Faculty Bibliography

The requirements for potent immunosuppression coupled with the formidable risk of irreversible antibody-mediated rejection (AMR) have thus far limited the expansion of ABO incompatible (ABOi) kidney transplantation. We present a retrospective review of our single-center experience with 60 consecutive ABOi kidney transplants and describe the evolution of our treatment protocol to one that consists only of a brief escalation in immunosuppression without long-term B-cell suppression from splenectomy or anti-CD20. The 1-, 3-, and 5-year graft survival rates for the cohort were 98.3%, 92.9%, and 88.7%, respectively, which is comparable with United Network for Organ Sharing data for compatible live donor transplants. No instances of hyperacute rejection were observed, and no grafts were lost secondary to AMR. In fact, fewer than 15% of the patients experienced a clinical episode of AMR, and rejections were mild. Elimination of B-cell ablative therapies did not result in an increased incidence of AMR. Excellent graft function persists with a current median creatinine clearance of 60 mL/min. The findings of this study and the relatively simple therapeutic regimen used should facilitate widespread application of ABOi kidney transplantation resulting in one of the most rapid escalations in access to organs in the modern era of kidney transplantation.

C4d deposition in peritubular capillaries is a specific marker for the presence of antidonor antibodies in renal transplant recipients and is usually associated with antibody-mediated rejection (AMR) in conventional allografts. In ABO-incompatible grafts, however, peritubular capillary C4d is often present on protocol biopsies lacking histologic features of AMR; the significance of C4d in this setting remains unclear. For addressing this, data from 33 patients who received ABO-incompatible renal allografts (after desensitization) were retrospectively reviewed. Protocol biopsies were performed at 1 and/or 3 and 6 mo after transplantation in each recipient and at 12 mo in 28 recipients. Twenty-one patients (group A) had strong, diffuse peritubular capillary C4d staining without histologic evidence of AMR or cellular rejection on their initial protocol biopsies. The remaining 12 patients (group B) had negative or weak, focal peritubular capillary C4d staining. Three grafts (two in group B) were lost but not as a result of AMR. Excluding these three patients, serum creatinine levels were similar in the two groups at 6 and 12 mo after transplantation and at last follow-up; however, recipients in group A developed significantly fewer overall chronic changes, as scored by the sum of Banff chronic indices, than group B during the first year after transplantation. These results suggest that diffuse peritubular capillary C4d deposition without rejection is associated with a lower risk for scarring in ABO-incompatible renal allografts; the generalizability of these results to conventional allografts remains unknown.

Caroli's disease is a rare autosomal recessive disorder characterized by intrahepatic cystic dilatation of the bile ducts that, when progressive, leads to intrahepatic stones, recurrent cholangitis, portal hypertension, cholangiocarcinoma, and liver failure. Liver transplantation is a promising curative option for advanced Caroli's disease. The aim of this study was to determine the outcomes of liver transplantation in unselected patients with Caroli's disease and recommend an evidence-based therapeutic algorithm for the management of Caroli's disease. Of the 78,124 patients transplanted in the United States between 1987 and 2006, 104 had Caroli's disease; 96 of these underwent liver alone, and 8 underwent combined liver/kidney transplantation. The patient survival and graft survival were analyzed by Kaplan-Meier survival analysis, and risk of death and risk of graft loss were analyzed by Cox proportional hazards regression. The overall 1-, 3-, and 5-year graft (79.9%, 72.4%, and 72.4%) and patient (86.3%, 78.4%, and 77%) survival rates were excellent for patients after liver transplantation. For combined liver/kidney transplantation (n = 8), the 1-year patient survival and graft survival were 100%. Proportional hazards analysis identified Asian ethnicity, elevated bilirubin, requirement of life support or hospitalization prior to transplantation, and a cold ischemia time greater than 12 hours as associated with increased risk of both graft loss and death. A history of prior transplant or prior abdominal surgery was also associated with increased risk of graft loss. In conclusion, liver transplantation is an excellent treatment option for patients with advanced Caroli's disease and should be considered in a timely fashion to prevent worsening complications including refractory cholangitis and cholangiocarcinoma.

PURPOSE OF REVIEW/OBJECTIVE:Recently, four organ recipients were infected with HIV through transplantation, raising questions about current serologic testing policies. Currently, the decision to use enzyme-linked immunosorbent assay or nucleic acid testing, an expensive and time-consuming method capable of detecting more recent infections, is left up to individual organ procurement organizations. The purpose of this review was to present estimates of the window period between infection and detection by enzyme-linked immunosorbent assay and nucleic acid testing for HIV, hepatitis B virus, and hepatitis C virus; and to evaluate the impact of those infections on posttransplant outcomes. RECENT FINDINGS/RESULTS:Nucleic acid testing for HIV can detect infections 12-13 days earlier than enzyme-linked immunosorbent assay; in the case of hepatitis B virus, infections are detected 21.8-36 days earlier; and in the case of hepatitis C virus, infections are detected 26-60 days earlier. Studies indicate that it is possible to manage all three infections posttransplant. HIV/hepatitis C virus coinfections seem to present the greatest posttransplant management challenges due to drug toxicities. SUMMARY/CONCLUSIONS:Nucleic acid testing can reduce the window period and thus increase the probability of detecting viral infections. HIV, hepatitis B virus, and hepatitis C virus positive organs may be appropriate for use in some situations; nucleic acid testing helps patients and physicians make informed decisions about their use.

BACKGROUND & AIMS/OBJECTIVE:Cholecystectomy is the most frequently performed gastrointestinal surgery in the United States. In this study, we characterized racial disparities in in-hospital mortality after cholecystectomy among patients with and without decompensated cirrhosis. METHODS:All patients who underwent cholecystectomy between 1998 and 2003 were queried from the Nationwide Inpatient Sample, the largest population-based and geographically representative all-payer database of hospital discharges in the United States. Crude mortality among races was determined for those with and without cirrhosis with portal hypertension and subsequently adjusted for demographic and clinical factors. RESULTS:In-hospital mortality associated with cholecystectomy was higher in the portal hypertensive group compared with those without portal hypertension (10.8% vs 1.4%; P < .0001). African Americans had greater adjusted mortality risk than whites in both the nonportal hypertensive (odds ratio [OR], 1.48; 95% CI, 1.35-1.63) and portal hypertensive (odds ratio [OR], 2.37; 95% CI, 1.47-3.84) groups, although the mortality gap was more pronounced in the latter. For portal hypertensive patients, undergoing cholecystectomy at a liver transplant center was associated with dramatically lower mortality (OR, 0.41; 95% CI, 0.25-0.69). CONCLUSIONS:In-patient mortality after cholecystectomy is 7.8-fold higher in patients with portal hypertension compared with those without portal hypertension. African Americans experienced higher mortality than whites after cholecystectomy, especially in the presence of portal hypertension. Cholecystectomy at a liver transplant center may offer survival benefit for patients with portal hypertension.

Although the majority of deceased-donor kidneys are donated after brain death, increased recovery of kidneys donated after cardiac death could reduce the organ shortage and is now a national priority. Racial disparities in donations after brain death have been well described for renal transplantation, but it is unknown whether similar disparities occur in donations after cardiac death. In this study, outcomes of adult deceased-donor renal transplant recipients included in the United Network for Organ Sharing database (1993 through 2006) were analyzed. Among black recipients of kidneys obtained after cardiac death, those who received kidneys from black donors had better long-term graft and patient survival than those who received kidneys from white donors. In addition, compared with standard-criteria kidneys from white donors after brain death, kidneys from black donors after cardiac death conferred a 70% reduction in the risk for graft loss (adjusted hazard ratio 0.30; 95% confidence interval 0.14 to 0.65; P = 0.002) and a 59% reduction in risk for death (adjusted hazard ratio 0.41; 95% confidence interval 0.2 to 0.87; P = 0.02) among black recipients. These findings suggest that kidneys obtained from black donors after cardiac death may afford the best long-term survival for black recipients.

BACKGROUND: Kidney paired donation (KPD) offers the best transplant option for patients with incompatible live kidney donors. Although studies suggest substantial expansion of the donor pool if fully used, few patients in the United States have undergone KPD. METHODS: We analyzed the 209 KPD and 89 list paired donation (LPD) transplants reported to United Network for Organ Sharing to better understand access to these modalities, clinical outcomes, and areas of potential expansion. RESULTS: Although many centers offer KPD/LPD, most centers have performed no more than a handful of transplants. As expected, outcomes with KPD/LPD were equivalent to direct donation matched controls. In analyzing current practice, we identified two limitations to KPD in its current use. First, KPD is likely limited now by benefiting mostly patients who are easy to identify and match (such as A donors with B recipients or B donors with A recipients). Second, although some expansion of local KPD availability has reduced travel requirements for patients in those areas, significant room for growth remains. CONCLUSIONS: Our results suggest that full utilization of KPD would encourage registration of and improve matching for patients who are more difficult to identify and match (such as highly sensitized recipients). Furthermore, expansion of KPD would likely reduce travel requirements and thereby improve access to this treatment modality.

BACKGROUND: When the United Network for Organ Sharing changed its algorithm for liver allocation to the model for end-stage liver disease (MELD) system in 2002, highest priority shifted to patients with renal insufficiency as a major component of their end-stage liver disease. An unintended consequence of the new system was a rapid increase in the number of simultaneous liver-kidney transplants (SLK) being performed yearly. METHODS: Adult recipients of deceased donor liver transplants (LT, n=19,137), kidney transplants (n=33,712), and SLK transplants (n=1,032) between 1987 and 2006 were evaluated based on United Network for Organ Sharing data. Recipients were stratified by donor subgroup, MELD score, pre- versus post-MELD era, and length of time on dialysis. Matched-control analyses were performed, and graft and patient survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: MELD era outcomes demonstrate a decline in patient survival after SLK. Using matched-control analysis, we are unable to demonstrate a benefit in the SLK cohort compared with LT, despite the fact that higher quality allografts are being used for SLK. Subgroup analysis of the SLK cohort did demonstrate an increase in overall 1-year patient and liver graft survival only in those patients on long-term dialysis (> or =3 months) compared with LT (84.5% vs. 70.8%, P=0.008; hazards ratio 0.57 [95% CI 0.34, 0.95], P=0.03). CONCLUSION: These findings suggest that SLK may be overused in the MELD era and that current prioritization of kidney grafts to those liver failure patients results in wasting of limited resources.

Current billing practices and mandates to report surgical outcomes are disincentives to surgical treatment of obese patients, who are at increased risk for longer hospital stays and higher complication rates. The objective of this study was to quantify the independent association between body mass index (BMI) and waiting time for kidney transplantation to identify potential provider bias against surgical treatment of the obese. A secondary data analysis was performed of a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006. Among all patients awaiting kidney transplantation, the likelihood of receiving a transplant decreased with increasing degree of obesity, categorized by ranges of BMI (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely obese, and 0.56 for morbidly obese, compared with a reference group of patients with normal BMI). Similarly, the likelihood of being bypassed when an organ became available increased in a graded manner with category of obesity (adjusted incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely obese, and 1.22 for morbidly obese). Although matching an available organ with an appropriate recipient requires clinical judgment, which could not be fully captured in this study, the observed differences are dramatic and warrant further studies to understand this effect better and to design a system that is less susceptible to unintended bias.