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PubMed2006

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Aged↗
PubMed1995

Changing demographics in renal transplant recipients: the 30 year Cleveland Clinic experience.

While it does appear that the most recent era of transplantation has not resulted in significant improvement in long-term allograft function, this appears to be due, at least in part, to the transplantation of increasing numbers of high-risk patients. It is noted that the improved results accomplished over prior eras of transplantation have been maintained despite the inclusion of these high-risk patients. Patients currently undergoing transplantation are more likely to be older, diabetic, obese or African American. All of these subgroups have poorer patient survival in the most recent transplant era and thus, death with a functioning graft has become a significant contributor to graft loss. Recipients were more likely to receive kidneys from cadaveric donors in the most recent era and within the live-donor groups, sibling donation has decreased. Hopefully, the recent trend of increased live-donor transplants (especially living, unrelated transplants) will continue. Cadaveric recipients were at higher risk for posttransplant ATN which, for the first time in the current era, had a significant adverse impact on graft survival. Long-term survival appeared to be associated with particular characteristics (optimal age at transplantation, optimal donor age, live donor, etc.), and can be achieved despite known risk factors, such as rejection or delayed graft function.

Adolescent↗
PubMed2000

The kidney in liver transplantation.

Early recognition and determination of the cause of renal failure in patients with ESLD can be difficult because of the potential interplay among various factors and the wide array of differential diagnoses. A systematic approach, however, assists clinicians to identify common and potentially reversible causes of ARF. It is crucial to distinguish patients with functional renal failure, such as HRS, from those with advanced irreversible renal disease. Isolated liver transplantation is the treatment of choice for the former, and CLKT may be a therapeutic option for the latter. Because of the ever-increasing shortage of donor organs, CLKT must be used judiciously. Kidney biopsy may resolve diagnostic dilemmas. Management of renal complications post-OLT remains a challenge for the physician caring for transplant patients. Modification of nephrotoxic immunosuppressive regimens to avoid postoperative ARF/CRI has met with variable results. Azathioprine has been used in place of cyclosporine. Therapy with polyclonal antilymphocyte preparations or anti-OKT3 monoclonal antibodies (Orthoclone) should be reserved for patients with delayed graft function and for the treatment of acute rejection. The routine use of these agents as prophylactic therapy is not recommended. Data on the impact of renal insufficiency on patient and allograft outcome are inconsistent. Nonetheless, the authors' literature review suggests that renal failure associated with sepsis and, except for patients with HRS, renal failure requiring dialysis are the most consistent features associated with a worse outcome. The need for preoperative or postoperative dialysis has no adverse effect on survival in patients with HRS. On long-term follow-up, despite a greater percentage of patients reaching ESRD in patients with HRS compared with their non-HRS counterparts, the overall outcome in patients with HRS following OLT is favorable. In patients with HRS requiring prolonged dialysis (i.e., greater than 4 weeks), however, irreversible renal failure may develop, necessitating CLKT. Ideally, timely referral of patients for OLT may avoid this complication and obviate the need for double organ transplantation.

Hepatorenal Syndrome↗
PubMed2002

Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

BACKGROUND: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. METHODS: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. RESULTS: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. CONCLUSION: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.

Actins↗
PubMed1992

The influence of nephrectomy of the primary allograft on retransplant graft outcome in the cyclosporine era.

The present analysis was undertaken to evaluate the influence of primary allograft nephrectomies on the early function, incidence of rejection, and short-term graft survival of subsequent renal retransplants. Among 95 consecutive cyclosporine treated retransplant recipients, 52 were retransplanted without primary allograft nephrectomy; 35 had removal of their primary grafts prior to retransplantation for fever and graft tenderness (30 patients) and persistent hematuria (5 patients); and 8 patients had an elective primary graft nephrectomy at the time of retransplantation. Demographic characteristics and immunosuppressive regimens were otherwise similar in all three groups. Nephrectomy of the primary allograft prior to retransplantation was associated with a significant subsequent rise in preformed cytotoxic antibody levels (57% having PRA greater than 30% compared with 33% in those with retention of primary grafts), a significantly higher incidence of delayed graft function among retransplants (63% compared with 30% in those who did not undergo primary allograft nephrectomy) and a trend toward decreased allograft survival in the subgroup who lost their primary allografts in the first year posttransplant. The incidence of acute rejection and 3-year posttransplant renal function in retransplants were not, however, influenced by nephrectomy of the primary allograft.

Adolescent↗
PubMed2004

Sensitivity of expanded-criteria donor kidneys to cold ischaemia time.

UNLABELLED: The United Network for Organ Sharing (UNOS), working in conjunction with organ procurement organizations and transplant programmes, has recently defined a class of cadaver kidney grafts for special allocation procedures to enhance utilization of those organs. The criteria defining these expanded-criteria donor (ECD) kidneys are donor age > or = 60 yr or donor age between 50 and 59 yr plus two of the following characteristics: donor history of cerebrovascular accident (CVA), donor history of hypertension (htn), and elevated creatinine (>1.5) at any time during donor management. Kidney grafts from ECD donors carry an increased relative risk of non-function compared to other cadaver kidney grafts. The goal of the special allocation procedure is to reduce the time associated with placement by matching ECD grafts with patients previously designated as being willing to accept them. In assessing the potential impact of these allocation procedures, the sensitivity of ECD grafts to cold ischaemia time (CIT) became of great significance. Specifically, we questioned whether minimization of CIT might reduce the relative risk of poor graft function, justifying reduction of the geographical range of placement and thereby reducing the time the grafts would spend in-transit. METHODS: To assess this, we queried the SEOPF database for cadaveric kidney transplants between 1/1/1997 and 15/8/2002. There were 1312 transplants from ECD donors during this period and 8451 from non-ECD donors. Between these groups, there were no significant differences in recipient gender, ethnicity, peak and most recent panel reactive antibody (PRA). Recipients of ECD kidneys were significantly older: 50.9 +/- 13.0 yr vs. 44.9 +/- 13.9 (mean age +/- SD, P < 0.0001). There were statistically significant but very small differences in the degree of AB and DR mismatch between the groups. RESULTS: Defining delayed graft function (DGF) as dialysis within the first week post-transplant and primary non-function (PNF) as dialysis within the first week and failure in the first year, we found an association with CIT as illustrated in Table 1. Overall, ECD kidneys had a significantly increased (P < 0.0001) incidence of PNF and DGF. Notably, PNF in ECD appeared to be uniformly distributed across CIT and while DGF was CIT-dependent, the DGF differences between ECD and non-ECD were fairly consistent across CIT. CONCLUSION: While CIT minimization is potentially beneficial, ECD kidneys do not appear to be more sensitive to it than non-ECD kidneys.

Cryopreservation↗
PubMed2000

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.

Adult↗
PubMed1997

Assessment of preservation induced reperfusion injury via intraoperative renal transplant blood flow and endothelin concentration studies.

PURPOSE: We investigated a possible relationship between levels of the vasoconstrictive peptide endothelin and renal transplant reperfusion injury, and modified a technique for measuring renal blood flow with an ultrasonic perivascular transit time flow probe. MATERIALS AND METHODS: Renal grafts in a swine transplant model were cold flushed with either Collins-2 or University of Wisconsin solution. Renal blood flow and renal vein endothelin levels after reperfusion of transplanted grafts, as well as histological parameters within the transplanted kidney were measured. The 5-minute post-reperfusion renal blood flow was used as the baseline allograft flow. The definition of reperfusion injury was a decrease in flow from baseline with no recovery within 1 hour of reperfusion. In 9 human recipients reperfusion injury was further verified by monitoring subsequent serum creatinine, urine output, graft survival and rejection episodes. RESULTS: In the swine model and human transplant recipients no evidence of post-reperfusion ischemia was noted by histological examination, supporting that moderate to mild reperfusion injury or ischemic injury cannot be clinically determined with this method. In the swine model the decrease flow from baseline in allograft post-reperfusion renal blood flow was significantly greater in kidneys preserved in Collins'-2 than in University of Wisconsin solution (41.75 +/- 5.69 versus 11.18 +/- 13.99 ml. per minute, p = 0.005), supporting that this technique can assess mild to moderate reperfusion injury. The increase in serum endothelin in the allografts from the swine model and in humans was not significantly different from baseline. Clinically, post-reperfusion renal blood flow changes correlated well with subsequent function. The 4 patients with renal transplant reperfusion injury had significantly higher serum creatinine values and lower urine output 1 week postoperatively than 5 patients with no evidence of injury (serum creatinine: 6.75 +/- 3.03 versus 2.08 +/- 1.28 mg./dl., p = 0.015). Reperfusion injury patients had more rejections (2 versus 1) and less graft survival (75% versus 100%) at 1-year followup compared to the nonreperfusion injury patients. CONCLUSIONS: Vasoactive factors other than endothelin most likely contribute to reperfusion injury. Furthermore, the ultrasonic transit time flow probe accurately measures post-reperfusion renal blood flow and offers a practical method for assessing acute reperfusion injury, which may help to optimize immunosuppressive strategies to decrease allograft loss associated with delayed graft function.

Animals↗
PubMed1990

[A study on the hemodialysis period following cadaveric kidney transplantation--a comparison between two centers sharing cadaver donor kidney pairs].

To study the hemodialysis period following cadaveric renal transplantation, we reviewed 18 consecutive cadaver donor kidney pairs of which one kidney was transplanted at Shiga University of Medical Science (SUMS) while the contralateral kidney was transplanted at Kyoto Prefectural Medical University (KPMU) between January 1983 and September 1988. Of these 18 pairs, graft function was satisfactory and the recipient was free from hemodialysis in 13 pairs. However, the postoperative hemodialysis periods were different between the two centers. To clarify the factors causing this difference, recipient factors, such as age, HLA matching, total ischemic time of the graft (TIT), immunosuppression, onset of diuresis and postoperative complications were studied. There were no significant differences in age, HLA matching, or immunosuppression. TIT of cases at SUMS was significantly longer than that of cases at KPMU. The postoperative hemodialysis period at SUMS was 25.8 days and that at KPMU was 17.8 days, however, the difference was not statistically significant. The results of this study indicate that TIT seems to be a major factor relating to delayed graft function in cadaveric renal transplantation.

Adolescent↗
PubMed2006

Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS: We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS: Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS: Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.

Adult↗
PubMed1997

Long-term renal function in type I diabetics after kidney or kidney-pancreas transplantation: influence of number, timing, and treatment of acute rejection episodes.

BACKGROUND: Previous studies comparing renal function in diabetic subjects receiving either a kidney or kidney-pancreas transplant generally have indicated no differences; however, these studies have been limited by inclusion of either a small number of patients or selected patients followed for relatively short periods of time. METHODS: To compare long-term renal function and factors affecting renal function in type I diabetic patients receiving either kidney or kidney-pancreas transplants, the slopes of regression lines generated by plotting the reciprocal of serum creatinine (1/Cr) versus time were measured in 109 consecutive patients followed for at least 12 and up to 102 months after transplantation. Multivariate analyses included linear regression using the slope of 1/Cr versus time as the dependent variable and logistic regression using a positive or negative slope as the dependent variable. RESULTS: Significant differences between kidney-pancreas (n=64) and kidney recipients (n=45) included a smaller proportion of African-Americans, lower rates of HLA matching, lower levels of panel-reactive antibodies, shorter cold ischemia times, a lower incidence of delayed graft function, and a higher incidence of acute renal allograft rejection episodes in the kidney-pancreas group. Trough cyclosporine blood levels were significantly higher in the kidney-pancreas group for the first 12 posttransplant months. The slopes of 1/Cr versus time were negative in each group with a trend toward a more negative slope in the kidney-pancreas group. Multivariate analyses indicated that a concomitant pancreas allograft did not influence long-term renal function. The total number of renal rejection episodes was the best independent predictor of a negative slope of 1/Cr versus time. However, use of OKT3 for the treatment of rejection within the first 3 months of transplantation exerted a surprisingly beneficial effect on long-term renal function, a phenomenon that was most apparent in the kidney-alone group. CONCLUSIONS: The frequency and timing of acute rejection episodes are more important than the influence of a simultaneously transplanted pancreatic allograft in determining long-term function of the transplanted kidney. A concerning trend toward late deterioration of renal function in kidney-pancreas recipients suggests that the benefits of sustained euglycemia, shorter cold ischemia times, lower rates of sensitization, and early use of OKT3 ultimately may be outweighed by the negative effects of more frequent renal rejection episodes.

Acute Disease↗
PubMed2005

Modulation factors of oxidative status in stable renal transplantation.

Reactive oxygen species (ROS) trigger a biomolecular alteration that causes functional and structural changes. In renal transplantation, there is an increase in oxidative phenomena related to endothelial dysfunction, inflammation, and atherosclerosis, the main cause of cardiovascular complications and chronic allograft failure. The present study was designed to assess the oxidative state of transplant patients with stable renal function, in order to establish differences in oxidative, biochemical, and clinical parameters between patients treated with tacrolimus versus cyclosporine. We studied 67 stable kidney transplant patients treated with calcineurin inhibitors who were not receiving cholesterol-lowering therapy, and 14 healthy subjects. Data were collected on biochemical parameters: lipid profile (apoA, apoB, total cholesterol and fractions, and triglycerides); urea; and creatinine; oxidative parameters: malondialdehyde (MDA) as a lipid peroxidation marker, glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD), glutathione reductase (GR), and antibodies against oxidized LDL; and clinical variables. Transplanted patients showed a higher oxidative status (MDA increase and GPx decrease) than healthy subjects. The oxidative status did not differ between the cyclosporine and tacrolimus cohorts. Some factors during the posttransplant period, such as delayed graft function, cytomegalovirus infection, and microalbuminuria, which may damage renal function, produce a decreased antioxidant capacity (lower GPx).

Cholesterol↗
PubMed2003

The influence of Duffy blood group on renal allograft outcome in African Americans.

BACKGROUND: African American patients demonstrate higher rates of acute allograft rejection and lower kidney-graft survival compared with white patients. Duffy antigen receptor for chemokines (DARC) on red blood cells has been suggested to have an anti-inflammatory role by acting as a "chemokine sink." We investigated the relationship of Duffy blood group type to renal allograft outcome in African American patient population. METHODS: A total of 163 African American kidney-transplant recipients were studied for Duffy blood group status. Patient outcomes were assessed at 6 to 42 months after transplantation and monitored for acute rejection episodes, graft function, and graft survival. RESULTS: A total of 117 (71.8%) patients were Duffy (a-b-), 14 (8.6%) Duffy (a+b-), 21 (12.9%) Duffy (a-b+), and 11 (6.8%) Duffy (a+b+). No significant differences were observed among the groups with respect to median serum-creatinine values or the incidence of biopsy-confirmed acute-rejection episodes. Although only 15.4% of the patients had Duffy (a+) antigen, none lost their allograft during the study period, and Kaplan-Meier graft survival was not significantly different compared to Duffy (a-) group (log-rank test, P=0.12). Duffy (a-b-) patients demonstrated lower allograft survival compared with the other three groups, although statistical significance was not reached (log-rank test P=0.15). Delayed graft function (DGF) was strongly associated with graft failure for only Duffy (a-b-) patients (log-rank test P=0.003). CONCLUSIONS: Duffy (a-b-) patients have lower allograft survival in the presence of DGF. DARC may attenuate the inflammatory effects of DGF by acting as a "chemokine sink," and DARC-negative patients may be more vulnerable to DGF.

Adolescent↗
PubMedDate not supplied

[Changes in renal function in renal transplantation. Predictive factors for functional deterioration].

Renal transplants may undergo changes secondary to the decrease of the renal mass, the effects of rejection, and various other risk factors that contribute to the progression of renal insufficiency. We have performed a prospective study of 285 cadaveric renal transplants recipients, that were receiving various maintenance immunosuppressives regimens, to study the evolution of their renal function and to evaluate the influence of various factors in the progression of renal insufficiency. All variables were analysed in a regression model of multivariate analysis. We found a progressive increase of the serum creatinine in the studied population. The mean initial creatinine was 1.70 +/- 0.84 mg/dl and final creatinine in the study 2.17 +/- 2.06 mg/dl, difference statistically significant (p = 0.000). We calculated the increase of creatinine in each patient. We observed that 113 patients (42.2%), had stable serum creatinine but the remaining 155 patients (57.8%) had a mean increase of 0.04 +/- 0.8 mg/dl/month. We analysed the patients according to various variables. Although in most the final creatinine is significantly greater than the initial, this increase of creatinine level was not present in patients with delayed graft function, in patients with no acute rejection, in the extreme age groups, in the grafts from younger donors and in those patients without initial proteinuria. The patients transplanted from younger donor had the best renal function, without any decrease in their function during the study. The advanced age of the donor has a great negative impact in the evolution of the renal transplant. According to our study, proteinuria and its quantity is a major predictor of progressive renal insufficiency. The multivariate analysis confirms that the age of the donor and initial proteinuria predict decrease of renal function. It is important to identify the factors that they could predict a greater progression to the failure of the graft. We have the possibility of acting on them, establishing immunosuppressive strategies that reduce the deleterious effects of the calcineurin inhibitors in the recipients of grafts from older donors' and to encourage the use of drugs which reduce proteinuria.

Adult↗
PubMed2001

2,500 living donor kidney transplants: a single-center experience.

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.

Adolescent↗
PubMed2004

Intraoperative fluid management in laparoscopic live-donor nephrectomy: challenging the dogma.

BACKGROUND: Patients undergoing laparoscopic live donor nephrectomy (LLDN) commonly receive large amounts of fluid intraoperatively to counter the negative effects of pneumoperitoneum on renal function. Our aim is to demonstrate that a low-volume fluid management strategy does not adversely affect donor or recipient outcomes. METHODS: Fifty-two patients underwent LLDN between December 2000 and January 2004. Data were collected in prospective databases, and augmented with retrospective medical record review. Donors were divided into two groups: the fluid-load group (n = 24) received > 10 ml/kg/h of intravenous crystalloids intraoperatively, while the fluid-restriction group (n = 28) received < 10 m/kg/h. RESULTS: Donors in the fluid-restriction group had a lower intraoperative urine output. There were no differences in postoperative creatinine levels (117.5 micromol/L vs 121.5 micromol/L, p = 0.8) or complications (4.2% vs 7.1%, p = 0.9). In the recipients, there were no differences in postoperative creatinine levels up to 12 months, incidence of delayed graft function (18% vs 10%, p = 0.7) or acute rejection (9% vs 5%, p = 1.0) between groups. CONCLUSION: Lower volume fluid management strategies in LLDN do not appear to worsen recipient outcomes nor are they detrimental to the donors.

Adult↗
PubMed2006

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients.

BACKGROUND: Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single-bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients. METHODS: A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA < 10%, n = 30) and sensitized group (PRA > or = 10%, n = 26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. Chi(2) test and t test were used to analyze the data. RESULTS: During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P = 0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P = 0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13 - 25 days (mean, 16.7 +/- 3.3) in the non-sensitized group and 14 - 29 days (mean, 16.2 +/- 3.1) in the sensitized group, respectively (P = 0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups. CONCLUSION: Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.

Adult↗
PubMed2007

Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors.

We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow-up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6 months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006) and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft-Gault GFR is the most important characteristic for predicting the recipient renal function.

Adult↗