First Report of Root Rot Caused by Phytophthora acerina on Metasequoia glyptostroboides in China.

Metasequoia glyptostroboides Hu & W. C. Cheng (Taxodiaceae), commonly called the Chinese redwood or dawn redwood, is a well-known "living fossil" and rare relict plant species endemic to China, which has been successfully cultivated throughout the world (Ma 2007). In July to September 2020, trees of Chinese redwood which were more than thirty years-old, showed symptoms of decline and death associated with branch dieback, root and collar rot (Fig. 1) in Yangtze River shelter-forests of Jiangling County in Hubei Province, China (112°15'19″E, 30°11'56″N; 40m). Diseased roots and rhizosphere soils were collected in September 2020 and April 2021. Using the baiting method, a homothallic Phytophthora sp. was recovered consistently from diseased roots and soil samples of Chinese redwood. All the isolates of this Phytophthora sp. formed similar colonies on V8 agar and corn meal agar (Fig. 2), and then three representative isolates (L4-5-4, L4-5-5 and L4-5-6) were randomly selected for morphological and molecular identification. In distilled water, semipapillate persistent sporangia were borne in simple sympodial branched sporangiophores. Sporangia were predominantly ovoid (Fig. 3a, d and f), but other shapes were observed including subglobose (Fig. 3b), limoniform (Fig. 3c) or distorted shapes (Fig. 3e), averaging 44.1 ± 7.7 µm (n=102) in length and 32.8 ± 5.2 µm (n=102) in width, with narrow exit pores of 8.0 ± 1.4 µm (n=93) and a length/breadth ratio of 1.3 ± 0.10 (n=102). Chlamydospores were not observed. Oogonia were globose or subglobose, 20.51 to 40.15 µm (av. 33.1 ± 3.9 µm) (n=119) in diameter, with smooth walls and paragynous antheridium (Fig. 3g-i). Oospores were globose or subglobose in elongated oogonia with medium wall thickness of 1.9 ± 0.5 µm (n=36), aplerotic or plerotic and 16.9 to 32.6 µm in diameter (av. 26.6 ± 3.8 µm) (n=40). According to the above morphological characteristics, this Phytophthora sp. was placed in Waterhouse's (1963) group III. The sequences of the internal transcribed spacers (ITS) region of nuclear ribosomal DNA of each isolate (GenBank Accession No. OK087320, OK087321 and OK087322) was 760 bp and had identity of 99.84% with three P. acerina isolates (JX951285, JX951291 and JX951296), while the 800 bp ß-tubulin (BTUB) sequences (OK140540, OK140541 and OK140542) showed 99.97% homology to the sequence of P. acerina (KC201283) (Ginetti, Moricca and Squires 2014) (Table 1). The ML phylogenetic trees were established by comparing ITS and BTUB sequences of three Phytophthora strains (L4-5-4, L4-5-5 and L4-5-6) with reference sequences of isolates of Phytophthora in ITS and BTUB in GenBank (Fig. 4-5). Based on the morphological and molecular characteristics, the strains were identified as namely P. acerina. In addition, pathogenicity assays were performed with one of the three strains (L4-5-4) on M. glyptostroboides using both one year old and three years old seedlings. Inoculum was prepared by subculturing agar plugs from edges of CMA cultures into V8 medium plates, incubating at 20 ℃ in darkness for 10 days. Six seedlings planted in pots filled with sterilized soil were inoculated by mycelium plug at root collar and stem wounded by a 8 mm diameter puncher. Six control seedlings were inoculated in the same manner as above, and sterile agar plugs were used. After 35 days, inoculated seedlings all had necrotic lesions at the inoculation sites, and some seedlings had the symptoms of foliage blight and dieback, whereas control seedlings remained healthy (Fig. 6). The number of fibrous roots after inoculation was significantly less than the control, and the roots of inoculated seedlings blackened or even rotted, while there were no obvious symptoms in the control (Fig. 7). Phytophthora isolates recovered from the symptomatic tissues of artificially inoculated plants were identical to isolate L4-5-4 in morphological characters and ITS sequencing. This is the first report of P. acerina causing root rot on the Chinese redwood in China. As only the seedlings were inoculated, further research is needed to address the epidemiology and pathogenicity of P. acerina to adult trees of Chinese red wood. References: Ginetti, B. et al. 2014. Plant Pathology, 63(4): 858-876. Ma, J. S. 2007. Bulletin of the Peabody Museum of Natural History, 48(2): 235-253. Waterhouse, G. M. 1963. Mycological Papers 92:1-22.

Circular RNAs add diversity to androgen receptor isoform repertoire in castration-resistant prostate cancer.

Deregulated expression of circular RNAs (circRNAs) is associated with various human diseases, including many types of cancer. Despite their growing links to cancer, there has been limited characterization of circRNAs in metastatic castration-resistant prostate cancer, the major cause of prostate cancer mortality. Here, through the analysis of an exome-capture RNA-seq dataset from 47 metastatic castration-resistant prostate cancer samples and ribodepletion and RNase R RNA-sequencing of patient-derived xenografts (PDXs) and cell models, we identified 13 circRNAs generated from the key prostate cancer driver gene-androgen receptor (AR). We validated and characterized the top four most abundant, clinically relevant AR circRNAs. Expression of these AR circRNAs was upregulated during castration-resistant progression of PDXs. The upregulation was not due to global increase of circRNA formation in these tumors. Instead, the levels of AR circRNAs correlated strongly with that of the linear AR transcripts (both AR and AR variants) in clinical samples and PDXs, indicating a transcriptional mechanism of regulation. In cultured cells, androgen suppressed the expression of these AR circRNAs and the linear AR transcripts, and the suppression was attenuated by an antiandrogen. Using nuclear/cytoplasmic fractionation and RNA in-situ hybridization assays, we demonstrated predominant cytoplasmic localization of these AR circRNAs, indicating likely cytoplasmic functions. Overall, this is the first comprehensive characterization of circRNAs arising from the AR gene. With greater resistance to exoribonuclease compared to the linear AR transcripts and detectability of AR circRNAs in patient plasma, these AR circRNAs may serve as surrogate circulating markers for AR/AR-variant expression and castration-resistant prostate cancer progression.

Gradient theories of brain activation: A novel application to studying the parental brain.

PURPOSE OF REVIEW: Parental brain research primarily employs general-linear-model-based (GLM-based) analyses to assess blood-oxygenation-level-dependent responses to infant auditory and visual cues, reporting common responses in shared cortical and subcortical structures. However, this approach does not reveal intermixed neural substrates related to different sensory modalities. We consider this notion in studying the parental brain. RECENT FINDINGS: Spatial independent component analysis (sICA) has been used to separate mixed source signals from overlapping functional networks. We explore relative differences between GLM-based analysis and sICA as applied to an fMRI dataset acquired from women while they listened to infant cries or viewed infant sad faces. SUMMARY: There is growing appreciation for the value of moving beyond GLM-based analyses to consider brain functional organization as continuous, distributive, and overlapping gradients of neural substrates related to different sensory modalities. Preliminary findings suggest sICA can be applied to the study of the parental brain.

Postrenal transplant infection: What is the effect of specific immunosuppressant agents?

BACKGROUND: Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections. METHODS: A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed. RESULTS: The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; P = .020) were protective. CONCLUSION: Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.

Donor-Specific Antibodies in Kidney Transplant Recipients.

Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. De novo donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient's immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.

Validity of a Newly-Designed Rectilinear Stepping Ergometer Submaximal Exercise Test to Assess Cardiorespiratory Fitness.

The maximum oxygen uptake (V̇O2 max), determined from graded maximal or submaximal exercise tests, is used to classify the cardiorespiratory fitness level of individuals. The purpose of this study was to examine the validity and reliability of the YMCA submaximal exercise test protocol performed on a newly-designed rectilinear stepping ergometer (RSE) that used up and down reciprocating vertical motion in place of conventional circular motion and giving precise measurement of workload, to determine V̇O2 max in young healthy male adults. Thirty-two young healthy male adults (32 males; age range: 20-35 years; height: 1.75 ± 0.05 m; weight: 67.5 ± 8.6 kg) firstly participated in a maximal-effort graded exercise test using a cycle ergometer (CE) to directly obtain measured V̇O2 max. Subjects then completed the progressive multistage test on the RSE beginning at 50W and including additional stages of 70, 90, 110, 130, and 150W, and the RSE YMCA submaximal test consisting of a workload increase every 3 minutes until the termination criterion was reached. A metabolic equation was derived from the RSE multistage exercise test to predict oxygen consumption (V̇O2) from power output (W) during the submaximal exercise test (V̇O2 (mL·min-1 )=12.4 ×W(watts)+3.5 mL·kg-1·min-1×M+160mL·min-1, R2= 0.91, standard error of the estimate (SEE) = 134.8mL·min-1). A high correlation was observed between the RSE YMCA estimated V̇O2 max and the CE measured V̇O2 max (r=0.87). The mean difference between estimated and measured V̇O2 max was 2.5 mL·kg-1·min-1, with an SEE of 3.55 mL·kg-1·min-1. The data suggest that the RSE YMCA submaximal exercise test is valid for predicting V̇O2 max in young healthy male adults. The findings show that the rectilinear stepping exercise is an effective submaximal exercise for predicting V̇O2 max. The newly-designed RSE may be potentially further developed as an alternative ergometer for assessing cardiorespiratory fitness and the promotion of personalized health interventions for health care professionals.

A comparison of three induction therapies on patients with delayed graft function after kidney transplantation.

We compare the outcomes of induction therapies with either methylprednisolone (group 1, n = 58), basiliximab (group 2, n = 56) or alemtuzumab (group 3, n = 98) in primary deceased donor kidney transplants with delayed graft function (DGF). Protocol biopsies were performed. Maintenance was tacrolimus and mycophenolate with steroid (group 1 and 2) or without steroid (group 3). One-year biopsy-confirmed acute rejection (AR) rates were 27.6, 19.6 and 10.2 % in group 1, 2 and 3 (p = 0.007). AR was significantly lower in group 3 (p = 0.002) and group 2 (p = 0.03) than in group 1. One-year graft survival rates were 90, 96 and 100 % in group 1, 2 and 3 (log rank p = 0.006). Group 1 had inferior graft survival than group 2 (p = 0.03) and group 3 (p = 0.002). The patient survival rates were not different (96.6, 98.2 and 100 %, log rank p = 0.81). Multivariable analysis using methylprednisolone induction as control indicated that alemtuzumab (OR 0.31, 95 % CI 0.11-0.82; p = 0.03) and basiliximab (OR 0.60, 95 % CI 0.23-0.98; p = 0.018) were associated with lower risk of AR. Therefore, alemtuzumab or basiliximab induction decreases AR and improves graft survival than methylprednisolone alone in patients with DGF. Alemtuzumab induction might also allow patients with DGF to be maintained with contemporary steroid-withdrawal protocol.

Large-scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses.

Functional magnetic resonance imaging (fMRI) studies regularly use univariate general-linear-model-based analyses (GLM). Their findings are often inconsistent across different studies, perhaps because of several fundamental brain properties including functional heterogeneity, balanced excitation and inhibition (E/I), and sparseness of neuronal activities. These properties stipulate heterogeneous neuronal activities in the same voxels and likely limit the sensitivity and specificity of GLM. This paper selectively reviews findings of histological and electrophysiological studies and fMRI spatial independent component analysis (sICA) and reports new findings by applying sICA to two existing datasets. The extant and new findings consistently demonstrate several novel features of brain functional organization not revealed by GLM. They include overlap of large-scale functional networks (FNs) and their concurrent opposite modulations, and no significant modulations in activity of most FNs across the whole brain during any task conditions. These novel features of brain functional organization are highly consistent with the brain's properties of functional heterogeneity, balanced E/I, and sparseness of neuronal activity, and may help reconcile inconsistent GLM findings.

Antineutrophil cytoplasmic antibodies crescentic allograft glomerulonephritis after sofosbuvir therapy.

Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis.

[Eyes-Brain-Hands Coordination Training System for Mental Retarded Children].

In order to help improving mental attention and sensory integration ability of mental retarded children, this paper proposes an interactive eyes-brain-hands coordination training system. This system realizes the principle of seeing, thinking and moving of hands by an interactive operation between the computer software custom icons and a touch control panel, so it can improve cognitive function and activity of daily living. The results show this training platform has a high degree of application and acceptance, and provides a portable training method for mental retarded children.

Generics: are all immunosuppression agents created equally?

BACKGROUND: The Affordable Care Act initiated innumerable cost-containment measures, including promoting generic conversion from brand medications and directing the Food and Drug Administration to decrease requirements for generic approvals. Despite this mandate, few data existed on generic conversion of immunosuppressant medications with narrow therapeutic troughs. METHODS: A retrospective analysis of our initial experience with generic tacrolimus (n = 39) was performed using a control cohort from our renal transplant database. A rejection and cost analysis was performed using a consecutive 2-year prior cohort (n = 159) as a control to determine the effect of generic conversion on tacrolimus a narrow therapeutic index immunosuppressant medication. RESULTS: During the first year after transplantation, the generic group had a greater drug variability (20% ± change in trough levels) that required more dosage adjustments (5.42 vs 3.59 drug dosage changes; P = .038) to obtain a stable dose, required increased number of intravenous magnesium infusions (4.95 vs 1.68 infusions; P = .001), and incurred a greater incidence of rejection (23.1% vs 10.2%; P = .024). A yearly institutional cost was evaluated against a negotiated $18,000/yearly central pharmacy cost savings compared with a $652,862 institutional cost to treat unanticipated rejections. CONCLUSION: Programmatic conversion from brand to generic tacrolimus resulted in increased drug variability, a greater incidence of magnesium wasting, and more episodes of rejection, leading to increases in institutional costs of care. This government-driven attempt at cost containment may be applicable to noncritical medications such as antibiotics and antihypertensives, but this policy should be reconsidered for narrow therapeutic index medications, such as tacrolimus and other immunosuppressant medications.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients.

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients. METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2(nd) month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041). CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.

Urine free light chains as a novel biomarker of acute kidney allograft injury.

BACKGROUND: We evaluated urine free light chains (FLC) as a potential biomarker for acute kidney allograft injury (AKAI). METHODS: Urine κ and λ FLC were compared with urine ß-2 microglobulin (ß2-M), retinol-binding protein (RBP), kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and microalbuminuria (MAB) in biopsy-confirmed acute rejection (AR) and acute tubular necrosis (ATN). Healthy volunteers (normal) and transplant recipients with normal allograft function (control) were used as references. RESULTS: Compared with control or normal group (N = 15), urine FLC, MAB, and RBP were higher in ATN (N = 29) and AR (N = 41) groups (p < 0.05). There was no difference in KIM-1, NGAL, or ß2-M between four groups. In the AR group, urine κFLC demonstrated the highest predictive value with sensitivity of 95.12% and specificity of 87.5% (p < 0.0001). Urine κFLC also performed best with a sensitivity of 96.55% and specificity of 93.33% (p < 0.0001) in the ATN group. The area under the receiver operating characteristic (ROC) curves (AUC) by ROC analysis is greatest in urine RBP (100%) and FLC (99%), and lowest in KIM-1 (53.5%), then NGAL (71.5%) in the AR group. The AUC is also greatest in urine FLC (100%) and RBP (99%), and lowest in urine KIM-1 (55.6%) and NGAL (69.9%) in the ATN group. CONCLUSIONS: Urine FLC appears sensitive for both AR and ATN, and it may be a novel AKAI biomarker.

Biodegradation-inspired bioproduction of methylacetoin and 2-methyl-2,3-butanediol.

Methylacetoin (3-hydroxy-3-methylbutan-2-one) and 2-methyl-2,3-butanediol are currently obtained exclusively via chemical synthesis. Here, we report, to the best of our knowledge, the first alternative route, using engineered Escherichia coli. The biological synthesis of methylacetoin was first accomplished by reversing its biodegradation, which involved modifying the enzyme complex involved, switching the reaction substrate, and coupling the process to an exothermic reaction. 2-Methyl-2,3-butanediol was then obtained by reducing methylacetoin by exploiting the substrate promiscuity of acetoin reductase. A complete biosynthetic pathway from renewable glucose and acetone was then established and optimized via in vivo enzyme screening and host metabolic engineering, which led to titers of 3.4 and 3.2 g l(-1) for methylacetoin and 2-methyl-2,3-butanediol, respectively. This work presents a biodegradation-inspired approach to creating new biosynthetic pathways for small molecules with no available natural biosynthetic pathway.

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients.

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin-angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan-Meier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

Obesity and metabolic syndrome in kidney transplantation.

The epidemic of obesity and metabolic syndrome (MS) contributes to the rapid growth of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is a reverse epidemiology, known as the "obesity paradox," in ESRD patients receiving maintenance dialysis. Obese patients are routinely referred for kidney transplant, and they have more surgical and medical complications than non-obese patients. However, compared to dialysis, kidney transplant provides a survival benefit for obese patients. After kidney transplant, obese patients tend to gain more body weight, and non-obese patients can develop new-onset obesity/MS. Obesity/MS is not only associated with serious morbidities, but also compromises the long-term graft and patient survival. The immunosuppressive drugs commonly used as maintenance therapy, including corticosteroids, calcineurin inhibitors and mammalian target-of-rapamycin inhibitors, contribute to obesity/MS. Development of novel immunosuppressive drugs free of metabolic adverse effects is needed, so that the full potential and benefits of kidney transplantation can be realized.

Essential concept of transplant immunology for clinical practice.

Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies (DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.

Successful transplantation of HIV patients: the Louisiana experience.

Human immunodeficiency virus (HIV) seropositivity has historically been an absolute contraindication for solid organ transplantation. However, the successful application of HAART (highly active anti-retroviral therapy) drug regimens has greatly prolonged the life expectancy of HIV-positive patients. Therefore, it has become appropriate to consider this patient population for transplantation. HIV positive transplants are being performed around the country in controlled settings, usually as part of a research protocol. The aim of our study is to describe the Louisiana experience with organ transplantation into HIV-positive patients. We identified seven HIV-positive patients who underwent kidney or kidney/pancreas transplantation at our center between 2007 and 2010. We performed a retrospective chart review to ascertain graft function, as well as virologic and immunologic status post-transplant. Renal function (glomerular filtration rate and serum creatinine concentrations) improved in all subjects post-transplant, and six of seven (85.8%) subjects remained virologically suppressed with no progression to Acquired Immunodeficiency Syndrome (AIDS). Overall, two-year graft and patient survival rates were 85.5%. HIV seropositive End Stage Renal Disease (ESRD) patients represent a new population of patients that can be successfully transplanted. This offers a new dimension in care for successful HAART therapy to prolong the life of HIV-infected patients.

Kidney transplantation alone in ESRD patients with hepatitis C cirrhosis.

BACKGROUND: Kidney transplantation (KTx) alone in patients with cirrhosis and renal failure (end-stage renal disease [ESRD]) infected with hepatitis C virus (HCV) is controversial. The aim of this study was to compare outcomes of HCV+ patients with ESRD and cirrhosis (C group) versus HCV+ patients with ESRD but with no cirrhosis (NC group) listed for KTx. METHODS: Ninety HCV+ patients with ESRD were evaluated for KTx between 2003 and 2010. Listed patients underwent transjugular liver biopsy with hepatic portal venous gradient (HPVG) measurements. Only patients with HPVG less than 10 mm Hg were considered for KTx alone. We analyzed patient demographics, waitlist/liver disease characteristics, and posttransplant outcomes between groups. RESULTS: Sixty-four patients listed for KTx alone were studied. Twelve patients (18.75%) showed biopsy-proven cirrhosis. Thirty-seven patients underwent KTx alone (9 from C and 28 from NC). No patients developed decompensation of their liver disease, although one patient for NC group developed metastatic hepatocellular carcinoma 16 months after transplantation. One- and three-year graft survival rates were 75% and 75% versus 92.1% and 75.1% for groups C and NC, respectively (P=0.72). One- and three-year patient survival rates were 88.9% and 88.9% versus 96.3% and 77.9% for groups C and NC, respectively (P=0.76). Only increasing recipient age and decreasing albumin levels were significantly associated with worse graft and patient survival. CONCLUSIONS: Our study suggests that KTx alone may be safe in patients with compensated HCV, cirrhosis, and ESRD with HPVG less than 10 mm Hg. A simultaneous liver-kidney transplantation may be an unnecessary use of a liver allograft in these patients.

Antibody induction therapy in adult kidney transplantation: A controversy continues.

Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients. Published data support antibody induction in patients with immunologic risk to reduce the incidence of acute rejection (AR) and graft loss from rejection. However, the choice of antibody remains controversial as the clinical studies were carried out on patients of different immunologic risk and in the context of varying maintenance regimens. Antibody selection should be guided by a comprehensive assessment of immunologic risk, patient comorbidities, financial burden as well as the maintenance immunosuppressives. Lymphocyte-depleting antibody (thymoglobulin, ATGAM or alemtuzumab) is usually recommended for those with high risk of rejection, although it increases the risk of infection and malignancy. For low risk patients, interleukin-2 receptor antibody (basiliximab or daclizumab) reduces the incidence of AR without much adverse effects, making its balance favorable in most patients. It should also be used in the high risk patients with other medical comorbidities that preclude usage of lymphocyte-depleting antibody safely. There are many patients with very low risk, who may be induced with intravenous steroids without any antibody, as long as combined potent immunosuppressives are kept as maintenance. In these patients, benefits with antibody induction may be too small to outweigh its adverse effects and financial cost. Rituximab can be used in desensitization protocols for ABO and/or HLA incompatible transplants. There are emerging data suggesting that alemtuzumab induction be more successful than other antibody for promoting less intensive maintenance protocols, such as steroid withdrawal, tacrolimus monotherapy or lower doses of tacrolimus and mycophenolic acid. However, the long-term efficacy and safety of these unconventional strategies remains unknown.