Xingxing Shelley Cheng

All Publications

• Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist. American journal of kidney diseases : the official journal of the National Kidney Foundation Cheng, X. S., Myers, J., Han, J., Stedman, M. R., Watford, D. J., Lee, J., Discipulo, K. V., Chan, K. N., Chertow, G. M., Tan, J. C. 2020

  Abstract

  Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists.Prospective observational cohort study.We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments.6MWT and STS test results.Primary - Time to adverse waitlist outcomes (removal from waitlist or death). Secondary - Time to transplantation, time to death.We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes.Median 6MWT and STS results were 393 meters (25th- 75th percentile range 305-455) and 17 repetitions (25th- 75th percentile range 12-21), respectively. Clinical characteristics and Estimated Post-Transplant Survival scores only accounted for 14-21% of the variance in 6MWT/STS results. 6MWT/STS results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% confidence interval 1.30-1.56 per 50-meter lower in 6MWT and 1.53 [95% confidence interval 1.33-1.75] per 5-repetition lower in STS), and with transplantation (adjusted sHR of 0.80 [95% confidence interval 0.72-0.88] per 50-meter lower in 6MWT and 0.80 [95% confidence interval 0.71-0.89] per 5-repetition lower in STS). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test p<0.001).Single-center observational study. Other measures of global health status (e.g., Fried frailty index or short physical performance battery) were not examined.Among waitlisted kidney transplant candidates with high Kidney Allocation Scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

  View details for DOI 10.1053/j.ajkd.2020.04.009

  View details for PubMedID 32512039

• To Kidney or Not to Kidney: Applying Lessons Learned from the Simultaneous Liver-Kidney Transplant Policy to Simultaneous Heart-Kidney Transplantation. Clinical transplantation Cheng, X. S., Khush, K. K., Wiseman, A., Teuteberg, J., Tan, J. C. 2020

  Abstract

  As the medical community is increasingly offering transplantation to patients with increasing comorbidity burdens, the number of simultaneous heart-kidney (SHK) transplants is rising in the United States. How to determine eligibility for SHK transplant versus heart transplant alone is an important unknown. In this review, we situate this problem in the broader picture of organ shortage. We critically appraise available literature on outcomes in SHK versus heart transplant alone. We posit staged kidney-after-heart transplantation as a plausible alternative to SHK transplantation and review the pros and cons. Drawing lessons from the field of simultaneous liver-kidney transplant, we argue for an analogous policy for SHK transplant with standardized minimal eligibility criteria and a modified Safety Net provision. The new policy will serve as a starting point for comparing simultaneous versus staged approaches and refining the medical eligibility criteria for SHK.

  View details for DOI 10.1111/ctr.13878

  View details for PubMedID 32279361

• Defining a willingness-to-transplant threshold in an era of organ scarcity: Simultaneous liver-kidney transplant as a case example. Transplantation Cheng, X. S., Goldhaber-Fiebert, J., Tan, J. C., Chertow, G. M., Kim, W. R., Wall, A. E. 2019

  Abstract

  Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multi-organ transplant, wherein a patient with multi-organ disease receives more than one organ from the same donor. Current allocation schemes give priority to multi-organ recipients over single-organ transplant recipients, which raises ethical questions regarding equity and utility.We use simultaneous liver-kidney (SLK) transplant, a type of multi-organ transplant, as a case study to examine the tension between equity and utility in multi-organ allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold.We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives.We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.

  View details for DOI 10.1097/TP.0000000000002788

  View details for PubMedID 31107820

• A New Approach to Kidney Waitlist Management in the Kidney Allocation System Era: Pilot Implementation and Evaluation. Clinical transplantation Cheng, X. S., Busque, S., Lee, J., Discipulo, K., Hartley, C., Tulu, Z., Scandling, J. D., Tan, J. C. 2018: e13406

  Abstract

  Kidney transplant waitlist management is becoming increasingly complex. We introduced a novel waitlist management strategy at our center, the Transplant Readiness Assessment Clinic (TRAC), whereby patients whose Kidney Allocation Scores surpass a threshold are actively managed. From January 1, 2016 through June 30, 2017, we evaluated 195 patients through TRAC. Compared to pre-TRAC systems at our institution, TRAC resulted in a higher proportion of activation at 18-months (38% versus 22-26%, p<0.0001), despite being enriched in patients with long dialysis duration. TRAC also resulted in a higher proportion of waitlist removal (15% versus 8-9%, p<0.05) although combined waitlist removal and death on waitlist did not differ (18% versus 16-17%). Median time-to-activation was 356 days from TRAC evaluation. Of the transplant barriers, need for cardiovascular studies was the most common (31%), followed by other medical issues (23%), poor functional status (13%), and psychosocial issues (10%). By concentrating center resources on patients most likely to be transplanted after activation and performing active patient management close to the time of transplant, TRAC has the potential to significantly enhance kidney transplant success in regions with long wait-times. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30218580

• Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis. Transplantation Cheng, X. S., Kim, W. R., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. 2018

  Abstract

  BACKGROUND: The proportion of patients with kidney failure at time of liver transplantation is at an historic high in the United States. The optimal timing of kidney transplantation with respect to the liver transplant is unknown.METHODS: We used a modified cost-effectiveness analysis to compare four strategies: the old system ("pre-OPTN"), the new Organ Procurement Transplant Network (OPTN) system since August 10, 2017 ("OPTN"), and two strategies which restrict simultaneous liver-kidney transplants ("safety net" and "stringent"). We measured "cost" by deployment of deceased donor kidneys (DDKs) to liver transplant recipients and effectiveness by life years (LYs) and quality-adjusted life years (QALYs) in liver transplant recipients. We validated our model against Scientific Registry for Transplant Recipients data.RESULTS: The OPTN, safety net and stringent strategies were on the efficient frontier. By rank order, OPTN > safety net > stringent strategy in terms of LY, QALY and DDK deployment. The pre-OPTN system was dominated, or outperformed, by all alternative strategies. The incremental LY per DDK between the strategies ranged from 1.30 to 1.85. The incremental QALY per DDK ranged from 1.11 to 2.03.CONCLUSION: These estimates quantify the "organ"-effectiveness of various kidney allocation strategies for liver transplant candidates. The OPTN system will likely deliver better liver transplant outcomes at the expense of more frequent deployment of DDKs to liver transplant recipients.

  View details for PubMedID 29554056

• FEASIBILITY AND EFFICACY OF NOREPINEPHRINE IN THE NON-ICU SETTING FOR TREATMENT OF HEPATORENAL SYNDROME Kwong, A. J., Cheng, X., Kwo, P. Y., Wang, U., Kim, W. WILEY. 2020: 1106

  View details for Web of Science ID 000574027004273

• Ethical decision-making in simultaneous heart-liver transplantation. Current opinion in organ transplantation Cheng, X. S., Wall, A., Teuteberg, J. 2020

  Abstract

  PURPOSE OF REVIEW: Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs.RECENT FINDINGS: The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed.SUMMARY: As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.

  View details for DOI 10.1097/MOT.0000000000000806

  View details for PubMedID 32881719

• Coronary Artery Disease Screening of Asymptomatic Kidney Transplant Candidates: A Web-Based Survey of Practice Patterns in the United States. Kidney medicine Cheng, X. S., Mathew, R. O., Parasuraman, R., Tantisattamo, E., Levea, S., Kapoor, R., Dadhania, D. M., Rangaswami, J. 2020; 2 (4): 505–7

  View details for DOI 10.1016/j.xkme.2020.04.006

  View details for PubMedID 32775996

• Histologic Case Definition of an Atypical Glomerular Immune-Complex Deposition Following Kidney Transplantation. Kidney international reports Chin, K., Charu, V., O'Shaughnessy, M. M., Troxell, M. L., Cheng, X. S. 2020; 5 (5): 632–42

  Abstract

  Introduction: Immune-complex deposition in the transplanted kidney can present as well-phenotyped recurrent or de novo glomerular disease. However, a subset, herein termed immune-complex glomerulopathy not otherwise specified (ICG-NOS), defies classification. We quantified, categorized, and characterized cases of transplant ICG-NOS occurring at a single US academic medical center.Methods: We retrospectively reviewed our single-institution pathology database (July 2007-July 2018) to identify and categorize all cases of immune-complex deposition in kidney allografts (based on immunofluorescence microscopy). We extracted clinicopathologic and outcome data for ICG-NOS (i.e., immune complex deposition not conforming to any well-characterized glomerular disease entity).Results: Of 104 patients with significant immune deposits, 28 (27%) were classified as ICG-NOS. We created 5 mutually exclusive ICG-NOS categories: Full-house, Quasi-full-house, IgA-rich, C1q-rich, and C1q-poor. Overall, 16 (57%) patients met criteria for definite or possible allograft rejection, including 9 (32%) with antibody-mediated rejection (ABMR), 3 (11%) suspicious for ABMR, 1 (4%) with T-cell-mediated rejection (TCMR), and 9 (32%) with borderline TCMR. After a median follow-up of 2.3 (range, 0.1-14.0) years after biopsy, 7 (25%) allografts had failed and an additional 8 (29%) had persistent renal dysfunction (hematuria, 14%; proteinuria, 21%; and estimated glomerular filtration rate<60 ml/min per 1.73 m2, 11%).Conclusion: In contrast to prior studies, our findings suggest that ICG-NOS is not necessarily a benign glomerular process and that there may be an association between ICG-NOS and alloimmunity. Our immunofluorescence-based classification provides a framework for future studies aiming to further elucidate ICG-NOS pathogenesis and prognosis.

  View details for DOI 10.1016/j.ekir.2020.01.022

  View details for PubMedID 32405585

• An overview of frailty in kidney transplantation: measurement, management and future considerations. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Harhay, M. N., Rao, M. K., Woodside, K. J., Johansen, K. L., Lentine, K. L., Tullius, S. G., Parsons, R. F., Alhamad, T., Berger, J., Cheng, X. S., Lappin, J., Lynch, R., Parajuli, S., Tan, J. C., Segev, D. L., Kaplan, B., Kobashigawa, J., Dadhania, D. M., McAdams-DeMarco, M. A. 2020

  Abstract

  The construct of frailty was first developed in gerontology to help identify older adults with increased vulnerability when confronted with a health stressor. This article is a review of studies in which frailty has been applied to pre- and post-kidney transplantation (KT) populations. Although KT is the optimal treatment for end-stage kidney disease (ESKD), KT candidates often must overcome numerous health challenges associated with ESKD before receiving KT. After KT, the impacts of surgery and immunosuppression represent additional health stressors that disproportionately impact individuals with frailty. Frailty metrics could improve the ability to identify KT candidates and recipients at risk for adverse health outcomes and those who could potentially benefit from interventions to improve their frail status. The Physical Frailty Phenotype (PFP) is the most commonly used frailty metric in ESKD research, and KT recipients who are frail at KT (~20% of recipients) are twice as likely to die as nonfrail recipients. In addition to the PFP, many other metrics are currently used to assess pre- and post-KT vulnerability in research and clinical practice, underscoring the need for a disease-specific frailty metric that can be used to monitor KT candidates and recipients. Although frailty is an independent risk factor for post-transplant adverse outcomes, it is not factored into the current transplant program risk-adjustment equations. Future studies are needed to explore pre- and post-KT interventions to improve or prevent frailty.

  View details for DOI 10.1093/ndt/gfaa016

  View details for PubMedID 32191296

• Recurrence of FSGS after Kidney Transplantation in Adults. Clinical journal of the American Society of Nephrology : CJASN Uffing, A., Pérez-Sáez, M. J., Mazzali, M., Manfro, R. C., Bauer, A. C., de Sottomaior Drumond, F., O'Shaughnessy, M. M., Cheng, X. S., Chin, K. K., Ventura, C. G., Agena, F., David-Neto, E., Mansur, J. B., Kirsztajn, G. M., Tedesco-Silva, H., Neto, G. M., Arias-Cabrales, C., Buxeda, A., Bugnazet, M., Jouve, T., Malvezzi, P., Akalin, E., Alani, O., Agrawal, N., La Manna, G., Comai, G., Bini, C., Muhsin, S. A., Riella, M. C., Hokazono, S. R., Farouk, S. S., Haverly, M., Mothi, S. S., Berger, S. P., Cravedi, P., Riella, L. V. 2020

  Abstract

  FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

  View details for DOI 10.2215/CJN.08970719

  View details for PubMedID 31974287

• Simultaneous Coccidioidomycosis and Phaeohyphomycosis in a Kidney Transplant Recipient: A Case Report and Literature Review. Transplant infectious disease : an official journal of the Transplantation Society Puing, A. G., Couture-Cossette, A., Wang, A. X., Zygourakis, C. C., Cheng, X., Stevens, B. A., Banaei, N., Novoa, R. A., Ho, D. Y., Subramanian, A. 2020: e13365

  Abstract

  Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

  View details for DOI 10.1111/tid.13365

  View details for PubMedID 32533741

• Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates. Clinical transplantation Watford, D. J., Cheng, X. S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C. 2020: e14173

  Abstract

  Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-minute walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

  View details for DOI 10.1111/ctr.14173

  View details for PubMedID 33247983

• Effect of low contrast medium-dose CTA on device sizing and access vessel assessment for TAVR. European journal of radiology Suchá, D., Kino, A., Bogart, K., Molvin, L., Cheng, X. S., Fearon, W. F., Fischbein, M. P., Fleischmann, D. 2020; 124: 108826

  Abstract

  Chronic kidney disease (CKD) is prevalent in transcatheter aortic valve replacement (TAVR) candidates, leading to concerns regarding contrast medium (CM) safety. We evaluated (a) the impact of low-CM imaging on pre-TAVR measurements and (b) postcontrast acute kidney injury (PC-AKI) prevalence after dual-source computed tomography (DSCT) in TAVR candidates.All TAVR candidates with CKD (SCr≥1.5 mg/dL) who underwent weight-based low-CM, low-pitch helical 3rd-generation DSCT in a one-year period were included, and matched to standard-CM, non-CKD controls (N = 50). Image quality (IQ) and pre-TAVR measurement interobserver variability were evaluated. Renal function change and PC-AKI were studied in the entire TAVR cohort, irrespective of scan mode (N = 153).Low-CM in CKD (N = 25) was performed with median 68 mL CM [52-87], 90 kV [80-90] and SCr 1.6 mg/dL [1.5-1.9], and standard-CM without CKD with median 116 mL CM [96-134], 100 kV [90-110] and SCr 1.0 mg/dL [0.9-1.1](P < 0.00). Low-CM IQ was good, though lower compared with standard-CM (P < 0.02). Interobserver measurement reliability was excellent (ICCs>0.85). Interobserver-agreement was lower in low-CM, causing prosthesis size disagreement in 5/25 (kappa-0.73) versus 0/25 with standard-CM (kappa-1.00), and transfemoral eligibility disagreement in 4/25 (kappa-0.68) versus 2/25 (kappa-0.84), respectively. Mean 1-month SCr-change in the low-CM TAVR cohort (N = 35) was -1 % [-12 to +7 %] and in standard-CM (N = 118) 0 % [-8 to +10 %](P > 0.3). PC-AKI occurred in none.Low-CM third-generation-DSCT achieves good IQ in TAVR candidates with CKD, and seems safe, with no apparent renal function deterioration or prevalence of PC-AKI. However, standard-CM protocols in non-CKD patients provide higher measurement reproducibility. Low-CM protocols should therefore be reserved for patients at high risk for PC-AKI.

  View details for DOI 10.1016/j.ejrad.2020.108826

  View details for PubMedID 32000074

• COVID-19 and Kidney Transplantation: Results from the TANGO International Transplant Consortium. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Cravedi, P., Suraj, S. M., Azzi, Y., Haverly, M., Farouk, S., Pérez-Sáez, M. J., Redondo-Pachón, M. D., Murphy, B., Florman, S., Cyrino, L. G., Grafals, M., Venkataraman, S., Cheng, X. S., Wang, A. X., Zaza, G., Ranghino, A., Furian, L., Manrique, J., Maggiore, U., Gandolfini, I., Agrawal, N., Patel, H., Akalin, E., Riella, L. V. 2020

  Abstract

  Kidney transplant recipients may be at high risk of developing critical COVID-19 illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the US, Italy and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression and treatment strategies were reviewed and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9,845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. 65% were male with a mean age of 60 (±12) years, 40% Hispanic and 25% African-American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%) and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, respiratory failure requiring intubation in 29%, and mortality was 32%. The 44 patients who died were older, had lower lymphocyte counts and eGFR, higher serum lactate dehydrogenase, procalcitonin and IL-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

  View details for DOI 10.1111/ajt.16185

  View details for PubMedID 32649791

• Implications of Frailty for Peritransplant Outcomes in Kidney Transplant Recipients. Current transplantation reports Cheng, X. S., Lentine, K. L., Koraishy, F. M., Myers, J., Tan, J. C. 2019; 6 (1): 16–25

  Abstract

  Purpose of Review: Research over the past few decades points to the importance of frailty, or the lack of physiologic reserve, in the natural history of chronic diseases and in modifying the impact of potential interventions. End-stage kidney disease (ESKD) and the intervention of kidney transplantation are no exception. We review the recent epidemiologic and cohort-based evidence on the association between frailty and kidney transplant outcomes and provide a framework of questions with which to approach future research endeavors and clinical practice.Recent Findings: Frailty in kidney transplant candidates can be measured in numerous ways, including descriptive phenotype, description scores, functional testing, and surrogate measures. Regardless of the metric, the presence of frailty is strongly associated with inferior pre- and posttransplant outcomes compared to the absence of frailty. However, some frail patients with ESKD can benefit from transplant over chronic dialysis. Evidence-based approaches for identifying frail ESKD patients who can benefit from transplant over dialysis, with acceptable posttransplant outcomes, are lacking. Interventional trials to improve frailty and physical function before transplant (prehabilitation) and after transplant (rehabilitation) are also lacking.Conclusion: Frailty is increasingly recognized as highly relevant to peritransplant outcomes, but more work is needed to: 1) tailor management to the unique needs of frail patients, both pre- and posttransplant; 2) define phenotypes of frail patients who are expected to benefit from transplant over dialysis; and 3) develop interventions to reverse frailty, both pre- and post-transplant.

  View details for DOI 10.1007/s40472-019-0227-z

  View details for PubMedID 31131186

• Perceptions and Practices Regarding Frailty in Kidney Transplantation: Results of A National Survey. Transplantation McAdams-DeMarco, M. A., Rasmussen, S. E., Chu, N. M., Agoons, D., Parsons, R. F., Alhamad, T., Johansen, K. L., Tullius, S. G., Lynch, R., Harhay, M. N., Rao, M. K., Berger, J., Cooper, M., Tan, J. C., Cheng, X. S., Woodside, K. J., Parajuli, S., Lentine, K. L., Kaplan, B., Segev, D. L., Kobashigawa, J. A., Dadhania, D. 2019

  Abstract

  Given the potential utility of frailty, a clinical phenotype of decreased physiologic reserve and resistance to stressors, to predict post-kidney transplant (KT) outcomes, we sought to understand the perceptions and practices regarding frailty measurement in US KT programs.Surveys were emailed to American Society of Transplantation Kidney/Pancreas Community of Practice members and 202 US transplant programs (11/2017-4/2018). Program characteristics were gleaned from SRTR.The 133 responding programs (response rate=66%) represented 77% of adult KTs and 79% of adult KT candidates in the US. Respondents considered frailty to be a useful concept in evaluating candidacy (99%) and endorsed a need to develop a frailty measurement specific to KT (92%). Frailty measurement was more common during candidacy evaluation (69%) than during KT admission (28%). Of the 202 programs, 38% performed frailty assessments in all candidates while 23% performed assessments only for older candidates. There was heterogeneity in the frailty assessment method; 18 different tools were utilized to measure frailty. The most common tool was a timed walk test (19%); 67% reported performing >1 tool. Among programs that measure frailty, 53% reported being less likely to list frail patients for KT.Among US KT programs, frailty is recognized as a clinically relevant construct and is commonly measured at evaluation. However, there is considerably heterogeneity in the tools used to measure frailty. Efforts to identify optimal measurement of frailty using either an existing or novel tool and subsequent standardization of its measurement and application across KT programs should be considered.

  View details for DOI 10.1097/TP.0000000000002779

  View details for PubMedID 31343576

• A large, international study on post-transplant glomerular diseases: the TANGO project BMC NEPHROLOGY Uffing, A., Jose Perez-Saez, M., La Manna, G., Comai, G., Fischman, C., Farouk, S., Manfro, R., Bauer, A., Lichtenfels, B., Mansur, J. B., Tedesco-Silva, H., Kirsztajn, G. M., Manonelles, A., Bestard, O., Riella, M., Hokazono, S., Arias-Cabrales, C., David-Neto, E., Ventura, C., Akalin, E., Mohammed, O., Khankin, E. V., Safa, K., Malvezzi, P., O'Shaughnessy, M., Cheng, X. S., Cravedi, P., Riella, L. V. 2018; 19: 229

  Abstract

  Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy.The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies.Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

  View details for PubMedID 30208881

• Native Kidney Cytomegalovirus Nephritis and Cytomegalovirus Prostatitis in a Kidney Transplant Recipient. Transplant infectious disease : an official journal of the Transplantation Society Tan, S. K., Cheng, X. S., Kao, C., Weber, J., Pinsky, B. A., Gill, H. S., Busque, S., Subramanian, A. K., Tan, J. C. 2018: e12998

  Abstract

  We present a case of cytomegalovirus (CMV) native kidney nephritis and prostatitis in a CMV D+/R- kidney transplant recipient who had completed six months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV disease. The patient had a history of benign prostatic hypertrophy and urinary retention that required self-catheterization to relieve high post-voiding residual volumes. At 7 months post-transplant, he was found to have a urinary tract infection, moderate hydronephrosis of the transplanted kidney, and severe hydroureteronephrosis of the native left kidney and ureter, and underwent native left nephrectomy and transurethral resection of the prostate. Histopathologic examination of kidney and prostate tissue revealed CMV inclusions consistent with invasive CMV disease. This case highlights that CMV may extend beyond the kidney allograft to involve other parts of the genitourinary tract, including the native kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors that preceded CMV tissue invasion. In addition to concurrent diagnoses, health care providers should have a low threshold for considering late-onset CMV disease in high-risk solid organ transplant recipients presenting with signs and symptoms of genitourinary tract pathology. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30203504

• Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases (Basel, Switzerland) Li, A. A., Cholankeril, G., Cheng, X. S., Tan, J. C., Kim, D., Toll, A. E., Nair, S., Ahmed, A. 2018; 6 (3)

  Abstract

  In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.

  View details for PubMedID 29996536

• Prehabilitation for Kidney Transplant Candidates: Is it Time? Clinical transplantation Cheng, X. S., Myers, J. N., Chertow, G. M., Rabkin, R., Chan, K. N., Chen, Y., Tan, J. C. 2017

  Abstract

  Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and health care utilization after kidney transplantation. Efforts to intervene with post-transplant physical therapy have been met with limited success, in large part due to high study drop-out. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.13020

  View details for PubMedID 28564126

• Home Dialysis in the Prospective Payment System Era. Journal of the American Society of Nephrology Lin, E., Cheng, X. S., Chin, K., Zubair, T., Chertow, G. M., Bendavid, E., Bhattacharya, J. 2017

  Abstract

  The ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance. The ESRD Prospective Payment System associated with a 5.0% (95% confidence interval [95% CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period. Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other forms of health insurance. The difference between these groups was not statistically significant (1.8%; 95% CI, -0.2% to 3.8%). Conversely, in both populations, the training add-on did not associate with increases in home dialysis use beyond the effect of the policy. The ESRD Prospective Payment System bundling, but not the training add-on, associated with substantial increases in home dialysis, which were identical for both Medicare and non-Medicare patients. These spill-over effects suggest that major payment changes in Medicare can affect all patients with ESRD.

  View details for DOI 10.1681/ASN.2017010041

  View details for PubMedID 28490435

• Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation TRANSPLANTATION Cheng, X. S., Stedman, M. R., Chertow, G. M., Kim, W. R., Tan, J. C. 2017; 101 (5): 1111-1119

  Abstract

  Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

  View details for DOI 10.1097/TP.0000000000001491

  View details for PubMedID 28437790

• Validating identification of patients with small vessel vasculitis, with or without renal involvement, using administrative healthcare records. Clinical nephrology O'Shaughnessy, M. M., Cheng, X. S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2017; 87 (2017) (3): 159-162

  View details for DOI 10.5414/CN109035

  View details for PubMedID 28102817

• Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease. Current transplantation reports Cheng, X. S., Glassock, R. J., Lentine, K. L., Chertow, G. M., Tan, J. C. 2017; 4 (4): 320–26

  Abstract

  The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors.The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life.The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.

  View details for PubMedID 29201600

• Management of Renal Failure in End-Stage Liver Disease: A Critical Appraisal LIVER TRANSPLANTATION Cheng, X. S., Tan, J. C., Kim, W. R. 2016; 22 (12): 1710-1719

  Abstract

  Renal failure is a late consequence of end-stage liver disease (ESLD). Even with liver transplantation, pretransplant renal impairment remains a strong predictor of posttransplant mortality. This review seeks to summarize and critically appraise common therapies used in this setting, including pharmacologic agents, procedures (transjugular intrahepatic portosystemic shunt, renal replacement therapy), and simultaneous liver-kidney transplantation. More experimental extracorporal modalities, eg, albumin dialysis or bioartificial livers, will not be discussed. A brief discussion on the definition and pathophysiologic underpinnings of renal failure in ESLD will be held at the beginning to lay the groundwork for the main section. Liver Transplantation 22 1710-1719 2016 AASLD.

  View details for DOI 10.1002/lt.24609

  View details for Web of Science ID 000389079500011

  View details for PubMedID 27875032

• An electronic alert to decrease Kayexalate ordering RENAL FAILURE Leaf, D. E., Cheng, X. S., Sanders, J. L., Mendu, M., Schiff, G. D., Mount, D. B., Bazari, H. 2016; 38 (10): 1752-1754

  Abstract

  Important safety concerns have recently emerged regarding the use of sodium polystyrene sulfonate (Kayexalate), a cation-exchange resin commonly used for the treatment of hyperkalemia. We implemented an electronic alert system at a tertiary care academic medical center to warn providers of the safety concerns of Kayexalate. We assessed the number of Kayexalate prescriptions per month, as well as the number of grams of Kayexalate ordered per month, one year before versus one year after implementing the alert. The mean (±SD) number of Kayexalate orders decreased from 123 (±12) to 76 (±14) orders/month (38% absolute reduction, p < 0.001) after implementing the alert. Additionally, the mean (±SD) amount of Kayexalate prescribed decreased from 3332 (±329) to 1885 (±358) g/month (43% absolute reduction, p < 0.001). We conclude that an electronic alert is an effective tool to decrease Kayexalate ordering.

  View details for DOI 10.1080/0886022X.2016.1185353

  View details for Web of Science ID 000392430900029

  View details for PubMedID 27183825

  View details for PubMedCentralID PMC5114173

• Beyond the last battle: a viewpoint from the frontiers of transplantation. American journal of kidney diseases : the official journal of the National Kidney Foundation Cheng, X. S. 2015; 66 (1): A15–7

  View details for DOI 10.1053/j.ajkd.2015.05.006

  View details for PubMedID 26111908

• The Root of This Evil: Microangiopathic Hemolytic Anemia and Renal Failure AMERICAN JOURNAL OF MEDICINE Cheng, X. S., Adusumalli, S., Singh, H., DePasse, J. W., Smith, R., Haupert, G. T. 2015; 128 (1): 21–23

  View details for DOI 10.1016/j.amjmed.2014.08.021

  View details for Web of Science ID 000347030100020

  View details for PubMedID 25218936

• Enhanced Creatinine and Estimated Glomerular Filtration Rate Reporting to Facilitate Detection of Acute Kidney Injury AMERICAN JOURNAL OF CLINICAL PATHOLOGY Baron, J. M., Cheng, X. S., Bazari, H., Bhan, I., Lofgren, C., Jaromin, R. T., Lewandrowski, K. B., Dighe, A. S. 2015; 143 (1): 42–49

  Abstract

  While acute kidney injury (AKI) can be diagnosed based on specified increases in a patient's plasma creatinine level, standard creatinine reporting methods typically only flag creatinine results as abnormal when outside the reference range and often fail to identify rising creatinine values indicative of AKI. Here, we evaluate the impact of this limitation in standard creatinine reporting and develop and implement an enhanced creatinine reporting algorithm.We evaluated 59,712 plasma creatinine results collected over approximately 3 months, using computational simulations and statistical analyses.Our analyses demonstrated that 29% of creatinine results substantially increased over the patient's baseline and concerning for AKI remained within the normal reference range. These concerning results would not be flagged as abnormal using standard reporting. Likewise, we found that simple delta checks are also insensitive at AKI detection. To improve creatinine reporting, we developed and implemented an algorithm within our laboratory information system to alert clinicians to rising creatinine results, which we describe in this report.While both creatinine reference limits and simple delta checks are insensitive for AKI identification, a simple algorithm can be implemented within a common laboratory information system to enhance AKI identification.

  View details for DOI 10.1309/AJCP05XBCQPHTLGQ

  View details for Web of Science ID 000346757900008

  View details for PubMedID 25511141

• Inhibitory Interactions between BK and JC Virus among Kidney Transplant Recipients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Cheng, X. S., Bohl, D. L., Storch, G. A., Ryschkewitsch, C., Gaudreault-Keener, M., Major, E. O., Randhawa, P., Hardinger, K. L., Brennan, D. C. 2011; 22 (5): 825–31

  Abstract

  BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.

  View details for DOI 10.1681/ASN.2010080877

  View details for Web of Science ID 000291519500009

  View details for PubMedID 21511831

  View details for PubMedCentralID PMC3269895