Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study.

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.

Renal transplantation outcomes in obese patients: a French cohort-based study.

BACKGROUND: Whilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort. METHODS: In this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. RESULTS: Among the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p < 0.0001). We observed a trend towards death censored graft survival (HR = 1.22, p = 0.0666) and no significant increased risk of early surgical complications. CONCLUSIONS: We showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.

Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome.

Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor-protein (MCP), C3 and factor B (CFB). At 5 years, death-censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M-TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies.

Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation.

Eculizumab (anti-C5) has been sporadically reported as an efficient therapy for atypical hemolytic uremic syndrome (aHUS). However, the lack of series precludes any firm conclusion about the optimal use of anti-C5 for preventing or treating aHUS posttransplant aHUS recurrence. We thoroughly studied 22 renal transplant recipients with aHUS who received off-label therapy with anti-C5, including 12 cases, which have not been reported yet. Nine patients, all carrying a complement genetic abnormality associated with a high risk of aHUS recurrence, received prophylactic anti-C5 therapy to prevent posttransplant recurrence. Eight of them had a successful recurrence-free posttransplant course and achieved a satisfactory graft function, while the remaining patient experienced early arterial thrombosis of the graft. Thirteen renal transplant recipients were given anti-C5 for posttransplant aHUS recurrence. A complete reversal of aHUS activity was obtained in all of them. Importantly, the delay of anti-C5 initiation after the onset of the aHUS episode inversely correlated with the degree of renal function improvement. Three patients in whom anti-C5 was subsequently stopped experienced a relapse. Altogether these data suggest that long-term eculizumab is highly effective for preventing and treating posttransplant aHUS recurrence. Our study also indicates that anti-C5 should be promptly started if a recurrence occurs.

Anti-Factor H autoantibodies in a fifth renal transplant recipient with atypical hemolytic and uremic syndrome.

Hemolytic uremic syndrome (HUS) associated with anti-Factor H (anti-FH) autoantibodies is a recently described pathophysiological entity. Monitoring of anti-FH IgG titer may be a sensitive marker of disease activity and guide treatment to eliminate circulating anti-FH antibodies. We report here a case of atypical HUS (aHUS) in which anti-FH autoantibodies were detected during the course of a fifth kidney transplant, 30 years after the first flare of aHUS. This exceptional case suggests that early, specific management based on immunosuppressive therapy and plasma exchanges monitored by anti-FH IgG titer may result in long-term graft survival.

Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation.

Mutations in one or more genes encoding complement-regulatory proteins predispose to atypical hemolytic uremic syndrome (aHUS) and its recurrence following kidney transplantation. We evaluated plasma complement level and performed a screening for mutations in genes encoding complement Factors H and I (CFH, CFI) and membrane cofactor protein (MCP) in 24 kidney transplant recipients experiencing de novo thrombotic microangiopathy (TMA). Six patients presented with low C3 and/or low Factor B levels suggestive complement alternative pathway. A mutation in the CFH or CFI gene was found in 7/24 patients (29%), two of whom had a mutation in both genes. On the contrary, no mutation was identified in a control kidney transplant patients group (n = 25) without TMA. Patients with or without mutations were similar with regard to clinical features. Eight out of 24 patients lost their graft within 1 year of posttransplantation including six patients with a CFH mutation or a decrease of C3 or CFB in plasma. To conclude, kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of CFH and CFI mutations. These results suggest that genetic abnormalities may represent risk factors for de novo TMA after kidney transplantation and raise the question of the best therapeutic strategy.

Posttransplant prophylactic intravenous immunoglobulin in kidney transplant patients at high immunological risk: a pilot study.

The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.

[Immunosuppression in kidney transplantation]. / Immunosuppression en transplantation rénale.

Kidney transplantation has become the treatment of choice in end-stage chronic renal failure since it significantly improves both the quality of life and the life duration of affected patients, when compared with dialysis. Some of these better results that were observed over the last thirty years are obviously due to significant improvements in the quality of immunosuppression. In the first part of this chapter, the allo-immune response is schematically described regarding the various signals. Then, the mechanisms of action of the available or future immunosuppressive therapies are described in the same order as the allo-immune response. In the third part, the various combinations of immunosuppressive regimens are presented from a historical perspective, outlining not only the positive aspects of each class of drugs but also their side effects and consequences on the practical use of immunosuppression over time. Finally, a brief review of current and future perspectives regarding the improvement of both efficacy and tolerability of immunosuppression in kidney transplantation is presented.

Adaptive hyperphagia in patients with postsurgical malabsorption.

The specific nutritional consequences of malabsorption after small-bowel surgery were studied in a consecutive series of 48 ambulatory patients who had had small-bowel resection (n = 43) or bypass (n = 5) and in 10 patients who had an ileal pouch (n = 10). The patients received a 3-day standardized oral regimen providing daily 30 kcal/kg of ideal body weight (IBW). Throughout the study, 41 patients had malabsorption (fecal fat greater than 5%); 17 had fecal fat less than 5% and served as controls. The malabsorption patients absorbed 70% of protein and 71% of fat. Twenty-one were normonourished and 20 had features of mild energy malnutrition, vs. 15 and 2 controls, respectively. Compared with controls, malabsorption patients had decreased body weight and triceps skin-fold but no features of protein malnutrition. their mean daily food intake at home was significantly enhanced (39.6 +/- 13.1 kcal/IBW kg) vs. controls (28.8 +/- 5.8 kcal/IBW kg, P less than 0.001). In the malabsorption group, caloric intake was higher in the normonourished patients than in those with mild malnutrition. This study shows that a chronic malabsorption has limited nutritional consequences. The patients compensate for their absorptive handicap by increasing their oral intake.

[Elemental feeding into the distal segment of a temporary small bowel]. / L'alimentation élémentaire dans le segment d'aval des grêles courts temporaires.

Patients who have an interruption of the small bowel with a high enterostomy usually need parenteral supply or reinfusion of chyme to maintain nutritional and electrolytic balances before restoring intestinal continuity. Ten patients (aged 28-76 years) with a terminal jejunostomy located within the first meter of jejunum were treated by infusion of an elemental diet into the distal small bowel (IEDDSB). In addition, five of these patients had an extensive small bowel resection. IEDDSB was started 32 days after operation and lasted 4 to 8 weeks. Mean daily caloric infusion was 1,732 +/- 666 kcal diluted in 2,860 +/- 808 ml; mean associated oral intake was 1,187 +/- 480 kcal/24 hr, and jejunal fecal losses averaged 3 kg per day. IEDDSB was well tolerated in 4 patients; 5 experienced transient abdominal pain or diarrhea; 1 developed severe and protracted diarrhea. Biological cholestasis was seen before IEDDSB and persisted in most patients; 1 patient developed biliary sludge. Through IEDDSB, nutritional status improved or remained satisfactory in 9 patients, and worsened in 1 patient with sepsis and a short lower intestine. Mean body weight, triceps skin fold, muscle circumference, serum albumin, serum transferrin did not change significantly. Digestive nitrogen balance performed in 6 patients showed a net absorption between 5 and 15 g/24 hr. Fluid and electrolyte balance was maintained in 9 patients and 1 received iterative intravenous saline. Digestive sodium balance showed a net absorption rate greater than 60 mmol/24 hr. in all patients, except the one who required intravenous supply. Postoperative recovery was uneventful in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Exclusive elemental enteral diet in cortico-resistant and cortico-dependent forms of Crohn's disease]. / L'alimentation entérale élémentaire exclusive dans les formes corticorésistantes et corticodépendantes de la maladie de Crohn.

The aim of this study was to investigate the value of elemental diet in steroid-resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid-dependent Crohn's disease. However, elemental diet does not prevent relapse.

[Malabsorption in alcoholic cirrhosis]. / Malabsorption au cours de la cirrhose alcoolique.

21 patients with alcoholic cirrhosis were worked up for malabsorption. In three patients, the fecal weight was over 200 g/24 h; three had a steatorrhea over 6 g/24 h and in four the creatorrhea was over 2 g/24 h. The D-xylose test was abnormal 4 times out of 18, but these 4 patients presented an ascites. Alpha-1-antitrypsin clearance was increased in 1 out of 9 patients. The Lundh test demonstrated in 5 out of 8 cases an external pancreatic insufficiency, but without any relation with the fecal losses. The 4 patients with malabsorption showed signs of malnutrition (anthropometric criteria). In the course of an alcoholic cirrhosis, malabsorption seems therefore infrequent, dissociated, and only observed in patients with signs of malnutrition.

[Does continuous enteral nutritional deficiencies in digestive system diseases? Results of a longitudinal study of 92 consecutive patients treated for 3 to 7 weeks]. / L'alimentation entérale continue corrige-t-elle la dénutrition des affections digestives? Résultats de l'étude longitudinale de 92 malades consécutifs traités pendant trois à sept semaines.

In order to assess the effectiveness and potential limitations of continuous enteral nutrition (CEN) to correct denutrition related to underlying digestive diseases, 10 nutritional criteria were measured weekly in 92 under-nourished patients fed with CEN for a 3-7 week period. All the patients received a standard non-elemental diet providing a mean daily energy intake of 52.8 kcal/kg BW (36.5 kcal/kg BW by tube feeding and 16.3 kcal/kg BW orally). The influence of preexisting intestinal malabsorption, hypercatabolic status, and post-radiation or inflammatory bowel disease was studied by an a posteriori classification of patients in one of the six following groups: I (no limiting factor), II (malabsorption), III (catabolic disease), IV (catabolic disease and malabsorption), V (colitis), VI (enteritis). During CEN, 8 patients had transient and one had persistent vomiting while 3 developed bronchopneumonia. Gains in body weight, triceps skinfold, midarm muscle circumference, creatinine-height index, urinary sodium and serum transferrin were significant as early as the 2nd week of CEN. Serum albumin and cholesterol, hemoglobin, and total count of lymphocytes were not significantly affected. Sixty-five patients (71 per cent) had an objective nutritional improvement and mean spontaneous oral intake increased from 17.8 to 28.7 kcal/kg BW per day. Significant increase of oral intake and objective nutritional improvement were observed in each group, but a longer period of CEN was necessary to achieve this result in groups II, IV and VI.(ABSTRACT TRUNCATED AT 250 WORDS)