Duodenal villous atrophy: a cause of chronic diarrhea after solid-organ transplantation.

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

[Pneumocystis jiroveci infection associated with organizing pneumonia in a kidney transplant patient]. / Infection à Pneumocystis jiroveci associée à une pneumopathie organisée chez une patiente transplantée rénale.

The authors report the association of organizing pneumonia (OP) and a Pneumocystis jiroveci infection in a woman who benefited from a kidney transplant 13 years before and was under corticoids, cyclosporine and mycophenolate mofetil. The diagnosis was based on progressive dyspnoea with fever with an alteration in the general state associated with diffuse micronodular pneumopathy suggesting bronchiolitis. The conformation was obtained by the analysis of the alveolar bronchial washings and the histological examination of the distal biopsies revealing endo-alveolar vegetant fibromas. Transbronchial biopsies may be used for the diagnosis and thereby, avoid an invasive surgical pulmonary biopsy. The aetiology of OP may be related to the immunosuppressant treatment or infection by Pneumocystis jiroveci. The evolution in this case was favourable with trimethoprime and sulfamethoxazole associated with a transient increase in the corticoid treatment. This association is rarely described in patients undergoing solid organ transplants.

Rationale for using belatacept in combination with sirolimus.

Kidney transplantation can be used to replace failing native kidneys; however, it requires long-term immunosuppression, and immunological tolerance for this is not yet achievable. The cornerstone of immunosuppression is based on calcineurin inhibitors, which are nephrotoxic. Therefore, new drugs are being developed that provide efficacious immunosuppression and almost no renal toxicity. The first family of drugs that have these properties are mammalian target of rapamycin inhibitors: these include sirolimus and everolimus. These two drugs, besides their immunosuppressive properties, also have beneficial effects regarding cytomegalovirus (CMV) infection, which is a very common posttransplantation complication. In phase III trials, belatacept, a costimulatory blocker, has also been shown to provide a good immunosuppressive effect and also gives a significantly better cardiovascular profile than cyclosporine-based immunosuppression. However, belatacept can potentially increase infections such as CMV. Thus, herein, we describe the rationale for combining belatacept with sirolimus for kidney transplant patients.