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.

Changes in bone mineral density after kidney transplantation: 2-year assessment of a French cohort.

INTRODUCTION: In renal transplant patients, bone loss may be related to the drugs patients are taking but also to their past history of chronic kidney disease. The purpose of this study was to assess changes in BMD 2 years after an initial assessment (performed 9 months post transplantation) and the factors associated with these changes. METHODS: This longitudinal study included patients who had undergone a renal transplantation between 2005 and 2011, and who were followed up at the Lille Regional University Hospital. Patients were included if they had a first bone evaluation (including bone densitometry, spine X-rays and biological assessment) and at least another BMD assessment. The first assessment was performed on average 9 months post transplantation. A second assessment was performed at 2 years. RESULTS: Two hundred fifty-nine out of 366 patients satisfied the inclusion criteria. The population included 96 women. Mean age at transplantation was 49.7 ± 12.1 years. Mean duration of dialysis was 3.2 ± 3.3 years. For 75 patients (29.0%), corticosteroid treatment was discontinued 7 days after transplantation without subsequent resumption during follow-up. Vertebral fractures assessed by X-rays at baseline were found in 28 patients (10.8%). According to the WHO classification, 106 patients (40.9%) patients had osteoporosis and 111 patients (42.8%) had osteopenia at the first assessment. Oral bisphosphonates were prescribed for 95 patients. The decision to prescribe bisphosphonates was taken jointly by rheumatologists and nephrologists based on BMD assessment, past history of fracture and corticosteroid management. In all patients, BMD gains at the second evaluation (2.2 ± 0.79 years) compared with baseline were significant (3.9 ± 6.6, 2.6% ± 7.6, 3.0 ± 7.2% at the lumbar spine, femoral neck and total hip respectively; p < 0.0001). The difference in gain between bisphosphonate-treated and untreated patients was significant (+ 5.0 ± 0.8% (p < 0.0001), + 2.5 ± 1.0% (p = 0.01) and + 2.7 ± 0.9% (p < 0.01) at the lumbar spine, femoral neck and total hip respectively. The patients who benefited early corticosteroid discontinuation had higher gains in BMD at the lumbar spine (+ 2.1 ± 0.9%; p = 0.02) and total hip (+ 2.0 ± 1.0%; p = 0.04) compared to those for whom corticosteroid therapy was maintained. Stepwise regression analysis (patients without bisphosphonates) showed associations between change in BMD (femoral neck) and duration of corticosteroid therapy, bone alkaline phosphatase level at baseline, and absence of vertebral fracture. No correlation was found between change in BMD and duration of dialysis or renal function. CONCLUSION: Kidney transplant recipients have an increased risk of bone fragility in the year following transplantation. Bisphosphonates and early corticosteroid discontinuation can improve BMD.

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

Fibrosis progression according to epithelial-mesenchymal transition profile: a randomized trial of everolimus versus CsA.

Markers of epithelial-mesenchymal transition (EMT) may identify patients at high risk of graft fibrogenesis who could benefit from early calcineurin inhibitor (CNI) withdrawal. In a randomized, open-label, 12-month trial, de novo kidney transplant patients received cyclosporine, enteric-coated mycophenolate sodium (EC-MPS) and steroids to month 3. Patients were stratified as EMT+ or EMT- based on month 3 biopsy, then randomized to start everolimus with half-dose EC-MPS (720 mg/day) and cyclosporine withdrawal (CNI-free) or continue cyclosporine with standard EC-MPS (CNI). The primary endpoint was progression of graft fibrosis (interstitial fibrosis/tubular atrophy [IF/TA] grade increase ≥1 between months 3-12) in EMT+ patients. 194 patients were randomized (96 CNI-free, 98 CNI); 153 (69 CNI-free, 84 CNI) were included in histological analyses. Fibrosis progression occurred in 46.2% (12/26) CNI-free EMT+ patients versus 51.6% (16/31) CNI EMT+ patients (p = 0.68). Biopsy-proven acute rejection (BPAR, including subclinical events) occurred in 25.0% and 5.1% of CNI-free and CNI patients, respectively (p < 0.001). In conclusion, early CNI withdrawal with everolimus initiation does not prevent interstitial fibrosis. Using this CNI-free protocol, in which everolimus exposure was relatively low and administered with half-dose EC-MPS, CNI-free patients were overwhelmingly under-immunosuppressed and experienced an increased risk of BPAR.

[Minimize kidney failure in transplantation patients with proliferation signal inhibitors]. / Minimiser l'insuffisance rénale avec les inhibiteurs du signal de prolifération chez les malades transplantés.

Chronic renal dysfunction is a multifactorial and frequent event after organ transplantation. The measurement or the estimation of glomerular filtration rate is essential to detect early progressive renal dysfunction. Proliferation signal inhibitors are nonnephrotoxic immunosuppressive drugs which may be useful to minimize calcineurin inhibitors-related side effects through a conversion strategy. Most studies in the setting of kidney transplantation showed improvement in glomerular filtration rate as high than conversion was early. Proliferation signal inhibitors may be included quickly in new immunosuppressive regimen for liver transplanted patients with chronic renal dysfunction.

PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study.

BACKGROUND: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. METHODS/DESIGN: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin. DISCUSSION: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849899 . Registered on 8 February 2016.

[Immunosuppressive strategies and chronic graft dysfunction in kidney transplantation]. / Stratégies immunosuppressives et dysfonction chronique du greffon en transplantation rénale.

Chronic graft dysfunction is a major cause of return to dialysis. In the majority of cases, it is correlated with histological signs of cellular and/or humoral rejection, the nephrotoxicity of anticalcineurins, or nonspecific lesions of interstitial fibrosis and tubular atrophy. Although the incidence of acute rejection has considerably decreased, renal toxicity of the calcineurin inhibitors remains problematic. In cases of established nephrotoxicity, the use of non-nephrotoxic immunosuppressors such as mycophenolic acid or the proliferation signal inhibitors makes it possible to reduce or even stop the anticalcineurins. In prevention of anticalcineurin nephrotoxicity, many attempts to minimize or wean patients from them have shown that improvement in renal function is only obtained at the cost of an increase in the incidence of acute rejection. This makes it necessary to select patients who may benefit from anticalcineurin-sparing treatment, based on clinical, histological, and biological markers. Finally, long-term follow-up is also fundamental in order to validate the positive impact on renal function of this strategy in terms of graft survival.

[Results of systematic subtotal parathyroidectomy with thymectomy for tertiary hyperparathyroidism after renal transplantation - 70 patients]. / Résultats de la parathyroïdectomie subtotale de principe associée à une thymectomie systématique pour le traitement de l'hyperparathyroïdisme tertiaire après transplantation rénale chez 70 patients.

BACKGROUND: Due to the relatively small number of patients involved, there is currently no consensus on what operation should be performed in patients with tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective analysis of the 70 patients with tertiary hyperparathyroidism who all underwent subtotal parathyroidectomy with transcervical thymectomy in the same institution between 1978 and 2003. RESULTS: The delay between transplantation and parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients. Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21 ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26 patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients (27%)]. One patient was successfully reoperated for persistent tertiary hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up. Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%) without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach permits not only to cure the majority of patients with tertiary hyperparathyroidism but also to avoid recurrence when the renal function declines. When medical management has failed, we recommend systematic subtotal parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism and this should usually be performed during the second year after transplantation.

Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment.

BACKGROUND: Strong correlations have been described between persistently elevated proportions of CD57+ (CD28-) CD8+high T lymphocytes and cytomegalovirus (CMV) infection, in healthy individuals as well as in transplant patients. We investigated whether secondary exposure to CMV triggers recall responses within the CD8 T cell compartment. METHODS: In a longitudinal study in 123 kidney recipients, we compared 17 primary CMV infections with 27 secondary CMV infections. Subset composition of the CD8 compartment was analyzed by flow cytometry. RESULTS: CD8 lymphocytosis occurred significantly earlier (by 17 days on average) in CMV reactivations than in primary infections. Both in primary and secondary infections, CD28+ CD8+high T lymphocytes were mainly recruited at the start. In formerly CMV-seropositive patients, preexisting CD57+ CD8+high T lymphocytes switched at the start from no expression of CD28 to high expression of CD28 and, concomitantly, from CD45RA to high expression of CD45RO. These cells reverted rapidly to a CD28- and CD45RA+ phenotype. Nevertheless, the accumulation of CD57+ (CD28-) CD8+high T cells was delayed similarly in primary and secondary CMV infection, progressing over a period between 2 and 8 weeks after the onset of CD8 lymphocytosis to plateau at 366 CD57+ CD8+high cells/ mm3 on average. CONCLUSIONS: The faster kinetics of CD8 lymphocytosis in secondary CMV infection suggests that a recall response triggers cycling "memory" cells within the CD28+ CD8+high subset, while preexistent CD57+ CD8+high T cells with a long-lived cell phenotype can also be mobilized, possibly through the transient acquisition of CD28 expression. The protracted accumulation of CD57+ (and CD28-) lymphocytes might then reflect an end-stage differentiation.

Immunomodulatory effect of pentoxifylline during human allograft rejection: involvement of tumor necrosis factor-alpha and adhesion molecules.

BACKGROUND: Pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, is poorly active as an immunosuppressant but prevents the synthesis of proinflammatory cytokines. In a randomized double-blind study comparing PTX versus placebo in 140 patients receiving cadaveric kidney grafts under cyclosporine and prednisone, we have shown that PTX weakened the consequences of rejection on graft survival. To assess the mechanism underlying the beneficial effect recorded during this trial, we analyzed the impact of PTX on tumor necrosis factor (TNF-alpha) production and expression of cell adhesion molecules. METHODS: Plasma levels of TNF-alpha and its soluble receptors (sTNF-RI, sTNF-RII) and of soluble vascular cell adhesion molecule 1 (sVCAM-1) were monitored over the 6 months postgraft period when PTX or placebo were administered. Expression of VCAM-1 and intercellular cell adhesion molecule 1 was scored by immunohistochemical staining of biopsy specimens from patients who underwent rejection crisis. Lymphocyte subset composition was analyzed longitudinally during cytomegalovirus (CMV) infections. RESULTS: Plasma TNF-alpha levels were significantly reduced in the PTX-treated group over the 6 months of administration, and specifically during isolated rejection episodes and during CMV infections. Plasma levels of sTNFR-I, sTNFR-II, and sVCAM-1 did not differ between the two groups of patients, but a decrease in renal tubular VCAM-1 expression was observed in the PTX group. During CMV infections, CD8 lymphocytosis and expansion of CD57+ (CD28-) CD8+ T cells were similar in the two groups. CONCLUSION: The data collected during this double-blind study point to an immunomodulatory role of PTX, the beneficial effect on graft survival resulting from a restraining effect of the drug on the inflammatory conditions involved in acute graft rejection.

Improvement in the outcome of rejection with pentoxifylline in renal transplantation: a randomized controlled trial.

BACKGROUND: Pentoxifylline (PTX), a methylxantine phosphodiesterase inhibitor commonly used to treat peripheral vascular disease, has been shown to decrease the production of proinflammatory cytokines and reactive oxygen species and to reduce the toxic effects of cyclosporine. Thus, administration of PTX to transplant patients, as an adjunct to immunosuppressive therapy, could prevent numerous posttransplantation complications. METHODS: One hundred forty consecutive patients receiving cadaveric kidney grafts were registered in a randomized double-blind study comparing PTX at a dose of 800 mg/day, then 1200 mg/day, versus placebo during the first 6 months after transplantation. All patients were followed up for 1 year. RESULTS: Rejection episodes were validated as the only independent risk factor for graft loss in this study. We compared graft survival rates in each group according to the presence or absence of acute rejection. Acute rejection reduced graft survival in the control group (graft survival rate at 1 year, 59% vs. 97%, P < 0.001), but this adverse effect was blunted in the PTX group (72% vs. 89%, NS). This improvement was confirmed by multivariate analysis for risk factors, with graft survival rates being described at best as the interaction between rejection and treatment (PTX vs. placebo, P = 0.045). CONCLUSION: Although PTX does not modify the incidence of any posttransplant complications, it weakens the consequences of rejection on graft survival.

Consecutive successful pregnancies in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

Pregnancy is now a common, but high-risk event, in young women who have received transplants. Consequences to the fetus are known, but pregnancy may also interfere with graft function. We report the outcome of two successive and successful pregnancies in a 29-year-old woman with type 1 hyperoxaluria, who received a combined liver and kidney transplant. Two healthy children were born at 35 and 37 weeks of gestation, with low birth weight. Liver function remained normal before, during, and after pregnancies up to 52 months after transplantation. Renal function was impaired before the first conception, worsened during both pregnancies, and returned to the previous level in both immediate postpartum periods. However, renal function has declined 17 months after the last delivery. This report shows the feasibility of successive pregnancies in multiple organ transplant recipients, but raises the question of long-term maternal kidney graft survival.

Pentoxifylline prevents upregulation of monocyte tissue factor in renal transplant recipients undergoing post-graft complications.

Pentoxifylline (PTX) has been demonstrated to improve graft survival in renal transplant recipients undergoing post graft complications. As activated monocytes are possible initiators of vascular damage through tissue factor (TF) expression, we evaluated the monocyte TF expression and endothelium activation markers in 140 consecutive patients receiving cadaveric kidney grafts, randomized in a double-blind study comparing PTX versus placebo. Monocyte TF expression and plasma von Willebrand factor, tissue plasminogen activator, thrombomodulin and tumor necrosis factor-alpha (TNF-alpha) levels were determined before transplantation and each month after. Additional samplings were realized in case of acute rejection. TF and TNF-alpha expression were significantly modified after graft. In patients with complications, PTX prevented the increase of TF expression at month one, and after rejection episodes. Endothelium activation markers were significantly modified after graft and in patients with complications but PTX had no significant effect on their plasma levels. These results suggest that the protective effect of PTX on graft survival could be related to the prevention of monocyte TF upregulation associated with complications.

Diagnostic and predictive value of an immunohistochemical profile in asymptomatic acute rejection of renal allografts.

We have retrospectively studied the diagnostic and predictive value of immunohistochemical characterization of adhesion molecules (ICAM-1, CD54, VCAM-1) and HLA-DR antigen in a homogeneous clinical group of 36 patients. Between 1 January 1991 and 31 January 1993, 130 patients received a kidney transplant in our unit. Biopsies of renal allografts were only performed in asymptomatic patients who had graft dysfunction, revealed by an isolated serum creatinine increase. Available frozen samples were included in this study (n = 44). The 35 cases of acute rejection diagnosed by biopsy corresponded to mild acute rejection according to the Banff classification criteria. First, we compared the expression of HLA-DR, ICAM-1 and VCAM-1 to morphological data to determine if the immunohistochemical data improved the histopathological diagnosis when the interstitial infiltrate was mild with slight tubulitis. We also studied the phenotype of infiltrating cells with monoclonal antibodies directed against T helper cells, T cytotoxic-suppressor cells, activated T cells and macrophages. Expression on tubular epithelium and density of each type of cell was graded semiquantitatively. Expression of HLA-DR, ICAM-1 and VCAM-1 was observed on tubular epithelium and endothelium in both acute rejection and other causes of graft dysfunction, limiting its diagnostic value. Activated T cells expressing CD69-AIM (activation inducer molecule) and/or HLA-DR were frequently observed in acute rejection (24/35 (69%) and 25/35 (71%) respectively) but not in other causes of renal dysfunction. We then studied the prognostic usefulness of the immunohistochemical profile in acute rejection. Of 27 patients, 12 had a progressively decreased renal function or returned to dialysis within one year after transplantation while the other 15 had a stable graft function after at least 18 months of follow-up. In the group of bad prognosis (n = 12), corticosteroid-resistant rejection episodes were significantly more frequent (p < 0.01). In this group, nine patients had an overexpression of HLA-DR on tubular epithelium versus one patient in the group of stable graft function (chi 2c = 10.57, p < 0.002). Seven patients included in the group of bad prognosis showed tubular overexpression of both ICAM-1 and VCAM-1 versus one patient in the other group chi 2c = 6.23, p < 0.02). Moreover, patients of the first group had a significantly higher number of interstitial macrophages as compared with those who had stable graft function (chi 2c = 4.87, p < 0.01). Thus, our data show that the immunohistochemical profile studied is of little value in the diagnosis of renal allograft rejection. However, an intense tubular expression of HLA-DR and/or both ICAM-1 and VCAM-1, and a high number of interstitial macrophages are significantly related to unfavorable graft outcome.

Selection of diabetic patients for islet transplantation. A single-center experience.

OBJECTIVE: Since the Edmonton protocol, islet transplantation (IT) offers the prospect of adequate glycemic control with no major surgical risk. In our single-center experience of IT, we studied the recruitment of eligible diabetic patients. METHODS: Between 1998 and 2002, we screened 79 diabetic patients that were divided into 2 groups according to their renal status: 41 were not receiving dialysis (ND) while 38 were receiving ongoing dialysis (D). RESULTS: In the ND group, 20 patients initiated the contact with our team, 8 patients were recruited during hospitalization for very poor glycemic imbalance, and 13 were referred by their diabetologist. 14/41 (34%) patients were ineligible for IT either because of very good glycemic balance, detectable C-peptide (C-p), kidney or liver problems, or plans for future pregnancy. 16/41 (39%) did not wish to proceed, 7 of whom were more interested by a pump. 11/41 (27%) were eligible, among which 8 are currently being assessed, 1 is on the waiting list and 2 have been transplanted. In the D group, 17/38 (45%) had a detectable C-p and received a kidney graft alone. Among the remaining 21 C-p negative diabetic patients, 3 were not eligible for kidney transplantation mainly for psychological reasons, and 4 were enlisted for kidney+pancreas transplantation. The remaining 14 C-p negative patients were kidney-transplanted. Among them, 6 were not eligible for IT, mainly for lack of motivation, slightly positive C-p stimulation tests, obesity, cancer, or increased creatininemia. The remaining 8/14 C-p negative kidney-engrafted patients were enlisted for IT. 3 had secondary failure with the pre-Edmonton immunosuppressive (IS) protocol. Five have been transplanted with the Edmonton-like IS regimen. CONCLUSION: Twenty-five per cent of the 79 patients for whom islet transplantation was considered underwent pregraft assessment and 12% (10 patients, 8 kidney-transplanted and 2 islet alone) of the 79 have been transplanted. The main eligibility criteria were undetectable Cpeptide, normal kidney function, average weight, glycemic imbalance, hypoglycemia unawareness, and glycemic brittleness.

Bilateral renal oncocytosis with renal failure.

Oncocytosis is a term recently used to describe diffuse renal involvement by numerous oncocytic nodules. We report herein a case of a 53-year-old man with end-stage renal disease requiring hemodialysis. His kidneys were involved by numerous tumors. Histologic examination revealed more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney.

Eligibility of diabetic patients receiving dialysis for islet after kidney transplantation.

INTRODUCTION: The aim of this study was to assess the selection of candidates among 38 dialyzed diabetic patients referred between January 1, 1998 and December 31 2002 for kidney followed by islet transplantation (IAK). The main criteria of eligibility for possible IAK were as follows: (1) plasma C-peptide negative; (2) need for a kidney graft; (3) kidney plus whole pancreas transplantation not desired by the patient; and (4) acceptable results of postkidney graft preislet transplantation evaluation. RESULTS: Seventeen of 38 patients with positive C-p diabetes received a kidney graft alone. Among the 21 C-p-negative diabetic patients, 3 were not eligible for kidney transplantation mainly for psychological reasons and 4 were eligible for kidney plus pancreas transplantation. The remaining 14 C-p-negative patients underwent kidney transplantation or had previously undergone kidney transplantation. Among them, 1 had moved away, 1 refused IAK, one had slightly positive stimulation tests, 1 was overweight, 1 had breast cancer, and 1 had postkidney graft complications. Among the remaining 8 of 14 C-p-negative, kidney-engrafted patients listed for IAK, 5 have undergone transplantation, 3 with a pre-Edmonton and 2 with the Edmonton protocol. CONCLUSION: In conclusion among this series of 38 diabetic patients undergoing dialysis, more than 90% were kidney-grafted. Approximately 50% were ineligible for pancreas transplantation or IAK because of a positive C-p, and 20% were enlisted for IAK. These results highlight the importance of C-p determinations in diabetic dialysis patients to identify eligible patients for pancreas transplantation or IAK.

[Chronic interstitial nephritis and mesalazine: 3 new cases?]. / Néphrite interstitielle chronique et mésalazine: 3 nouveaux cas?

We report three new cases of chronic interstitial nephritis occurring in two patients with Crohn's disease and one patient with ulcerative colitis treated with mesalazine. In the three cases asymptomatic renal disease was revealed by an increase in serum creatinine which was normal before treatment. Renal biopsy showed features of severe chronic interstitial nephritis. Mesalazine withdrawal and administration of steroids in two cases led to partial improvement of renal function. Mechanism of renal toxicity of mesalazine is unknown. These observations stress the need for monitoring renal function in patients with inflammatory bowel disease treated with mesalazine.

[Incidence and clinical expressions of microvascular complications in patients receiving kidney graft and treated with cyclosporine]. / Incidence et expressions cliniques des complications microvasculaires chez les greffés rénaux traités par ciclosporine.

Reported cases of HUS/TTP (hemolytic uremic syndrome/thrombotic thrombopenic purpura) with cyclosporin (CsA) are more and more frequent, which led us to evaluate the incidence of microangiopathic process in kidney graft patients. In our first retrospective study we noted 9.4 percent of HUS/TTP among 117 patients. We tried to detect infraclinical hemolytic events prospectively in 40 new patients by systematic measurement of haptoglobin levels after introduction of CsA. The incidence of falls in haptoglobin levels was 25 percent. The immunological context was always noted: rejection crisis in 5 cases, cytomegalovirus infection in 3 cases, isolated markers of lymphocyte-activity in 2 cases. We never found a clinical or infraclinical form of microangiopathic process without a symptomatic or asymptomatic immunological complication. Monitoring haptoglobin levels make it possible to detect early endothelial injuries which could be linked to the future arteriolopathy described with CsA therapy.

[Evaluation of verification of brain death and coordination with hospital organ procurement at the University Hospital at Lille]. / Evaluation du recensement des morts encéphaliques par la coordination hospitalière de prélèvement au CHU de Lille.

OBJECTIVES: To determine the incidence of brain death (BD) and to evaluate the registration of potential organ donors (PD) by the organ procurement team (OPT). STUDY DESIGN: Two-year prospective audit in the French university hospital of Lille. PATIENTS AND METHODS: All deaths occurring in the intensive care units or the emergency department were studied. If death was consecutive to brain damage, on-site review of medical records and charts was performed. Death cause, presence of criteria for brain death and reference to the OPT were recorded for each death. A medical expert staff evaluated the incidence of and reasons for unsuitability for organ donation. After 12 months of observation, a protocol for "systematic alert of the OPT when brain death is suspected" was broadcast and evaluated during the next 12 months. RESULTS: During the first period, 277 BD occurred and 119 PD were suitable for organ donation. The OPT recorded 80 PD (67.2% of all PD) and 45 multi-organ procurements (MOP) were performed. Physicians opposed two major reasons for not calling OPT: anticipation of a non-validated medical contraindication in 18 cases and approach of the family without the OPT team in 21 cases. After broadcast of the protocol, 110 PD were identified and the OPT was called in 93 cases (84.5% of all PD, p < 0.004 versus first period). Fifty-three MOP were performed. CONCLUSION: The OPT was not called to manage one-third of the PD. The protocol for "systematic alert of the OPT when brain death is suspected" improves the call of the OPT and increases MOP.