Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function.

BACKGROUND: Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus. MATERIAL AND METHODS: From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv <104 copies (cp)/mL (n=573), (B) ≥104 Upv <107 cp/mL (n=100), and (C) Upv ≥107 cp/mL (n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only, as 14 patients (subgroup Cb) were at risk for graft rejection. RESULTS: The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P<.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome. CONCLUSION: The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.

Morphological Retrospective Study of Peritoneal Biopsies from Patients with Encapsulating Peritoneal Sclerosis: Underestimated Role of Adipocytes as New Fibroblasts Lineage?

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [α-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS.

Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome.

Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2-2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6-3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0-5.4]). Area under the curve of the ROC curve (0.77 [0.74-0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001). Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.

Mycobacterium fortuitum and Polymicrobial Peritoneal Dialysis-Related Peritonitis: A Case Report and Review of the Literature.

Mycobacterium fortuitum is a ubiquitous, rapidly growing nontuberculous mycobacterium (NTM). It is the most commonly reported NTM in peritoneal dialysis (PD) associated peritonitis. We report a case of a 52-year-old man on PD, who developed refractory polymicrobial peritonitis necessitating PD catheter removal and shift to hemodialysis. Thereafter, M. fortuitum was identified in the PD catheter culture and in successive cultures of initial peritoneal effluent and patient was treated with amikacin and ciprofloxacin for six months with a good and sustained clinical response. Months after completion of the course of antibiotics, the patient successfully returned to PD. To our knowledge, this is the first reported case of M. fortuitum peritonitis in the field of polymicrobial PD peritonitis. It demonstrates the diagnostic yield of pursuing further investigations in cases of refractory PD peritonitis. In a systematic review of the literature, only 20 reports of M. fortuitum PD peritonitis were identified. Similar to our case, a delay in microbiological diagnosis was frequently noted and the Tenckhoff catheter was commonly removed. However, the type and duration of antibiotic therapy varied widely making the optimal treatment unclear.