Initial Graft Function Research Articles

A single nucleotide polymorphism of Toll-like receptor 4 identifies the risk of developing graft failure after liver transplantation

While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to the pathophysiology of ischemia/reperfusion (IR) injury and liver fibrosis, the relevance of TLR4 activation after human liver transplantation is unknown. The TLR4 single nucleotide polymorphism (SNP) D299G is situated within the extracellular domain and diminishes receptor binding to danger-associated molecular patterns. We studied the influence of TLR4 D299G on IR injury and graft survival in 430 deceased donor LT recipients. Compared with livers expressing wild-type (WT) alleles, livers with a TLR4 loss-of-function allele were significantly more likely to have initial good graft function (IGGF) (OR 2.20, p=0.01). In contrast, there was no effect of recipient TLR4 genotype on the rate of IGGF. The effect of TLR4 D299G on long-term graft survival was analyzed based on hepatitis C virus (HCV) serostatus. In HCV infected recipients, multivariate Cox regression analysis demonstrated a significant association between the presence of recipient, but not donor TLR4 D299G and long-term graft failure (HR 2.48, CI 1.28-4.81; p=0.007). There was no difference in graft survival between TLR4 mutant and WT recipients among non-HCV infected recipients. Collectively, these results demonstrate the differential effects of donor and recipient TLR4 signaling in human liver transplantation. Donor TLR4 contributed to sterile injury following cold preservation and the recipient TLR4 genotype was linked with poor allograft survival among HCV infected recipients.

Caspase inhibition in liver transplantation: from basic research to clinical studies

Caspase inhibition in liver transplantation: from basic research to clinical studies

Diabetes Mellitus: A Risk Factor for Delayed Graft Function after Deceased Donor Kidney Transplantation

Early graft function is a major determinant of long-term outcomes after renal transplantation. Recently, recipient diabetes was identified as a risk factor for poor initial graft function in living donor renal transplantation. To further explore this association, we performed a paired analysis of deceased donor renal transplants from January 1994 to December 2005. A total of 25,523 transplant pairs were analyzed via conditional logistic regression. Diabetic recipients were older (53.16 vs. 46.75 years, p < 0.01), had a lower average panel reactive antibody (12% vs. 15%, p < 0.01) and fewer prior transplants (0.07 vs. 0.12, p < 0.01). Recipient diabetes, age, male gender, African American race, elevated peak panel reactive antibody and increased cold ischemia time were independent risk factors for delayed graft function. Specifically, diabetic recipients had increased risk of DGF on univariate analysis (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.23-1.42, p < 0.01). Multivariable analysis confirmed this association but the risk differed by recipient gender; with diabetes having a greater effect in women (OR 1.66, 95% CI 1.45-1.91, p < 0.01) compared to men (OR 1.28, 95% CI 1.15-1.43, p < 0.01). It is unknown whether the deleterious impact of recipient diabetes on graft function after renal transplantation results from perioperative hyperglycemia or the chronic sequelae of diabetes.

Regulatory T Cells in Kidney Allograft Infiltrates Correlate With Initial Inflammation and Graft Function

The relevance of borderline change (BL) and subclinical cellular rejection (SCR) observed in renal transplantation remains to be determined. Several studies have shown in BL and SCR the presence of a Th1 immune response, qualitatively similar to but quantitatively reduced in comparison with infiltrates typical of acute cellular rejection (ACR). To elucidate the role of regulatory T cells (Tregs) in the local control of the allogenic response, we studied their presence by immunohistochemistry in 24 biopsies with graft dysfunction (12 ACR and 12 BL) and in 16 protocol biopsies at 1 year (eight SCR and eight subclinical BL). The proportion of Tregs in CD4 T infiltrates was higher in BL and SCR when compared with ACR. Moreover, their presence was correlated with the intensity of interstitial inflammation (r=-0.35, P=0.027, n=40) and with graft function at the time of the biopsy (r=-0.37, P=0.018, n=40). These data suggest Treg recruitment at the acute phase of the allogenic response, where they could act to diminish the interstitial inflammation and its associated lesions.

Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation

Initial graft function is a major factor influencing the clinical outcome after liver transplantation (LTX), but a reliable method for assessing and predicting graft dysfunction directly after LTX is not available. Ninety-nine patients undergoing deceased-donor LTX were studied in a prospective pilot study to evaluate the LiMAx test, the indocyanine green test, and conventional biochemical parameters with respect to their sensitivity and prognostic power for the diagnosis of initial graft dysfunction. Patients suffering from initial graft dysfunction (defined as technical complications or primary nonfunction (n = 8)) had significantly decreased LiMAx readouts (43 +/- 18 versus 184 +/- 98 mug/kg/hour, P < 0.001) immediately after LTX. Univariate analysis also showed significant differences for serum bilirubin, ammonia, glutamate dehydrogenase, and the international normalized ratio (P < 0.05), but multivariate analysis revealed LiMAx as the single independent predictor of initial dysfunction (P = 0.008) with an area under the receiver operating characteristic curve (AUROC) of 0.960 (95% confidence interval = 0.921-0.998, P < 0.001). In addition, the diagnosis of primary nonfunction (n = 3) was evaluated with LiMAx and aspartate aminotransferase (AST) activity on the first postoperative day. The calculated AUROC values were 0.992 (0.975-1.0, P = 0.004) for LiMAx and 0.967 (0.929-1.0, P = 0.006) for AST. By a combination of test results obtained directly after LTX and on the first day, LiMAx indicated primary nonfunction with a sensitivity of 1.0 (0.31-1.0) and a positive predictive value of 1.0 (0.31-1.0), whereas AST classification showed a sensitivity of 0.67 (0.13-0.98) and a positive predictive value of 0.29 (0.05-0.70). In conclusion, the assessment of initial graft function using the LiMAx test might be effective for identifying critical complications that could threaten graft survival within 24 hours after LTX.

Editorial Comment

This study demonstrates the technical feasibility and initial outcomes after laparoendoscopic single-site, or “single-port,” donor nephrectomy. The authors present their experience with 13 live donor nephrectomy procedures and show results comparable with standard laparoscopy. In addition to technical feasibility in all cases, mean operative times, blood loss, warm ischemic time, vascular and ureteral length, postoperative pain scores, and initial graft function were similar to standard laparoscopic live donor nephrectomy. Laparoendoscopic Single-site Donor Nephrectomy: A Single-center ExperienceUrologyVol. 74Issue 6PreviewTo present our experience with 13 patients undergoing laparoendoscopic single-site live donor nephrectomy. Full-Text PDF

Hypothermic reconditioning after cold storage improves postischemic graft function in isolated porcine kidneys

Delayed graft function still represents a major complication in clinical kidney transplantation. Here we tested the possibility to improve functional outcome of cold stored kidneys a posteriori by short-term hypothermic machine perfusion immediately prior to reperfusion. A total of 18 kidneys from female German Landrace pigs was flushed with Histidine-Tryptophan-Ketoglutarate solution and cold-stored for 18 h (control). Some grafts were subsequently subjected to 90 min of hypothermic reconditioning by hypothermic machine perfusion with (HR+O(2)) or without (HR-O(2)) oxygenation of the perfusate. Early graft function of all kidneys was assessed thereafter by warm reperfusion in vitro (n = 6, respectively). Renal function upon reperfusion was significantly enhanced by HR+O(2) with more than threefold increase in renal clearances of creatinine and urea. HR+O(2) also led to significantly higher urinary flow rates and abrogated the activation of caspase 3. By contrast, HR-O(2) was far less effective and only resulted in minor differences compared to control. It is derived from the present data that initial graft function can be significantly improved by 2 h of oxygenated machine perfusion after arrival of the preserved organ in the transplantation clinic.

Role of Postreperfusion Subcapsular Wedge Biopsies in Predicting Initially Poor Graft Function After Liver Transplantation

Preservation injury is a major contributing factor to primary allograft failure or poor initial graft function after an orthotopic liver transplant (OLT). We examined the histopathological findings from postreperfusion wedge biopsy specimens in relation to early graft function during the first postoperative week among OLT patients at our center. We reanalyzed subcapsular postreperfusion biopsy specimens from 88 patients to histologically grade the lesions. Grafts were grouped as good function, initial poor function (an alanine aminotransferase or aspartate aminotransferase level >1500 IU/L during week 1), or primary nonfunction (death or retransplantation). Only 1 patient experienced primary nonfunction; the remaining patients fell into the other 2 groups: ie, good function or initial poor function. When patients were compared using numerous morphologic and clinical features, no statistical relation was observed regarding clinical data on bile duct complications, donor type, graft volume, patient age, or type of stent. Histological features of neutrophilic infiltration of the subcapsular region, hepatocellular ballooning, and macro/microvesicular steatosis were not related to initial poor graft function; in contrast, there were prominent sinusoidal neutrophilic infiltrations and hepatocellular necrosis. Preservation-reperfusion injury (grade 2 or grade 3 neutrophilic infiltration) occurred in 78.6% of initial poor function patients and in 39.7% of good function patients. Subcapsular neutrophilic infiltration, a sign of surgical hepatitis, did not provide prognostic information about graft survival. Similar to other studies, we observed neutrophilic infiltration and necrosis away from the capsule to predict subsequent graft function.

Impact of Slow and Delayed Graft Function on Kidney Graft Survival Between Various Subgroups Among Renal Transplant Patients

Renal allografts with excellent graft function show good long-term outcomes, while grafts with delayed function have been associated with poor long-term survivals, although few reports have analyzed outcomes among these groups. We compared first-week postoperative graft function among renal transplant patients to analyze the impact of slow graft function (SGF) and delayed graft function (DGF) on graft survival. Renal transplantations were performed from 362 unrelated, 46 related, and 163 deceased donors. Kidney transplant patients were divided into 3 groups according to their initial graft function. First-week dialyzed patients formed the DGF group. Nondialyzed patients were divided into a SGF or an excellent graft function (EGF) cohort according to whether the serum creatinine at day 7 was higher vs lower than 2.5 mg/dL, respectively. Of the 570 renal transplant recipients, DGF was observed in 39 patients (6.8%), SGF in 64 (11.2%), and EGF in 467 (81.8%). There was no significant difference in SGF vs DGF between patients who received kidneys from unrelated vs related living or deceased donors. Graft survival was worse among the DGF than the SGF or EGF patients, with no significant difference between the last 2 groups. The 6-month graft survivals were 74%, 93%, and 96%; the 3-year graft survivals were 70%, 88%, and 90%, respectively (P < .001). We observed a similar impact of EGF and SGF on kidney graft survival. Kidney transplant recipients who developed DGF showed worse graft survival than those with EGF or SGF.

Optimal utilization of extended hepatic grafts

Orthotopic liver transplantation has emerged as the standard treatment for end-stage liver disease. In the United States, the number of listed patients has tripled in the last two decades. Organ availability during the same period has plateaued at approximately 6000 grafts annually, resulting in a fivefold increase in wait-list mortality. The problem is not specific to the United States; European and Asian registries report similar shortages. Donor pool expansion strategies such as the use of living donors, cadaveric split livers, and "extended criteria donors"; (ECD) are being pursued. Used judiciously, ECD grafts provide an opportunity for addressing the shortage. Although there is no universally accepted definition of ECD, the term generally refers to donor factors predisposing recipients to poor initial graft function and/or increased long-term risk. These factors include advanced donor age, hypernatremia, prolonged warm ischemic time, pressor requirement, and donation after cardiac death. The transplant community is scrutinizing all factors to evaluate the degree of risk they impart on the recipient and the extent to which grafts can be "matched"; to maintain acceptable outcomes. We review the importance of selected factors and the impact of a "matching"; strategy to minimize recipient risk while optimizing graft use.

No difference in clinical transplant outcomes for local and imported liver allografts

In the United States, liver allograft allocation is strictly regulated. Local centers have the first option to accept a donor liver; this is followed by regional allocation for those donor livers not used locally and then by national allocation for those donor livers not accepted regionally. This study reviews the outcomes of all liver allografts used over 6 years (2001-2007) and evaluates initial and long-term function stratified by the geographic source of the donor liver allograft. The records for 845 consecutive deceased donor liver transplants at a single center were reviewed. The geographic origin of the allograft was recorded along with donor and graft characteristics to determine the probable reason for graft refusal. Within our local organ procurement organization, there is 1 liver transplant center, and within the region, there are 8 active centers. Early graft failure included any graft loss within 7 days of transplant, and initial function was measured with liver enzymes 30 days post-transplant. Graft survival and patient survival were evaluated with Kaplan-Meier and Cox survival modeling. Median follow-up was 43 months. The geographic distribution of organs included local organs (562, 66%), regionally imported organs (126, 15%), and nationally imported organs (157, 19%). There were no differences between the 3 groups in initial graft function, intraoperative death, or early graft loss. Survival curves for the 3 study groups demonstrated no difference in survival up to 5 years post-transplant. In conclusion, liver allografts rejected for use by a large number of transplant centers can still be successfully used without early graft function or long-term survival being affected.

The utility of using bispectral index monitoring as an early intraoperative indicator of initial poor graft function after orthotopic or split-graft liver transplantation

We refer to our recent publication ( Gut 2008; 57 :77–83) showing that bispectral index (BIS) monitoring, an electroencephalographic (EEG)-derived parameter, is a useful measure for grading and monitoring the...

Improvement of pulmonary microcirculation after lung transplantation using phosphodiesterase-5 inhibitor modified preservation solution

Optimising the preservation modality and thus maintaining the post-transplanted organ function remains a point of interest in research in order to prevent deleterious ischaemia/reperfusion injury. Microcirculation allows the assessment of initial graft function before obvious functional parameters. It was the aim of our study to compare the effects of epoprostenol and sildenafil on the pulmonary microcirculation and haemodynamics, when used in the preservation solution in lung transplantation. Twenty-one pigs underwent single LuTx after 24h graft-ischaemia, preserved with buffered low potassium-dextran solution (I, control); with addition of 0.66 microg/kg/bw epoprostenol (II) or with 0.15 mg/kg/bw sildenafil (III). The pulmonary microcirculation, alveolar capillary diameter (ACD), red blood cell (RBC) velocity and functional capillary density (FCD), were assessed by intravital microscopy (OPS-imaging) hourly until 6h after reperfusion. Haemodynamics and blood gas exchange were monitored at all timepoints. ACD was increased in group III directly after reperfusion (132+/-4.4% vs 121+/-3.1%, in % of baseline, III vs I; mean+/-SEM; p<0.05) and decreased during the experiment. RBC velocity did not reach statistical significance (256+/-93 vs 263+/-85 and 283+/-66 microm/s, III vs II and I; mean+/-SD). FCD in group III was higher than in I and II beginning 3h after reperfusion (10.1+/-1.4 vs 6.1+/-1.9 microm/microm(2), III vs I; mean+/-SEM; p<0.05). Our study demonstrated a significantly improved microcirculation after application of PDF V during organ procurement, probably because of better distribution of the preservation solution. Further studies are necessary, to prove the long-term effects of this observation.

Hepatic Neutrophil Activation During Reperfusion May Not Contribute to Initial Graft Function After Short Cold Ischemia in Human Liver Transplantation

Background Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear. Methods In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated. Results Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7–1.0]; 1.4 [0.9–1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2–0.5]; 1.7 [1.3–3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation. Conclusions Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.

Acute liver failure due to concomitant arterial, portal and biliary injury during laparoscopic cholecystectomy: is transplantation a valid life-saving strategy? A case report

BackgroundCombined iatrogenic vascular and biliary injury during cholecystectomy resulting in ischemic hepatic necrosis is a very rare cause of acute liver failure. We describe a patient who developed fulminant liver failure as a result of severe cholestasis and liver gangrene secondary to iatrogenic combine injury or the hepatic pedicle (i.e. hepatic artery, portal vein and bile duct) during laparoscopic cholecystectomy.Case presentationA 40-years-old woman underwent laparoscopic cholecystectomy for acute cholecystitis. During laparoscopy, a severe bleeding at the liver hilum motivated the conversion to open surgery. Many sutures were placed across the parenchyma for bleeding control. After 48 hours, she rapidly deteriorated with encephalopathy, coagulopathy, persistent hypotension and progressive organ dysfunction including acute renal failure requiring hemodialysis and mechanical ventilation. An angiography documented an occlusion of right hepatic artery and right portal vein. In the clinical of acute liver failure secondary to liver gangrene, severe coagulopathy and progressive secondary multi-organ failure, the patient was included in the waiting list for liver transplantation. Two days later, the patient was successfully transplanted with initial adequate liver graft function. However, she developed bilateral pneumonia and severe gastrointestinal bleeding and finally died 24 days after transplantation due to bilateral necrotizing pneumonia.ConclusionThe occurrence of acute liver failure due to portal triad injury during laparoscopic cholecystectomy is a catastrophic complication. Probably, the indication of liver transplantation as a life-saving strategy in patients with late diagnosis, acute liver failure, severe coagulopathy and progressive secondary multi-organ failure could be considered but only minimizing immunosuppressive regimen to avoid postoperative infections.

Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German Single Center Experience.

Adult living donor liver transplantations (ALDLTs) across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins) were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR). Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety.

Impact of the donor liver with steatosis in patients with hepatitis C virus: Not so FAst

It is currently estimated that 20% to 25% of the adult population has nonalcoholic fatty liver disease. Hepatic steatosis is one of the features of metabolic syndrome, which includes diabetes mellitus, hypercholesterolemia, and hypertension. These features are significant risk factors leading to cardiovascular and cerebrovascular mortality. Hepatic steatosis is therefore present in many older donors. Impairment in cognitive function associated with acute alcohol intoxication is a major factor contributing to mortality from motor vehicle and other accidents. Approximately 12% to 20% of organ donations stem from injuries precipitated by alcohol use, andmany of these individuals are found to have hepatic steatosis. As a result, hepatic steatosis is found in about 15% to 25% of potential organ donors. The negative impact of severe hepatic steatosis on graft dysfunction during the immediate posttransplant period has long been recognized. Donor livers containing greater than 30% to 50% steatosis are at increased risk of developing primary nonfunction and delayed function and are associated with reduced graft and patient survival. Historically, these livers were not routinely used for liver transplantation (LT) unless the potential recipient was critically ill and/or the transplant team was willing to accept these risks. Persons with significant hepatic steatosis have also been excluded as candidates for living liver donation because of similar concerns. Over the past decade, the number of patients on the LT waiting list, the waiting time to receive a donor liver, and pre–LT mortality have all increased. In an effort to blunt this trend, the use of so-called marginal donor livers, including those with significant steatosis, has increased substantially. Chronic hepatitis C virus (HCV) is the most common indication for LT. Nearly half of all LT recipients in North and South America, Europe, and Australia develop cirrhosis and/or hepatocellular carcinoma secondary to chronic HCV. The recurrence of chronic HCV following LT is universal, and progression to advanced bridging fibrosis or cirrhosis occurs in approximately 30% of these patients within 5 years and in approximately 40% within 10 years of LT. Numerous studies have attempted to define those factors that are associated with progressive fibrosis in LT recipients with recurrent HCV. Many different factors have been implicated in various studies. However, the one consistent finding in nearly all of these studies has been allograft rejection and its subsequent treatment with either high-dose steroids and/or monoclonal antibody preparations. Hepatic steatosis is known to lead to more rapid fibrosis progression in patients with chronic HCV, and a recent study has demonstrated that this also contributes to progressive fibrosis of the LT allograft in patients with recurrent HCV. Several studies have examined the impact of steatosis within the donor graft on the severity of recurrent HCV and/or survival following LT. The most recent of these studies by Briceno and colleagues from Reina Sofia University Hospital (Cordoba, Spain) appears in this issue of Liver Transplantation. The study by Briceno et al. suggests that severe steatosis of the donor graft is associated with earlier recurrence of chronic HCV, more rapid fibrosis progression, and a reduction in graft survival. An extensive list of donor and recipient factors were evaluated with univariate analysis and then multivariate analysis to identify those factors associated with decreased graft survival in this study. Donor graft steatosis greater than 30%, donor age greater than 55 years, and a cold ischemic time greater

Favorable Outcome of Orthotopic Liver Transplantation in Very High-Risk Situations

Background Favorable outcomes of marginal liver grafts depends on optimal perioperative control and good recipient parameters. The aim of this study was to assess the results of marginal liver grafts associated with prolonged ischemic times and high-risk recipients. Methods We retrospectively reviewed data from patients who underwent orthotopic liver transplantation between 2001 and 2005. The patients were divided into two groups: group 1 received marginal liver grafts with ischemia times ≥ 12 hours and recipient United Network for Organ Sharing (UNOS) status 1, 2A, and 2B. Patients who had marginal liver grafts with ischemic times less than 12 hours and/or better UNOS status were classified as group 2. We compared initial graft function as well as patient and graft survivals at 1 year between the two groups. Results Among 31 patients who were reviewed, four were excluded because of incomplete data and 24/27 received marginal liver grafts. Seven patients were classified into group 1, and 17 into group 2. The initial poor function rate was 85.7% (6/7 patients) and 76.47% (13/17 patients) in groups 1 and 2, respectively. The 1-year survival rate in group 1 was 85.7% (6/7 patients) and 94.12% (16/17 patients) in group 2. Conclusion Marginal liver grafts can be used with favorable outcomes even in high-risk situations, such as prolonged ischemia times and high-risk recipients.

Survival, Complications, and Analysis of Risk Factors after Renal Transplantation in Cats

To report survival, complications, and analyze risk factors for survival after renal transplantation (RTr) and cyclosporine-A based immunosuppression in cats. Historical cohort. Cats (n=60). Data were obtained from medical records of cats that had RTr. Influence of various perioperative factors on survival and complications was evaluated. Occurrence of postoperative hypertension (HT), seizures, infection, acute allograft rejection (AR), congestive heart failure (CHF), and delayed graft function (DGF) was evaluated. Survival to discharge after RTr was 77.5%. Estimated median overall survival time was 613 days; 6 month and 3 year overall survival proportions were 65% and 40%, respectively. Age, weight, and blood pressure influenced overall survival. Increased preoperative creatinine concentration, blood urea nitrogen, postoperative creatinine concentration, left ventricular wall thickness, and reduced creatinine reduction ratio influenced survival until discharge. HT was identified in 9/30 (30%) cats; however, no risk factors were identified, nor was HT related to seizures. AR was identified in 8/62 (13%) grafts. Infection, predominantly bacterial, developed in 22/60 (37%) cats. CHF occurred in 7/60 (12%) cats before discharge. Cats experiencing CHF were younger, had an increased incidence of heart murmurs, and poor initial graft function. DGF was identified in 5 cats and seizures in 2 cats. RTr affords cats with CRF long survival times. Older cats and cats with severe azotemia, HT, and cardiovascular disease may have increased mortality after RTr. Complications after RTr were common. Clinicians should be aware of these risk factors when recommending feline RTr.

Potential influence of tacrolimus and steroid avoidance on early graft function in pediatric renal transplantation

With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (DeltaCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (> or =14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.