Renal disease burden following liver transplantation

Significant chronic kidney disease (CKD) occurs following orthotopic liver transplant (OLT). Since CKD is associated with increased cardiovascular events, mortality, and hepatic allograft dysfunction, early recognition of CKD and implementation of changes may improve the long-term outcome. The purpose of this study was to determine the burden of renal disease following OLT. PATIENTS AND METHODS: We retrospectively reviewed our OLT recipients from 1997 until 2004. We calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease study (MDRD) method. The GFRs were further subdivided into pre-MELD and post-MELD eras. RESULTS: During the study period, we performed 407 OLTs. We censored data from living donor liver transplants (n = 14), combined liver-kidney transplants (n = 12), and from patients whom we did not have complete data for 6 months after transplant (n = 40). Mean MELD score at the time of transplant was 18 +/- 7 (mean +/- standard deviation). The mean GFR at 6 months following OLT was 63.7 +/- 30.2 mL/min per 1.73 m(2). Only 14% (n = 47) of our patients had normal renal function at 6 months, while 78% (n = 266) of our patients had mild to moderate risk for renal failure. Eight percent (n = 28) had stage 4 or 5 CKD. There were no differences between the pre-MELD and post-MELD GFRs. CONCLUSIONS: The burden of renal disease is significant in our patient population at 6 months posttransplantation. It may be important to introduce CKD management as early as 6 months after transplant to impact the outcomes of OLT recipients.     

Evolution of immunoglobulin deposition in C3-dominant membranoproliferative glomerulopathy

Background

Complement 3 glomerulopathy (C3GN) is a newly proposed subcategory of glomerular disease with features including membranoproliferative glomerulonephritis (MPGN), C3-dominant immunofluorescent staining without appreciable immunoglobulin deposition, and electron-dense deposits. Aberrations of alternative complement pathway (AP) have been found in many C3GN patients.

Case-diagnosis/treatment

A 13-year-old boy presented with edema in association with an upper respiratory infection. Studies demonstrated nephrotic syndrome with hematuria and markedly low C3 and C4. Initial renal biopsy showed MPGN with strong C3 and immunoglobulin deposition. The patient partially responded to immunosuppression. Follow-up biopsies at 10 months and 3 years demonstrated MPGN with strong C3, with little to no immunoglobulin deposition. Based on this and elevated SC5b-9, treatment was changed to eculizumab with further decrease in proteinuria.

Conclusions

Serial biopsies illustrated marked variability in immunoglobulin deposition in MPGN with persistently strong C3 deposition. Whether this evolution was related to the course of disease or to therapeutic intervention, the pathologic progression documented in this series of biopsies challenges the newly proposed subcategories of MPGN.     

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain-dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood-based EVLP.     

The effect of task complexity on planning in preterm-born children

Abstract

Objective: Planning is an important executive function (EF) skill that is fundamental to the capacity to achieve everyday goals that require a series of intermediate steps. This study examined the effect of preterm birth on planning skills in early and middle childhood using Tower problems that made different cognitive workload demands. Method: We administered a novel touchscreen Tower of Hanoi task (Monkey Tree Task; MTT) in three age cohorts (3, 6, and 9 years) to 485 children born between 2000 and 2010 (105 extremely low birth weight [ELBW], 248 late preterm [LP], and 132 term-born [Term]). Results: Children born with ELBW completed significantly fewer Tower problems with higher cognitive demands than children born at Term or LP. Likewise, Term- and LP-born children completed more Tower problems than children born with ELBW. In the youngest cohort, Term-born children solved Tower problems more efficiently than either preterm group, and LP-born children solved problems more efficiently than those born with ELBW. However, there were no group differences in efficiency in the older age cohorts. Significant correlations between our MTT measures and performance on other EF tasks were found. Conclusions: The MTT captured significant performance differences in planning skills between children born term vs. preterm. This study provides important information on the impact that cognitive workload, as a function of Tower problem complexity, has on planning skills in preterm children. This study adds to a growing body of research that distinguishes LP birth as having subtle, but distinguishable, adverse neuropsychological outcomes at earlier ages.     

Trends in body mass index and waist circumference among New Zealand adolescents, 1997/1998–2005

The objective of the current study is to examine changes in body mass index (BMI) and waist circumference among New Zealand adolescents between 1997/1998 and 2005. Data were drawn from two cross-sectional studies of high school students in an economically disadvantaged region of Auckland. In total, 608 adolescents from the 1998 survey and 897 adolescents from the 2005 survey participated. The prevalence of obesity increased from 19.4% in 1997/1998 to 30.7% in 2005. The mean BMI among adolescents significantly increased from 25.3 in 1997/1998 to 27.2 in 2005, with the greatest increases at the high end of the distribution. Increases in BMI did not differ by age, gender or ethnicity. The mean waist circumference increased from 76.2 cm in 1997/1998 to 89.4 cm in 2005, with increases in waist circumference measurements at all points in the distribution. The prevalence of obesity is increasing rapidly in this sample of ethnically diverse adolescents. Corresponding increases in waist circumference measurements suggest that this population of New Zealand adolescents are at increased risk for related chronic conditions.     

The burden of disease associated with infection with human papillomavirus

Human Papillomavirus is associated with a significant burden of disease globally, particularly with cancer of the cervix, for which persistent infection with high-risk types of HPV is necessary for the development of cervical cancer. Other cancers associated with HPV infection, particularly with HPV 16, include cancer of the vulva, vagina, penis, anus and some head and neck cancers. Globally approximately 600 000 cancers can be attributed to HPV infection. The advent of two commercially available vaccines had provided a new paradigm for the prevention of infection with HPV, particularly HPV infections associated with cancer.     

Intravenous fat emulsion: A potential novel antidote

Intravenous fat emulsions (IFE) are traditionally used as a component of parenteral nutrition therapy. Recently, IFE was used to resuscitate severe local anesthetic drug toxicity. This review focuses on the potential role of IFE in treatment of toxicity due to local anesthetics and other lipid-soluble drugs. The general properties of IFE, metabolic fate, and associated adverse events are described. Cases of local anesthetic toxicity treated with IFE are presented along with a discussion of the possible antidotal mechanisms. Initial investigations into the antidotal use of IFE for lipophilic central nervous and cardiovascular drug toxicity are also reviewed.     

Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome

The cytokine tumor necrosis factor (TNF) was assayed in the sera (n = 31) and cerebrospinal fluid (n = 26) of children with acquired immunodeficiency syndrome, using a competitive radioimmunoassay. Elevated serum levels of TNF were found in 15 (79%) of 19 patients with progressive encephalopathy (PE), compared with 1 (8%) of 12 patients without neurologic involvement. There was a significant association of PE with elevated serum TNF levels. Conversely, of 16 patients with elevated serum TNF levels, 15 (94%) were found to have PE, and of 8 patients with serum TNF levels greater than 100 pg/ml, all 8 (100%) had PE. No association was found between cerebrospinal fluid levels of TNF and PE. Neither serum nor cerebrospinal fluid TNF levels correlated with the degree of cachexia. These data suggest that circulating TNF may be responsible for the myelin damage that occurs in human immunodeficiency virus type 1-associated PE.     

Vitamin D (soltriol), light, and reproduction

Evidence from autoradiographic studies with 1,25(OH)2-vitamin D3 (vitamin D, soltriol) labeled with tritium and from the literature indicates that the steroid hormone soltriol regulates and modulates reproductive processes in the female, as it does in the male. Nuclear receptors for soltriol have been discovered in the uterus, oviduct, ovary, mammary gland, placenta, and fetal membranes, as well as in the pituitary and hypothalamus. Soltriol is recognized as a transducer and hormonal messenger of sunlight, acting as a somatotropic activator and modulator of vital processes for the seasonal and estival adaptation of growth, development, and procreation. Its influence on calcium equilibrium is just one of its many functions to serve this goal. This article reviews experimental, clinical, and epidemiologic evidence that suggests the involvement of soltriol in the control of reproductive processes, noting its importance for the onset of puberty, fertility, pregnancy, lactation, and probably sexual behavior. Cooperative actions between soltriol and other steroid hormones, especially estradiol, are pointed out.