Hepatitis E in hemodialysis and kidney transplant patients in south-east Italy

AIM:To investigate the serovirological prevalence and clinical features of hepatitis E virus(HEV) infection in end-stage renal failure patients and in the healthy population.METHODS:HEV infection is a viral disease that can cause sporadic and epidemic hepatitis.Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects,including hemodialysis(HD)patients and patients who had undergone kidney transplant.A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy(Foggia and S.Giovanni Rotondo,Apulia).The seroprevalence of HEV was determined in 801 subjects;231 HD patients,120 renal transplant recipients,and450 health individuals.All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy,and were included progressively in this study.Serum samples were tested for HEV antibodies(Ig G/Ig M);in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA,and the HEV genotypes were determined.RESULTS:A total of 30/801(3.7%)patients were positive for anti-HEV Ig(Ig G and/or Ig M)and by Western blot.The healthy population presented with a prevalence of 2.7%,HD patients had a prevalence of 6.0%,and transplant recipients had a prevalence of 3.3%.The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%.The rates of exposure to HEV(positivity of HEV-Ig G/M in the early samples)were lower in the healthy controls,but the difference among the three groups was not statistically significant(P>0.05).Positivity for anti-HEV/Ig M was detected in 4/30(13.33%)anti-HEV Ig positive individuals,in 2/14 HD patients,in1/4 transplant individuals,and in 1/12 of the healthy population.The relative risk of being HEV-Ig M-positive was significantly higher among transplant recipients compared to the other two groups(OR=65.4,95%CI:7.2-592.7,P<0.001),but the subjects with HEV-Ig M positivity were numerically too few to calculate a significant difference.No patient presented with chronic hepatitis from HEV infection alone.CONCLUSION:This study indicated a higher,but not significant,circulation of HEV in hemodialysis patients vs the healthy population.Chronic hepatitis due to the HEV virus was not observed.

Ego strength and health: An empiric study in hemodialysis patients

Introduction: Ego strength represents an important variable that could be predictable about health and compliance in chronic diseases. In this study we propose a new questionnaire, E.F.E. “Ego Functioning Experience”, able to reveal the psychological functioning profile in Hemodialysis patients. The aim of this work, is to underline the existing relations between emotional profile and compliance, whit E.F.E., that may be predictive of a state of psychologycal health in hemodialysis patients. Methods: Study population included 90 hemodialysis patients. The study protocol was made by three psychological tests: the E.F.E. Questionnaire, the DMI, the Self-Liking and Self-Competence Scale. Results: Factor analysis extracts three factors: 1) “Need of Ego support”;2) “Ego activity oriented to treatment”;3) “Ego strength”. The correlation coefficients between the E.F.E. Questionnaire factors (three factors) and other measures, showed a direct correlation with the first factor and “turning against object” TAO of the DMI test (correlation is significant at the 0.001 level) and an inverse relation with set mechanisms of “Principalization”, PRN of the DMI (correlation is significant at the 0.005 level). The correlations of the second and the third factors with other measures, were not statistically significant. No relations were found about other variables. Conclusions: The E.F.E. questionnaire is a simple evaluation to detect hemo-dialysis patients who may need greater attention to the psychological health and therefore the need for treatment such as psychological support. In fact, lower presence of ego strength is indicative of poor compliance to clinical treatment in hemodialysis, but also of worsening of psychiatric symptoms such as demoralization and depressed mood. In conclusion, an increased social support is needed in hemodialysis patient in order to achieve better compliance and achieve a better state of psychological health in chronic hemodialysis patients.

Current protocols and outcomes of ABO-incompatible kidney transplantation

One of the principal obstacles in transplantation from living donors is that approximately 30%are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyte antigen system of the donor or because of the incompatibility of the ABO system.The aim of this review is to describe the more recent data from the literature on the different protocols used and the clinical outcomes of ABO-incompatible kidney transplantation.Two different strategies are used to overcome these barriers:desensitization of the recipient to remove the antibodies and to prevent their rebound after transplantation and the exchange of organs between two or more pairs.The largest part of this review is dedicated to describing the techniques of desensitization.Even if the first reports of successful renal transplantation between ABO-incompatible pairs have been published by 1980,the number of ABO-incompatible transplants increased substantially in this century because of our improved knowledge of the immune system and the availability of new drugs.Rituximab has substantially replaced splenectomy.The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects.Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation.

Hepatitis C and renal transplantation in era of new antiviral agents

Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.

Microbiota,renal disease and renal transplantation

Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation.The microbiota has a relevant role in conditioning the healthy status and the diseases.In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system.The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear.This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins.Similarly,after renal transplantation the microbiota changes with the appearance of pathobionts,principally in the first period because of the assumption of immunosuppressive drugs and antibiotics.These changes may deeply interfere with the graft outcome causing acute rejection,renal infections,diarrhea,and renal interstitial fibrosis.In addition,change in the microbiota may modify the metabolism of immunosuppressive drugs causing in some patients the need of modifying the immunosuppressant dosing.The restoration of the indigenous microbiota after transplantation is important,either to avoiding the complications that impair the normal renal graft,and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft.The use of prebiotics,probiotics,smart bacteria and diet modification may restore the indigenous microbiota,but these studies are just at their beginning and more data are needed to draw definitive conclusions.

Successful Treatment of Peritoneal Dialysis Related Peritonitis from Multi-Drug Resistant Sphingomonas paucimobilis with Combination Therapy: A Case Report

Sphingomonas paucimobilis is an emerging gram-negative aerobic bacterium, generally causing infections in immunocompromised patients. Few data are available about peritonitis in peritoneal dialysis due to this pathogen. The clinical courses and outcomes of peritonitis are variable, with a high frequency of catheter removal and peritoneal dialysis withdrawal. No guidelines are available for the treatment of Sphingomonas paucimobilis related peritonitis, due to its emerging role as pathogen, the high antibiotic resistance and unpredictable antibiotic sensitivity. Here, we describe a case of Sphingomonas paucimobilis peritonitis in a 52-year-old diabetic patient in Continuous Cycler-Assisted Peritoneal Dialysis (CCPD) for 4 months, successfully treated with a combined intraperitoneally administration of meropenem (250 mg/L) and ciprofloxacin (100 mg/L) for 21 days. No hospital admission and change of peritoneal dialysis scheme were needed;no relapses of peritonitis were observed during 18 months of follow-up.

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Organ shortage represents one of the major limitations to the development of kidney transplantation.To increase the donor pool and to answer the ever increasing kidney request,physicians are recurring to marginal kidneys as kidneys from older donors,from hypertensive or diabetic donors and from nonheart beating donors.These kidneys are known to have frequently a worse outcome in the recipients.To date major problem is to evaluate such kidneys in order to use or to discard them before transplantation.The use of such kidneys create other relevant question as whether to use them as single or dual transplant and to allocate them fairly according transplant programs.The pre-transplant histological evaluation,the clinical evaluation of the donor or both the criteria joined has been used and according the time each criterion prevailed over the others.Aim of this review has been to examine the advantages and the drawbacks of any criterion and how they have changed with time.To date any criterion has several limitations and several authors have argued for the development of new guidelines in the field of the kidney evaluation for transplantation.Several authors argue that the use of omic technologies should improve the organ evaluation and studies are ongoing to evaluate these technologies either in the donor urine or in the biopsies taken before transplantation.

Immunoglobulin G4-related kidney diseases: An updated review

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases( IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4+ cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the secondline treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. Differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR < 60 mL/min vs patients with e GFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

Therapeutic apheresis in kidney transplantation: An updated review

Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased-or living-donor transplantation. Postoperatively,additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.

Pharmacogenetics of immunosuppressant drugs:A new aspect for individualized therapy

In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.