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The long-term impact of early subclinical inflammation (SCI) through surveillance biopsy has not been well studied. To do this, we recruited a prospective observational cohort that included 1000 sequential patients who received a kidney transplant from 2013-2017 at our center. A total of 586 patients who underwent a surveillance biopsy in their first year post-transplant were included after excluding those with clinical rejections, and those who were unable to undergo a surveillance biopsy. Patients were classified based on their biopsy findings: 282 with NSI (No Significant Inflammation) and 304 with SCI-T (SCI and Tubulitis) which was further subdivided into 182 with SC-BLR (Subclinical Borderline Changes) and 122 with SC-TCMR (Subclinical T Cell Mediated Rejection, Banff 2019 classification of 1A or more). We followed the clinical and immunological events including Clinical Biopsy Proven Acute Rejection [C-BPAR], long-term kidney function and death-censored graft loss over a median follow-up of five years. Episodes of C-BPAR were noted at a median of two years post-transplant. Adjusted odds of having a subsequent C-BPAR was significantly higher in the SCI-T group [SC-BLR and SC-TCMR] compared to NSI 3.8 (2.1-7.5). The adjusted hazard for death-censored graft loss was significantly higher with SCI-T compared to NSI [1.99 (1.04-3.84)]. Overall, SCI detected through surveillance biopsy within the first year post-transplant is a harbinger for subsequent immunological events and is associated with a significantly greater hazard for subsequent C-BPAR and death-censored graft loss. Thus, our study highlights the need for identifying patients with SCI through surveillance biopsy and develop strategies to prevent further alloimmune injuries.

For assessing human leukocyte antigen compatibility in deceased donor kidney transplantation, virtual crossmatch is used as an alternative to physical crossmatch and has potential to reduce cold ischemia time. The 2014 United States kidney allocation system prioritized highly sensitized candidates but led to increased shipping of kidneys. Using data from the Scientific Registry of Transplant Recipients, we evaluated changes in virtual crossmatch use with the new allocation policy and the impact of virtual crossmatch use on cold ischemia time and transplant outcomes. This was a retrospective cohort study of adult deceased donor kidney recipients in the United States (2011-2018) transplanted with either 9,632 virtual or 71,839 physical crossmatches. Before allocation change, only 9% of transplants were performed relying on a virtual crossmatch. After the 2014 allocation change, this increased by 2.4%/year so that 18% transplants in 2018 were performed with just a virtual crossmatch. There was significant variation in virtual crossmatch use among transplant regions (range 0.7-36%) and higher use was noted among large volume centers. Compared to physical crossmatches, virtual crossmatches were significantly associated with shorter cold ischemia times (mean 15.0 vs 16.5 hours) and similar death-censored graft loss and mortality (both hazard ratios HR 0.99) at a median follow-up of 2.9 years. Thus, our results show that virtual crossmatch is an attractive strategy for shortening cold ischemia time without negatively impacting transplant outcomes. Hence, strategies to optimize use and reduce practice variation may allow for maximizing benefits from virtual crossmatch.

High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both.We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group.High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33).The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

Rationale & Objective In patients with severe hyponatremia in the setting of acute kidney injury or end-stage kidney disease, continuous renal replacement therapy (CRRT) using standard-sodium (140 mEq/L) fluids may lead to excessively rapid correction of plasma sodium concentration. Use of dialysate and replacement fluids with reduced sodium concentrations can provide a controlled rate of correction of plasma sodium concentration. Study Design We performed a single-center retrospective analysis of the safety and effectiveness of this approach in patients with plasma sodium concentrations ≤ 126 mEq/L who underwent CRRT for 24 or more hours using low-sodium (119 or 126 mEq/L) dialysate and replacement fluids. Change in plasma sodium level was assessed at 24 and 48 hours after initiation of low-sodium CRRT and at the end of treatment. Setting & Participants Between January 2016 and June 2018, a total of 23 hyponatremic patients underwent continuous venovenous hemodiafiltration using low-sodium dialysate and replacement fluids; 4 patients were excluded from analysis because of CRRT duration less than 6 mEq/L at 24 hours. Mean changes in plasma sodium levels at 24 and 48 hours and at the time of CRRT discontinuation were 3, 3, and 6 mEq/L, respectively. None of the patients developed osmotic demyelination syndrome. Limitations Key limitations were small sample size and lack of a control group. Conclusions Use of low-sodium dialysate and replacement fluids is a safe strategy for the prevention of overly rapid correction of plasma sodium levels in hyponatremic patients undergoing CRRT., Graphical abstract

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P.001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.

Transplantation of kidneys from shorter donors into taller recipients may lead to suboptimal allograft survival. The effect of discrepancy in donor and recipient heights (ΔHeight) on long term transplant outcomes is not known. Adult patients ≥18 years undergoing living or deceased donor (LD or DD) kidney transplants alone from donors ≥18 years between 2000 and 2016 in the United States were included in this observational study. The cohort was divided into three groups based on ΔHeight of 5 inches as 1) Recipient < Donor (DD: 31,688, LD: 12,384), 2) Recipient = Donor (DD: 84,711, LD: 54,709), and 3) Recipient > Donor (DD: 21,741, LD: 18,753). Univariate analysis showed a higher risk of DCGL and mortality in both DD and LD (p < 0.001 for both). The absolute difference in graft and patient survival between the two extremes of ΔHeight was 5.7% and 5.7% for DD, and 0.4% and 1.4% for LD. On multivariate analysis, the HR of DCGL for Recipient < Donor and Recipient > Donor was 0.95 (p = 0.05) and 1.07 (p = 0.01) in DD and 0.98 (p = 0.55) and 1.14 (p < 0.001) in LD. Similarly, the corresponding HR of mortality were 0.97 (p = 0.07) and 1.07 (p = 0.003) for DD and 1.01 (p < 0.001) and 1.05 (p = 0.13) for LD. For DGF, the HR were 1.04 (p = 0.1) and 1.01 (p = 0.7) for DD and 1.07 (p = 0.45) and 0.89 (p = 0.13) for LD. Height mismatch between the donor and recipient influences kidney transplant outcomes.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24-months posttransplant, and at last follow-up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12-months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor-specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long-term implications for kidney allograft function.

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.

Background. Early acute kidney rejection remains an important clinical issue. Methods. The current study included 552 recipients who had 1–2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell–mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. Results. The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P

This prospective observational cohort study compared the impact of subclinical tubulitis with or without interstitial inflammation to interstitial inflammation alone and to no inflammation in early post kidney transplant biopsies. A study cohort of 415 patients (living and deceased donor recipients) was divided into three groups on the basis of their three-month biopsy: 149 patients with No Inflammation (NI), 83 patients with Isolated Interstitial Inflammation (IIF), and 183 patients with Tubulitis [(with or without interstitial inflammation) (TIF) but not meeting criteria for Banff IA]. TIF was further divided into 56 patients with tubulitis without interstitial inflammation (TIF0) and 127 patients with tubulitis alongside interstitial inflammation (TIF1). TIF was significantly associated with higher incidence of subsequent T-cell mediated rejection (clinical or subclinical) at one year compared to IIF (31% vs 15%) and NI (31% vs 17%). Chronicity on one-year biopsy was significantly higher in TIF compared to IIF (22% vs 11%) and NI (22% vs 7%). De novo donor-specific antibody development was significantly higher in TIF compared to NI (6% vs 0.7%). Tubulitis subgroups (TIF0 and TIF1) revealed comparable effects on de novo donor-specific antibody and interstitial fibrosis/tubular atrophy development. However, tubulitis with interstitial inflammation had a significantly higher incidence of subsequent rejection and posed an increased hazard for the composite end point (subsequent acute rejection and death censored graft loss) compared to other groups [adjusted hazard 2.1 (95% confidence interval 1.2-3.5)]. Thus, subclinical tubulitis is a marker of adverse immunological events, but tubulitis with interstitial inflammation has a worse prognosis. Hence, the Banff 1997 (TIF1) and Banff 2005 classifications (TIF) for borderline change may have different implications.

Renal complications are common following heart and/or lung transplantation and lead to increased morbidity and mortality. Renal dysfunction is also associated with increased mortality for patients on the transplant wait list. Dialysis dependence is a relative contraindication for heart or lung transplantation at most centers, and such patients are often listed for a simultaneous kidney transplant. Several factors contribute to the impaired renal function in patients undergoing heart and/or lung transplantation, including the interplay between cardiopulmonary and renal hemodynamics, complex perioperative issues, and exposure to nephrotoxic medications, mainly calcineurin inhibitors.

Background The burden of cytomegalovirus infection in CMV high-risk (donor positive to recipient negative) kidney transplant recipients getting thymoglobulin induction and six months of valganciclovir is not well characterized. Additionally, the role of post-prophylaxis surveillance remains unclear. Methods One-year observational study of forty-eight high-risk CMV kidney transplant recipients transplanted under thymoglobulin between January 2013 and July 2014. All received valganciclovir for six months, followed by monthly CMV PCR for three months. Results CMV infection defined as viremia with or without symptoms occurred in 40% (19/48). Of these, 47% (9/19) occurred during prophylaxis, 32% (6/19) during surveillance and 21% (4/19) during post-surveillance period (9–12 months). Among breakthrough infections, suboptimal valganciclovir dosing was present in 55% (5/9). With routine surveillance, there was a trend toward lower CMV-related hospitalization (17% vs 56% and 75% during prophylaxis and post-surveillance, respectively [P=.23]) and lower mean peak viral loads (19 432 copies/mL vs 97 925 copies/mL and 536 021 copies/mL during prophylaxis and post-surveillance, respectively [P=.07]). Conclusion CMV infection remains a significant problem with thymoglobulin induction despite six months of valganciclovir. Suboptimal valganciclovir dosing was common among breakthrough infections. Monthly surveillance post-prophylaxis appears to detect early CMV infection with lower degree of viremias requiring fewer hospitalizations.

Background The utility of coronary angiography in patients with diabetes mellitus undergoing kidney transplant evaluation is unclear. Predictors of critical angiography lesions in these patients will aid in appropriate use of angiography. Methods Single-center study of 80 patients with ≥15 years of diabetes mellitus who underwent a screening coronary angiography despite a negative cardiac stress test. Risk factors for needing coronary intervention (CI) (percutaneous or bypass grafting) were analyzed. Results Eighteen patients (23%) had a ≥70% occlusion in one or more major coronary vessel(s), with right coronary artery being the most commonly involved (71%). Fifteen patients (19%) underwent coronary intervention: ten percutaneously and five with bypass surgery. Risk factors for needing CI were not being on statin (OR 3.54, P = 0.047) and history of stroke or peripheral vascular disease (PVD; OR 3.5, P = 0.034). A model that included statin use, stroke/PVD history, and glycosylated hemoglobin had a receiver operating characteristic curve area under the curve of 0.8 to predict CI. Conclusion Despite a negative stress test, the prevalence of critical coronary lesions was high among kidney transplant candidates with long-standing diabetes. Risk factors for needing coronary intervention were absence of statin use and a history of stroke or peripheral vascular disease.

Background The prevalence of atrial fibrillation (AF) in patients undergoing renal (RT) or liver transplantation (LT) has increased during the last decades. Yet, there is still uncertainty on the association between AF and patient and graft survival. Methods Multiple electronic databases were searched using various combinations of keywords and MeSH terms pertinent to the exposure (AF), and outcomes (graft and patient survival). Randomized or quasi-randomized controlled studies, cohort and case-control studies on adults with documented AF undergoing RT or LT were included. The quality of studies was assessed using the Newcastle-Ottawa Assessment Scale. When appropriate, data on the primary and secondary outcomes were pooled in a meta-analysis using the random-effect model. The Odds ratio was used for patients undergoing LT and the hazard ratio was used for patients who underwent renal transplantation. Results A total of 50,362 publications were identified. Six studies, with a total of 136,331 patients, satisfied the inclusion criteria. LT was performed on 2861 patients and RT was performed on 133,470 recipients. Overall, AF affected 6652 (4.8%) transplant recipients. Among them, 153 received a LT and 6499 underwent RT. The OR for mortality after LT was 2.375 (95% CI; 1.532–3.682) (P = 0.000) in AF(+) recipients and the HR was 1.859 (95% CI; 1.031–3.354) (P = 0.039) after RT. The OR for graft loss in AF(+) after LT r was 1.088 (95% CI; 0.311–3.804) (P = 0.894) and the HR for graft loss was 1.632 (95% CI; 1.200–2.218) (P = 0.002) after RT. Conclusions To the best of our knowledge, this is the first systematic review and meta-analysis to explore the association between AF and patient and graft survival after RT or LT. Our findings suggest that the presence of AF is associated with inferior patient survival. For renal transplant recipients, AF is also associated with inferior graft survival.

Background: Recent studies have reported a significant decrease in wound problems and hospital stay in obese patients undergoing renal transplantation by robotic-assisted minimally invasive techniques with no difference in graft function. Objective: Due to the lack of cost-benefit studies on the use of robotic-assisted renal transplantation versus open surgical procedure, the primary aim of our study is to develop a Markov model to analyze the cost-benefit of robotic surgery versus open traditional surgery in obese patients in need of a renal transplant. Methods: Electronic searches will be conducted to identify studies comparing open renal transplantation versus robotic-assisted renal transplantation. Costs associated with the two surgical techniques will incorporate the expenses of the resources used for the operations. A decision analysis model will be developed to simulate a randomized controlled trial comparing three interventional arms: (1) continuation of renal replacement therapy for patients who are considered non-suitable candidates for renal transplantation due to obesity, (2) transplant recipients undergoing open transplant surgery, and (3) transplant patients undergoing robotic-assisted renal transplantation. TreeAge Pro 2017 R1 TreeAge Software, Williamstown, MA, USA) will be used to create a Markov model and microsimulation will be used to compare costs and benefits for the two competing surgical interventions. Results: The model will simulate a randomized controlled trial of adult obese patients affected by end-stage renal disease undergoing renal transplantation. The absorbing state of the model will be patients' death from any cause. By choosing death as the absorbing state, we will be able simulate the population of renal transplant recipients from the day of their randomization to transplant surgery or continuation on renal replacement therapy to their death and perform sensitivity analysis around patients' age at the time of randomization to determine if age is a critical variable for cost-benefit analysis or cost-effectiveness analysis comparing renal replacement therapy, robotic-assisted surgery or open renal transplant surgery. After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. Conclusions: After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. [JMIR Res Protoc 2018;7(3):e74]

Background and objectives Management strategies are unclear for late-onset cytomegalovirus infection occurring beyond 6 months of antiviral prophylaxis in cytomegalovirus high-risk (cytomegalovirus IgG positive to cytomegalovirus IgG negative) kidney transplant recipients. Hybrid strategies (prophylaxis followed by screening) have been investigated but with inconclusive results. There are clinical and potential cost benefits of preventing cytomegalovirus-related hospitalizations and associated increased risks of patient and graft failure. We used decision analysis to evaluate the utility of postprophylaxis screening for late-onset cytomegalovirus infection. Design, setting, participants, & measurements We used the Markov decision analysis model incorporating costs and utilities for various cytomegalovirus clinical states (asymptomatic cytomegalovirus, mild cytomegalovirus infection, and cytomegalovirus infection necessitating hospitalization) to estimate cost-effectiveness of postprophylaxis cytomegalovirus screening strategies. Five strategies were compared: no screening and screening at 1-, 2-, 3-, or 4-week intervals. Progression to severe cytomegalovirus infection was modeled on cytomegalovirus replication kinetics. Incremental cost-effectiveness ratios were calculated as a ratio of cost difference between two strategies to difference in quality-adjusted life-years starting with the low-cost strategy. One-way and probabilistic sensitivity analyses were performed to test model’s robustness. Results There was an incremental gain in quality-adjusted life-years with increasing screening frequency. Incremental cost-effectiveness ratios were $783 per quality-adjusted life-year (every 4 weeks over no screening), $1861 per quality-adjusted life-year (every 3 weeks over every 4 weeks), $10,947 per quality-adjusted life-year (every 2 weeks over every 3 weeks), and $197,086 per quality-adjusted life-year (weekly over every 2 weeks). Findings were sensitive to screening cost, cost of hospitalization, postprophylaxis cytomegalovirus incidence, and graft loss after cytomegalovirus infection. No screening was favored when willingness to pay threshold was $185,000 per quality-adjusted life-year. Screening every 2 weeks was the dominant strategy between willingness to pay range of $14,000–$185,000 per quality-adjusted life-year. Conclusions In cytomegalovirus high-risk kidney transplant recipients, compared with no screening, screening for postprophylactic cytomegalovirus viremia is associated with gains in quality-adjusted life-years and seems to be cost effective. A strategy of screening every 2 weeks was the most cost-effective strategy across a wide range of willingness to pay thresholds. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_12_18_CJASNPodcast_18_2_P.mp3

BACKGROUND Recent studies have reported a significant decrease in wound problems and hospital stay in obese patients undergoing renal transplantation by robotic-assisted minimally invasive techniques with no difference in graft function. OBJECTIVE Due to the lack of cost-benefit studies on the use of robotic-assisted renal transplantation versus open surgical procedure, the primary aim of our study is to develop a Markov model to analyze the cost-benefit of robotic surgery versus open traditional surgery in obese patients in need of a renal transplant. METHODS Electronic searches will be conducted to identify studies comparing open renal transplantation versus robotic-assisted renal transplantation. Costs associated with the two surgical techniques will incorporate the expenses of the resources used for the operations. A decision analysis model will be developed to simulate a randomized controlled trial comparing three interventional arms: (1) continuation of renal replacement therapy for patients who are considered non-suitable candidates for renal transplantation due to obesity, (2) transplant recipients undergoing open transplant surgery, and (3) transplant patients undergoing robotic-assisted renal transplantation. TreeAge Pro 2017 R1 TreeAge Software, Williamstown, MA, USA) will be used to create a Markov model and microsimulation will be used to compare costs and benefits for the two competing surgical interventions. RESULTS The model will simulate a randomized controlled trial of adult obese patients affected by end-stage renal disease undergoing renal transplantation. The absorbing state of the model will be patients' death from any cause. By choosing death as the absorbing state, we will be able simulate the population of renal transplant recipients from the day of their randomization to transplant surgery or continuation on renal replacement therapy to their death and perform sensitivity analysis around patients' age at the time of randomization to determine if age is a critical variable for cost-benefit analysis or cost-effectiveness analysis comparing renal replacement therapy, robotic-assisted surgery or open renal transplant surgery. After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. CONCLUSIONS After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values.

Substantial strides have been made in improving the short-term success after kidney transplantation. Although there has been some progress, there has not been a robust improvement with respect to long-term outcomes. However, there remain many potentially modifiable transplant-specific risks to long-term patient and graft survival. In this chapter, we detail the current state of five important short-term transplant-specific clinical events. The early post-transplant events that negatively impact long-term survival discussed in this chapter are: acute T cell mediated rejection, acute antibody mediated rejection, delayed graft function, post-transplant viral infections, and recurrent and de novo diseases after transplantation. This chapter focuses on unmet needs and outlines important goals, specific to each of the topics, that hold promise for achieving better long-term graft survival in kidney transplant patients. Consistent across all five areas are: the need for better standardization and improvement in diagnosis and testing, identification of relevant clinical surrogate markers in the design of new studies, newer immunosuppressive agents, anti-viral agents and targeted therapy for certain diseases, and innovative newer clinical trials. A multifaceted approach will further enhance long-term kidney transplant survival.

Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation.

Background. Data on dialysis and renal transplantation (RT) after intestinal transplantation (IT) are sparse. Whether changes in immunosuppression and surgical techniques have modified these outcomes is unknown. Methods. Two hundred eighty-eight adult intestinal transplants performed between 1990 and 2014 at the University of Pittsburgh were analyzed for incidence, risk factors and outcomes after dialysis and RT. Cohort was divided into 3 eras based on immunosuppression and surgical technique (1990-1994, 1995-2001, and 2001-2014). Receiving RT, or dialysis for 90 days or longer was considered as end-stage renal disease (ESRD). Results. During a median follow-up of 5.7 years, 71 (24.7%) patients required dialysis, 38 (13.2%) required long-term dialysis and 17 (6%) received RT after IT. One-, 3-, and 5-year ESRD risk was 2%, 7%, and 14%, respectively. No significant era-based differences were noted. Higher baseline creatinine (hazard ratio [HR], 3.40 per unit increase, P < 0.01) and use of liver containing grafts (HR, 2.01; P = 0.04) had an increased ESRD risk. Median patient survival after dialysis initiation was 6 months, with a 3-year survival of 21%. Any dialysis (HR, 12.74; 95% CI 8.46-19.20; P < 0.01) and ESRD (HR, 9.53; 95% CI, 5.87-15.49; P < 0.01) had higher mortality after adjusting for covariates. For renal after IT, 1- and 3-year kidney and patient survivals were 70% and 49%, respectively. All graft losses were from death with a functioning graft, primarily related to infectious complications (55%). Conclusions. In intestinal transplant recipients, renal failure requiring dialysis or RT is high and is associated with increased mortality. Additionally, the outcomes for kidney after IT are suboptimal due to death with a functioning graft.

Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF). The purpose of this study was to characterize the prevalence of AF and atrial flutter (AFl) in patients with porphyrias. A single-center retrospective cohort study was designed using data from chart reviews of patients who were admitted to the hospital from January 2000 to June 2008. Fifty-six distinct cases were found with a discharge diagnosis of porphyria including all its subtypes. From the same database, age- and gender-matched controls were identified using computer-generated random numbers. We selected 1 age- and gender-matched control for each case. Electrocardiograms and echocardiograms were reviewed by 2 independent reviewers. Only patients with available 12-lead electrocardiograms that showed AF/AFl were labeled with that diagnosis. All patients with a diagnosis of porphyria were included in the study irrespective of their age. Seven of 56 patients with porphyria met inclusion criteria, yielding a prevalence of AF/AFl of 12.5%. This association was significant (p = 0.028, relative risk 7.45, 95% confidence interval 1.01 to 66.14) compared with the age- and gender-matched control group (2%). In conclusion, our observations suggest that porphyria may be significantly associated with AF/AFl.

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

Kidney transplantation is the preferred therapy for patients with end-stage renal disease (ESRD). With improvements in allograft and patient outcomes, patients with prior kidney allograft failures are increasingly becoming candidates for repeat transplantation.1 According to the annual Scientific Registry for Transplant Recipients (SRTR) report for the year 2011, approximately 12% of kidney transplant recipients had prior renal allograft failure.2 In addition, renal failure is common in recipients of other nonrenal solid organ transplants with rates of CKD of up to 16% and in those with CKD, an ESRD incidence of up to 30% over 36 months post-nonrenal organ transplantation which varies from organ to organ.3-6 With improvements in medical care, patients with nonrenal solid organ transplants are living longer to become candidates for kidney after solid organ transplantation.7 This group which constituted less than 1% of the waitlist candidates before 1995 increased to 3.3% in 2008 and were more likely to be listed preemptively (38% vs 21% in those without prior nonrenal solid organ transplantation).8 According to the SRTR annual report, 2.6% of transplants performed in year 2011 were in recipients of prior nonrenal solid organ transplants.2 Only a few previous studies have compared renal allograft outcomes in recipients who have undergone other solid organ transplants compared with those undergoing primary or repeat kidney transplantation. These previous studies were based on national databases with large center to center variations in practices and issues with nonuniform coding.9,10 The current study is a retrospective single-center study that analyzes specifically the renal allograft outcome after primary kidney, repeat kidney and kidney-after-other solid organ transplant. We evaluated various demographic, donor/recipient, and posttransplant variables across the 3 groups.

Proton pump inhibitors (PPIs) are widely prescribed to treat gastrointestinal diseases. However, concerns have been raised regarding their long-term use. Gastric acid suppression may decrease iron absorption, and it remains uncertain whether iron-deficiency anemia may result from chronic PPI therapy. We aimed to explore the association between chronic PPI use and iron-deficiency anemia. We conducted a retrospective cohort study of adult patients in an academic outpatient setting who received PPI therapy for at least 1 year between January 1, 2004 and January 1, 2006. We compared the change in hematologic indices among patients receiving PPI therapy for at least 1 year with matched controls. Of the 98 patients on chronic PPI therapy who met inclusion criteria, 35% had no documented indication for such therapy. At baseline, demographics and hematologic indices were similar between PPI-users and controls. Among patients on PPI therapy, all hematologic indices decreased from baseline, including hemoglobin (−0.19 g/dL, P = 0.03), hematocrit (−0.63%, P = 0.02), and mean corpuscular volume (−0.49 fL, P = 0.05). PPI users had significant decreases in mean hemoglobin and hematocrit (P

Background Dermatomyositis is an idiopathic inflammatory myopathy, often associated with an underlying malignancy. Its prevalence rate is approximately one per 100,000 in the general population, and is even rarer without evidence of a cancer. Dermatomyositis rarely involves myocardial muscle fibers, but has shown to be associated with cardiac arrhythmias. Case Presentation We present a case of a young female patient with known history of dermatomyositis who presented to hospital with a flare up of her disease. She also complained of paroxysms of palpitation. Telemetry monitoring revealed several episodes of paroxysmal supraventricular tachycardia with heart rate reaching up to 220 beats per minute. Conclusion Cardiac involvement in dermatomyositis is a very rare, but well known entity. Dermatomyositis patients with palpitations should be monitored on a Holter monitor, and appropriate therapy initiated if found to have a significant arrhythmia.

Background Mediastinal widening is a common finding on chest radiograph, and can be caused by numerous conditions. Most of these diseases have grave prognosis if accompanied by chest pain, and require immediate attention. However, mediastinal lipomatosis is a very benign condition caused by deposition of adipose tissue in the mediastinum. Case presentation We present a case of a morbidly obese female patient who presented to emergency department with a fall. She had mediastinal widening on chest radiograph, and borderline low voltage on electrocardiogram. On computed tomography, mediastinal lipomatosis was evident. Conclusion Obesity is a major epidemic in United States, and can lead to deposition of fat in the chest. Mediastinal lipomatosis is very benign condition, which rarely causes grave consequences.

A 72-year-old man presented with a 3-week history of gradually worsening pain and bluish discoloration in his right index, middle, and ring fingers. He was a nonsmoker and reported having had no history of Raynaud's phenomenon, trauma, atrial fibrillation, or any invasive vascular procedure. The physical examination showed bluish discoloration of the distal phalanges and absent ulnar pulse in the right arm. A modified Allen's test was positive (video). Computed tomographic angiography confirmed occlusion of the right ulnar artery. The results of further evaluation with a hypercoagulable workup and transesophageal echocardiography were normal. The patient was treated with antiplatelet agents . . .

Patients with cancer are considered hypercoagulable since their risk of thromboembolic events is significantly higher than patients without cancer. Thromboelastography (TEG) was used to investigate hypercoagulation in cancer patients. TEG continually measures over time the physical visco-elastic properties of blood as it transforms from a free flowing fluid to a gel-like clot. Our hypothesis was that blood from cancer patients would form a clot at a faster rate than blood from non-cancer patients hospitalized for thrombo-embolic disease. We studied 75 patients mean age was 57±14 composed of 46 females and 29 males. The patients were divided into 3 different groups: 14 patients with malignancy and thrombosis, 47 malignancy without thrombosis and 14 thrombosis without malignancy. TEG was performed using whole blood stimulated with two agonists: tissue factor and kaolin. Rate of clot development was increased in the cancer patients with and without thrombosis when compared to non-cancer thrombosis group and was localized to the humoral phase of coagulation (p

Background Calcification of thoracic aorta is very common in old people, especially ones with hypertension. This can sometime be visible on plain chest radiograph. Case Presentation We present a case of a male patient who had extensive deposition of calcium in the thoracic aorta. Conclusion The relationship between aortic calcification and coronary atherosclerosis remains contentious. Computed tomography of the thorax can display this calcification which appears like 'solar eclipse'.