Acute kidney injury in non-critical care setting: elaboration and validation of an in-hospital death prognosis score.

BACKGROUND: Acute kidney injury (AKI) is still characterized by a high mortality rate. While most patients with AKI are admitted in conventional medical units, current available data are still obtained from studies designed for patients admitted in intensive care units (ICU). Our study aimed to elaborate and validate an in-hospital death prognosis score for AKI admitted in conventional medical care units. METHODS: We included two prospective cohorts of consecutive patients with AKI admitted between 2001 and 2004 (elaboration cohort (EC)) and between 2010 and 2014 (validation cohort (VC)). We developed a scoring system from clinical and biological parameters recorded at admission from the EC to predict in-hospital mortality. This score was then tested for validation in the VC. RESULTS: Three-hundred and twenty-three and 534 patients were included in the EC and VC cohorts, respectively. The proportion of in-hospital death were 15.5% (EC) and 8.9% (VC), mainly due to sepsis. The parameters independently associated with the in-hospital death in the EC were Glasgow score, oxygen requirement, fluid overload, blood diastolic pressure, multiple myeloma and prothrombin time. The in-hospital death prognosis score AUC was 0.845 +/- 0.297 (p < 0.001) after validation in the VC. CONCLUSIONS: Our in-hospital death prognosis score is the first to be prospectively developed and validated for AKI admitted in a conventional medical care unit. Based on current parameters, easily collected at time of admission, this score could be a useful tool for physicians and nephrologists to determine the in-hospital death prognosis of this AKI population.

Pilot non dialysis chronic renal insufficiency study (P-ND-CRIS): a pilot study of an open prospective hospital-based French cohort.

BACKGROUND: Before establishing a prospective cohort, an initial pilot study is recommended. However, there are no precise guidelines on this subject. This paper reports the findings of a French regional pilot study carried out in three nephrology departments, before realizing a major prospective Non Dialysis Chronic Renal Insufficiency study (ND-CRIS). METHODS: We carried out an internal pilot study. The objectives of this pilot study were to validate the feasibility (regulatory approval, providing patients with information, availability of variables, refusal rate of eligible patients) and quality criteria (missing data, rate of patients lost to follow-up, characteristics of the patients included and non-included eligible patients, quality control of the data gathered) and estimate the human resources necessary (number of clinical research associates required). RESULTS: The authorizations obtained (CCTIRS - CNIL) and the contracts signed with hospitals have fulfilled the regulatory requirements. After validating the information on the study provided to patients, 1849 of them were included in three centres (university hospital, intercommunal hospital, town hospital) between April 2012 and September 2015. The low refusal rate (51 patients) and the characteristics of non-included patients have confirmed the benefit for patients of participating in the study and provide evidence of the feasibility and representativeness of the population studied. The lack of missing data on the variables studied, the quality of the data analyzed and the low number of patients lost to follow-up are evidence of the quality of the study. By taking into account the time spent by CRAs to enter data and to travel, as well as the annual patient numbers in each hospital, we estimate that five CRAs will be required in total. CONCLUSION: With no specific guidelines on how to realize a pilot study before implementing a major prospective cohort, we considered it pertinent to report our experience of P-ND-CRIS. This experience confirms that i) feasibility, ii) quality of data and iii) evaluating the resources required must be validated before carrying out a large prospective cohort study such as ND-CRIS.

The Non-Dialysis Chronic Renal Insufficiency study (ND-CRIS): an open prospective hospital-based cohort study in France.

BACKGROUND: Chronic kidney disease (CKD) amounts to a heavy burden for health services. There is no long-running epidemiological tool for CKD before dialysis. We here present the protocol for a cohort of patients with "non-dialysis" CKD receiving care in the Bourgogne-Franche-Comté region of France. The aim of this cohort was to periodically describe the characteristics of patients included and their care provision, to analyse evolution in care and patients' kidney function outcomes. METHODS: The ND-CRIS cohort is prevalent and incident. Patients are included in the cohort if over 18, with a glomerula filtration rate (GFR) <60 ml/min/1.73 m2, non-dialysed, informed on the research and not having opposed it, and followed by a nephrologist in one of the 9 centres in the region, (3 pilot centres joined by 6 others in 2015). All the patients are followed up, with varying time lapses according to the degree of GFR deterioration. Data is collected by clinical research assistants (CRAs) using a dedicated computerised case-report form (CRF). Professional practices are assessed using indicators defined by the French Health Authority. The follow-up of patients included should enable assessment of the evolution of their GFR and co-morbidities. The periodic descriptions should give insight into evolution in epidemiological terms. DISCUSSION: The ND-CRIS meets a need in epidemiological tools in France for CKD. The cohort does claim to be representative, of ND-CKD patients receiving care from nephrologists. The open and incident nature of the cohort and the number of patients included in the ND-CRIS should provide answers to questions that cannot be answered by smaller solely prevalent cohorts. The numbers of patients included over the study period (2391 patients in 3 centres in 3 years) suggests that the figure of 5000 patients should be reached by 2017. The participation of nephrologists and the rate of inclusions point to the feasibility of the implementation of this cohort. Beyond the information to be found in the CRFs, this cohort should also enable ad hoc studies, in particular in the area of pharmaco-epidemiology, and it could later serve as a research platform and as a public health surveillance tool.

Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.

Cytomegalovirus exposure and cardiovascular disease in kidney transplant recipients.

Some data suggest that cytomegalovirus (CMV) may be involved in atherogenesis. However, there are few data suggesting that CMV may contribute to posttransplantation atherosclerosis. We studied a cohort of 570 consecutive renal transplant recipients. The impact of CMV on atherosclerotic events was analyzed with respect to other known main cardiovascular risk factors. The mean follow-up duration (± SD) was 87 ± 31 months. A total of 357 patients were considered to be CMV exposed, and 213 were considered to be CMV naive. Cox regression analysis revealed that CMV exposure (hazard ratio [HR], 1.80 [95% confidence interval {CI}, 1.06-3.05]; P = .030) was an independent risk factor for atherosclerotic events. A total of 213 patients remained CMV negative during follow-up, 225 CMV-positive patients had no replication after transplantation, and 132 CMV-positive patients experienced CMV replication after transplantation. Atherosclerotic event rates were 8.5%, 13.3%, and 18.2%, respectively (P = .034). Cox regression analysis revealed that patients with posttransplantation CMV replication had an increased risk of atherosclerotic events (HR, 2.06 [95% CI, 1.03-4.15]; P = .042) and death (HR, 1.76 [95% CI, 1.08-2.89]; P = .024). There was also a trend toward an increased risk of atherosclerotic events in CMV-positive patients without posttransplantation replication (HR, 1.62 [95% CI, .91-3.05]; P = .098). Both pretransplantation CMV exposure and posttransplantation CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.

Obesity and atherosclerotic events in chronic hemodialysis patients: a prospective study.

BACKGROUND: Studies exploring the impact of overweight on mortality have reported controversial results in dialysis patients; some have found overweight to increase mortality, whereas others suggest that it offers a survival advantage. We conducted a prospective study to evaluate the impact of overweight on atherosclerotic events (AE) in dialysis patients with special respect to the malnutrition/inflammation complex syndrome (MICS). METHODS: Five hundred and forty-one hemodialysis patients from 11 dialysis centers in France were included. A number of baseline parameters including traditional and non-traditional cardiovascular (CV) risk factors were measured and the cohort was followed prospectively. RESULTS: Over a mean follow-up of 39 months, 207 patients (38.3%) experienced an AE. Overweight, defined by a body mass index greater than 25 kg/m(2), was associated with increased risk of AEs [RR: 1.68 (CI: 1.11-3.56)], and CV mortality [RR: 1.51 (CI: 1.07-2.13)]. The effect of overweight was different in patients with and without MICS. Age, diabetes, a previous history of CV disease, high serum levels of homocysteine and MICS were also associated with an increased risk of AEs. CONCLUSIONS: Similar to the general population, overweight contributes to an increased risk for AEs and CV mortality in hemodialysis patients. The presence or absence of MICS can modify the impact of overweight on development of AEs and mortality in this population.

Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients.

The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 ± 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P=0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naïve patients (4.7 ± 2.6 vs. 6.7 ± 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.17-2.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.02-4.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 ± 20 vs. 9 ± 8%; P < 0.0001), whereas CD8+CD57+IL2- cells were more frequent in CMV-exposed patients. Our results highly suggest that CMV increases the risk of cancer after transplantation.

Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre-transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs.

Prolonged CD4 T cell lymphopenia increases morbidity and mortality after renal transplantation.

Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts <300/mm3 and 36 (12%) died during follow-up. We observed a higher death rate in patients with CD4 T cell lymphopenia persisting for >1 year (24.1 versus 7.6%; P < 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P = 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3+ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P = 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P = 0.013). In summary, prolonged polyclonal anti-thymocyte globulin-induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections.

Pretransplant serum vitamin D levels and risk of cancer after renal transplantation.

BACKGROUND: Serum levels of 25-OH-D3 inversely correlate with the incidence of various types of cancers in the general population. Because risk factors and incidence of cancer in renal transplant recipients (RTRs) are different from the general population, this study was designed to determine whether pretransplant 25-OH-D3 levels could be predictive of cancer risk in RTRs. METHODS: Pretransplant 25-OH-D3 levels were reviewed in 363 consecutive RTRs. The impact of 25-OH-D3 levels on the development of cancer was then analyzed with respect to other known risk factors. RESULTS: One hundred twenty-four patients (34.2%) showed vitamin D deficiency, 185 (51%) vitamin D insufficiency, and 54 (14.8%) with normal vitamin D levels. Thirty-two cancers (8.8%) occurred in 32 patients. A higher incidence of cancer was observed in patients with vitamin D deficiency (13.7% vs. 7% for patients with vitamin D insufficiency [P=0.068] and 3.7% for those with normal vitamin D levels [P=0.007]). 25-OH-D3 levels were lower in patients who developed cancer after transplantation (13.7+/-6 vs. 18.3+/-17.8 ng/mL, P=0.022). Age (hazard ratio, 1.06; 95% confidence interval, 1.02-1.11, for each 1 year increase; P=0.009) and low 25-OH-D3 levels (hazard ratio, 1.12; 95% confidence interval, 1.04-1.23, for every 1 ng/mL decrease; P=0.021) were independent risk factors for development of cancer. CONCLUSION: Pretransplant level of 25-OH-D3 is an important determinant for subsequent development of cancer after transplantation. Future studies should examine whether 25-OH-D3 supplementation can effectively decrease the incidence of cancer in RTRs.

Lymphocyte subsets in renal transplant recipients with de novo genitourinary malignancies.

INTRODUCTION: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence. PATIENTS AND METHODS: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry. RESULTS AND CONCLUSION: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR.

Metabolic syndrome and atherosclerotic events in renal transplant recipients.

BACKGROUND: Metabolic syndrome (MS) is a known cardiovascular risk factor in the general population. We explored the influence of MS on the occurrence of atherosclerotic events (AEs) after renal transplantation. METHODS: Three hundred thirty-seven renal transplant recipients were included in the study. Various parameters (e.g., anthropometric and biological) were measured 1 year after transplant. RESULTS: One year after transplant, 32% of the study population met criteria for MS. Older age, male gender, pretransplant high body mass index, and an increase in body mass index>or=5% in the first year after transplant were predictive factors for development of MS at 1 year after transplant. Forty-two patients (12.4%) experienced AEs during the 8 years of follow-up. The cumulated incidence of AEs was greater in patients with MS compared with others without MS (25% vs. 7%; P<0.001). In multivariate analysis, patients with MS at 1 year after transplant had an increased risk of AE (hazard ratio 3.40, 95% confidence interval 1.58-7.32, P=0.002). Older age, low creatinine clearance, high C-reactive protein level, and a past history of cardiovascular disease were other independent risk factors for AE. CONCLUSIONS: Similar to the general population, MS is an independent risk factor for AE after renal transplantation. Relevant preventive measures targeting different aspects of MS would then have a potential impact on prevalence of AE in this population.

No evidence of association between NOD2/CARD15 gene polymorphism and atherosclerotic events after renal transplantation.

Stable renal transplant recipients (RTR) display high rates of atherosclerotic events (AE). Innate immunity and especially vascular inflammation play a role in the pathogenesis of atherosclerosis. It is illustrated both by an increased occurrence of postrenal transplant cardiovascular events in patients with elevated levels of C-reactive protein and by a correlation between posttransplant AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro-inflammatory activity and macrophage is present in early atherosclerotic lesions. The incidence of single nucleotide polymorphism (SNP) in the three major polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR and the correlation between such polymorphism and the development of AE was analyzed. No correlation was observed between NOD2 gene polymorphism and the occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does not appear to influence cardiovascular complications in RTR.

Posttransplant diabetes mellitus and atherosclerotic events in renal transplant recipients: a prospective study.

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a frequent complication in renal-transplant recipients (RTRs). We conducted a prospective study to assess the potential role of PTDM in the development of atherosclerotic events (AE) in RTRs. METHODS: Three hundred fifty-seven consecutive RTRs were enrolled in this study. The incidence of various AE were assessed with respect to the presence of PTDM and a number of cardiovascular (CV) risk factors. RESULTS: The patients were followed for a mean duration of 60+/-14 months. Thirty-nine (11%) patients had PTDM. Fifty AE occurred in 48 (13.4%) patients. Although AE were more frequent in RTRs with PTDM compared with nondiabetic patients (33% vs. 8.8%; P=0.007), PTDM was only modestly associated with AE in the multivariate Cox regression analysis (relative risk [RR] 1.34; 95% confidence interval [CI], 1.04-2.18), mostly caused by significant interactions between PTDM and three confounding variables that were independently associated with AE: age, serum C-reactive protein (CRP) level, and serum high-density lipoprotein cholesterol concentration. Patients with high levels of homocysteine showed a significantly increased risk of AE (RR 4.67; 95% CI 1.82-15.87), as did those with high serum levels of CRP (RR 2.57; 95% CI 1.57-6.23). CONCLUSIONS: Our study shows a significant association between PTDM and AE. Nevertheless, a large amount of the excess risk of posttransplant diabetic RTR is explained by the coexistence of other CV risk factors. Moreover, high serum levels of CRP and hyperhomocystinemia were found to be among the nontraditional factors contributing to AE in our patients.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

BACKGROUND: Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. METHODS: This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. RESULTS: Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). CONCLUSION: Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Cytomegalovirus-associated venous thromboembolism in renal transplant recipients: a report of 7 cases.

Renal-transplant recipients have a higher prevalence of thromboembolic events compared with the general population. This elevated risk has been attributed to immunosuppressive drugs as well as metabolic and immunologic factors. Cytomegalovirus (CMV) infection, a frequent complication of transplantation, is known to modify endothelial phenotype from anticoagulant into procoagulant. There are few reports addressing the association of venous thromboembolism with CMV infection in immunocompetent patients. Some authors have also reported cases of arterial thrombosis in transplant recipients presenting CMV infection. However, the association of venous thromboembolic events with CMV infection has not yet been discussed in these patients. We present seven cases of simultaneous acute CMV infection and venous thromboembolism in renal-transplant recipients and suggest a potential causative effect.

Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients.

BACKGROUND: We conducted a prospective, uncontrolled, open study to assess the relationship between homocysteine (tHcy) and oxidative stress in chronic, stable, renal transplant recipients (RTR). METHODS: Included in the study were 17 chronic, stable RTR. All the patients received folic acid (5 mg/day). tHcy and total antioxidant capacity (TAOC) were measured before and at the end of the study period. RESULTS: Mean tHcy concentration was 26+/-10 micromol/L. tHcy significantly decreased during the study period (26+/-10 vs. 18+/-7 micromol/L; P<0.001). There was a significant inverse relationship between TAOC and tHcy (r= -0.33; P=0.01). TAOC significantly increased during the study period (1.49+/-0.23-1.78+/-0.6; P<0.001). There was an inverse relationship between the variation in tHcy and the variation in TAOC (r= -0.44; P=0.01). CONCLUSION: Our results demonstrate that hyperhomocysteinemia contributed to increased oxidative stress in RTR. tHcy-lowering treatment with folic acid may lower oxidative stress.

Long-term toxicity of antithymocyte globulin induction may vary with choice of agent: a single-center retrospective study.

BACKGROUND: Antithymocyte globulin (ATG) preparations are frequently used as induction treatment in renal transplantation, but little is known about the clinical equivalence of these different agents. We performed a retrospective, single-center study to compare the long-term clinical effects of ATG Fresenius (ATGF) and Thymoglobulin (SangStat, Fremont, CA) in renal transplant recipients. PATIENTS AND METHODS: A total of 194 consecutive renal transplant recipients were included who had undergone transplantation in our center between June 1993 and April 2001 and had received ATGF or Thymoglobulin as induction treatment. RESULTS: A total of 129 patients received ATGF and 65 patients received Thymoglobulin. Thirty patients (23%) in the ATGF group demonstrated cytomegalovirus (CMV) disease, whereas 24 patients (37%) in the Thymoglobulin group demonstrated CMV (P =0.02). Five patients (3.9%) in the ATGF group and eight patients (12.3%) in the Thymoglobulin group developed posttransplant malignancy (P =0.01). Five patients (3.9%) in the ATGF group and nine patients (13.8%) in the Thymoglobulin group died during follow-up (P =0.005). Cox regression analysis revealed that Thymoglobulin was an independent predictor of CMV disease (relative risk [RR] 2.16, confidence interval [CI] 95% [1.04-4.48]), malignancy (RR 2.16, CI 95% [1.04-4.48]), and death (RR 4.14, CI 95% [1.36-12.6]). CONCLUSION: In renal transplant recipients, induction therapy with Thymoglobulin seems to be associated with a significantly greater incidence of CMV disease, malignancy, and death compared with ATGF.

Flow cytometric evaluation of pregnancy-induced anti-HLA immunization and blood transfusion-induced reactivation.

BACKGROUND: Pregnancy-induced alloimmunization (PIA) may decrease to a level that becomes undetectable by complement-dependent cytotoxicity (CDC). Nevertheless, such alloimmunization may provoke acute rejections after kidney transplantation and lead to broad-spectrum immunizations after transfusion. Flow-cytometry (FC) was used to estimate the frequency of low-level PIA and to evaluate its influence on posttransfusion alloimmunization profiles. METHODS: To evaluate the frequency of low-level PIA, the sera of 36 women, free of CDC-detectable anti-HLA IgG (CDC-IgG- negative), were cross-matched by FC against their husband's or offspring's lymphocytes and further analyzed with human leukocyte antigen (HLA) Ag-coated microbeads (Flow-PRA One-Lambda, Canoga Park, CA). To evaluate the influence of low-level alloimmunization on posttransfusion appearance of CDC-IgG, pretransfusion sera of a second cohort of 43 women, also CDC-IgG-negative and included in a transfusion protocol, were analyzed by Flow-PRA. Posttransfusion sera were analyzed for the development of cytotoxic IgG. RESULTS: Ten of the first cohort of 36 (27.8%) CDC-IgG-negative women showed a positive FC cross-match against the husband or offspring lymphocytes. Flow-PRA analysis confirmed that 9 of 10 positive cross-matched sera contained anti-HLA IgG. Among the 43 transfused patients, 11 of 16 (68.7%) of the women who were CDC-IgG-positive after blood transfusion showed FC-detectable IgG before transfusion; although 2 of 27 (7.4%) of the patients who remained CDC-IgG-negative after transfusion showed FC-detectable IgG before transfusion (P <0.001). CONCLUSION: Most of the de novo anti-HLA immunizations detected by CDC after transfusion in previously pregnant women can be detected by Flow-PRA before transfusion.