Angello Lin

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease

Abstract: Background. Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the l‐valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high‐risk renal and pancreas transplant recipients.

A Randomized Controlled Trial to Evaluate the Effect of Glycemic Control on Renal Transplantation Outcomes

CONTEXT Outcomes from intensive glycemic control postrenal transplant have not been studied. OBJECTIVE Our objective was to observe the optimal management of hyperglycemia in patients with diabetes or impaired glucose tolerance receiving renal transplantation. DESIGN, SETTING, AND PATIENTS We conducted a randomized controlled trial with patients undergoing renal transplantation randomized to either i.v. insulin therapy (intensive) or standard s.c. insulin therapy while the patients were admitted to the hospital. INTERVENTIONS The study consisted of a 3-day postrenal transplant group treated with intensive i.v. insulin [blood glucose (BG) = 70-110 mg/dl] or a control group treated with s.c. insulin (BG = 70-180 mg/dl). MAIN OUTCOME MEASURE The primary endpoint was delayed graft function (DGF). Secondary endpoints were glycemic control, graft survival, and acute rejection episodes. RESULTS A total of 104 patients were screened and randomized to either the intensive or control condition; however, the intention-to-treat analysis set consisted of only the 93 participants (n = 44 intensive, n = 49 control) that underwent a renal transplant. DGF was present in 18% (eight of 44) of the intensive group and 24% (12 of 49) of the control group (P = 0.46). The occurrence of severe hypoglycemia (BG < 40 mg/dl) and severe hyperglycemia (BG > 350 mg/dl) were the primary safety outcome measures. There were nine participants with hypoglycemia identified, seven of which (78%) were in the intensive treatment group (P = 0.08). There were 30 instances of hyperglycemia with five participants (11%) in the intensive group and 12 participants (24%) in the control group having at least one hyperglycemic event (P = 0.10). For the 11 rejection episodes, nine were in the intensive treatment group (P = 0.013). CONCLUSIONS The primary outcome measure of DGF was not statistically different for the two treatment groups. Regarding longer-term rejection and graft survival, the intensively treated participants were at higher risk for a rejection episode.

Further improvements in laparoscopic donor nephrectomy: decreased pain and accelerated recovery

Fear of postoperative pain is a disincentive to living donor kidney transplantation. Laparoscopic donor nephrectomy (LDN) was developed in part to dispel this disincentive. The dramatic increase in the number of laparoscopic donor nephrectomies performed at our institution has been in part due to the reduction in postoperative pain as compared to traditional, open donor nephrectomy. We sought to further diminish the pain associated with this surgical technique. The purpose of this study was to compare the efficacy of three different postoperative pain management regimens after LDN. All living kidney donors performed laparoscopically (n=43) between September 1998 and April 2000 were included for analysis. Primary endpoints included postoperative narcotic requirements and length of stay. Narcotic usage was converted to morphine equivalents (ME) for comparison purposes. Patients received one of three pain control regimens (group I: oral and intravenous narcotics; group II: oral and intravenous narcotics and the On‐Q™ pump delivering a continuous infusion of subfascial bupivicaine 0.5%; and group III: oral and intravenous narcotics and subfascial bupivicaine 0.5% injection). Postoperative intravenous and oral narcotic use as measured in morphine equivalents was significantly less in group III versus groups I and II (group III: 28.7 ME versus group I: 40.2 ME, group II: 44.8 ME; P<0.05). Postoperative length of stay was also shorter for group III (1.8 days) versus group I (2.5 days) and group II (2.9 days). LDN has been shown to be a viable alternative to traditional open donor nephrectomy for living kidney donation. We observed that the use of combined oral and intravenous narcotics alone is associated with greater postoperative narcotic use and increased length of stay compared to either a combined oral and intravenous narcotics plus continuous or single injection subfascial administration of bupivicaine. The progressive modification of our analgesic regimen has resulted in decreased postoperative oral and intravenous narcotic use and a reduction in the length of stay. We recommend subfascial infiltration with bupivicaine to the three laparoscopic sites and the pfannenstiel incision at the conclusion of the procedure to reduce postoperative pain. We believe this improvement in postoperative pain management will continue to make LDN even more appealing to the potential living kidney donor.

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation.

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemicenteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean ± standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI ≦24.9 (mean 21.7 ± 2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI ≧25 (mean 27.7 ± 2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P = NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P = 0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27 ± 1.9) was significantly higher than in patients who did not develop a leak (24 ± 3.7; P = 0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm

The aim of this study was to assess the long‐term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single‐center, 10‐yr follow‐up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low‐risk recipients. This study initially compared fat assessment based on frozen‐section Ehrlichs hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30–60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non‐function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.

Long-term efficacy of induction therapy with anti-interleukin-2 receptor antibodies or thymoglobulin compared with no induction therapy in renal transplantation.

BACKGROUND Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates. METHODS This retrospective analysis compared 3 patient groups-those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction. RESULTS Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 +/- 0.7, IL-2RA induction 2.0 +/- 1.0, and thymoglobulin induction 1.9 +/- 1.2; P = .47) were similar between all groups. CONCLUSION The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.

Parenchymal Transection of the Kidney Inflicted by Endocatch Bag Entrapment During a Laparoscopic Donor Nephrectomy

We present a case of inadvertent decapsulation and grade IV renal parenchyma laceration during laparoscopic donor nephrectomy. The kidney was repaired, used and functioned immediately. There were no complications in the donor. To our knowledge, this type of injury has not been reported previously and the purpose of this report is to focus attention on the potential for this unusual injury, which can occur during delivery of the kidney using the endocatch bag.

Heparin-induced thrombocytopenia in a renal transplant recipient.

Heparin‐induced thrombocytopenia (HIT) type II is an immunologically mediated reduction in platelets that increases the risk of arterial or venous thrombosis. It has been reported in up to 5% of patients receiving unfractionated heparin. Unlike other thrombocytopenic coagulopathies, HIT is associated with a high risk of thromboembolic events if not treated with an appropriate anticoagulant alternative. Diagnosis is dependent on assessment of platelet reduction, identification of previous heparin exposure, detection of thrombotic complications and evaluation of laboratory assays. HIT has been well described in surgical patient populations; however, the abdominal organ transplant population is an exception. HIT should be included in the differential diagnosis of patients presenting with thrombocytopenia after transplantation in order to prevent or treat thrombotic complications that can pose a risk to patient or graft survival.

Effect of Ethnicity on Outcome of Simultaneous Pancreas and Kidney Transplantation

The influence of ethnicity on outcome of simultaneous pancreas‐kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African‐Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One‐, 3‐, and 5‐year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One‐, 3‐, and 5‐year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One‐, 3‐, and 5‐year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.