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PubMed2006

Molecular markers in stored kidneys using perfluorocarbon-based preservation solution: preliminary results.

BACKGROUND: Delayed graft function (DGF) is a problem in kidney transplantation and cold ischemia has been identified as a risk factor. Perfluorocarbons (PFC) have an enhanced ability to dissolve and release oxygen. We evaluated histologically and a number of molecular changes induced by ischemia in stored kidneys with University of Wisconsin (UW) and PFC-based preservation solutions (PFC-UW). MATERIALS AND METHODS: ACI rats were used as kidney donors. UW (control group) or PFC-UW (study group) preservation solutions were used for kidney perfusion. All kidneys were stored at 4 degrees C for 12, 24, and 36 hours. After this time, intragraft histologic evaluation as well as mRNA HO-1 and iNOS levels were also analyzed. RESULTS: In the kidneys stored at 24 hours, mRNA HO-1 levels were elevated in the study group when compared with the control and mRNA iNOS was decreased. CONCLUSION: We observed overexpression of HO-1 and underexpression of iNOS in the kidney tissue stored with PFC-UW solution at 24 hours. These preliminary data suggest that increasing oxygen delivery by PFC added to the perfusion solution triggers cytoprotective mechanism in kidney transplantation.

Adenosine↗
PubMed2006

Healing of surgical incision in kidney transplantation: a single transplant center's experience.

INTRODUCTION: Impaired healing of the surgical incision represents a common complication after kidney transplantation. We led a retrospective study seeking to understand the factors linked to these complications and reasons for their reduction during the last year. PATIENTS AND METHODS: From January 2000 to April 2004, 170 consecutive kidney transplantations were performed in a homogenous patient population. We evaluated the influence of following factors to determine impaired healing of the incision: antirejection drugs, overweight/obesity, age, delayed graft function (DGF), diabetes, and abdominal wall reconstruction technique. RESULTS: Among 165 patients we observed 26 (15.76%) cases of impaired healing of the surgical incision: 17 (65,38%) with first-level and nine with second-level wound complications. CONCLUSIONS: Impaired healing of the surgical incision influences the outcome of kidney transplant patients. In our study we observed that cyclosporine and tacrolimus similary affected the incision's healing. It was not possible to evaluate the role of basiliximab. A univariate analysis of the factors related to complications revealed overweight and DGF. However, all patients developing second-level complications showed more risk factors. Patients who had not had reconstruction of the muscle layers showed a greater incidence of surgical complications, whereas patients who had skin sutured with an intradermic technique did not show an increased risk.

Graft Survival↗
PubMed2006

Combined liver-kidney transplantation: the experience of the University of Bologna and the case of preoperative positive cross-match.

Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney.

Adult↗
PubMed2006

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).

Adult↗
PubMed2006

Long-term results of kidney transplantation with cyclosporine- and everolimus-based immunosuppression.

The aim of the study was to evaluate safety and efficacy of everolimus with cyclosporine (CsA) in de novo renal transplant recipients. The immunosuppressive regimen, including basiliximab, everolimus (3 mg), and low-dose CsA, was administered to 17 patients, of whom 15 were part of a multicenter randomized study that stipulated cessation of steroids at 7 days posttransplantation in 5 recipients. Five patients underwent dialysis after transplantation for delayed graft function (DGF; 29%), all of whom showed a good recovery within 3 weeks. The mean follow-up was 45.7 months (SD +/- 13). The 1-year graft survival was 100%. We observed one acute rejection episode. No patient experienced a cytomegalovirus infection. Increased cholesterol and triglyceride levels were reported in almost all patients. Severe arthralgia (n = 3) was treated by everolimus dose reduction to maintain trough levels at 3 ng/mL. We noted a high rate of switch to mycophenolate mofetil (MMF) throughout follow-up (n = 7), due to everolimus-induced side effects. However, we did not observe normalization of lipids after the switch: patients always required stain treatment, resulting in slightly lower serum cholesterol and triglycerides. Everolimus plus CsA was effective to prevent acute rejection after kidney transplantation. To manage the induced side effects of the drugs C(2) monitoring is mandatory, targeting 350 ng/mL during 1 year and 200 to 250 ng/mL thereafter. Careful reduction of everolimus trough levels to 3 ng/mL is recommended for patients with arthralgia.

Adult↗
PubMedDate not supplied

Cadaveric donor factor variations during a 12-year period: influence on kidney transplant outcomes.

UNLABELLED: Our purpose was to evaluate changes in cadaveric donor factors between 1993 and 2004 and their impact on the short- and long-term outcomes of renal transplants in a single center. PATIENTS AND METHODS: Cadaveric renal transplants performed in our unit between 1993 and 2004 were divided in two groups of identical length: A (n = 455; 1993-1998) and B (n = 465; 1999-2004). Major differences related to donor, graft, and recipient factors were analyzed between groups and correlated with main outcome parameters. Recipient age, gender, weight, etiology of end-stage renal disease, average length of dialysis, and cold ischemia were not different in the two periods. RESULTS: Grafts harvested in our hospital were more frequent in group A (92.3 vs 78.2%; P < .005). Traumatic causes of death were more frequent before 1999: 90.9 vs 70.9% (P < .001). Mean donor age was higher after 1999: 31.37 vs 35.94 years (P < .005). Female donors were more frequent in the second period: 20.5 vs 26.6% (P < .05). Mean donor weight was also higher: 52.36 vs 67.86 kg (P < .05). All of these differences were unfavourable characteristics regarding graft outcomes. Delayed graft function (A = 13%, B = 24.2%), acute rejection episodes (A = 41.2%, B = 28%), and chronic allograft dysfunction (A = 23.5%, B = 14.4%) were also significantly different between the two cohorts (P < .005). Graft function (serum creatinine at 1 and 2 years), patient and graft survivals, causes of graft loss, and of patient death were similar across time. CONCLUSION: The unfavorable tendency in the quality of cadaveric donors during the last 12 years had no negative impact on graft function and patient outcome.

Adult↗
PubMedDate not supplied

Renal transplantation in patients over 60 years of age: a single-center experience.

The prevalence of end-stage renal disease (ESRD) increases with advancing age. In most countries renal transplant recipients are getting older, too. Transplantation must be considered for ESRD patients older than 60 years; however, there are few data regarding outcomes in this population. We retrospectively reviewed the clinical course of recipients aged > or =60 years (n = 43) who underwent primary or repeated grafts from August 1988 to December 2004. We then compared recipient and donor characteristics as well as graft and patient survivals with recipients aged 18 to 59 years (n = 1058) who were transplanted during the same time. Donor age tended to be higher among the oldest recipient group (P < .001). Mean follow-up was significantly shorter in the group aged > or =60 years (P < .001), as our institution only recently has frequently accepted patients > or =60 years. Older recipients showed more frequent delayed graft function (P = .007), longer initial hospitalization (P = .005), and a significantly lower incidence of posttransplant acute rejection episodes (P = .015). Patient (P = .057), graft (P = .407), and death-censored graft (P = .649) survivals were not different between the two groups. Seven recipients aged > or =60 years died; the main cause of which was cardiovascular in origin. The loss of organs (n = 11) in the older patients was mainly due to death with a functioning kidney (54.5%). Our results confirm that renal transplant must be considered in selected patients older than 60 years as patient and graft survivals are similar to those of younger patients.

Adolescent↗
PubMed2006

Outcome of laparoscopic live donor nephrectomy in 2005: National survey of Japanese transplantation centers.

The increased acceptance of laparoscopic nephrectomy (LN) has been a driving force for live donor kidney transplantation. However, the outcomes of LN in live donors has not yet been clarified in Japan. In this study, we surveyed 125 Japanese kidney transplantation centers to investigate the current status of live donor LN. Of 125 centers, the 98 that responded had performed 695 live donor nephrectomies. Among these centers, 43 had performed LN. Among the 695 nephrectomies, 441 donors had undergone LN and 254, open nephrectomies. In 43 centers, 16 were performed as hand-assisted (HA) LN; 20, non-HA; 3, both HA and non-HA; and 5 laparoscope-assisted. Ten centers used a peritoneal approach; 30, a retroperitoneal; and 3, both. In 441 LN donors, 1 had a life-threatening complication of deep venous thrombosis and survived. Blood transfusions were performed in 7 donors. Open conversions from LN were necessary in 24. Minor complications not requiring prolonged hospital stay were reported in 52. The mortality of LN was zero. In contrast, among the 441 recipients, 1 case was reported as primary nonfunction after venous misadventure in the operation and 30 recipients needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 11 recipients. This survey presented the current status of the procedure, providing a base for informed consent from potential donors.

Blood Loss, Surgical↗
PubMed2006

Genomic profiling of kidney ischemia-reperfusion reveals expression of specific alloimmunity-associated genes: Linking "immune" and "nonimmune" injury events.

Increased organ ischemia time leads to delayed graft function (DGF), increased acute rejection (AR), enhanced chronic allograft nephropathy (CAN), and reduced long-term allograft survival. The mechanisms by which IRI predisposes to AR and CAN are unknown. We hypothesized that gene expression profiling of ischemia-reperfusion injury (IRI)-affected kidney would identify how IRI predisposes to AR and CAN. Furthermore, we examined how current immunosuppressive drug molecular targets are altered by IRI. C57BL/6J mice were exposed to 30 (n = 3) or 60 (n = 3) minutes of bilateral kidney ischemia or sham surgery (n = 5). At 36 hour kidney tissue was collected and analyzed using Affymetrix 430MOEA (22626 genes) array and GC-RMA-SAM pipeline. Genes with the false discovery rate (q < 1%) and +/-50% fold change (FC) were considered affected by IRI. Genes coding for histocompatibility and antigen-presenting factors, calcineurin, and mammalian target of rapamycin (mTOR) pathway-associated proteins were selected using Gene Ontology (GO) analysis. GO analysis identified 10 and 17 alloimmunity-related genes affected by IRI induced by 30 and 60 minutes of ischemia, respectively, including Traf6 (FC = 2.99) and H2-D1 (FC = 2.58). We also detected significant IRI genomic responses in calcineurin and mTOR pathways represented by Fkbp5 (FC = 4.18) and Fkbp1a (FC = 2.0), and Eif4ebp1 (FC = 16.8) and Akt1 (FC = 3.64), respectively. These data demonstrated that IRI up-regulates expression of several alloimmunity-associated genes, which can in turn enhance alloimune responses. Our discovery of IRI-induced up-regulation of genes associated with calcineurin and mTOR pathways are consistent with clinical observations that FK506 and Rapamycin can alter the course of DGF. Further validation and dissection of these pathways can lead to novel approaches by which improved management of early "nonimmune" transplant events can decrease susceptibility to more classic "immune" changes and CAN.

Animals↗
PubMed2006

Microscopic intrarenal particles after pulsatile machine preservation do not adversely affect outcomes after renal transplantation.

INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. RESULTS: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.

Adult↗
PubMed2006

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

Acute Disease↗
PubMed2006

The aetiology and pathogenesis of chronic allograft nephropathy.

Renal transplantation is the ultimate form of renal replacement therapy, and is the treatment of choice for many patients with end-stage renal failure. The advent of calcineurin inhibitor based immunosuppression resulted in the 1-year renal allograft failure rate dropping from around 50% twenty years ago to less than 10% in more recent times. Despite a massive improvement in renal allograft survival in the first year following transplantation 10-year graft survival can be as low as 50%. Chronic allograft nephropathy (CAN) is recognised as the main cause of renal allograft failure following the first year after transplantation. The diagnosis of CAN can only be made histologically. Typically biopsy specimens in grafts with CAN demonstrate an overall fibrotic appearance effecting the vascular endothelium, renal tubules, interstitium, and glomerulus. The risk factors for CAN are divided into alloimmune and alloimmune independent. Alloimmune dependent factors include acute cellular rejection, severity of rejection, subclinical rejection and HLA mismatch. Alloimmune independent factors such as delayed graft function, donor age, Cytomegalovirus infection, donor/recipient co-morbidity and of course calcineurin inhibitor toxicity are important in the development of CAN. The pathogenesis of CAN is complex, multifactorial, and unfortunately incompletely understood. There are a number of pivotal steps in the initiation and propagation of the fibrosis seen in biopsy specimens from kidneys with CAN. Endothelial activation in response to one or more of the aforementioned risk factors stimulates leukocyte activation and recruitment. Recruited leukocytes subsequently infiltrate through the endothelium and induce key effector cells to secrete excessive and abnormal extracellular matrix (ECM). Enhanced deposition of ECM is a histological hallmark of CAN. This paper aims to present a concise yet accurate and up-to-date review of the literature concerning the aetiological factors and pathological processes which are present in the generation of CAN.

Animals↗
PubMed2000

Severe glomerular sclerosis is not associated with poor outcome after kidney transplantation.

BACKGROUND: The increased utilization of expanded criteria kidney donors has necessitated the reevaluation of multiple donor risk factors to insure the best outcome from this valuable resource. Reports of decreased graft survival in recipients of kidneys from donors with > or =20% glomerular sclerosis (GS) have led many transplant centers to refuse these donor kidneys. The purpose of this study is to compare outcome in recipients of cadaveric donor kidneys with > or =20% GS versus those with <20% or no GS at our center. METHODS: We retrospectively reviewed 18 donor and 19 recipient and outcome variables in 89 recipients of kidneys, which were biopsied at the time of transplantation, between February 1995 and November 1998. We evaluated outcome based upon the percent of GS and the degree of vasculopathy. RESULTS: Donors with > or =20% GS were older and had more hypertension. Recipients of kidneys with > or =20% GS were older, had higher serum creatinine values at 1 and 2 years, but similar rates of delayed graft function and 2-year graft survival. Vasculopathy did not correlate to any important donor criteria except the percent GS. However, serum creatinine was significantly higher in recipients of kidneys with moderate vasculopathy versus none, up to 2 years after transplantation. There was no significant difference in graft loss based upon vasculopathy. CONCLUSION: Kidneys from donors with > or =20% GS provide excellent outcome similar to kidneys from donors with no GS.

Adult↗
PubMed2003

Long-term results of renal transplantation using kidneys harvested from non-heartbeating donors: a 15-year experience.

PURPOSE: To expand the pool of suitable organ donors we developed an organ procurement program of non-heartbeating donors during the last 15 years. We compare graft survival in patients receiving renal transplants procured from non-heartbeating with recipients of kidneys from heartbeating donors. MATERIALS AND METHODS: From 1986 to 1999, 60 renal transplantations were performed with kidneys harvested from non-heartbeating donors (Mastrich category IV). Kidneys were procured using a double balloon triple lumen catheter inserted into the femoral artery. The 60 kidneys were selected from 70 non-heartbeating donors based on age younger than 50 years, warm ischemia less than 30 minutes, creatinine less than 200 micromol./l., and no hypertension or major histological lesions. Long-term results of graft survival and complications were compared with a series of 1,065 renal transplantations performed during the same period with kidneys procured from heartbeating donors. RESULTS: Mean age of the recipients was statistically different as non-heartbeating donors were older. However, the 10-year graft survival rates were similar in both groups (50% versus 53%). Incidence of ureteral stenosis and fistula, arterial stenosis and thrombosis was not statistically different in both groups. On the other hand, delay graft function was more frequent in non-heartbeating donors (60% versus 40%, p = 0.01). CONCLUSIONS: Despite a high rate of acute tubular necrosis, kidneys harvested from non-heartbeating donors had the same graft survival rates as those procured from heartbeating donors. Surgical complications were not different. Transplantation of selected kidneys procured from non-heartbeating donors should be promoted as a response to organ shortage.

Adult↗
PubMed1992

A novel method of induced renal hypothermia.

When the kidney is removed from cold storage for implantation into the recipient it gradually rewarms (second warm ischaemic time) and a prolonged second warm ischaemic time is a risk factor for delayed graft function. A cooling jacket has been designed to prevent this rewarming during transplantation. This study evaluates the efficacy of this device. Surface and core temperatures of less than 15 degrees Centigrade were maintained for 120 minutes. Renal function was significantly better in cooled than in uncooled kidneys in a single kidney canine model. Induced renal hypothermia, using a device such as this, should be a routine manoeuvre in renal transplantation.

Animals↗
PubMed1991

Transplantation of kidneys from pediatric cadaver donors to adult recipients.

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.

Adult↗
PubMed1987

Significance of immediate preoperative bacteriuria with pyuria in renal transplant recipients.

The presence of bacteriuria and pyuria on urinalysis immediately before renal transplantation has resulted in cancellation of surgery because of concern about post-transplant wound infection. Of 113 renal transplant recipients reviewed 41 (36 per cent) had 5 or more white blood cells per high power field with bacteria in either a voided urine or bladder washout specimen obtained just before grafting. Of those 41 patients 2 suffered postoperative wound infections. Of 72 patients (64 per cent) with less than 5 white blood cells or no bacteria on a preoperative specimen 1 suffered a wound infection (p not significant by Fisher's exact test). Preoperative urine cultures and operative bladder cultures of all 3 patients failed to yield the organisms found later in the wound infections. The factors of sex, insulin-dependent diabetes, delayed graft function, living related versus cadaver donor and pre-transplant splenectomy had no significant relationship to wound infection rates. Renal transplantation can be performed safely in patients who have pyuria and bacteriuria but no signs or symptoms of infection.

Adult↗
PubMed2003

Sirolimus: a single center experience in combination with calcineurin inhibitors.

A retrospective survey was performed to establish patient and graft outcome for all 41 patients at our centre receiving sirolimus (SRL) in combination with calcineurin inhibition (CNI) as primary therapy for the 6 years prior to March 2002. Patient mortality [12%; n = 5 (TTP, lymphoma, mucormycosis, and small bowel perforation] was significantly higher at 3 months compared with those not receiving SRL, but not thereafter. 12.8% had delayed graft function and 33% had one or more episodes of rejection in the first 6 months. Mean GFR at 12 months was significantly lower (47.3 mL/min) in the SRL group compared with those not receiving SRL (51.3 mL/min). Twenty-two patients had a 12-month protocol biopsy; CNI toxicity was present in 36%. SRL was associated with significant hyperlipidaemia (serum cholesterol, 5.2 +/- 1.4 at baseline vs 7.3 +/- 1.7 mmol/L at 3 months, P <.001; triglycerides, 2.3 +/- 1.4 at baseline vs 2.7 +/- 1.1 mmol/L at 3 months, P <.05). Mild thrombocytopenia occurred in 23% but was not associated with haemorrhagic events. LDH increased by 62%, remaining elevated out to 2 years post engraftment. Seven patients developed insulin requiring diabetes mellitus, similar to the rate observed in our general transplant population.Thus, in this early experience, SRL in combination with CNI was associated with significant mortality and morbidity including CNI toxicity, presumably a reflection of a heavy burden of immunosuppression. However, 1-year graft survival on SRL was similar to the mean Australia-wide graft survival regardless of immunosuppression. The future use of SRL may center around CNI sparing and avoidance type protocols.

Adrenal Cortex Hormones↗