Treatment of BK virus with a stepwise immunosuppression reduction and intravenous immunoglobulin in pediatric kidney transplant.

BACKGROUND: BKV and BKVN are common in pediatric kidney transplant, but there is limited data on treatment approaches. Our objective was to study the prevalence of BKV and BKVN utilizing only plasma qPCR and report treatment outcomes with stepwise IR and IVIG. METHODS: A retrospective study of all pediatric kidney transplants from 2013 to 2020. Excluded patients >21 years at transplant and immediate graft failure. Surveillance was conducted using only plasma BK qPCR at 1, 3, 6, 9, 12, 18, and 24 months and annually. BKV defined as ≥250 copies/ml and resolution as <250 copies/ml. Presumed BKVN as >10 000 copies/ml despite IR; and BKVN if confirmed on histology. RESULTS: Fifty-six patients were included in the study; 20 (35.7%) had BKV. BKV was associated with longer duration of stent, 40 vs. 33.5 days (p = .004). Two patients (3.5%) had confirmed, and 2(3.5%) had presumed BKVN. The first-line treatment was IR in 100% of patients. BKVN confirmed and presumed received IVIG every month for six doses. Viral resolution was achieved in 70%, and no difference was noted in estimated glomerular filtration rate between BKV and non-BKV group (p = .438). There were no rejection episodes, and graft survival was 100% over median follow-up of 3 years. CONCLUSIONS: Plasma qPCR alone is adequate for screening and monitoring treatment of BKV and BKVN. A stepwise IR and IVIG resulted in BKV resolution in the majority of patients. Larger studies are required to study the role of IVIG in the treatment of BKVN.

Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.

Ethylene signaling regulates natural variation in the abundance of antifungal acetylated diferuloylsucroses and Fusarium graminearum resistance in maize seedling roots.

The production and regulation of defensive specialized metabolites play a central role in pathogen resistance in maize (Zea mays) and other plants. Therefore, identification of genes involved in plant specialized metabolism can contribute to improved disease resistance. We used comparative metabolomics to identify previously unknown antifungal metabolites in maize seedling roots, and investigated the genetic and physiological mechanisms underlying their natural variation using quantitative trait locus mapping and comparative transcriptomics approaches. Two maize metabolites, smilaside A (3,6-diferuloyl-3',6'-diacetylsucrose) and smiglaside C (3,6-diferuloyl-2',3',6'-triacetylsucrose), were identified that could contribute to maize resistance against Fusarium graminearum and other fungal pathogens. Elevated expression of an ethylene signaling gene, ETHYLENE INSENSITIVE 2 (ZmEIN2), co-segregated with a decreased smilaside A : smiglaside C ratio. Pharmacological and genetic manipulation of ethylene availability and sensitivity in vivo indicated that, whereas ethylene was required for the production of both metabolites, the smilaside A : smiglaside C ratio was negatively regulated by ethylene sensitivity. This ratio, rather than the absolute abundance of these two metabolites, was important for maize seedling root defense against F. graminearum. Ethylene signaling regulates the relative abundance of the two F. graminearum-resistance-related metabolites and affects resistance against F. graminearum in maize seedling roots.

Emphysematous pyelonephritis in renal allograft related to antibody-mediated rejection: A case report and literature review.

Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody-mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end-stage renal disease secondary to diabetes mellitus. Cross-match test was negative but she had remote history of anti-HLA-A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti-thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post-operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non-functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non-viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor-specific antibody (DSA) returned positive with high intensity anti-HLA-A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti-B-cell and/or anti-plasma cell therapies for historical DSA and strict post-operative follow-up in immunologically high-risk recipients to detect early signs of rejection and avoid deleterious outcomes.

Exception Policy Change Increased the Simultaneous Kidney-Liver Transplant Probability of Polycystic Disease in the Centers With High Median MELD at Transplantation.

BACKGROUND: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD). METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras. RESULTS: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P  = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P  = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P  = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P  = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 ( P  = 0.006), it became comparable in Era 2 ( P  = 0.54). CONCLUSIONS: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.

COF-300 synthesis and colloidal stabilization with substituted benzoic acids.

Colloidal covalent organic framework (COF) synthesis enables morphological control of crystallite size and shape. Despite numerous examples of 2D COF colloids with various linkage chemistries, 3D imine-linked COF colloids are more challenging synthetic targets. Here we report a rapid (15 min-5 day) synthesis of hydrated COF-300 colloids ranging in length (251 nm-4.6 µm) with high crystallinity and moderate surface areas (150 m2 g-1). These materials are characterized by pair distribution function analysis, which is consistent with the known average structure for this material alongside different degrees of atomic disorder at different length scales. Additionally, we investigate a series of para-substituted benzoic acid catalysts, finding that 4-cyano and 4-fluoro substituted benzoic acids produce the largest COF-300 crystallites with lengths of 1-2 µm. In situ dynamic light scattering experiments are used to assess time to nucleation in conjunction with 1H NMR model compound studies to probe the impact of catalyst acidity on the imine condensation equilibrium. We observe cationically stabilized colloids with a zeta potential of up to +14.35 mV in benzonitrile as a result of the carboxylic acid catalyst protonating surface amine groups. We leverage these surface chemistry insights to synthesize small COF-300 colloids using sterically hindered diortho-substituted carboxylic acid catalysts. This fundamental study of COF-300 colloid synthesis and surface chemistry will provide new insights into the role of acid catalysts both as imine condensation catalysts and as colloid stabilizing agents.

Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy.

Minimally invasive procedures are considered to be safe and effective approaches to the management of surgical liver disease. However, this indication remains controversial for living donor hepatectomy. Between 2000 and 2011, living donor right hepatectomy (LDRH) was performed 58 times. Standard right hepatectomy was performed in 30 patients via a subcostal incision with a midline extension. Minimally invasive procedures began to be used for LDRH in 2008. A hybrid technique (hand-assisted laparoscopic liver mobilization and minilaparotomy for parenchymal dissection) was developed and used in 19 patients. In 2010, an upper midline incision (10 cm) without laparoscopic assistance for LDRH was innovated, and this technique was used in 9 patients. The perioperative factors were compared, and the indications for minimally invasive LDRH were investigated. The operative blood loss was significantly less for the patients undergoing a minimally invasive procedure versus the patients undergoing the standard procedure (212 versus 316 mL, P = 0.001), and the operative times were comparable. The length of the hospital stay was significantly shorter for the minimally invasive technique group (5.9 versus 7.8 days, P < 0.001). The complication rates were 23% and 25% for the standard technique and minimally invasive technique groups, respectively (P = 0.88). Patients undergoing minilaparotomy LDRH had a body mass index (24.0 kg/m(2)) similar to that of the hybrid technique patients (25.8 kg/m(2), P = 0.36), but the graft size was smaller (780 versus 948 mL, P = 0.22). In conclusion, minimally invasive LDRH can be performed without safety being impaired. LDRH with a 10-cm upper midline incision and without laparoscopic assistance may be appropriate for donors with a smaller body mass. Laparoscopic assistance can be added as needed for larger donors. This type of LDRH with a 10-cm incision is innovative and is recommended for experienced centers.

Transjugular intrahepatic portosystemic shunt following liver transplantation: can outcomes be predicted?

Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re-transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS.

Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. METHODS: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. RESULTS: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. CONCLUSIONS: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.

Risk of Ipsilateral Deep Vein Thrombosis After Kidney Transplantation: A Retrospective Study.

OBJECTIVE: To investigate the incidence and characteristics of deep vein thrombosis (DVT) in kidney transplantation recipients and analyze whether the anatomical side of DVT was associated with the side of the transplanted organ. METHODS: A single-center retrospective medical record review of patients who received a kidney transplant between January 2004 and July 2019 and who subsequently developed DVT. Only patients who received unilateral kidney transplants were included in the study. Patients who underwent concomitant pancreatic transplants, bilateral kidney transplants, or repeat procedures were excluded. RESULTS: Of the 2449 kidney transplants performed during the study period, 1482 were included in the analysis (948 men [64%]; mean age 61 years). Of 606 duplex ultrasound tests, 115 results confirmed the presence of DVT. The incidence of symptomatic DVT was 4.7%. The most common time of DVT diagnosis was within four weeks after transplantation. Type 2 diabetes, heart failure, acute myocardial infarction, sepsis, chronic obstructive pulmonary disease/abnormal pulmonary function, and being confined to bed were associated with DVT after kidney transplant (all P < 0.05). Patients with ultrasound-confirmed DVT had higher mean Caprini scores than patients with negative duplex ultrasounds (P < 0.5). Approximately 53% of transplant patients with ultrasound-confirmed DVT had a 1:1 correlation of transplant side to the side of DVT. Cohen kappa statistic 0.03 indicated no correlation between the side of DVT and the side of transplant. CONCLUSIONS: The incidence of DVT after kidney transplant was lower than the incidence reported in the literature. Being confined to a bed may be a risk factor for DVT after transplant surgery. Kidney transplant recipients who had a positive duplex ultrasound had higher Caprini risk assessment scores than transplant recipients who had negative duplex ultrasounds. There was no correlation between the side of the DVT and the side of the transplant.

Large-Scale CRISPRi and Transcriptomics of Staphylococcus epidermidis Identify Genetic Factors Implicated in Lifestyle Versatility.

Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.

Prerenal Transplant Education and Evaluation Positively Impacts Outcomes.

Introduction: An outstanding question in kidney transplantation is how to prepare candidates and their social supports for optimal posttransplant outcomes. Project Aims: This program evaluation assessed whether a pretransplant quality improvement clinic improved clinical outcomes in the year posttransplant compared to recipients receiving standard of care. Design: The Countdown to Transplant Clinic was implemented with kidney transplant candidates expected to receive a transplant within the next few months. The clinic included an enhanced education session on posttransplant lifestyle management, confirmation of support (≥2 adults), and evaluations by transplant social work, psychology, and nephrology. Results: Seventy-five patients participated in the clinic and underwent a transplant. A retrospective chart review of posttransplant laboratory values, rehospitalizations (within 3-months posttransplant), biopsy-confirmed graft failure, and mortality (within 1-year posttransplant) were collected from both groups. Univariate and multivariate propensity score-weighted linear or logistic regression models were used to evaluate the association between clinic participation and outcomes. In models adjusting for relevant covariates, participation in The Countdown to Transplant Clinic (vs standard care) was associated with a lower coefficient of variation of serum tacrolimus (all values collected 3-12 months posttransplant), 30-day posttransplant white blood cell counts (but not 90-day), 90-day posttransplant potassium, and 30 and 31 to 90 days rehospitalizations. Clinic participation did not predict serum glucose levels at 30- or 90-days posttransplant. Due to low rates of rejection and mortality, meaningful comparisons were not possible. Conclusion: Participation in a pretransplant, multicomponent clinic may improve certain outcomes of interest posttransplantation. Pilot testing for feasibility for randomized controlled trials is a necessary next step.

Robot-assisted Transplant Ureteral Repair to Treat Transplant Ureteral Strictures in Patients after Robot-assisted Kidney Transplant: A Case Series.

OBJECTIVE: To describe the use of robotic-assisted transplant ureteral repair (RATUR) for treating transplant ureteral stricture (TUS) in 3 patients who had undergone robot assisted kidney transplant (RAKT). METHOD: We reviewed the medical records of 3 patients who experienced TUS after RAKT and who underwent RATUR between 2017 and 2020. The patients' RAKT, post-transplant clinical course, endourological interventions, reoperation, and recovery were assessed. RESULTS: All patients diagnosed with TUS presented with deterioration of kidney function after RAKT. Method of diagnosis included ultrasound, antegrade ureterogram, and CT scan. All 3 patients had a short (<1 cm) area of TUS and underwent RATUR. For 2 patients, distal strictures were bypassed with modified Lich-Gregoir ureteroneocystostomy reimplantation. One patient was treated with pyelo-ureterostomy to the contralateral native ureter. No intraoperative complications, conversions to open surgery, or significant operative blood loss requiring blood transfusion for any patient were observed. Also, no patients had urine leaks in the immediate or late postoperative period. After RATUR, 2 patients developed Clavien grade II complications with rectus hematoma or urinary tract infection. CONCLUSION: RATUR is a technically feasible operation for kidney transplant patients with TUS after RAKT. This procedure may provide the same benefits of open operation without promoting certain comorbidities that may occur from open surgical procedures.

Modifications in the Intestinal Functionality, Morphology and Microbiome Following Intra-Amniotic Administration (Gallus gallus) of Grape (Vitis vinifera) Stilbenes (Resveratrol and Pterostilbene).

This efficacy trial evaluated the effects of two polyphenolic stilbenes, resveratrol and pterostilbene, mostly found in grapes, on the brush border membrane functionality, morphology and gut microbiome. This study applied the validated Gallus gallus intra-amniotic approach to investigate the effects of stilbene administration versus the controls. Three treatment groups (5% resveratrol; 5% pterostilbene; and synergistic: 4.75% resveratrol and 0.25% pterostilbene) and three controls (18 MΩ H2O; no injection; 5% inulin) were employed. We observed beneficial morphological changes, specifically an increase in the villus length, diameter, depth of crypts and goblet cell diameter in the pterostilbene and synergistic groups, with concomitant increases in the serum iron and zinc concentrations. Further, the alterations in gene expression of the mineral metabolism proteins and pro-inflammatory cytokines indicate a potential improvement in gut health and mineral bioavailability. The cecal microbiota was analyzed using 16S rRNA sequencing. A lower α-diversity was observed in the synergistic group compared with the other treatment groups. However, beneficial compositional and functional alterations in the gut microbiome were detected. Several key microbial metabolic pathways were differentially enriched in the pterostilbene treatment group. These observations demonstrate a significant bacterial-host interaction that contributed to enhancements in intestinal functionality, morphology and physiological status. Our data demonstrate a novel understanding of the nutritional benefits of dietary stilbenes and their effects on intestinal functionality, morphology and gut microbiota in vivo.

Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study.

OBJECTIVES: In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15. METHODS: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19. RESULTS: The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20. CONCLUSION: The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21. CT.GOV IDENTIFIER: NCT01950819.

Renal insufficiency after liver transplantation in the MELD era compared to the pre-MELD era.

Because the model for end-stage liver disease (MELD) system for liver allocation gives priority to patients with a higher creatinine, and because pre-transplant renal function is one determinant of post-transplant renal function, this study compares the burden of renal insufficiency in the pre-MELD and MELD eras. Two hundred and eleven patients, at our institution, transplanted in the pre-MELD era, were compared to 143 in the MELD era. The GFR (mL/min/1.73 m2) was significantly higher in the MELD cohort than the pre-MELD cohort at time of transplant, discharge, and 12 months post-transplant (95.5 vs. 85.3, p = 0.039; 90.4 vs. 77.4, p = 0.002; 66.8 vs. 60.3, p = 0.026). There was no difference between the two groups in time to renal failure. There was a higher rate of sirolimus use in the MELD era (27% vs. 18%: p = 0.042) and a slightly higher use of kidney-liver transplant in the MELD era (p = 0.056). We did not identify greater renal insufficiency in the MELD era. There was greater renal function in the MELD era at time of transplant, discharge and month 12. Potential explanations include: absence of an increase in renal insufficiency prior to transplant in the MELD era, greater use of renal sparing immunotherapy and growing use of kidney-liver transplant.

Psychiatric Profile of Patients Currently Listed for Kidney Transplantation: Evidence of the Need for More Thorough Pretransplant Psychiatric Evaluations.

BACKGROUND: Patients with end-stage renal disease are at increased risk for psychiatric and cognitive pathologies. Despite this, there is little standardization of the psychosocial and/or psychiatric evaluation of renal transplant candidates. The purpose of this study is to report the frequency of psychiatric and cognitive pathologies and corresponding psychiatric recommendations in a sample of patients actively listed for kidney transplant. METHODS: We performed a retrospective chart review of 104 patients listed for kidney transplant who underwent semistructured psychiatric assessments as part of a novel clinical protocol. Transplant psychiatry routinely administers brief screeners of cognitive functioning and health literacy, also collected from patients' charts. RESULTS: There were a number of primary psychiatric disorders, including active substance abuse. Even using a conservative cutoff, 52.4% of patients' charts indicated evidence of cognitive impairment, and 28.9% indicated limited health literacy. In addition, there were numerous additional recommendations made within every category (educational, psychotherapeutic/psychiatric, cognitive, cessation of substance use, substance abuse treatment, and mobilizing support for transplant). With the exclusion of the recommendation for more education regarding the transplant process, most patients had at least 1 to 3 recommendations (n = 72, 69.2%). CONCLUSIONS: We have identified a number of concerning psychosocial and psychiatric factors in patients who were evaluated and listed for kidney transplantation that can adversely impact transplant outcomes. The findings provide support for more in-depth and ongoing psychiatric assessments as standard clinical protocol for kidney transplant candidates.

Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.