Suzon Collette

BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches.

Abstract BK polyomavirus is ubiquitous, with a seropositivity rate of over 75% in the adult population. Primary infection is thought to occur in the respiratory tract, but asymptomatic BK virus latency is established in the urothelium. In immunocompromised host, the virus can reactivate but rarely compromises kidney function except in renal grafts, where it causes a tubulointerstitial inflammatory response similar to acute rejection. Restoring host immunity against the virus is the cornerstone of treatment. This review covers the virus-intrinsic features, the posttransplant microenvironment as well as the host immune factors that underlie the pathophysiology of polyomavirus-associated nephropathy. Current and promising therapeutic approaches to treat or prevent this complication are discussed in relation to the complex immunopathology of this condition.

Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature.

In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined.

The incidence, management, and evolution of rapamycin-related side effects in kidney transplant recipients

Conversion from a calcineurin‐inhibitor‐based immunosuppression to a rapamycin‐based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31, 2008 and who received rapamycin to replace calcineurin inhibitors. In 219 patients studied, 98% presented ≥1 side effects after starting rapamycin. Side effects occurring in ≥10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45–59%), peripheral edema (37%, 95%CI: 31–43%), cytopenia (36%, 95% CI: 30–42%), acne (29%, 95% CI: 23–35%), proteinuria (23%, 95% CI: 17–29%), and oral ulcers 14% (95% CI: 10–18%). Proteinuria, ulcers, and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40–52%). Age (odds ratio [OR] per 10‐yr increase: 1.29, 95% CI: 1.05–1.59) and obesity (OR: 2.57, 95% CI: 1.10–6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner and younger patients are less likely to discontinue rapamycin due to side effects.

Sirolimus Immunoprophylaxis and Renal Histological Changes in Long-Term Cardiac Transplant Recipients A Pilot Study

Background: The effects of sirolimus (SIR), as a substitution for calcineurin inhibitor (CNI) immunoprophylaxis, on renal function in very-long-term cardiac transplant recipients have been a matter of controversy. Objective: To assess the impacts of SIR as a substitution for CNI on renal function up to 24 months in long-term cardiac recipients as well as the renal histological changes in patients with suspected CNI-induced nephrotoxicity. Methods: A total of 23 cardiac transplant recipients aged 57.7 ± 11.2 years, 91 months post–cardiac transplantation were recruited; 15 patients were randomized to CNI-free immune suppression with SIR, and 8 patients were allocated to continue their CNI regimens. Serum creatinine and calculated serum creatinine clearance were measured at prespecified time points up to 24 months. Renal structure and function were assessed by renal biopsies, renal ultrasound, and magnetic resonance imaging at baseline. Results: There were no significant changes in creatinine clearance during the course of the study in patients treated with SIR. However, SIR-treated patients exhibited a significant decrease in 24-hours and nighttime systolic and diastolic blood pressures. Typical findings of significant hypertensive renal disease were detected in 9 of the 11 (82%) patients. Features of chronic CNI toxicity were detected in 6 (55%) patients. Conclusions: There is a very high rate of hypertensive renal disease concomitantly with some degree of CNI toxicity in long-term cardiac transplant recipients with renal dysfunction. This very high rate of hypertension-related disease may limit the impact of SIR on improving renal function long term following cardiac transplantation.

Retrospective Study Looking at Cinacalcet in the Management of Hyperparathyroidism after Kidney Transplantation

Objectives. The primary objective of this study is to evaluate the use of cinacalcet in the management of hyperparathyroidism in kidney transplant recipients. The secondary objective is to identify baseline factors that predict cinacalcet use after transplantation. Methods. In this single-center retrospective study, we conducted a chart review of all patients having been transplanted from 2003 to 2012 and having received cinacalcet up to kidney transplantation and/or thereafter. Results. Twenty-seven patients were included with a mean follow-up of 2.9 ± 2.4 years. Twenty-one were already taking cinacalcet at the time of transplantation. Cinacalcet was stopped within the first month in 12 of these patients of which 7 had to restart therapy. The main reason for restarting cinacalcet was hypercalcemia. Length of treatment was 23 ± 26 months. There were only 3 cases of mild hypocalcemia. There was no statistically significant association between baseline factors and cinacalcet status a year later. Conclusions. Discontinuing cinacalcet within the first month of kidney transplantation often leads to hypercalcemia. Cinacalcet appears to be an effective treatment of hypercalcemic hyperparathyroidism in kidney transplant recipients. Further studies are needed to evaluate safety and long-term benefits.