Santiago R. Vera

Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts

Transplantation of kidneys from older donors is being advocated to expand the organ donor pool. However, the prevalence of atherosclerosis and age-induced renal structural alterations account for the variable function of allografts procured from these older donors. Pretransplant biopsies are sometimes used to evaluate kidneys from older donors, but to date there are no defined criteria correlating the extent of structural alterations in these kidneys to subsequent function. We investigated the effect of glomerulosclerosis, a marker for nephrosclerosis, on graft outcome. Sixty-five baseline biopsies of kidney allografts were retrospectively analyzed to identify a referent point of glomerulosclerosis that correlated with inferior graft outcome. Age and death from non-traumatic cerebrovascular injuries were the main correlates for donor glomerulosclerosis (P<0.001). Allografts with poor function at 6 months defined as serum creatinine >2.5 mg/dl (n=13) or nephrectomy (n=4) had a mean of 20% glomerulosclerosis at the time of implantation compared with only 2% sclerosis in allografts with good function (P<0.05). Delayed graft function occurred in 22% and 33% of recipients with no glomerulosclerosis and those with less than 20% glomerulosclerosis, respectively. In contrast, patients receiving kidneys with >20% sclerosis had an 87% incidence of delayed function (P<0.05). Moreover, graft loss occurred in 7% of recipients of kidneys with less than 20% sclerosis and in 38% of recipients with >20% sclerosis (P<0.04). Measurements of serum creatinine in the donors did not distinguish the different degrees of glomerulosclerosis found on biopsy. Our data indicate that donor glomerulosclerosis greater than 20% increases the risk of delayed graft function and poor outcome of transplanted kidneys. Therefore, we advocate the use of routine biopsies of kidneys from older (>50 yrs) donors and those donors with nontraumatic cerebrovascular accidents, despite seemingly normal preprocurement serum creatinine.

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation

Introduction. This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. Methods. Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. Results. The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4±20.0 mL/min vs. 50.5±20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). Conclusions. Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction.

ObjectiveTo report the authors’ experience with adult living donor liver transplantation (ALDLT) without venovenous bypass and to describe modifications that will allow for a direct duct-to-duct biliary reconstruction. Summary Background DataAdult living donor liver transplantation is being evaluated as a method to alleviate the organ shortage. Descriptions of the procedure have emphasized the use of venovenous bypass, portocaval decompression, and the mandatory use of a Roux-en-Y biliary enteric anastomosis. The authors describe a technique for ALDLT without venovenous bypass, portocaval decompression, or caval clamping in 11 recipients and describe the modifications to the procedure that may allow a duct-to-duct biliary reconstruction in certain cases. MethodsBetween March 1999 and March 2000, 11 ALDLTs were performed at the authors’ institution. All procedures were performed without venovenous bypass, portocaval decompression, or caval clamping. After a modification to the procedure, five of the last six recipients underwent biliary reconstruction with a direct duct-to-duct anastomosis. Data regarding donor, recipient, and graft survival, complications, and graft function were collected. ResultsRecipients comprised five women and six men, mean age 48 years. Donors comprised five women and six men, mean age 36.5 years. Donor to recipient relationships included sibling, spouse, son, and daughter. Indications for transplantation were hepatitis C, hepatitis C with hepatocellular carcinoma, primary biliary cirrhosis, primary sclerosing cholangitis, ethanol, and cryptogenic. No case required venovenous bypass or portocaval shunting. The right hepatic vein of the donor graft was anastomosed to the confluence of the left and middle hepatic veins in all cases. All donors are alive and well, with no adverse complications reported. Recipient and graft survival rates were 91% and 82%, respectively, for ALDLT versus 92% and 92% for recipients of cadaveric organs during the same time period. One recipient died of multiple organ failure and sepsis. Biliary reconstruction was performed by Roux-en-Y hepaticojejunostomy in the six cases. In five of the last six recipients, direct duct-to-duct biliary reconstruction with a T tube was used. No anastomotic leaks or strictures occurred in the patients undergoing duct-to-duct reconstruction. ConclusionsAdult living donor liver transplantation can be performed safely and may help alleviate the organ shortage. Neither venovenous bypass nor portocaval shunting is necessary to perform the procedure, and modifications to both the donor and recipient hepatectomy procedures may allow biliary reconstruction to be performed by a direct duct-to-duct anastomosis in selected cases.

Polyomavirus in kidney and kidney-pancreas transplant recipients

Abstract: Purpose. To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney–pancreas transplant (KPTX) recipients.

Choice of surgical technique influences perioperative outcomes in liver transplantation.

OBJECTIVE To examine how the choice of surgical technique influenced perioperative outcomes in liver transplantation. SUMMARY BACKGROUND DATA The standard technique of orthotopic liver transplantation with venovenous bypass (VVB) is commonly used to facilitate hemodynamic stability. However, this traditional procedure is associated with unique complications that can be avoided by using the technique of liver resection without caval excision (the piggyback technique). METHODS A prospective comparison of the two procedures was conducted in 90 patients (34 piggyback and 56 with VVB) during a 2.5-year period. Although both groups had similar donor and recipient demographic characteristics, posttransplant outcomes were significantly better for the patients undergoing the piggyback technique. The effect of surgical technique was examined using a stepwise approach that considered its impact on two levels of perioperative and postoperative events. RESULTS The analysis of the first level of perioperative events found that the piggyback procedure resulted in a 50% decrease in the duration of the anhepatic phase. The analysis of the second level of perioperative events found a significant relation between the anhepatic phase and the duration of surgery and between the anhepatic phase and the need for blood replacement. The analysis of the first level of postoperative events found that the intensive care unit stay was significantly related to both the duration of surgery and the need for blood replacement. The intensive care unit stay was in turn related to the second level of postoperative events, namely the length of hospital stay. Finally, total charges were directly related to length of hospital stay. The overall 1-year actuarial patient and graft survival rates were 94% in the piggyback and 96% in the VVB groups, respectively. CONCLUSIONS These data demonstrate that surgical choices in complex procedures such as orthotopic liver transplantation trigger a chain of events that can significantly affect resource utilization. In the current healthcare climate, examination of the sequence of events that follow a specific treatment may provide a more complete framework for choosing between treatment alternatives.

Duct-to-duct biliary reconstruction in right lobe adult living donor liver transplantation

At the present time the preferred technique for biliary reconstruction in adult living donor liver transplantation (ALDLT) is the Roux-en-Y hepaticojejunostomy (HJ). Patients undergoing HJ are not drained through the normal physiologic route and may suffer from repeated bouts of ascending cholangitis. The inability to evaluate and treat biliary strictures and leaks by endoscopic retrograde cholangiography (ERCP) may complicate the postoperative management of patients undergoing HJ. Modifications aimed at preserving the blood supply to both the donor and recipient bile ducts may allow a direct duct-to-duct (D-D) biliary reconstruction in selected patients, and aid in visualization of the biliary tree and eliminate complications related to reflux cholangitis. Adult living donor liver transplantation, using a right lobe, is emerging as an effective treatment option for selected patients awaiting liver transplantation. Though many variations in technique exist between centers performing this procedure, most surgeons use an HJ as the preferred method for biliary-enteric reconstruction. The rationale for use of the HJ for biliary reconstruction in segmental liver grafts, such as those used in pediatric recipients, derives from the small size of the recipient bile duct and inadequate length of the donor bile duct. In addition, the underlying liver disease (eg, biliary atresia) often mandates an HJ. Finally, there are concerns relating to the vascular integrity of the anastomosis, especially with left-sided grafts, because important blood vessels may arise to the left hepatic duct from segment IV vessels. Although HJ remains the standard of care in pediatric segmental grafts, the use of HJ in adult segmental grafts, such as those used in ALDLT, would not appear to be mandatory for several reasons. First, most adult liver diseases do not prohibit a choledocho-choledochostomy. Second, the size of the adult bile duct is not a restricting factor; and finally, the vascular integrity of the anastomosis can be preserved by careful attention to surgical technique and a greater understanding of the vascular supply to the bile ducts. The fact that a D-D anastomosis is the preferred method for biliary reconstruction in cadaveric liver transplantation relates to its preservation of the normal physiologic sphincter mechanism and consequent reduction in the incidence of reflux cholangitis. In addition, it reduces operative time, allows easier access for radiologic evaluation of the biliary tract by ERCP, and avoids creation of an enteric anastomosis that may leak, cause infection, or act as a site for internal hernias. This article describes a modification of our standard procedure for ALDLT, which allows a well-vascularized and tension-free D-D anastomosis.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation

Abstract: Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long‐term HBIG/3TC has been shown to prevent short‐term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short‐term HBIG, long‐term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee‐Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)‐positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre‐transplant demographic characteristics such as age, gender, weight, and pre‐transplant diagnosis. Owing to the retrospective study design, median follow‐up was longer for the no‐prophylaxis (5.6 years) and the HBIG‐alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no‐prophylaxis and 71% in the HBIG‐alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no‐prophylaxis and 86% in the HBIG‐alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no‐prophylaxis era was 100% and 21% in the HBIG‐alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG‐alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA‐positive recipients was 100% in the no‐prophylaxis era, 30% in the HBIG‐alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG‐alone group had a nearly two‐fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post‐transplant compared to recipients in the HBIG/3TC group despite similar pre‐transplant HBV serology. This increased HBIG requirement in the HBIG‐alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group (

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole

47,367 at 6 months;

Randomized Double-Blind Study of Standard Versus Low-Dose OKT3 Induction Therapy in Renal Allograft Recipients

84,280 at 12 months) compared to the HBIG/3TC group (

Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation

25,931 at 6 months;