Gabriel C. Oniscu

Impact of Cadaveric Renal Transplantation on Survival in Patients Listed for Transplantation

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.

Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study

Abstract Objective To examine the access to the renal transplant waiting list and renal transplantation in Scotland. Design Cohort study. Setting Renal and transplant units in Scotland. Participants 4523 adults starting renal replacement therapy in Scotland between 1 January 1989 and 31 December 1999. Main outcome measures Impact of age, sex, social deprivation, primary renal disease, renal or transplant unit, and geography on access to the waiting list and renal transplantation. Results 1736 of 4523 (38.4%) patients were placed on the waiting list for renal transplantation and 1095 (24.2%) underwent transplantation up to 31 December 2000, the end of the study period. Patients were less likely to be placed on the list if they were female, older, had diabetes, were in a high deprivation category, and were treated in a renal unit in a hospital with no transplant unit. Patients living furthest away from the transplant centre were listed more quickly. The only factors governing access to transplantation once on the list were age, primary renal disease, and year of listing. A significant centre effect was found in access to the waiting list and renal transplantation. Conclusions A major disparity exists in access to the renal transplant waiting list and renal transplantation in Scotland. Comorbidity may be an important factor.

How Old is Old for Transplantation

Elderly patients are the fastest growing group requiring renal transplantation. This study investigates whether transplantation is worthwhile in the elderly and whether there is evidence supporting an age limit for transplantation.

In Situ Normothermic Regional Perfusion for Controlled Donation After Circulatory Death—The United Kingdom Experience

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty‐one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty‐three organs were recovered. Forty‐nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10–23 min). Thirty‐two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min–18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72–222) and 121 µmol/L (range 63–157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58–3043). One patient had primary nonfunction. Two combined pancreas–kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short‐term outcomes.

Classification of liver and pancreatic trauma

The liver is the most frequently injured intra-abdominal organ and associated injury to other organs increases the risk of complications and death. This has highlighted the critical need for an accurate classification system as a basis for the clinical decision-making process. Several classification systems have been proposed in an attempt to incorporate the aetiology, anatomy and extent of injury and correlate it with subsequent clinical management and outcome. The widely accepted Organ Injury Scale is based on anatomical criteria that quantify the disruption of the liver parenchyma and defines six groups which may influence management strategies and relate to outcome. The less common pancreatic injury remains a major source of morbidity and mortality due to the likelihood of associated solid or hollow-organ injuries. The implication of a delay in diagnosis and management emphasizes the need for an accurate classification system. The Organ Injury Scale is widely used for pancreas trauma and recognizes the importance of progressive parenchymal injury and in particular ductal injury. Advances in imaging techniques have led to the development of newer radiological classification systems; however, validation of their accuracy remains to be proven. An accurate classification of liver and pancreatic trauma is fundamental for the development of treatment protocols in which clinical decisions are based on the severity of injury.

Expanding the evidence base in transplantation: The complementary roles of randomized controlled trials and outcomes research

Transplantation offers a unique opportunity to demonstrate the complementary roles of randomized controlled trials and outcome research. The surgery and collaboration necessary for the transplant procedure makes randomization and blinding difficult. Because essentially every recipient is included in a transplant registry, sampling bias is minimized. Regulatory agencies generally do not consider outcomes research when assessing efficacy of new drugs or medical interventions. This workgroup summary examines the suitability of outcomes research to complement results of randomized controlled trials and related issues: efficacy versus effectiveness, internal versus external validity, data types, limitations, and analysis methodologies. Many advances in outcomes research have been pioneered in transplantation. A case is made for regulatory and reimbursement authorities to use outcomes research when making efficacy, effectiveness, and coverage decisions in transplantation.

A case‐controlled study of the safety and efficacy of transjugular intrahepatic portosystemic shunts after liver transplantation

The role of transjugular intrahepatic portosystemic shunt (TIPS) insertion in managing the complications of portal hypertension is well established, but its utility in patients who have previously undergone liver transplantation is not well documented. Twenty‐two orthotopic liver transplantation (OLT) patients and 44 nontransplant patients (matched controls) who underwent TIPS were analyzed. In the OLT patients, the TIPS procedure was performed at a median of 44.8 months (range = 0.3‐143 months) after transplantation. Eight (36.4%) had variceal bleeding, and 14 (63.6%) had refractory ascites. The underlying liver disease was cholestatic in 10 (45.4%) and viral in 4 (18.2%). The mean pre‐TIPS Model for End‐Stage Liver Disease (MELD) score was 13.4 ± 5.1. There were no significant differences in age, sex, indication, etiology, or MELD score with respect to the control group. The mean initial portal pressure gradients (PPGs) were similar in the 2 groups (21.0 versus 22.4 mm Hg for the OLT patients and controls, respectively), but the final PPG was lower in the control group (9.9 versus 6.9 mm Hg, P < 0.05). The rates of both technical success and clinical success were higher in the control group versus the OLT group [95.5% versus 68.2% (P < 0.05) and 93.2% versus 77.2% (P < 0.05), respectively]. The rates of complications and post‐TIPS encephalopathy were similar in the 2 groups, and there was a trend toward increased rates of shunt insufficiency in the OLT group. The mortality rate of the patients with a pre‐TIPS MELD score > 15 was significantly higher in the OLT group [hazard ratio (HR) = 4.32, 95% confidence interval (CI) = 1.45‐12.88, P < 0.05], but the mortality rates of the patients with a pre‐TIPS MELD score < 15 were similar in the 2 groups. In the OLT group, the predictors of increased mortality were the pre‐TIPS MELD score (HR = 1.161, 95% CI = 1.036‐1.305, P < 0.05) and pre‐TIPS MELD scores > 15 (HR = 5.846, 95% CI = 1.754‐19.485, P < 0.05). In conclusion, TIPS insertion is feasible in transplant recipients, although its efficacy is lower in these patients versus control patients. Outcomes are poor for OLT recipients with a pre‐TIPS MELD score > 15. Liver Transpl 17:771‐778, 2011.

A Systematic Review of the Prevalence and Associations of Limited Health Literacy in CKD

BACKGROUND AND OBJECTIVES The self-management and decision-making skills required to manage CKD successfully may be diminished in those with low health literacy. A 2012 review identified five papers reporting the prevalence of limited health literacy in CKD, largely from United States dialysis populations. The literature has expanded considerably since. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used systematic review, pooled prevalence analysis, metaregression, and exploration of heterogeneity in studies of patients with CKD (all stages). RESULTS From 433 studies, 15 new studies met the inclusion criteria and were analyzed together with five studies from the 2012 review. These included 13 cross-sectional surveys, five cohort studies (using baseline data), and two using baseline clinical trial data. Most (19 of 20) were from the United States. In total, 12,324 patients were studied (3529 nondialysis CKD, 5289 dialysis, 2560 transplant, and 946 with unspecified CKD; median =198.5; IQR, 128.5-260 per study). Median prevalence of limited health literacy within studies was 23% (IQR, 16%-33%), and pooled prevalence was 25% (95% confidence interval, 20% to 30%) with significant between-study heterogeneity (I2=97%). Pooled prevalence of limited health literacy was 25% (95% confidence interval, 16% to 33%; I2=97%) among patients with CKD not on dialysis, 27% (95% confidence interval, 19% to 35%; I2=96%) among patients on dialysis, and 14% (95% confidence interval, 7% to 21%; I2=97%) among patients with transplants. A higher proportion of nonwhite participants was associated with increased limited health literacy prevalence (P=0.04), but participant age was not (P=0.40). Within studies, nonwhite ethnicity and low socioeconomic status were consistently and independently associated with limited health literacy. Studies were of low or moderate quality. Within-study participant selection criteria had potential to introduce bias. CONCLUSIONS Limited health literacy is common in CKD, especially among individuals with low socioeconomic status and nonwhite ethnicity. This has implications for the design of self-management and decision-making initiatives to promote equity of care and improve quality. Lower prevalence among patients with transplants may reflect selection of patients with higher health literacy for transplantation either because of less comorbidity in this group or as a direct effect of health literacy on access to transplantation.

Variations in the Assessment Practice for Renal Transplantation Across the United Kingdom

Background. To investigate whether there are any variations in the evaluation of adult candidates for cadaveric renal transplantation among transplant centers in the United Kingdom. Methods. An online survey of transplant units in the United Kingdom, including nephrologists, surgeons, and transplant coordinators, measured differences in the assessment process and evaluation of patients age, body mass index (BMI), cardiovascular comorbidity, and viral serology. Results. A response was received from 20 out of the 23 centers (87%). These centers perform 90% of all renal transplants in the United Kingdom. In 30% of the units, there is no formal transplant assessment clinic. There is no cutoff age limit for assessment across the United Kingdom, but 12 centers (60%) exclude patients with a high BMI, with a median cutoff BMI of 35. Eight out of the 20 centers do not give cytomegalovirus (CMV)-negative patients the option to receive kidneys from a CMV-positive donor. Hepatitis C antibody–positive donors are not used in 50% of the units. There is considerable variation in the investigation of cardiovascular disease and exclusion criteria based on cardiovascular status of the patients. Five units have no consistent policy of re-evaluating patients once they are listed. Conclusions. There is evidence, from this study, of significant variations in the assessment of patients for renal transplantation across the United Kingdom. Further research and better-defined guidelines are required for a uniform assessment process and to ensure equity of access to the renal transplant waiting list.

Global trends and challenges in deceased donor kidney allocation

Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade.