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Innovative strategies in living donor kidney transplantation

Segev, Dorry L
In an effort to increase living donor transplantation while minimizing risk and morbidity, recent advances have been made in surgical technique, kidney paired donation, desensitization, identification of living donors and research into living donor outcomes. Single-port nephrectomy and vaginal extraction have reduced donor nephrectomy incision size. Transport of live donor kidneys has reduced geographic barriers to kidney paired donation, and participation of compatible pairs and nondirected donors has increased match opportunities for incompatible pairs participating in this modality. ABO-incompatible transplantation can now be successfully performed without high-intensity immunomodulation, and HLA-incompatible transplantation has been shown in a large single-center study to provide profound survival benefit compared with waiting for a compatible donor. Complement inhibition is an exciting, emerging approach that may facilitate incompatible transplantation and treat antibody-mediated rejection. Educational and communications interventions are proving valuable in helping patients find living donors, and large studies continue to provide reassurance to carefully screened living donors that risks are very low. As living donors are critical to addressing the profound organ shortage, efforts to increase living donation remain important.
PMID: 22549232
ISSN: 1759-507x
CID: 5130142

Impact of donor hepatitis C virus infection status on death and need for liver transplant in hepatitis C virus-positive kidney transplant recipients

Kucirka, Lauren M; Peters, Thomas G; Segev, Dorry L
BACKGROUND:Only 29% of deceased donor kidney recipients with hepatitis C virus (HCV) receive HCV-positive (HCV+) kidneys. These kidneys are discarded 2.5 times more often than their HCV-negative (HCV-) counterparts, possibly due to the sense that an HCV+ kidney may adversely affect recipient liver function. The goals of this study were to characterize liver disease in HCV+ kidney recipients and compare rates of liver-related outcomes by kidney donor HCV status. STUDY DESIGN/METHODS:Observational cohort study. SETTING & PARTICIPANTS/METHODS:6,250 patients with HCV who had a kidney transplant in 1995-2008 as captured in the United Network for Organ Sharing (UNOS) database. Liver-related outcomes were assessed by cross-linking with the liver waitlist and transplant data sets. PREDICTOR/METHODS:HCV status of transplanted kidney. OUTCOMES/RESULTS:Joining the liver waitlist, receiving a liver transplant, death. MEASUREMENTS/METHODS:Time to event. RESULTS:Only 63 (1%) of HCV+ kidney recipients eventually joined the liver waitlist during the 13-year study period. Those who received HCV+ kidneys had a 2.6-fold higher hazard of joining the liver list (P < 0.001); however, the absolute difference in rate of listing between recipients of HCV- and HCV+ kidneys was <2%. This is consistent with findings of only 2% lower patient survival at 3 years in HCV+ patients receiving HCV+ versus HCV- kidneys. LIMITATIONS/CONCLUSIONS:We lacked data for HCV viral load and genotype of both HCV+ recipients and transplanted HCV+ kidneys. CONCLUSIONS:Because transplant with an HCV+ kidney may reduce waiting-time by more than a year for an HCV+ patient and there is a high risk of kidney waitlist mortality, a 2% increased rate of adverse liver outcomes and 2% increased rate of death at 3 years should not universally preclude the use of HCV+ kidneys when the intended recipient is also HCV+.
PMID: 22560841
ISSN: 1523-6838
CID: 5130152

Living kidney donors and their family caregivers: developing an evidence-based educational and social support website

Taylor, Laura A; Bahreman, Nasreen; Hayat, Matthew J; Hoey, Frank; Rajasekaran, Geetha; Segev, Dorry L
CONTEXT/BACKGROUND:Although graft and patient survival rates for living kidney donation are improved, some healthcare providers question whether volunteer donors and their informal caregivers are fully informed of the donation process and the risks involved. Donors and their family caregivers have reported that they receive limited information about the predonation and donor recovery process. Offering web-based information and social support is one way to address this gap. STRATEGY/METHODS:Living kidney donor candidates and their family caregivers participating in the Living Donor Information Network for Caregiving (LINC) have access to a variety of online informational resources and a social support discussion forum throughout their living kidney donation experience. Strategies in the development and implementation of an online information and social-support resource are presented. CONCLUSIONS:Use of the LINC website for information and support may assist health care providers in identifying potential barriers in the current donation process and provide direction for enhancing knowledge and confidence among donors and family caregivers.
PMCID:3499029
PMID: 22878067
ISSN: 1526-9248
CID: 5130172

Activity of daily living disability and dialysis mortality: better prediction using metrics of aging [Letter]

McAdams-Demarco, Mara A; Law, Andrew; Garonzik-Wang, Jacqueline M; Gimenez, Luis; Jaar, Bernard G; Walston, Jeremy D; Segev, Dorry L
PMCID:4580268
PMID: 23057455
ISSN: 1532-5415
CID: 5130192

Vascular disease, ESRD, and death: interpreting competing risk analyses

Grams, Morgan E; Coresh, Josef; Segev, Dorry L; Kucirka, Lauren M; Tighiouart, Hocine; Sarnak, Mark J
BACKGROUND AND OBJECTIVES/OBJECTIVE:Vascular disease, a common condition in CKD, is a risk factor for mortality and ESRD. Optimal patient care requires accurate estimation and ordering of these competing risks. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:This is a prospective cohort study of screened (n=885) and randomized participants (n=837) in the Modification of Diet in Renal Disease study (original study enrollment, 1989-1992), evaluating the association of vascular disease with ESRD and pre-ESRD mortality using standard survival analysis and competing risk regression. RESULTS:The method of analysis resulted in markedly different estimates. Cumulative incidence by standard analysis (censoring at the competing event) implied that, with vascular disease, the 15-year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more accurate representation of absolute risk was estimated with competing risk regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death, respectively. For the association of vascular disease with pre-ESRD death, estimates of relative risk by the two methods were similar (standard survival analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20-2.20; competing risk regression adjusted subhazard ratio, 1.57; 95% confidence interval, 1.15-2.14). In contrast, the hazard and subhazard ratios differed substantially for other associations, such as GFR and pre-ESRD mortality. CONCLUSIONS:When competing events exist, absolute risk is better estimated using competing risk regression, but etiologic associations by this method must be carefully interpreted. The presence of vascular disease in CKD decreases the likelihood of survival to ESRD, independent of age and other risk factors.
PMCID:3463208
PMID: 22859747
ISSN: 1555-905x
CID: 5102162

Recipient age and time spent hospitalized in the year before and after kidney transplantation

Grams, Morgan E; McAdams Demarco, Mara A; Kucirka, Lauren M; Segev, Dorry L
BACKGROUND:Kidney transplantation (KT) is a life-prolonging therapy in certain older end-stage renal disease patients, but concerns regarding peritransplantation morbidity remain. We estimate the relative increase in time spent hospitalized in the year post-KT for older versus younger end-stage renal disease patients. METHODS:This was a retrospective analysis of 27,247 Medicare-primary KT recipients from 2000 to 2005 using United States Renal Data System and Organ Procurement and Transplantation Network data. Time spent hospitalized was enumerated in the year pre-KT and post-KT from Medicare Part A claims. Excess inpatient days were the difference in an individual's post-KT and pre-KT hospital and skilled nursing facility days, standardized by time spent alive in the year post-KT. RESULTS:The median excess inpatient days were similar by age group (9 in recipients 65 years or older vs. 7 in recipients younger than 65 years); however, the distribution was skewed, such that many more older adults had large increases in inpatient time (8.6% totaled >120 excess inpatient days vs. 4.2% in younger recipients). Among older recipients, risk factors for poor outcomes included recipient age, donor age, longer dialysis vintage, diabetic nephropathy, and congestive heart failure. Reasons for posttransplantation hospitalization were similar by age with the exception of rehabilitation, which was common only in the 65+ age group. Mean inpatient costs were equivalent pretransplantation by age but significantly higher posttransplantation among older KT recipients. CONCLUSIONS:Posttransplantation morbidity may not be so different in most of the older individuals selected for KT; however, a minority fares much worse.
PMCID:3465472
PMID: 22932116
ISSN: 1534-6080
CID: 5102172

National trends in surgical procedures for hepatocellular carcinoma: 1998-2008

Nathan, Hari; Segev, Dorry L; Mayo, Skye C; Choti, Michael A; Cameron, Andrew M; Wolfgang, Christopher L; Hirose, Kenzo; Edil, Barish H; Schulick, Richard D; Pawlik, Timothy M
BACKGROUND:The incidence of hepatocellular carcinoma (HCC) is rising, and the options for surgical therapy of HCC have evolved recently, but use of surgical therapy has not been characterized on a representative, nationwide basis. We quantified trends in use, mortality, and patient and hospital characteristics for 3 surgical therapies for HCC (resection, ablation, and transplantation) in the United States from 1998 to 2008. METHODS:Hospital discharge data from the Nationwide Inpatient Sample were used to quantify procedure-related data for each year. Trends over time were summarized as the average annual percent change (AAPC) and corresponding 95% confidence interval (CI). RESULTS:The number of surgical procedures for HCC increased from 1416 to 6769 (AAPC, 13.5%; 95% CI, 10.2%-16.8%). Volumes increased for all surgical procedures, most notably for ablation (AAPC, 17.3%; 95% CI, 6.6%-29.2%) and transplantation (AAPC, 20.9%; 95% CI, 14.1%-28.1%). When analyzed as a proportion of total procedures, there were declines in the relative use of major hepatectomy (35% to 16%; AAPC, -7.2%, 95% CI, -8.8% to -5.6%) and wedge resection (37% to 22%; AAPC, -4.8%; 95% CI, -6.2% to -3.4%), while the proportion accounted for by transplantation increased (16% to 35%; AAPC, 4.4%; 95% CI, 0.2%-8.9%). Inpatient mortality decreased for each procedure individually and overall from 7.3% to 4.6% (AAPC, -7.7%; 95% CI, -10.8% to -4.5%), despite increasing age and comorbidity burden. CONCLUSIONS:The use of surgical therapy for HCC has increased dramatically over the last decade, with a relative shift away from liver resection and toward liver transplantation. These therapeutic modalities must be better targeted to make the most appropriate use of limited health care resources.
PMID: 22009384
ISSN: 1097-0142
CID: 4742002

Operative start times and complications after kidney transplantation

Shaw, Tavis M; Lonze, Bonnie E; Feyssa, Eyob L; Segev, Dorry L; May, Noah; Parsikia, Afshin; Campos, Stalin; Khanmoradi, Kamran; Zaki, Radi F; Ortiz, Jorge A
The worldwide focus on work hour regulations and patient safety has led to the re-examination of the merits of night-time surgery, including kidney transplantation. The risks of operating during nontraditional work hours with potentially fatigued surgeons and staff must be weighed against the negative effects of prolonged cold ischemic time with resultant graft compromise. The aim of this study was to evaluate the impact of performing renal transplantation procedures during evening versus day time hours. The main outcome measures assessed between the day and night cohorts included comparisons of the postoperative complication rates and survival outcomes for both the renal allograft and the patient. A retrospective review of 633 deceased donor renal transplants performed at a single institution was analyzed. Three statistically significant results were noted, namely, a decrease in vascular complications in the nighttime cohort, an increase in urologic complications on subgroup analysis in the 3 AM to 6 AM cohort, and the 12 AM to 3 AM subgroup had the greatest odds of any complication. There was no statistical difference in either patient or graft survival over a twelve month period following transplantation. We conclude that although the complication rate varied among cohorts this was clinically insignificant and there was no overall clinically relevant impact on patient or graft survival.
PMID: 22563648
ISSN: 1399-0012
CID: 2209392

Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis

Deshpande, Neha A; James, Nathan T; Kucirka, Lauren M; Boyarsky, Brian J; Garonzik-Wang, Jacqueline M; Cameron, Andrew M; Singer, Andrew L; Dagher, Nabil N; Segev, Dorry L
Approximately 14,000 women of reproductive age are currently living in the United States after liver transplantation (LT), and another 500 undergo LT each year. Although LT improves reproductive function in women with advanced liver disease, the associated pregnancy outcomes and maternal-fetal risks have not been quantified in a broad manner. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles that were published between 2000 and 2011 and reported pregnancy-related outcomes for LT recipients. Eight of 578 unique studies met the inclusion criteria, and these studies represented 450 pregnancies in 306 LT recipients. The post-LT live birth rate [76.9%, 95% confidence interval (CI) = 72.7%-80.7%] was higher than the live birth rate for the US general population (66.7%) but was similar to the post-kidney transplantation (KT) live birth rate (73.5%). The post-LT miscarriage rate (15.6%, 95% CI = 12.3%-19.2%) was lower than the miscarriage rate for the general population (17.1%) but was similar to the post-KT miscarriage rate (14.0%). The rates of pre-eclampsia (21.9%, 95% CI = 17.7%-26.4%), cesarean section delivery (44.6%, 95% CI = 39.2%-50.1%), and preterm delivery (39.4%, 95% CI = 33.1%-46.0%) were higher than the rates for the US general population (3.8%, 31.9%, and 12.5%, respectively) but lower than the post-KT rates (27.0%, 56.9%, and 45.6%, respectively). Both the mean gestational age and the mean birth weight were significantly greater (P < 0.001) for LT recipients versus KT recipients (36.5 versus 35.6 weeks and 2866 versus 2420 g). Although pregnancy after LT is feasible, the complication rates are relatively high and should be considered during patient counseling and clinical decision making. More case and center reports are necessary so that information on post-LT pregnancy outcomes and complications can be gathered to improve the clinical management of pregnant LT recipients. Continued reporting to active registries is highly encouraged at the center level.
PMID: 22344967
ISSN: 1527-6473
CID: 2159762

Role of MDCT angiography in selection and presurgical planning of potential renal donors

Chu, Linda C; Sheth, Sheila; Segev, Dorry L; Montgomery, Robert A; Fishman, Elliot K
OBJECTIVE: The purpose of this study was to determine the prevalence and types of renal and extrarenal abnormalities that preclude renal donation or lead to alteration of the surgical approach on the basis of abdominal CT angiography (CTA) in a large group of potential renal donors. MATERIALS AND METHODS: In this retrospective study, 654 potential renal donors undergoing dual-phase CTA were identified from January 2005 to January 2009. The CT reports were systemically reviewed by two radiologists to determine the presence of renal and extrarenal abnormalities. The operative notes of the renal donors were reviewed by one radiologist to determine whether the presence of renal pathology had affected the surgical approach. In the candidates who did not proceed to kidney donation, the reasons that precluded kidney donation were abstracted from the transplant database. RESULTS: Four hundred seventeen potential donors (269 men and 385 women; mean age, 44.0 years; age range, 17-79 years) proceeded to renal donation and 237 did not. The most common renal abnormalities were cysts (34%) and renal stones (4.4%). Renal artery disease was identified in 3.4% of potential donors, including renal artery stenosis, possible fibromuscular dysplasia, and renal artery aneurysm. Suspicious renal masses were incidentally found in 0.5% of potential donors. The most common extrarenal pathology was an incidental adrenal nodule (2.6%). Other significant extrarenal pathology identified included gallbladder mass (0.2%), Crohn disease (0.2%), ovarian mass (0.2%), and possible sarcoidosis (0.2%). Although renal and extrarenal abnormalities were present in 41% of potential renal donors, abnormalities seen on CT only contributed to exclusion of 27 potential donors (4.1%). The most common reason for exclusion was the presence of renal stones or scarring (1.8%). Significant CT findings also contributed to the selection of the right kidney in 29 donors, most commonly due to presence of ipsilateral vascular disease or complex left vascular anatomy. CONCLUSION: Renal parenchymal and vascular abnormalities are common in asymptomatic potential kidney donors. Although most of these represent incidental CT findings, abnormalities can exclude potential renal donors and alter the surgical approach in a small minority of cases.
PMID: 23096176
ISSN: 1546-3141
CID: 1980122