Comparison of Kidney Paired Donation Transplantations with Living Related Donor Kidney Transplantation: Implications for National Kidney Paired Donation Program

Background: Kidney Paired Donation (KPD) is a rapidly growing modality for facilitating living related donor kidney transplantation (LRDKTx) for patients who are incompatible with their healthy, willing, and living donors. Data scarcity on the outcome of KPD versus LRDKTx prompted us to review our experience. Materials and methods: This was a single-center study of 224 patients on regular follow-up, who underwent LRDRTx from January 2010 to June 2012 at our institute. The aim of this study was to compare short-term graft survival, patient survival and rejection rates of KPD (group 1, n = 34) with those of LRDKTx (group 2, n = 190). All the recipients received triple immunosuppression and thymoglobulin induction in KPD group. Kaplan–Meier curves were used for survival analysis. In group 1, mean recipient age was 35.5 ± 13.2 years, 29 were men and mean donor age was 44.4 ± 8.17 years, 10 were men. In group 2, mean recipient age was 29.1 ± 10 years, 155 were men and mean donor age was 47.5 ± 9.69 years, 74 were men. Mean human leukocyte antigen (HLA) matching in group 1 and 2 was 1 versus 3.2 (p < 0.05). Results: One- and two-year patient survival showed no significant difference between the two groups (97.1%, 97.1% vs. 96.2%, 94.8%, respectively, p = 0.81). Death-censored graft survival also showed no significant difference between the two groups (97.1%, 97.1%, vs. 97.6%, 97.6%, p = 0.73). Acute rejection incidence was also similar (8.7% vs. 9.9%, p > 0.62). Conclusions: Our study showed similar graft survival, patient survival and rejection rates of KPD versus LRDKTx over 2 years post-transplantation, encouraging the use of this approach for national KPD program.     

Barriers to access by Indigenous Australians to kidney transplantation: the IMPAKT study

Although Indigenous Australians represent less than 2% of the national population, they account for 8-10% of new patients commencing treatment for end-stage renal disease (ESRD). Almost half come from remote regions lacking renal disease treatment services. In those regions, their incidence of ESRD is up to 30 times the incidence for all Australians. Kidney transplantation is the optimal treatment for ESRD. Compared with long-term dialysis, it results in better quality of life, longer life expectancy and lower costs of health care. Indigenous Australians with ESRD receive transplants at approximately one-third the rate of non-Indigenous patients. There are similar disparities in access to kidney transplants for Native Americans, Aboriginal Canadians and New Zealander Maori. The reasons for such disparities have not been studied in any detail. IMPAKT (Improving Patient Access to Kidney Transplantation) is an NHMRC-funded study, involving eight major renal units. It aims to identify the reasons for Indigenous Australians' poor access to transplantation. It will systematically examine each of the steps a new dialysis patient must negotiate in order to receive a transplant. Each of these steps can become a barrier.     

Impact of single centre kidney paired donation transplantation to increase donor pool in India: a cohort study

In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost‐effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single‐centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross‐match (n = 59) and better matching (n = 19). A total of 124 two‐way (n = 248), 14 three‐way (n = 42), one four‐way (n = 4) and one six‐way exchange (n = 6) yielded 300 KPD transplants. Death‐censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow‐up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high‐volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large‐scale evidence for the expansion of single‐centre LDKT via KPD when national programmes do not exist.     

Chronic renal outcome after living donor liver transplantation

Chronic kidney disease (CKD) is one of the common complications after deceased donor liver transplantation. Although the worldwide pressing shortage in deceased donors has directed attention to living donor liver transplantation (LDLT), LDLT cohort data focusing on chronic renal dysfunction is limited. A total of 280 adult LDLT recipients (median 49 yr, 156 men) at the University of Tokyo hospital between 1996 and 2006 were reviewed. A total of 224 pre‐transplant liver failure patients (80.0%) showed an estimated glomerular filtration rate (eGFR) of more than 60 mL/min/1.73 m². However, during follow‐up at a mean of 1222 d after transplantation, eGFR declined to 60 mL/min/1.73 m² and 30 mL/min/1.73 m² in 150 (53.2%) and 21 (7.5%), respectively, and four patients (1.4%) required maintenance renal replacement therapy. Multivariate Cox proportional hazard model regression analysis revealed that recipient age (HR, 3.42 per 10‐yr increment; p < 0.001) and pre‐transplant eGFR (HR, 0.85 per 10‐mL/min/1.73 m² increment; p = 0.04) were associated independently with a post‐transplant decrease in eGFR to less than 30 mL/min/1.73 m². We conclude that higher age and lower pre‐transplant eGFR of an LDLT recipient indicate a high likelihood of subsequent development of advanced CKD. Preventive or therapeutic intervention should be optimized for these high‐risk patients.     

Broken Chains and Reneging: A Review of 1748 Kidney Paired Donation Transplants

Concerns regarding the potential for broken chains and “reneges” within kidney paired donation (KPD) and its effect on chain length have been raised previously. Although these concerns have been tested in simulation studies, real‐world data have yet to be evaluated. The purpose of this study was to evaluate the actual rate and causes of broken chains within a large KPD program. All patients undergoing renal transplantation through the National Kidney Registry from 2008 through May 2016 were included for analysis. Broken chains and loops were identified. A total of 344 chains and 78 loops were completed during the study period, yielding a total of 1748 transplants. Twenty broken chains and one broken loop were identified. The mean chain length (number of transplants) within broken chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common causes of a broken chain were donor medical issues incurred while acting as a bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being declined by the recipient surgeon (n = 4). All recipients involved in a broken chain subsequently received a transplant. Based on the results, broken chains are infrequent, are rarely due to lack of donor motivation, and have no significant impact on chain length.     

Kidney transplantation in valvular heart disease and pulmonary hypertension: Consensus in waiting

Kidney transplantation induces a lesser anesthetic, surgical, and physiological alterations than other solid organ transplantation. Concomitant valvular pathologies expose these patients to poor postoperative outcome. There is a critical gap in knowledge and lack of coherence in the guidelines related to the management in patients with end‐stage renal disease with valvular heart disease. The individualized diagnostic and management plan should be based on the assessment of perioperative outcomes. Similarly, pulmonary hypertension in end‐stage renal disease poses a unique challenge, it can manifest in isolation or may be associated with other cardiac lesions, namely left‐sided valvular heart disease and left ventricular systolic and diastolic dysfunction. Quantification and stratification according to etiology are needed in pulmonary hypertension to ensure an adequate management plan to minimize the adverse perioperative outcomes. Lack of randomized controlled trials has imposed hindrance in proposing a unified approach to clinical decision‐making in these scenarios. In this review, we have described the magnitude of the problems, pathophysiologic interactions, impact on clinical outcomes and have also proposed a management algorithm for both the scenarios.     

The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10–562) days. The ADP is a viable method to support time limited donors in a KPD network.     

The Roles of Dominos and Nonsimultaneous Chains in Kidney Paired Donation

Efforts to expand kidney paired donation have included matching nondirected donors (NDDs) to incompatible pairs. In domino paired donation (DPD), an NDD gives to the recipient of an incompatible pair, beginning a string of simultaneous transplants that ends with a living donor giving to a recipient on the deceased donor waitlist. Recently, nonsimultaneous extended altruistic donor (NEAD) chains were introduced. In a NEAD chain, the last donor of the string of transplants initiated by an NDD is reserved to donate at a later time. Our aim was to project the impact of each of these strategies over 2 years of operation for paired donation programs that also allocate a given number of NDDs. Each NDD facilitated an average of 1.99 transplants using DPD versus 1.90 transplants using NEAD chains (p = 0.3), or 1.0 transplants donating directly to the waitlist (p < 0.001). NEAD chains did not yield more transplants compared with simultaneous DPD. Both DPD and NEAD chains relax reciprocality requirements and rebalance the blood-type distribution of donors. Because traditional paired donation will leave many incompatible pairs unmatched, novel approaches like DPD and NEAD chains must be explored if paired donation programs are to help a greater number of people.     

Ethnic and Gender Related Differences in the Risk of End‐Stage Renal Disease After Living Kidney Donation

There is limited data pertaining to the risk of End Stage Renal Disease (ESRD) after living kidney donation. The Organ Procurement and Transplantation Network and the Center for Medicare and Medicaid Services databases were used to identify living kidney donors (LKDs) who subsequently developed ESRD and to calculate LKD ESRD rates. We found 126 cases of ESRD among 56 458 LKDs (0.22%) who donated during October 1, 1987–March 31, 2003. The overall LKD ESRD rate was 0.134 per 1000 years at risk, with an average duration of follow‐up of 9.8 years. ESRD rates for LKDs overall and for Black, White, male and female donors compared favorably to the ESRD incidence in the general population. The LKD ESRD rate was nearly five times higher for Blacks than for Whites and two times higher for males than females. However, these ethnic and gender‐related differences were similar to those previously reported for ESRD in the general population. Our findings do not show an increase in the risk of ESRD for LKDs and support the current practice of living kidney donation. Further research is needed to determine if improved donor screening or follow‐up will reduce the risk of postdonation ESRD.     

Characterization of Waiting Times in a Simulation of Kidney Paired Donation

A national kidney paired donation (KPD) program will substantially increase transplant opportunities for recipients with blood type incompatible or cross-match positive donors. It seems likely that donor-recipient pairs with certain blood types, races or restrictions will wait longer than others for a match, although no data exist to confirm this assumption. We simulated patients and characterized the predicted waiting times for different blood type sub-groups, as well as the effects of patient-imposed restrictions on waiting time. We also compared waiting times of different racial sub-groups. Almost all patients with panel-reactive antibody (PRA) less than 80% match within a few months in a national KPD program, with the longest waiting time seen by O recipients with AB donors. Highly sensitized patients wait considerably longer, especially those unwilling to travel or accept older donors, and those with AB or B donors may not match in a timely manner. Although patients are better served by matching in a combined pool than within their own race, racial inequalities exist and bonus points can offset some of these differences. These data provide the first waiting time predictions that can aid patients with incompatible donors in choosing between KPD and desensitization, and can also facilitate planning for a national KPD program.     

Association of thrombocytopenia with outcome following adult living donor liver transplantation

This study aimed to evaluate the association of postoperative thrombocytopenia with outcome following adult living donor liver transplantation (LDLT) for end‐stage liver disease (ESLD). It was a prospective study of 120 consecutive adult LDLT from September 2012 to May 2015. Preoperative platelet counts (PLTs) and postoperative PLTs were recorded at regular intervals till 3 months after LDLT. Univariate and multivariate analyses were performed. The median pretransplant PLT was 61 × 10⁹/l. The lowest median PLT after LDLT was observed on POD 3. Patients were stratified into low platelet group (n = 83) with PLT <30 × 10⁹/l and high platelet group (n = 37) with PLT ≥30 × 10⁹/l. Patients with PLT <30 × 10⁹/l had statistically significant higher grade III/IV complication (P = 0.001), early graft dysfunction (P = 0.01), sepsis (P = 0.001), and prolonged ascites drainage (P = 0.002). On multivariate analysis, PLT<30 × 10⁹/l was identified as an independent risk factor for grade III/IV complications (P = 0.005). Overall, patients survival was significantly different between two groups (P = 0.04), but this predictive value was lost in patients who survived more than 90 days (P = 0.37). Postoperative PLT of <30 × 10⁹/l was a strong predictor of major postoperative complications and is associated with early graft dysfunction, prolonged ascites drainage, and sepsis. The perioperative mortality rate was high in the thrombocytopenia group.     

Limited health literacy is associated with reduced access to kidney transplantation

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Simultaneous liver kidney transplantation

Kidney injury is frequently seen in patients with end‐stage liver disease from cirrhosis and liver failure. Among selected patients, simultaneous liver kidney (SLK) transplantation provides improved post‐transplant graft and patient outcomes compared to liver transplantation (LT) alone. We conducted the review of the existing literature on SLK transplant criteria and outcomes. Since the introduction of the model for end‐stage disease (MELD) score in 2002, there has been an increased use of SLK transplantation. The criteria for SLK allocation are relatively homogeneous among patients with end‐stage renal disease with cirrhosis and among patients with cirrhosis and chronic kidney disease. However, these are quite heterogeneous among patients with cirrhosis and acute kidney injury (AKI), mainly because of inability to accurately differentiate cause of AKI, especially hepatorenal syndrome versus intrarenal aetiology. Clearly, there is an unmet need of urine biomarkers of tubular injury and/or clinical models to accurately stratify AKI aetiology and to predict renal recovery after LT as basis to best utilize the scarce donor kidney pool. In this regard, it remains to be seen whether recently implemented policies by the organ procurement transplant network can fulfil the goal of saving donor kidneys and optimal allocation of SLK.     

Living-donor kidney transplantation: risks of the donor – benefits of the recipient

Abstract:  For patients with end-stage renal disease, kidney transplantation is the optimal therapy. Due to organ shortage, however, most patients have to wait on dialysis for a considerable period of time prior to transplantation. Living-donor kidney transplantation is a valid option to expand the organ pool and to reduce waiting time. The risk–benefit ratio of living-donor kidney transplantation needs to be evaluated critically, as healthy persons voluntarily donate an organ for transplantation. The available data from the literature seem to prove that the donor operation can be performed with a minimal perioperative risk. Regarding the long-term course after kidney donation, the published data suggest that the risk is minimal for well-selected healthy donors who are closely followed postoperatively. The potential donor, however, needs to be completely informed regarding the potential short- and long-term risks of kidney donation prior to the planned procedure. From the recipient point of view, transplantation of a kidney from a living donor is a very good if not the optimal option, as the short- and long-term outcomes seem to be favorable compared with cadaveric kidney transplantation. With donor safety being constantly monitored, it seems to be justified to further pursue living-donor kidney transplantation programs.     

Racial Differences in Determinants of Live Donor Kidney Transplantation in the United States

Few studies have compared determinants of live donor kidney transplantation (LDKT) across all major US racial‐ethnic groups. We compared determinants of racial‐ethnic differences in LDKT among 208 736 patients who initiated treatment for end‐stage kidney disease during 2005–2008. We performed proportional hazards and bootstrap analyses to estimate differences in LDKT attributable to sociodemographic and clinical factors. Mean LDKT rates were lowest among blacks (1.19 per 100 person‐years [95% CI: 1.12–1.26]), American Indians/Alaska Natives‐AI/ANs (1.40 [1.06–1.84]) and Pacific Islanders (1.10 [0.78–1.84]), intermediate among Hispanics (2.53 [2.39–2.67]) and Asians (3.89 [3.51–4.32]), and highest among whites (6.46 [6.31–6.61]). Compared with whites, the largest proportion of the disparity among blacks (20%) and AI/ANs (29%) was attributed to measures of predialysis care, while the largest proportion among Hispanics (14%) was attributed to health insurance coverage. Contextual poverty accounted for 16%, 4%, 18%, and 6% of the disparity among blacks, Hispanics, AI/ANs and Pacific Islanders but none of the disparity among Asians. In the United States, significant disparities in rates of LDKT persist, but determinants of these disparities vary by race‐ethnicity. Efforts to expand preESKD insurance coverage, to improve access to high‐quality predialysis care and to overcome socioeconomic barriers are important targets for addressing disparities in LDKT.     

Gender imbalance among donors in living kidney transplantation: the Norwegian experience.

BACKGROUND: In living donor (LD) kidney transplantation, a predominance of female-to-male donations has been observed. Gender demographics of living donors and outcomes of LD kidney transplantations in Norway were assessed, as this has not been explored previously. METHODS: Data from the Norwegian Renal Registry of first LD kidney transplantations (n = 1319) in the period 1985-2002 were used. RESULTS: The majority of all LD was female (57.8%; P<0.001), while 62.7% of the recipients were men (P<0.001). Females dominated as donors in the spousal group and the parental group (P<0.0001). However, no gender difference was observed in the parental group when the recipients were <30 years old (P = 0.65). In opposite-sex pairs, female-to-male donations were as expected based on the incidence of end-stage renal disease. Donor sex affected neither the incidence of acute rejections nor graft survival. Serum creatinine was higher in renal allografts from female donors to male recipients in the first 4 years after transplantation. Donor age also had significant impact on graft function measured as serum creatinine. CONCLUSIONS: Gender disparities in LD transplantation result from a higher proportion of female-to-female and a lower proportion of male-to-male donations than expected. Both donor age and donor sex influence graft function during the first years. Graft survival and acute rejection episodes appear not to be affected by donor sex in LD kidney transplantation.