Risk aversion in the use of complex kidneys in paired exchange programs: Opportunities for even more transplants?

This retrospective review of the largest United States kidney exchange reports characteristics, utilization, and recipient outcomes of kidneys with simple compared to complex anatomy and extrapolates reluctance to accept these kidneys. Of 3105 transplants performed, only 12.8% were right kidneys and 23.1% had multiple renal arteries. 59.3% of centers used fewer right kidneys than expected and 12.1% transplanted zero right kidneys or kidneys with more than 1 artery. Five centers transplanted a third of these kidneys (35.8% of right kidneys and 36.7% of kidneys with multiple renal arteries). 22.5% and 25.5% of centers currently will not entertain a match offer for a left or right kidney with more than one artery, respectively. There were no significant differences in all-cause graft failure or death-censored graft loss for kidneys with multiple arteries, and a very small increased risk of graft failure for right kidneys versus left of limited clinical relevance for most recipients. Kidneys with complex anatomy can be used with excellent outcomes at many centers. Variation in use (lack of demand) for these kidneys reduces the number of transplants, so systems to facilitate use could increase demand. We cannot know how many donors are turned away because perceived demand is limited.

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants.

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m2 ) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.

Motivations and outcomes of compatible living donor-recipient pairs in paired exchange.

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m², p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m², p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.

Ensuring the need is met: A 50-year simulation study of the National Kidney Registry's family voucher program.

The National Kidney Registry (NKR) Advanced Donation Program enables living donors the opportunity to donate altruistically, or in advance of a potential recipient's transplant, and to receive a voucher that can be redeemed for a future transplant facilitated by the NKR. Family vouchers allow a donor to identify multiple individuals within their immediate family, with the first person in that group in need of a transplant being prioritized to receive a kidney. An increase in vouchers introduces concerns that demand for future voucher redemptions could exceed the supply of available donors and kidneys. A Monte Carlo simulation model was constructed to estimate the annual number of voucher redemptions relative to the number of kidneys available over a 50-year time horizon under several projected scenarios for growth of the program. In all simulated scenarios, the number of available kidneys exceeded voucher redemptions every year. While not able to account for all real-life scenarios, this simulation study found that the NKR should be able to satisfy the likely redemption of increasing numbers of vouchers under a range of possible scenarios over a 50-year time horizon. This modeling exercise suggests that a donor family's future needs can be satisfied through the voucher program.

Early graft losses in paired kidney exchange: Experience from 10 years of the National Kidney Registry.

Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There are sparse data on the rate of primary nonfunction (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (February 14, 2009 to December 31, 2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first-year posttransplant and assessed potential risk factors. Of 2364 transplants, there were 38 grafts (1.6%) lost within the first year, 13 (0.5%) with PNF. When compared to functioning grafts, there were no clinically significant differences in blood type compatibility, degree of HLA mismatch, number of veins/arteries, cold ischemia, and travel times. Of 13 PNF cases, 2 were due to early venous thrombosis, 2 to arterial thrombosis, and 2 to failure of desensitization and development of antibody-mediated rejection (AMR). Given the low rate of PNF, the NKR created a policy to allocate chain-end kidneys to recipients with PNF following event review and attributable to surgical issues of donor nephrectomy. It is expected that demonstration of low incidence of poor early graft outcomes and the presence of a "safety net" would further encourage program participation in national KPD.

Dramatic secular changes in prognosis for kidney transplant candidates in the United States.

Over recent decades, numerous clinical advances and policy changes have affected outcomes for candidates of kidney transplantation in the United States. We examined the national Scientific Registry for Transplant Recipients for adult (18+) solitary kidney transplant candidates placed on the waiting list for primary listing from 2001 to 2015. We evaluated rates of mortality, transplantation, and waitlist removal. Among 340 115 candidates there were significant declines in mortality (52 deaths/1000 patient years in 2001-04 vs 38 deaths/1000 patient years in 2012-15) and transplant rates (304 transplants/1000 patient years in 2001-04 vs 212 transplants/1000 patient years in 2012-15) and increases in waitlist removals (15 removals/1000 patient years in 2001-04 vs 25/1000 patient years in 2012-15) within the first year after listing. At 5 years an estimated 37% of candidates listed in 2012-15 were alive without transplant as compared to 22% in 2001-04. Declines in mortality over time were significantly more pronounced among African Americans, candidates with longer dialysis duration, and those with diabetes (P < .001). Cumulatively, results indicate dramatic changes in prognoses for adult kidney transplant candidates, likely impacted by selection criteria, donor availability, regulatory oversight, and clinical care. These trends are important considerations for prospective policy development and research, clinical and patient decision-making, and evaluating the impact on access to care.

Shipping living donor kidneys and transplant recipient outcomes.

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25-23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02-1.09, P < .01). However, there was not a significant association between CIT and all-cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98-1.04, P = .4), death-censored graft failure ( [aHR]: 1.02, 95% CI, 0.98-1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96-1.04, P > .9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.

The first 9 years of kidney paired donation through the National Kidney Registry: Characteristics of donors and recipients compared with National Live Donor Transplant Registries.

The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR. Compared with all United Network for Organ Sharing (UNOS) live donor transplant patients (49 610), all UNOS living unrelated transplant patients (23 319), and all other KPD transplant patients (4236), the demographic and clinical characteristics of NKR transplant patients (2037) appear similar to contemporary national trends. In particular, among the NKR patients, there were a significantly (P < .001) greater number of retransplants (25.6% vs 11.5%), hyperimmunized recipients (22.7% vs 4.3% were cPRA >80%), female recipients (45.9% vs 37.6%), black recipients (18.2% vs 13%), and those on public insurance (49.7% vs 41.8%) compared with controls. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible pairs and even chains initiated by deceased donors, to unlock more opportunities for those harder-to-match pairs.

Residential Area Life Expectancy: Association With Outcomes and Processes of Care for Patients With ESRD in the United States.

BACKGROUND: The effects of underlying noncodified risks are unclear on the prognosis of patients with end-stage renal disease (ESRD). We aimed to evaluate the association of residential area life expectancy with outcomes and processes of care for patients with ESRD in the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult patients with incident ESRD between 2006 and 2013 recorded in the US Renal Data System (n=606,046). PREDICTOR: The primary exposure was life expectancy in the patient's residential county estimated by the Institute for Health Metrics and Evaluation. OUTCOMES: Death, placement on the kidney transplant wait list, living and deceased donor kidney transplantation, and posttransplantation graft loss. RESULTS: Median life expectancies of patients' residences were 75.6 (males) and 80.4 years (females). Compared to the highest life expectancy quintile and adjusted for demographic factors, disease cause, and multiple comorbid conditions, the lowest quintile had adjusted HRs for mortality of 1.20 (95% CI, 1.18-1.22); placement onto the waiting list, 0.68 (95% CI, 0.67-0.70); living donor transplantation, 0.53 (95% CI, 0.51-0.56); posttransplantation graft loss, 1.35 (95% CI, 1.27-1.43); and posttransplantation mortality, 1.29 (95% CI, 1.19-1.39). Patients living in areas with lower life expectancy were less likely to be informed about transplantation, be under the care of a nephrologist, or receive an arteriovenous fistula as the initial dialysis access. Results remained consistent with additional adjustment for zip code-level median income, population size, and urban-rural locality. LIMITATIONS: Potential residual confounding and attribution of effects to individuals based on residential area-level data. CONCLUSIONS: Residential area life expectancy, a proxy for socioeconomic, environmental, genetic, and behavioral factors, was independently associated with mortality and process-of-care measures for patients with ESRD. These results emphasize the underlying effect on health outcomes of the environment in which patients live, independent of patient-level factors. These findings may have implications for provider assessments.

The role of laparoscopy-assisted renal autotransplantation in the treatment of primary ureteral tumor.

BACKGROUND: To evaluate the effect and safety of laparoscopy-assisted renal autotransplantation treatment for primary ureteral cancer (PUC). METHODS: Medical records of patients undergoing hand-assisted retroperitoneoscopic nephroureterectomy­extracorporeal total ureterectomy­renal autotransplantation­pyelocystostomy (Lap AutoTx) were analyzed. Demographic, intraoperative, and postoperative data were assessed. RESULTS: Fifteen patients diagnosed with PUC underwent this novel approach. Three kidneys were abandoned owing to the detection of residual cancer on the renal pelvic junction, surgeon's judgment on three severe atherosclerotic arteries, and palpable pelvic lymph nodes proven to be evidence of metastatic disease by frozen section analysis. Twelve patients (mean ± SD age 67.5 ± 7.5 years) were treated with Lap AutoTx for PUC successfully. No perioperative mortality occurred. One patient with solitary kidney experienced delayed graft function that required short-term hemodialysis. Three recurrent superficial diseases in three patients were treated with transurethral resection. The mean ± SD follow-up duration was 12.1 ± 6.7 months (range 3­24 months). The renal pelvicaliceal system was easily examined by flexible cystoscopy. CONCLUSIONS: Lap AutoTx is less invasive compared with the traditional two-incisional manner and can be performed safely even among elderly patients. Compared with other currently used therapies, this novel treatment can be used to successfully treat PUC with the added advantages of total resection of the ureteral lesion, preservation of the renal function, and simplification of follow-up procedures.Primary ureteral cancer (PUC) is an aggressive disease and has a poor prognosis.1 Studies have shown high prevalence and invasiveness of PUC in Taiwan.2,3 Nephroureterectomy with excision of the bladder cuff is still believed to be the gold standard treatment for PUC.4 Most PUC occurs among individuals aged more than 60 years, and most of these patients are also at high risk of chronic kidney disease (CKD).5,6 Nephroureterectomy not only results in excessive loss of renal function, but also puts the patient at risk of CKD, which contributes to the progression of end-stage renal disease requiring dialysis. In addition, diminished renal function after nephroureterectomy compromises the possible use of adjuvant chemotherapy for advanced disease.Endoscopic surgery (ES) and segmental resection (SR) can be used for renal preservation in PUC cases, but there still are limitations to these approaches, and indefinite invasive ureteroscopy is required during follow-up. Only a few studies have focused on renal autotransplantation (AutoTx) after extracorporeal total ureterectomy (ETU) for PUC. This type of treatment possesses advantages of total resection of malignant ureteral lesions, preservation of renal function, and simplification of follow-up protocols. In two reported case series, all cases involved surgery performed with the traditional 2-incision approach, and only a few cases involved pure PUC.7,8 We have reported that hand-assisted retroperitoneoscopic nephroureterectomy (HARNU) for the treatment of PUC is less invasive and results in better functional outcomes with fewer complications and comparable oncologic control compared with open nephroureterectomy.9 In this study, we report our experience of this treatment combined with ETU and AutoTx for pure PUC.

Disseminated adenoviral infection masquerading as lower urinary tract voiding dysfunction in a kidney transplant recipient.

Viral infections continue to cause significant morbidity in immunosuppressed kidney transplant patients. Although cytomegalovirus, Epstein-Barr virus and polyoma "BK" virus are more frequently encountered, the Adenovirus can cause multi-organ system infections, and may be difficult to diagnose because it is not often considered in the initial work up in kidney transplant recipients. We present an unusual case of a kidney recipient 1 year post-transplant with disseminated adenoviral infection, who had an initial presentation of lower urinary tract voiding dysfunction with hematuria and sterile pyuria. This progressed to a severe tubulointerstitial nephritis and acute kidney injury that improved with reduction of immunosuppression. Serial blood viral loads are useful for monitoring the course of infection. Urinary adenoviral infection should be considered in the differential diagnosis whenever a kidney transplant recipient presents with unexplained lower tract voiding dysfunction, hematuria, and sterile pyuria. The allograft kidney and bladder can be targets of viral proliferation. Early diagnosis with reduction of immunosuppressive therapy is essential to clear the virus and maintain allograft function.

Contrasting patterns of viral load response in transplant recipients with BK polyomavirus DNAemia on leflunomide therapy.

BACKGROUND: Reduction in immunosuppression is considered the therapy of proven benefit for BKV infection in renal transplantation, but the use of leflunomide has also been reported. It was observed at this center that the patterns of viral load response while on leflunomide appear to fall into two distinct types. METHODS: Medical records of 22 kidney and kidney-pancreas recipients at a single center who received leflunomide therapy for BKV DNAemia were reviewed. Information was collected on demographics, BKV viral loads, other antiviral therapy, immunosuppressive drug levels and doses, adverse effects, and graft and patient outcomes. RESULTS: Eighteen of 22 cleared BKV viremia, and 12 of 22 had preserved allograft function; only two graft losses occurred in the screening era among leflunomide-treated patients. Two patterns of viral load reduction were observed, termed the "smooth" and the "zigzag" pattern, which differed in mean time to clear of BKV DNA (2.9 vs. 19.5 months, p = 0.0073). Graft preservation was correlated with lower serum creatinine (SCr) at the start of leflunomide therapy. CONCLUSIONS: Long courses and "zigzag" fluctuations in viral load can occur in patients who eventually clear BKV on leflunomide with preserved allograft function. Intermittent increases in viral load do not necessarily portend therapeutic failure. Although the utility of leflunomide is still debated in the transplant community, this information may be useful to clinicians who choose to use it in selected patients.

The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation.

We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.

Can the nephron be spared?

The search continues for the best role for mTOR inhibitor drugs in renal transplantation-principally to avoid or minimize the nephrotoxicity of the CNI class of immunosuppressive agents. The Spare the Nephron Trial describes the popular approach of early conversion from a CNI to the mTOR agent sirolimus for patients maintained on mycophenolate mofetil and steroids. At 1-2 years the glomerular filtration rate (GFR) was superior for the sirolimus group, with a loss of tolerability for about 20%.

Renal autotransplantation and modified pyelovesicostomy for intractable metabolic stone disease.

PURPOSE: Some patients with intractable metabolic stone disease experience narcotic dependence, which cannot be managed with standard treatments. We offered these patients renal autotransplantation with a modified pyelovesicostomy as an alternative solution. MATERIALS AND METHODS: Renal autotransplantation with pyelovesicostomy was performed for 15 kidneys in 12 patients (3 bilateral, 2 solitary), 9 female and 3 male, with a mean age of 33.8 years (range 16 to 55). The etiology of metabolic stone disease was calcium oxalate (40%), cystinuria (33%), type 1 renal tubular acidosis (14%), calcium oxalate/urate (7%) and medullary sponge kidney (7%). Patients reported that lifetime stone events ranged from 10 to more than 70, that underwent an average of 3 to 4 surgical interventions per year in the previous 2 years and that they were dependent on daily oral narcotics for stone related pain. RESULTS: All 15 kidneys were successfully autotransplanted with a mean followup of 41.8 months (range 3 to 74). We used a modified pyelovesicostomy with ureteral strip in 13 and standard Boari tube in 2 cases. All patients continued to pass small stone debris per urethra with minimal symptoms. Of 12 patients 11 (92%) were weaned off daily narcotics. There have been 17 stone episodes in 4 patients (3 cystinuria) for which medical intervention and pain medication was required. The number of urological procedures/patients before (155/12 [12.9]) and after (8/12 [0.66]) autotransplantation was dramatically reduced (paired t test p = 0.0001). The preoperative mean estimated glomerular filtration rate was 77.2 cc/minute, and 73.5, 71.9, 79.2 cc/minute at 12, 36 and 60 months, respectively. CONCLUSIONS: Renal autotransplantation and pyelovesicostomy offer patients with intractable metabolic stone disease the opportunity to improve quality of life and to decrease daily narcotic use.