Effects of Rituximab on Atherosclerotic Biomarkers in Kidney Transplant Recipients.

INTRODUCTION: Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. METHODS: All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. RESULTS: There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti-oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. DISCUSSION: Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.

Prevalence of Human Herpesvirus-8 and BK Polyoma Virus Infections in End-stage Renal Disease and the Influence of Renal Transplantation.

Viral infections lead to significant morbidity and mortality in kidney transplant recipients. We evaluated 49 kidney transplant recipients for human herpesvirus 8 (HHV-8) and BK polyomavirus infections in conjunction with data obtained from 43 donors. The seroprevalence of HHV-8 was 6.9% in donors and 12.2% in recipients. HHV-8 DNA was detected below the limit of quantification (<5000 copies/mL) in a recipient with HHV-8 seropositivity at the pretransplant period and was undetectable at month 3 after transplantation. Transient viruria with BK polyomavirus was recorded in 10.2% of recipients without viremia. Multiple factors contribute to viral reactivation, particularly immunosuppressive treatment. Reduction in maintenance immunosuppression seems beneficial in terms of viral reactivation. At our center, routine use of valganciclovir for antiviral prophylaxis may be effective for the prevention of HHV-8 reactivation.

Eculizumab for Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: A Single-Center Experience.

Antibody-mediated rejection (AMR) is responsible for up to 20%-30% of acute rejection episodes after kidney transplantation. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, a monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present 8 cases that were resistant to conventional therapy and in which eculizumab was given as a salvage treatment. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.

Eculizumab for salvage treatment of refractory antibody-mediated rejection in kidney transplant patients: case reports.

Antibody-mediated rejection (AMR) in a group of preoperatively desensitized patients may follow a dreadful course and result in loss of the transplanted kidney. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD 20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present two cases of acute-onset AMR in preoperatively desensitized patients. Eculizumab was used as a salvage agent in addition to conventional therapy. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.

Endothelial dysfunction in peritoneal dialysis patients with and without failed renal transplants.

BACKGROUND: Endothelial dysfunction (ED) is a common, early abnormality that predisposes patients to develop atherosclerosis and cardiovascular events; inflammation is associated with atherosclerosis and malnutrition. Patients with failed transplants are usually complicated by inflammation; however, ED in this group of patients has not been well defined. In this cross-sectional study, we sought to investigate ED among naïve peritoneal dialysis (nPD) patients who were never transplanted as well as patients with failed renal transplants who were re-starting peritoneal dialysis (fTxPD). METHODS: Twenty-five nPD patients (15 female/10 males; mean age, 44 +/- 11 years), and 12 fTxPD patients (4 males; mean age, 37 +/- 10 years) were included in the study. Coronary flow reserve (CFR) measurements were used to evaluate ED. Serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin, and intact parathyroid hormone (iPTH) were measured. Also, highly sensitive C-reactive protein (hs-CRP) levels and weekly Kt/V were determined as possible confounding factors. Results were compared between the 2 groups. RESULTS: There were no significant differences regarding age, gender, mean systolic and diastolic blood pressures, or smoking status. Mean duration on PD, peritoneal transport characteristics, PD modality and doses, frequency of peritonitis episodes, as well as serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin and iPTH levels were similar between the 2 groups. Weekly Kt/V of both groups were similar as well. However, hs-CRP levels were significantly higher (34 +/- 52 vs 6.7 +/- 7.5 mg/L; P = .017) and CFR significantly lower among patients with fTxPD compared with nPD patients (1.52 +/- 0.20 vs 1.91 +/- 0.53; P = .022). CONCLUSION: ED was more prominent among patients with failed transplants than nPD cases, suggesting that the failed allograft may be responsible for this abnormality.