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.     

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.     

Risk Appreciation for Living Kidney Donors: Another New Subspecialty?

Quantitative estimates of the risk of end stage renal disease (ESRD) for living donors would seem essential to defensible donor selection practices, as the 'safe/unsafe' model for donor selection is not viable. All kidney donors take risk, and four fundamental, qualitative criteria should instead be used to decide when donor rejection is justified. These criteria are lack of donor education about transplantation, donor irrationality, lack of free and voluntary donation, and/or that donor acceptance would unavoidably threaten the public trust or the integrity of the center's selection procedures. Such a data-based selection policy, with explicit documentation of unbiased and comprehensive donor education, will help neutralize the center's self interest in a more defensible way than by rejecting 'complicated' kidney donors out of hand, and in a more practical way than by the creation of center-independent donor counselors or waiting for donor registries to come to fruition. Living kidney donors with isolated medical abnormalities comprise a sizable subset of at risk donors for whom center acceptance practices vary markedly. This population provides a paradigm opportunity for quantitative risk estimation and counseling.     

亲属活体供肾移植86例近期并发症分析

目的：总结和分析86例亲属活体供肾移植的近期并发症和诊治经验。方法：回顾性分析2003年11月～2009年4月86例亲属活体肾移植的临床资料。其中6例为夫妻间供肾,80例为直系血缘亲属供肾。供体均为开放手术取肾,受体首次移植84例,再次移植2例,术后采用环孢素A（或他克莫司）加霉酚酸酯（或硫唑嘌呤）加泼尼松预防排斥反应。结果：86例供体取肾术后7～10天出院,所有供体随访3～12个月,肾功能正常。86例受者中术后发生急性排斥反应8例,均经甲泼尼龙或抗胸腺细胞球蛋白治疗逆转。6例发生术后肺部感染,死亡2例。4例发生移植肾功能延迟恢复,其中1例并发移植肾周血肿合并弥漫性血管内凝血,最后因多器官功能衰竭死亡。术后移植肾周血肿再次手术6例,5例治愈。发生尿瘘6例,经保守治疗痊愈。83例存活者随访至今,其中术后1年发生慢性移植物失功2例,移植肾功能正常81例。结论：活体亲属供肾移植安全、疗效好,术后应高度重视和正确处理并发症,以获得人肾的长期存活。     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

The Impact of the New Kidney Allocation System on Prior Living Kidney Donors’ Access to Deceased Donor Kidney Transplants: An Early Look

This study investigated the early effects of the new kidney allocation system (KAS) on the access of prior living kidney donors (PLDs) to deceased donor kidney transplants. Using data from the Organ Procurement and Transplantation Network, we compared prevalent and incident cohorts of PLDs in the 1‐year periods before and after KAS implementation (pre‐KAS group: December 4, 2013, to December 3, 2014, n = 50 [newly listed PLDs]; post‐KAS group: December 4, 2014, to December 3, 2015, n = 39). We assessed transplant rates per active patient‐year, waiting times, and Kidney Donor Profile Index (KDPI) of transplanted kidneys. Transplant rates were not statistically different before and after KAS implementation for either prevalent (2.37 vs. 2.29, relative risk [RR] 0.96; 95% confidence interval [CI] 0.62–1.49) or incident (4.76 vs. 4.36, RR 0.92; 95% CI 0.53–1.60) candidates. Median waiting time (MWT) to deceased donor kidney transplant for prevalent PLDs in the post‐KAS cohort was 102.6 days compared with 82.3 days in the pre‐KAS cohort (p = 0.98). The median KDPI for PLD recipients was 31% with KAS versus 23% before KAS (p = 0.02). Despite a sharp decrease in the MWT for highly prioritized candidates with calculated panel reactive antibodies of 98–100% (from >7000 to 1164 days), PLDs still had much shorter waiting times (MWT 102.6 days). The new system continues to provide quick access to high‐quality organs for PLDs.     

Optimizing Outcomes in Pediatric Renal Transplantation Through the Australian Paired Kidney Exchange Program

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high‐level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor‐specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor–recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m² (range 46–94 mL) and a follow‐up range of 8–54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.     

Reciprocity to Increase Participation of Compatible Living Donor and Recipient Pairs in Kidney Paired Donation

Inclusion of compatible living donor and recipient pairs (CPs) in kidney paired donation (KPD) programs could increase living donor transplantation. We introduce the concept of a reciprocity‐based strategy in which the recipient of a CP who participates in KPD receives priority for a repeat deceased donor transplant in the event their primary living donor KPD transplant fails, and then we review the practical and ethical considerations of this strategy. The strategy limits prioritization to CPs already committed to living donation, minimizing the risk of unduly influencing donor behavior. The provision of a tangible benefit independent of the CP's actual KPD match avoids many of the practical and ethical challenges with strategies that rely on finding the CP recipient a better‐matched kidney that might provide the CP recipient a future benefit to increase KPD participation. Specifically, the strategy avoids the potential to misrepresent the degree of future benefit of a better‐matched kidney to the CP recipient and minimizes delays in transplantation related to finding a better‐matched kidney. Preliminary estimates suggest the strategy has significant potential to increase the number of living donor transplants. Further evaluation of the acceptance of this strategy by CPs and by waitlisted patients is warranted.     

Utilizing List Exchange and Nondirected Donation through ''Chain'' Paired Kidney Donations

In a list exchange (LE), the intended recipient in an incompatible pair receives priority on the deceased donor waitlist (DD-waitlist) after the paired incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist candidate. These two established practices would help even more transplant candidates if they were integrated with kidney paired donation (KPD). We consider a scenario in which the donor of an LE intended recipient (LE-IR) donates to a compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to the waitlist (an LE-chain). We consider a similar scenario in which an ND-D donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using data derived from the New England Program for Kidney Exchange (NEPKE) and from OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D) and ND-D who are ABO-O result in the highest number of additional transplants, while results for ABO-A and B donors are similar to each other. We recommend that both LE and ND donations be utilized through chain exchanges.     

Successful Expansion of the Living Donor Pool by Alternative Living Donation Programs

Between January 2000 and December 2007, 786 potential recipients and 1059 potential donors attended our pretransplant unit with the request for a living-donor renal transplant procedure. The recipients brought one potential donor in 77.2% and two or more donors in 22.8% of cases. In the regular living donor program, a compatible donor was found for 467 recipients. Without considering alternative donation, 579 donors would have been refused. Alternative living donation programs led to 114 compatible combinations: kidney-exchange program (35), ABO-incompatible donation (25), anonymous donation (37) and domino-paired anonymous donation (17). Together, the 114 alternative program donations and the 467 regular living donations led to 581 living donor transplantations (24.4% increase). Eventually for 54.9% (581/1059) of our donors, a compatible combination was found. Donor–recipient incompatibility comprised 19.4% (89/458) in the final refused population, which is 8.8% of the potential donor–recipient couples. Without considering alternative donation, 30.1% (174/579) of the refused donors would have been refused on incompatibility and 6.4% (37/579) because they were anonymous. This is 20% of the potential donor population (211/1059). The implementation of alternative living donation programs led to a significant increase in the number of transplantations, while transplantations via the direct donation program steadily increased.     

Clinical Outcomes of Multicenter Domino Kidney Paired Donation

Domino kidney paired donation (KPD) is a method by which an altruistic living nondirected donor (LND) is allocated to a pool of incompatible donor–recipient pairs (DRP) and a series of KPDs is initiated. To evaluate the feasibility and clinical outcomes of multicenter domino KPD, we retrospectively analyzed a cohort of DRPs who underwent domino KPD between February 2001 and July 2007 at one of 16 transplant centers. One hundred seventy-nine kidney transplants were performed, with 70 domino chains initiated by altruistic LND. There were 45 two-pair chains, 15 three-pair chains, 7 four-pair chains, 2 five-pair chains and 1 six-pair chain. A majority of donors were spouses (47.5%) or altruistic LNDs (39.1%). DRPs with a blood type O recipient or an AB donor comprised 45.9% of transplanted DRPs. HLA mismatch improved in transplanted donors compared to intended donors in pairs enrolled to improve HLA mismatch (3.4 ± 0.7 vs. 4.8 ± 1.0, p < 0.001). One-year and 5-year graft survival rates were 98.3% and 87.7%, respectively, with a median follow-up of 46 months. One-year and 5-year patient survival rates were 97.2% and 90.8%, respectively. In conclusion, multicenter domino KPD could multiply the benefits of donation from LNDs, with patients and graft survival rates comparable to those seen with conventional KPD.     

重肾双输尿管畸形活体供肾移植2例报告并文献复习

目的：探讨重肾双输尿管畸形供肾在亲属活体肾移植中的应用.方法：回顾性分析2005～2009年2例确诊为重肾双输尿管畸形供者行亲属活体肾移植的临床病例资料,总结治疗经验.结果：2供者术程顺利,无手术并发症,术后肾功能正常,2受者术后肾功能恢复良好,无手术并发症.结论：重肾双输尿管畸形供肾应列入边缘供体范畴,术前应充分评估,我们的处治方法是安全可行的.     

活体供肾者健康状况分析

目的：评价活体供肾术对供肾者健康状况的影响，探讨供肾时机及安全性。方法：对30例活体供肾者进行随访，分析活体供肾术后供肾者的患病率、长期肾功能、生活质量的变化。结果：30例活体供肾者中2例术后出现气胸，经处理恢复，余均未出现并发症，安全度过围手术期。经2～85个月随访，其中2例供者术后6个月内尿常规检查发现红细胞3～5个／HP，2例出现微量白蛋白尿，经治疗痊愈；2例出现尿路结石，处理后结石排出；1例血肌酐轻度升高，2例出现焦虑情绪。3例出现切口疼痛，18例感手术侧不适，经处理后逐步缓解，均未影响日常生活及工作。结论：活体供肾移植有很多优点，要把握供肾的时机，加强对供肾者术后的健康随访，确保活体供肾者的安全性。     

A Risk Index for Living Donor Kidney Transplantation

Choosing between multiple living kidney donors, or evaluating offers in kidney paired donation, can be challenging because no metric currently exists for living donor quality. Furthermore, some deceased donor (DD) kidneys can result in better outcomes than some living donor kidneys, yet there is no way to compare them on the same scale. To better inform clinical decision‐making, we created a living kidney donor profile index (LKDPI) on the same scale as the DD KDPI, using Cox regression and adjusting for recipient characteristics. Donor age over 50 (hazard ratio [HR] per 10 years = _1.151.24_1.33), elevated BMI (HR per 10 units = _1.011.09_1.16), African‐American race (HR = _1.151.25_1.37), cigarette use (HR = _1.091.16_1.23), as well as ABO incompatibility (HR = _1.031.27_1.58), HLA B (HR = _1.031.08_1.14) mismatches, and DR (HR = _1.041.09_1.15) mismatches were associated with greater risk of graft loss after living donor transplantation (all p < 0.05). Median (interquartile range) LKDPI score was 13 (1–27); 24.2% of donors had LKDPI < 0 (less risk than any DD kidney), and 4.4% of donors had LKDPI > 50 (more risk than the median DD kidney). The LKDPI is a useful tool for comparing living donor kidneys to each other and to deceased donor kidneys.