Short- and Long-Term Outcome of Chronic Dialyzed Patients Admitted to the ICU and Assessment of Prognosis Factors: Results of a 6-Year Cohort Study.

OBJECTIVES: Data about end-stage kidney disease patients admitted to the ICU are scarce, dated, and mostly limited to short-term survival. The aim of this study was to assess the short- and long-term outcome and to determine the prognostic factors for end-stage kidney disease patients admitted to the ICU. DESIGN: Prospective observational study. SETTING: Medical ICUs in two university hospitals. PATIENTS: Consecutive end-stage kidney disease patients admitted in two ICUs between 2012 and 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Renal replacement therapy variables, demographic, clinical, and biological data were collected. The requirement of mechanical ventilation and vasopressive drugs were also collected. In-ICU and one-year mortality were estimated and all data were analyzed in order to identify predictive factors of short and long-term mortality. A total of 140 patients were included, representing 1.7% of total admissions over the study period. Septic shock was the main reason for admission mostly of pulmonary origin. Median Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score were at 63 and 6.7, respectively. In-ICU, hospital, and 1-year mortality were 41.4%, 46.4%, and 63%, respectively. ICU mortality was significantly higher as compared with ICU control group non-end-stage kidney disease (25% vs 41.4%; p = 0.005). By multivariate analysis, the short-term outcome was significantly associated with nonrenal Sequential Organ Failure Assessment score, and with the requirement of mechanical ventilation or/and vasoconstrictive agents during ICU stay. One-year mortality was associated with increased dialysis duration (> 3 yr) and phosphatemia (> 2.5 mmol/L), with lower albuminemia (< 30 g/L) and nonrenal Sequential Organ Failure Assessment greater than 8. CONCLUSIONS: End-stage kidney disease patients presented frequently severe complications requiring critical care that induced significant short- and long-term mortality. ICU and hospital mortality depended mainly on the severity of the critical event reflected by Sequential Organ Failure Assessment score and the need of mechanical ventilation and/or catecholamines. One-year mortality was associated with both albuminemia and phosphatemia and with prior duration of chronic dialysis treatment, and with organ failure at ICU admission.

Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival.

Post-transplant lymphoproliferative disorder (PTLD) is an uncontrolled proliferation of transformed lymphocytes fostered by immunosuppression. In addition to chemotherapy, treatment of PTLD includes a reduction of maintenance immunosuppression. Patients with PTLD have an increased risk of graft loss, suggesting that reduced immunosuppression strategy needs to be optimized with regard to graft outcome. Here we retrospectively reviewed 101 cases involving PTLD to identify the risks associated with graft loss. During a median follow-up of 70 months, 39 patients died and 21 lost their graft. Multivariate analysis found that an eGFR under 30 ml/min per 1.73 m(2) at PTLD diagnosis, a biopsy-proven acute rejection episode following reduction of immunosuppression, and the absence of calcineurin inhibition in maintenance immunosuppression are independent risk factors for allograft loss. Neither the type of PTLD nor the chemotherapy regimen was predictive of allograft failure. Histological analysis of graft biopsies showed that maintaining calcineurin inhibition after the diagnosis of PTLD reduced the risk of developing de novo anti-HLA antibodies and humoral rejection. Remarkably, calcineurin inhibitor maintenance was neither associated with higher mortality nor with worse progression-free survival. Thus, maintaining calcineurin inhibition at a reduced dose after the diagnosis of PTLD seems safe and may improve renal graft outcome, possibly through better control of the recipient's humoral immune response.

C5b-9 Glomerular Deposits Are Associated With Poor Renal Survival in Membranous Nephropathy.

Introduction: Membranous nephropathy (MN) is the first cause of nephrotic syndrome in patients without diabetes. Its prognosis is variable, and treatment remains controversial because of potential toxicity. Currently, there is no reliable prognostic marker common to all etiologies of MN and routinely available to predict the disease course and guide therapeutic management. Despite the major role of complement in the glomerular damage of MN, its prognostic impact has never been studied. We investigated the frequency and prognostic impact of glomerular deposition of C5b-9 in MN. Methods: We retrospectively selected adults diagnosed with MN (primary or secondary) at Montpellier University Hospital between December 2004 and December 2015. To be included, all patients were required to have complete medical data and a kidney tissue sample for further immunohistochemistry. We performed PLA2R1, C4d, and C5b-9 staining by immunohistochemistry. Results: Sixty-four adults were included: 45 with primary MN and 19 with secondary MN. C4d was positive in the glomeruli of 61 adults (95.3%). Twenty-nine adults (45.3%) had glomerular deposition of C5b-9. Patients with glomerular deposition of C5b-9 had more severe nephrotic syndrome on diagnosis and lower remission and renal survival rates than adults without. Conclusion: C5b-9 glomerular staining is a powerful and easily accessible tool for stratifying adults according to their renal prognosis. The efficacy of complement inhibitors should be tested in adults with glomerular deposition of C5b-9.

[Human retrovirus XMRV: The end of an exciting story?] / Rétrovirus humain XMRV : la fin d'une histoire séduisante ?

Viruses represent an important cause of cancer in humans: infections are estimated to account for close to one cancer case out of five.With the ongoing discovery of new infectious agents, this number should be raising in the near future. In 2006, the discovery of a new _-retrovirus in prostate cancer biopsies launched an intense research activity: could this new xenotropic MLV-related virus (XMRV) be the cause of prostate cancer? Five years later, the initial enthusiasm of retrovirologists has dramatically diminished. One by one, arguments favouring the hypothesis of human infection with XMRV are being refuted. The aim of this review article is to present the discovery of XMRV and to analyze recent data arguing against its existence in humans. A synthetic interpretation of XMRV literature will then be suggested.

C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection.

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.

Heparin-free renal replacement therapy for chronic hemodialyzed patients at high risk for bleeding: a comparison of on-line predilution hemodiafiltration with conventional hemodialysis.

BACKGROUND: In chronic hemodialysis patients with high risk of bleeding, optimal anticoagulation of the extracorporeal circuit is challenging. Heparin-free hemodialysis (HD) with heparin-coated AN69ST dialyzer is now considered as a good option and recommended by experts. Predilutional hemodiafiltration (HDF) may represent also a feasible alternative but has been poorly investigated. In this study, our aim was to evaluate the performance of on-line automated predilution heparin-free HDF as compared to conventional heparin-free HD with a heparin-coated membrane. METHODS: We prospectively studied chronic hemodialysis patients at high risk of bleeding consecutively admitted to hospital who underwent heparin-free renal replacement therapy (RRT) in our nephrology department. During 1 year, we routinely used heparin-free HD and on-line HDF in these settings. By using a propensity score, we compared HDF to HD regarding to session failure and efficiency. RESULTS: One hundred and seventy-nine patients were included in the study. Clotting phenomena necessitating premature termination of RRT sessions were encountered in 19% of them. After propensity score matching, the comparison of 77 HD and 77 HDF sessions showed no significant differences in duration of the sessions and in dialyzer clotting. By multivariate analysis, a blood flow less than 250 mL/min and recent surgery were the only parameters associated with extracorporeal circuit thrombosis. CONCLUSION: Heparin-free on-line predilutional HDF is a safe and effective technique for chronic hemodialysis patients with increased bleeding risk. The use of an automatic substitution volume that avoids filters hemoconcentration and of a blood flow above 250 mL/min strongly contribute to the observed performance. Further studies are, however, intended to confirm these results.

Stricturing Crohn's disease-like colitis in a patient treated with belatacept.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.

Primary sclerosing cholangitis: a new cause of distal renal tubular acidosis.

We describe the first case of distal renal tubular acidosis (dRTA) associated with primary sclerosing cholangitis. A 26-year-old Lao-Thai male patient presented with severe jaundice, metabolic acidosis and hypokalaemia. He was diagnosed of dRTA. Liver transplantation resulted in correction of electrolyte disturbances and hyperbilirubinaemia. A fludrocortisone-furosemide test revealed normal urinary acidification, demonstrating no residual dRTA. This observation suggests that dRTA may be an early manifestation of bilirubin-associated nephropathy or the consequence of an immune mechanism.

[Infectious and neoplasic complications after kidney transplantation]. / Complications infectieuses et néoplasiques après transplantation rénale.

Infections and malignancies are the expected complications of immunosuppressive therapy, which non-specifically impairs cellular and humoral immune responses in renal transplant recipients. Infections were usually frequent and severe during the early post-transplant period (first year). Recent diagnostic methods (molecular biology) and availability of new antivirals, antifungal and antibiotic drugs made rapid diagnosis and systematic preventive strategies much easier and this resulted in a significant reduction of infections and infectious death in this population. However, new infectious agents like BK polyomavirus, hepatitis E virus, parvovirus (as well as Chigunkunya, West Nile and others in particular areas) were recently recognized as responsible of aggressive infections in the immunocompromised host. Malignancies are also common after transplantation, due to the intensity and duration of immunosuppression. Skin cancers and lymphoproliferative disorders are the most common and are undoubtedly caused by viral infections, but incidence of non-skin cancers is also increased. After reduction of immunosuppression, treatment is similar to non-transplant patients: Results are usually poor and cancer is now the third cause of death in transplant recipients. Due to their anti-proliferative and anti-tumoral properties, incidence of de novo cancer significantly decreased in patients receiving mTor inhibitors as maintenance immunosuppression; furthermore, in patients already diagnosed with Kaposi sarcoma or recurrent skin cancers, introduction of mTor was associated with stabilisation and/or regression of malignant lesions.

Mortality Associated with Night and Weekend Admissions to ICU with On-Site Intensivist Coverage: Results of a Nine-Year Cohort Study (2006-2014).

BACKGROUND: The association between mortality and time of admission to ICU has been extensively studied but remains controversial. We revaluate the impact of time of admission on ICU mortality by retrospectively investigating a recent (2006-2014) and large ICU cohort with on-site intensivist coverage. PATIENTS AND METHODS: All adults (≥ 18 years) admitted to a tertiary care medical ICU were included in the study. Patients' characteristics, medical management, and mortality were prospectively collected. Patients were classified according to their admission time: week working days on- and off-hours, and weekends. ICU mortality was the primary outcome and adjusted Hazard-ratios (HR) of death were analysed by multivariate Cox model. RESULTS: 2,428 patients were included: age 62±18 years; male: 1,515 (62%); and median SAPSII score: 38 (27-52). Overall ICU mortality rate was 13.7%. Admissions to ICU occurred during open-hours in 680 cases (28%), during night-time working days in 1,099 cases (45%) and during weekends in 649 cases (27%). Baseline characteristics of patients were similar between groups except that patients admitted during the second part of night (00:00 to 07:59) have a significantly higher SAPS II score than others. ICU mortality was comparable between patients admitted during different time periods but was significantly higher for those admitted during the second part of the night. Multivariate analysis showed however that admission during weeknights and weekends was not associated with an increased ICU mortality as compared with open-hours admissions. CONCLUSION: Time of admission, especially weeknight and weekend (off-hour admissions), did not influence the prognosis of ICU patients. The higher illness severity of patients admitted during the second part of the night (00:00-07:59) may explain the observed increased mortality.