimus-based immunotherapy in renal transplantation.

Tacrolimus is a cornerstone immunosuppressive agent in renal transplantation and compared with cyclosporin, its use is associated with a reduced incidence of acute rejection. Optimizing immunosuppressive management in the early post-transplant period is important for achieving long-term graft function and survival. In attempts to improve the long-term outcomes of renal transplantation further, tacrolimus has been combined with two novel immunosuppressive agents, mycophenolate mofetil (MMF) and sirolimus, with encouraging results in terms of patient and graft survival, acute rejection rates and renal graft function. Tacrolimus in combination with MMF adjunctive therapy showed significantly better graft survival in patients with delayed graft function, fewer episodes of corticosteroid-resistant rejection and better renal function at the 3-year follow-up compared with cyclosporin microemulsion plus MMF immunosuppression. A tacrolimus plus MMF regimen was also effective for renal transplant recipients at our centre in Pennsylvania, resulting in excellent survival and rejection rates at 1 year post-transplantation. The 3-month results of a US multicentre study comparing tacrolimus in combination with either MMF or sirolimus showed these two treatment regimens to be equivalent in terms of patient and graft survival, delayed graft function, the incidence of biopsy-confirmed acute rejection and renal graft function, although differences were apparent in terms of acute tubular necrosis and hyperlipidaemia. In conclusion, the development of a new immunosuppressive regimen in renal transplantation should take account of factors that influence graft function, both in the short and long term, as a way of optimizing individual maintenance therapy.

Clinical Trials as Topic↗

PubMed1995

Combined simultaneous kidney/bone marrow transplantation.

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Adolescent↗

PubMed2003

Recipient outcome following living donor kidney transplantation using kidneys procured laparoscopically.

BACKGROUND: Laparoscopic live donor nephrectomy is becoming increasingly popular as it has been shown to minimize donor morbidity, length of hospital stay and length of time to return to work. Initial experience suggested that kidneys procured laparoscopically had higher rates of delayed graft function and ureteric complications but with increasing experience, these complications have become less common. METHODS: Retrospective chart review of all patients who underwent living donor kidney transplant using kidneys procured laparoscopically at our centre was performed. From the initiation of the laparoscopic donor nephrectomy programme at our institution in November 1998 until February 2002, we performed 71 living donor kidney transplants (69 kidneys procured laparoscopically and two procured by open donor nephrectomy after failed laparoscopic approach). Donor left kidney was used in all except in one patient. Mean duration of warm ischaemia time was 206 +/- 79 s. RESULTS: The mean age of the recipients was 42 +/- 15 years (range 1-68) including five paediatric recipients (age < 18 years). There were 48 males and 23 females. Nine (13%) were retransplants (seven second transplants and one each of third and fourth transplants). Two patients died with functioning grafts and four patients lost the graft (three thrombosis, one anastomotic rupture). No patient developed ureteric complications. The incidence of delayed graft function (need for dialysis in the first week post-transplant) was 4%. Patient and graft survival rates (actual) were 97% and 91%, respectively. Mean length of hospital stay was 9 +/- 7 days (median 7 days). CONCLUSIONS: Recipient outcome is not compromised and excellent results can be achieved with living donor kidney transplantation using laparoscopically procured kidneys.

Adolescent↗