Practice Variation in the Immediate Postoperative Care of Pediatric Kidney Transplantation: A National Survey.

INTRODUCTION: Advances in organ allocation, surgical technique, immunosuppression, and long-term follow-up have led to a significant improvement in kidney transplant outcomes. Although there are clear recommendations for several aspects of kidney transplant management, there are no pediatric-specific guidelines for immediate postoperative care. The aim of this survey is to examine practice variations in the immediate postoperative care of pediatric kidney transplant patients. METHODS: We surveyed medical directors of Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)-affiliated pediatric intensive care units regarding center-specific immediate postoperative management of pediatric kidney transplantation. RESULTS: The majority of PALISI centers admit patients to the pediatric intensive care unit postoperatively, and 97% of the centers involve a pediatric nephrologist in immediate postoperative care. Most patients undergo invasive hemodynamic monitoring; 97% of centers monitor invasive arterial blood pressure and 88% monitor central venous pressure. Most centers monitor serum electrolytes every 4 to 6 hours. Wide variation exists regarding blood pressure goal, fluid replacement type, frequency of obtaining kidney ultrasound, and use of prophylactic anticoagulation. CONCLUSION: There is consistent practice across PALISI centers in regards to many aspects of immediate postoperative management of pediatric kidney transplantation. However, variation still exists in some management aspects that warrant further discussions to reach a national consensus.

Fulminant Clostridium perfringens Sepsis in Kidney Transplant: A Case Report.

BACKGROUND: Infections, particularly urinary tract infections, and cardiovascular accidents are the main causes of morbidity and mortality during the 1st year after kidney transplantation (KT). Bacteria and viruses, such as Escherichia coli, Enteroccoci, and Polyoma BK virus are common in the 1st 6 months, so they are controlled routinely. On the other hand, Clostridium perfringens infection is a rare life-threatening condition, associated with a high mortality rate especially in the transplant population, that is not controlled routinely. CASE REPORT: A 50-year-old man with end-stage renal disease secondary to hypertension and focal segmental glomerulosclerosis underwent living-related KT. He recovered well and was discharged 11 days after KT. Two weeks after his discharge, he presented with severe abdominal pain, fever, and vomiting. Radiologic assessment showed pneumoperitoneum. Urgent exploratory laparotomy revealed significant amount of gas and no bowel perforation. However, right retroperitoneal gas collection was noted and drained. Blood culture was positive for C perfringens. Patient died after 48 hours, with signs of multiorgan failure. CONCLUSIONS: Clostridium perfringens sepsis is severe and usually lethal in the transplant population. Prevention is difficult because the origin of the infection is unclear. Keeping high suspicion in patients with sudden and unexplained septic shock and aggressive surgical and medical treatment are fundamental.

Effect of desensitization in solid organ transplant recipients depends on some cytokines genes polymorphism.

Desensitization (DS) is widely used to decrease PRA in solid organs transplant candidates (TC). Various numbers of cycles of DS are required to reduce or eliminate donor specific antibodies (DSA). The goal of this study was to investigate if there was a correlation between polymorphism (PM) of some cytokine genes and intensity of DS required to make the recipient/donor cross match compatible. Thirty-one TCs were included in the study. Antibody specificity, percent of reactive antibodies (PRA) and serum concentration of cytokines were analyzed using the LUMINEX platform. PCR-SSP method was used for IL-1alpha, IL-1beta, IL-1R, IL-1Ralpha, IL-4Ralpha, IL-12, IFNgamma, TGFbeta1, TNFalpha, IL-2, IL-4, IL-6 and IL-10 gene PM analysis. Significant relationship between PM of genes encoding IL-4Ralpha, IFNgamma and IL-12 (p70) and susceptibility to DS was demonstrated (p=0.04, p=0.01 and p=0.05 respectively). Correlation between elevated serum level of IL-12 (p70) and A/A or C/A genotype at -1188 position was found in resistant to DS TCs (p=0.015). These results indicate that analysis PM of genes encoding IL-4R, IFNgamma and IL-12 enables to define the DS strategy in TCs more accurately regarding the number of plasmapheresis (PP) cycles and dose of intravenous immunoglobulin (IVIG).

Organ preservation with histidine-tryptophan ketogluatarate solution in clinical pancreas transplantation: an update of the indiana university experience.

In May 2003, University of Wisconsin (UW) solution was replaced with Histidine-Tryptophan Ketoglutarate (HTK) solution as the preservation fluid for abdominal organ procurements in our center. Herein we have reported our updated results with HTK in pancreas transplantation. Between May 2003 and October 2006, 152 pancreas transplantations were performed in which 146 used HTK. The procedures were as follows: simultaneous kidney pancreas transplantation (n = 85; 55%), pancreas after kidney transplantation (n = 41; 30%), and solitary pancreas transplantation (n = 20; 15%). Donor and recipient data were collected with primary outcomes as primary nonfunction (PNF), and 30-day and 1-year graft and patient survival. Patient demographics are as follows: age (36 +/- 12 years), gender (males, 89: females, 57), race (white, 135; African American, 11). Mean flush volume was 3.8 +/- 1 L. The mean cold ischemia time was 8 +/- 3 hours. Mean warm ischemia time was 48 +/- 23 minutes. There were no cases of PNF in this cohort. Thirty-day and 1-year patient survival rates were 99% and 95%, respectively. The 30-day and 1-year graft survivals rates were 95% and 93%, respectively. There were 10 grafts lost with 7 vascular complications (6 venous and 1 arterial thrombosis). There were 2 cases of chronic rejection and 1 graft lost to noncompliance. These statistics compare favorably with International Pancreas Transplant Registry reported 1-year survival for pancreas allografts. All other patients were insulin independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation to those of a historical UW cohort. Within this range of cold ischemia times, HTK appears to provide effective pancreas preservation.

Follow-up experience using histidine-tryptophan ketoglutarate solution in clinical pancreas transplantation.

In May 2003, at Indiana University, the standard cold preservation solution University of Wisconsin (UW) solution was replaced by histidine-tryptophan ketogluatarate (HTK) solution. Earlier, we presented our initial experience with HTK in pancreas preservation with an analysis of the first 10 pancreas transplants. Here we report updated results with HTK in pancreas transplantation over the past 18 months. Between May 2003 and March 2005, a total of 87 pancreas transplants were performed with 78 of these organs utilizing HTK. Seventy five patients received 78 organ transplants. Surgical procedures performed were: simultaneous kidney pancreas transplantation (n = 50, 64%), pancreas after kidney transplantation (n = 19, 24%), solitary pancreas transplantation (n = 9, 12%). Donor and recipient data were collected with primary outcomes as primary nonfunction and 30-day graft and patient survivals, and compared to the UW cohort from our original report. Donor and recipient demographics were similar. Mean follow-up time is 12 +/- 6 months. The mean cold ischemia time was 9 +/- 3 hours. There were no cases of primary graft nonfunction. Thirty-day and 1-year patient survivals were 99% and 93%. The 30-day and 1-year graft survivals were 96% and 93%. There were five grafts lost, including three within the first month (two venous and one arterial thrombosis). There was one case of chronic rejection and one noncompliance. All other patients were insulin-independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation. Within this range of cold ischemia time, HTK appears to provide effective pancreas preservation.

Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin solutions as primary preservation in renal allografts undergoing pulsatile perfusion.

INTRODUCTION: University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK) solution has been used increasingly for kidney, pancreas, and liver transplantation. This study compared HTK and UW used during kidney procurement with subsequent pulsatile perfusion. METHODS: Between January and October 2003, 91 deceased renal and simultaneous kidney pancreas transplants were performed (UW, n = 41, and HTK, n = 50). There were no differences with regard to donor and recipient demographics or cold ischemia. RESULTS: Delayed graft function occurred in 3 (7%) of UW and 4 (8%) of HTK-preserved kidneys (P = NS). There were no significant differences between patient or graft survival. There was an anticipated difference between total preservative volumes used (HTK: 4.1 +/- 1.0 vs UW: 3.0 +/- 0.5; P < .005). CONCLUSION: UW and HTK appear to have similar efficacy in kidney preservation with pulsatile perfusion. HTK preservation solution can be used safely in conjunction with pulsatile preservation for cold storage of renal allografts.

The immunologic role of IFN-gamma in ACI to Lewis kidney transplantation.

BACKGROUND: One of the proposed mechanisms of tolerance induction is the Th-1/Th-2 paradigm. The Th-1 cell is proinflammatory, secreting IFN-gamma and IL-2. Conversely, the Th-2 cell is anti-inflammatory, secreting IL-4 and IL-10. In our earlier studies a shift toward Th-2 dominance was required for tolerance induction in this model. MATERIALS AND METHODS: ACI and Lewis rats were used as donors and recipients, respectively. Twelve hours prior to engraftment, rapamycin 1.5 mg/kg po and cyclosporin 10 mg/kg sc were given, followed by 5 mg/kg sc postop (days 1-7). Lewis rats were used as isografts. Functional allograft tolerance was induced consistently in 100% of the recipients with 50% of the allografts exhibiting normal histology beyond 120 days. Qualitative RT-PCR was performed on the grafts to determine IFN-gamma expression with beta-actin housekeeping gene as control. RESULTS: IFN-gamma was expressed in all untreated allografts (5/5) and all treated, yet rejecting, allografts (4/4). None of the isografts (0/5) or histologically tolerant allografts (0/4) expressed IFN-gamma. This distribution was statistically significant (P < 0.001, Fischer's exact test). CONCLUSION: Our findings support a shift from Th-2 to Th-1 predominance as the corollary mechanism responsible for preventing histologic tolerance.

Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression.

The induction of transplantation tolerance is one of the primary goals following solid organ transplantation. The combination of a single dose of rapamycin (RAPA) with a short course of cyclosporine (CsA) has been shown to induce transplantation tolerance in the nonfunctional rat heterotopic cardiac transplant model. The purpose of this study was to assess this effective induction protocol in a functional renal transplant model. Male ACI (RTl(a)) and Lewis (RT1(1)) rats were used as donor and recipients respectively. Allografts received a single RAPA dose of (1.5 mg/kg) combined with CsA (10 mg/kg) 12-14 hr prior to transplantation. CsA (5 mg/kg) was given daily on days +1 - +7. Untreated Lewis to Lewis isografts served as histological controls. Chimerism, assessed in recipient skin, and intragraft interleukin (IL) 10 expression was determined utilizing PCR and RT-PCR techniques respectively. Treated animals and isografts were sacrificed 120-130 days posttransplant for functional and histological evaluation. Allografts (n=9) were functionally tolerant with serum creatinine (0.77+/-0.1 vs. 0.88+/-0.1; P=0.275), blood urea nitrogen (37.6+/-4.6 vs. 23.3+/-1.9; P=0.123), and 24 hr protein excretion (27.0+/-4.4 vs. 17.9+/-5.2; P=0.131) similar to single kidney ACI controls. Histologically, 45% (4/9) allografts were indistinguishable from isografts with no evidence of rejection, and were considered immunologically tolerant. Donor/recipient chimerism was not detected. All immunologically tolerant allografts had evidence of intragraft IL-10 expression. Rejecting allografts and isografts did not express intragraft IL-10. This study confirms the efficacy of pre-engraftment single-dose RAPA combined with CsA in inducing true immunologic tolerance in this stringent functional renal transplant model. The expression of intragraft IL-10 in tolerant recipients suggests a Th-2 shift as the mechanism of tolerance in this model.

The impact of a positive crossmatch upon outcome after liver transplantation.

Recent reports have shown that liver allografts transplanted against a positive lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of rejection, and decreases in patient and graft survival. The implication of a positive flow cytometric crossmatch (FCXM+) in liver transplantation remains controversial. The purpose of this study was to determine what impact a pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome following liver transplantation. Preoperative crossmatch status was determined prospectively in 110 consecutive liver transplants performed between July 1991 and January 1995. Allografts were divided into three groups: negative crossmatch (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic crossmatch CDC+. Crossmatch status did not impact patient or graft survival. Actuarial patient survival was similar between groups at 12 months (88% vs. 95% vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs. FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a significant increase in early rejection episodes compared with NXM (46% vs. 7%, CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+) (P=0.006). CDC+ allografts experienced significantly more rejection episodes per year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs. 23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in numbers of additional nonconventional therapeutic interventions compared to NXM allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of cytotoxic antibodies pretransplantation is associated with increased incidences of early rejection, and rejection episodes per year. With careful monitoring and aggressive therapeutic interventions the presence of cytotoxic antibodies are not deleterious to patient or liver allograft survival.

Effect of single-dose rapamycin-based immunosuppression on the development of cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy is the major cause of graft loss more than 1 year after transplantation. Daily rapamycin dosing has been shown to inhibit arterial intimal thickening caused by both alloimmune and mechanical injury. The combination of a single preoperative dose of rapamycin with a short (7 day) course of cyclosporine A has been shown to extend cardiac allograft survival, but its effects on the development of cardiac allograft vasculopathy has not been reported. METHODS: The ACI (RT1(a)) to Lewis (RT1(1)) heterotopic cardiac allograft model was used to assess the development of cardiac allograft vasculopathy and rejection. Treatment groups included nonimmunosuppressed control, cyclosporine A, cyclosporine A/donor-specific transfusion, and rapamycin/cyclosporine A. RESULTS: The addition of a single preoperative dose of rapamycin to a short course of cyclosporine A significantly reduced the prevalence of cardiac allograft vasculopathy in small (1.18 +/- 1.4 versus 0.05 +/- 0.3; p = 0.0001), medium (2.05 +/- 1.09 versus 0.26 +/- 0.62; p = 0.0001), and large (2.57 +/- 0.84 versus 1.43 +/- 1.2; p = 0.0008) vessels when compared with that in allografts treated with a single preoperative donor-specific transfusion and the same cyclosporine A schedule. Cardiac allograft vasculopathy did not develop in the nonimmunosuppressed control grafts or the group treated with cyclosporine A alone, because of the short survival times in these groups. In addition, there was a reduction of the rejection score in the rapamycin-treated allografts compared with that in the other treatment groups (4.0 +/- 0.0 versus 3.25 +/- 0.5; p = 0.0006). CONCLUSIONS: These results suggest that a single preoperative dose of rapamycin is efficacious in preventing the development of cardiac allograft vasculopathy, and continued immunosuppression with rapamycin may be unnecessary.