Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents.

The direct-acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end-stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon-free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy-proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment-related side effects.

Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder(☠).

Reduction of immunosuppression (RI) is commonly used to treat posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. We investigated the efficacy, safety and predictors of response to RI in adult patients with PTLD. Sixty-seven patients were managed with RI alone and 30 patients were treated with surgical excision followed by adjuvant RI. The response rate to RI alone was 45% (complete response-37%, partial response-8%). The relapse rate in complete responders was 17%. Adjuvant RI resulted in a 27% relapse rate. The acute rejection rate following RI-containing strategies was 32% and a second transplant was feasible without relapse of PTLD. The median survival was 44 months in patients treated with RI alone and 9.5 months in patients who remained on full immunosuppression (p = 0.07). Bulky disease, advanced stage and older age predicted lack of response to RI. Survival analysis demonstrated predictors of poor outcome-age, dyspnea, B symptoms, LDH level, hepatitis C, bone marrow and liver involvement. Patients with none or one of these factors had a 3-year overall survival of 100% and 79%, respectively. These findings support the use of RI alone in low-risk PTLD and suggest factors that predict response and survival.

Successful Treatment of Renal Infiltration Complicated by Atypical Hemolytic Uremic Syndrome in a Leukemic Child.

Renal infiltration in children with acute leukemia has been reported previously; however, it has rarely been described in association with atypical hemolytic uremic syndrome (aHUS). We present a case of 9-year-old boy who developed life-threatening aHUS in the 1st week of Burkitt leukemia/lymphoma diagnosis with renal infiltration. Complete resolution of aHUS was achieved after therapeutic plasma exchange. This is an uncommon complication of Burkitt leukemia/lymphoma in a pediatric case.

Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease.

OBJECTIVE: To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. DESIGN: Prospective, controlled trial. SETTING: Referral clinic and hospitalized patients in a university medical center. PARTICIPANTS: Eighty patients with CSD and 57 healthy control subjects of similar age. MAIN OUTCOME MEASURES: The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. RESULTS: Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. CONCLUSION: Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD.

The evolution and future of immunosuppression in renal transplantation.

Since the early 1960s, a number of new immunosuppressive agents have been introduced to clinical transplantation. This review will be confined to mechanism of actions, and important gains and concerns of new microemulsion formulation of cyclosporine A (Neoral), mycophenolate mofetil (MMF), FK506, brequinar sodium, sirolimus (rapamycin), leflunomide, and 15-deoxyspergualin. We will also review some of the recent studies with monoclonal antibodies.

Transplantation for the millennium: attaining tolerance in our time--the Holy Grail.

Despite tremendous advances in organ transplantation over the past 40 years, life-long immunosuppression is still required to maintain the transplanted organ. The induction of human tolerance to defined foreign antigens while maintaining completely intact all the rest of the immune repertoire, in the absence of maintenance immunosuppression, continues to be the dream of the transplant scientist and clinician, the "Holy Grail," the quest which energizes much recent research. This article presents an overview on recent developments on transplantation tolerance.

Renal transplantation.

Renal Transplantation has progressed from an experiment in surgery, nephrology, and immunology to the preferred means of renal replacement therapy for patients with end-stage renal disease. Patient and graft survival rates are spectacular in the short run and improving steadily in the long. The current state of the art reflects deepened understanding of the alloimmune response and the T lymphocyte activation cascade in part driving the discovery of ever more potent immunosuppressive agents. Important issues remain such as chronic allograft dysfunction, the organ shortage, and tolerance induction. In this review, we will look at the history, the expanding treatment options based on better understanding of the immunobiology of alloantigen response, and the persistent challenges awaiting.

Detection of Rochalimaea henselae DNA by polymerase chain reaction from suppurative nodes of children with cat-scratch disease.

A polymerase chain reaction (PCR) assay was designed to amplify DNA from Rochalimaea henselae, Rochalimaea quintana and Afipia felis in the purulent material from lymph nodes in three patients with clinical cat-scratch disease (CSD) and two patients with lymphadenitis from other causes. All of the patients with CSD had positive immunofluorescent antibody serology for R. henselae, while none of the controls was positive. PCR amplification confirmed the presence of R. henselae DNA and the absence of R. quintana and A. felis DNA in the purulent material from CSD patients. PCR samples from control patients were negative. The PCR amplification of R. henselae DNA was performed quickly and with great sensitivity and specificity. It confirmed the presence of R. henselae in the CSD patients and eliminated the need for more extensive diagnostic and therapeutic procedures.

Long-term renal function in heart transplant recipients receiving cyclosporine therapy.

BACKGROUND: Immunosuppression with cyclosporine has improved allograft function and reduced both morbidity and mortality in organ transplantation. However, cyclosporine-induced nephrotoxicity still is a concern. The purpose of our study was to evaluate the effects of cyclosporine on renal function in orthotopic heart transplant recipients. METHODS: Thirty-nine patients who received transplants from 1985 to 1991 and had at least three yearly glomerular filtration rate measurements posttransplantation by 125I-iothalamate clearance method were included in the study. In addition, serum creatinine (before and after transplantation) and cyclosporine doses were analyzed. RESULTS: Maintenance immunosuppression at 1 year consisted of prednisone (0.1 mg/kg/day), azathioprine (2 mg/kg/day), and cyclosporine (12-hour trough level 100 to 150 ng/ml by fluorescence polarization immunoassay). The mean serum creatinine at 1 year was significantly higher than the mean pretransplantation serum creatinine (1.51 +/- 0.32 versus 1.28 +/- 0.38, p < 0.05) and stabilized after the first year. The mean glomerular filtration rate by 125I-iothalamate clearance method was 70.6 +/- 20.3 ml/min/1.73 m2 (range 32 to 105) at 1 year and remained relatively stable during the follow-up period of up to 7 years. Creatinine clearance calculated by the Cockcroft and Gault formula overestimated the true glomerular filtration rate after the third year. The mean cyclosporine dosage was significantly lower after the first-year dose of 3.9 +/- 1.8 mg/kg/day (p < 0.05). Three patients in 39 started hemodialysis at 5, 7, and 10 years after transplantation. CONCLUSION: Our data indicate that the adequacy of renal function is preserved with long-term cyclosporine therapy in heart transplant recipients.

Acyclovir prophylaxis for cytomegalovirus disease in high-risk renal transplant recipients: is it effective?

Cytomegalovirus (CMV) is a significant cause of post-transplantation morbidity and mortality in renal transplant recipients. The risk of CMV infection is between 60 to 88% in CMV seronegative patients who receive kidneys from CMV seropositive donors (D+, R-). In order to evaluate the efficacy of oral acyclovir in prevention of CMV infection after transplantation, we retrospectively reviewed the records of 25 patients (D+, R-) who were transplanted between January 1993 and December 1995. Eighteen of 25 patients received prophylaxis with variable doses of acyclovir (600 to 4000 mg/day, adjusted for their renal function) for 4 to 7 months. CMV disease was defined as fever (> or = 38 degrees C) for at least three days which could not be attributed to other causes with positive cultures or seroconversion for CMV, and presence of either leukopenia, pneumonitis, gastroenteritis or elevated liver enzymes. Twelve of the 18 patients (66.6%) who received acyclovir prophylaxis developed CMV disease. Seven patients were hospitalized and treated with i.v. ganciclovir. One patient died from CMV pneumonia associated with invasive fungal infection five months after transplantation. Of the 7 patients who did not receive prophylactic acyclovir, 5 (71.4%) developed CMV disease (2 patients were hospitalized and treated with ganciclovir). Our results failed to confirm the efficacy of oral acyclovir as a prophylaxis against CMV disease in a small group of high-risk patients. We conclude that other strategies should be tested.

Emphysematous pyelonephritis in a nonfunctioning renal allograft of a patient undergoing hemodialysis.

A hemodialysis patient with insulin-dependent diabetes mellitus and a non-functioning renal allograft in whom fever, low blood pressure, and confusion developed is reported. She underwent extensive evaluation and allograft nephrectomy for emphysematous pyelonephritis that was diagnosed by the presence of air in the collecting system of the transplanted kidney during computerized tomography of the abdomen. In nine patients with emphysematous pyelonephritis in renal allografts reported previously, this is the first instance of emphysematous pyelonephritis in a renal allograft with coagulase-negative staphylococcus.

Acute renal failure due to sulfinpyrazone.

A case of sulfinpyrazone-associated acute renal failure is reported. Sulfinpyrazone can cause reversible acute renal failure from acute tubular necrosis in patients with volume depletion. Brown tubular casts on urine microscopy and a fractional excretion of sodium greater than 1 are helpful in the diagnosis. Uric acid nephropathy and allergic interstitial nephritis should be included in the differential diagnosis of sulfinpyrazone-associated acute renal failure. Acute reduction of renal blood flow due to inhibition of renal prostaglandin synthesis and kallikrein activity by the drug is a possible mechanism. Treatment of sulfinpyrazone-induced acute tubular necrosis consists of intravascular hydration, supportive care, and withholding sulfinpyrazone. The patients at risk for acute renal failure due to sulfinpyrazone are those who have intravascular volume depletion as sensed by the kidneys.

[The insecto-fungicidal preparation, gaupsin, isolated from Pseudomonas aureofaciens strains]. / Insektofungitsidnyi preparat gaupsin na osnove shtammov Pseudomonas aureofaciens.

The integrated insectofungicidal preparation Gaupsin was developed on the basis of the Pseudomonas aureofaciens strains UKM V-111, which is active against bacterial and fungal phytopathogens, and UKM V-306, active against codling moth larvae. Gaupsin is an effective means for protection of orchards against moths and fungi. A method for production of Gaupsin in the liquid form with a titer of not less than 1 x 10(10) cells/ml under aeration conditions was elaborated. After spraying, the preparation remained on apple leaves for seven days. The efficiency of Gaupsin against codling moth was 88-94%. The effect of a fungal attack decreased 10 to 25-fold.