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.

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.

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.

Peritoneal dialysis reduces the number of hospitalization days in heart failure patients refractory to diuretics.

BACKGROUND: Previous small studies have reported favorable results of peritoneal dialysis (PD) in the setting of chronic refractory heart failure (CRHF). We evaluated the impact of PD in a larger cohort of patients with CHRF where end-stage renal disease was excluded. ♢ METHODS: All patients who received PD therapy for CRHF between January 1995 and December 2010 in two medical centers in France were included in this retrospective study. Baseline characteristics were compared with clinical parameters during the first year after initiation of PD. Mortality, safety, and sustainability of PD were also analyzed. ♢ RESULTS: The 126 patients included had a mean age of 72 ± 11 years and an estimated glomerular filtration rate of 33.5 ± 15.1 mL/min/1.73 m2. Mean time on PD was 16 ± 16.6 months. During the first year, patients with a left ventricular ejection fraction (LVEF) of 30% or less experienced improvement in cardiac function (30% ± 10% vs 20% ± 6%, p < 0.0001). We observed a significant reduction in the number of days of hospitalization for acute decompensated heart failure after PD initiation (3.3 ± 2.6 days/patient-month vs 0.3 ± 0.5 days/patient-month, p < 0.0001). One-year mortality was 42%. ♢ CONCLUSIONS: In CRHF, PD significantly reduces the number of days of hospitalization for acute heart failure. Improved LVEF may have led to the comparatively good 1-year survival in this cohort.

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.

Influence of fractalkine receptor gene polymorphisms V249I-T280M on cancer occurrence after renal transplantation.

BACKGROUND: Fractalkine (CX3CL1) and its receptor (CX3CR1) are involved in antitumor immunity. Two common single nucleotide polymorphisms of the CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine signaling characterized by decreased adhesive function, signaling, and chemotaxis of leukocytes. We hypothesized that a renal transplant recipient (RTR) carrying the homozygous I249M280 genotype could experience more cancer due to lower CX3CL1-dependent antitumorigenic effects. METHODS: We studied the association between these polymorphisms and cancer incidence in two independent cohorts of RTR, including a total of 622 patients. RESULTS: The median follow-up was 8.7 and 7.9 years for the first and second cohorts, respectively. Analysis of 622 patients identified 20 (3.2%) I249M280 homozygous patients, 321 (51.6%) V249T280 homozygous patients, and 281 (45.2%) heterozygous patients. I249M280 homozygotes have an independent increased risk of cancer (hazard ratio [95% confidence interval], 3.3 [1.04-10.52], P=0.043 for cohort 1 and 9.2 [1.67-50.91], P=0.011 for cohort 2) compared with other patients. Age and male gender were also risk factors for cancer occurrence. CONCLUSIONS: CX3CR1 gene polymorphism is associated with a higher rate of cancer in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management.

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.

Renal transplantation outcome in selected recipients with IgA nephropathy as native disease: a bicentric study.

BACKGROUND: IgA nephropathy (IgAN) is the causative disease of at most 10% of patients on dialysis and waiting for kidney transplantation. The disease can recur on the graft and it is important to know the exact impact of such recurrence on overall results of transplantation in this subgroup of young recipients. MATERIAL/METHODS: This is a retrospective study done in two closed centers over three decades with a final number of 142 recipients (111 men; median age of 42.2 years at surgery) with biopsy-proven IgAN among 1979 transplanted patients (7.2%). The mean follow-up time was 6.6 years. Recurrence was defined clinically as proteinuria over 1 g/day ± haematuria and associated with ≥1+ IgA mesangial deposits on the graft biopsy. We used Cox regression and Kaplan-Meier survival curves to study the event. RESULTS: Patient survival was excellent: 92% at 10 y; graft survival was 53% at 10y and similar to other recipients. The clinico-pathological (full) recurrence (CPR) was observed overall in 25 cases (17.6%) leading to graft loss in 10 cases (7%). The cumulative rate at 10 y of full recurrence and graft loss due to CPR was 21% and 13% respectively. We could not demonstrate any major influence of immunosuppression (induction or maintenance) or other factors on full recurrence. In addition, 10.5% of recipients disclosed only pathological recurrence without significant clinical consequences. CONCLUSIONS: Despite significant prevalence of full recurrence after grafting, the overall good results observed still validate renal transplantation in this subgroup of IgAN recipients.

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.

The interleukin-6 gene promoter polymorphism -174 and atherosclerotic events in overweight transplanted patients.

Chronic inflammation plays a pivotal role in atherosclerosis. We hypothesized that combining overweight and a greater genetic capacity to produce IL-6 predicted by IL-6 gene promoter polymorphism at position -174 (G→C) may allow to identify individuals exhibiting higher IL-6 and C-reactive protein (CRP) concentrations with a higher risk of atherosclerotic events (AE). The occurrence of AE was analyzed with respect to body mass index, IL-6 gene promoter polymorphism at position -174 (G→C), and other relevant risk factors, retrospectively, in 217 renal transplant recipients and, prospectively, in 132. Circulating IL-6 concentrations were closely related to BMI (r = 0.55, P = .0005). In overweight patients, serum IL-6 concentration was found to be significantly lower in C carriers than in GG patients (4.2 [1.0-5.1] versus 7.3 pg/mL [4.4-100]; P = .025). The incidence of AE was higher in overweight GG patients (29.5% versus 10.1%; P = .0003). In multivariate analysis, overweight-GG had an increased risk to develop AE (HR 2.96 [95% CI 1.09-8.04], P = .034 in the retrospective cohort, and HR 2.99 [95% CI 0.92-9.33], P = .069 in the prospective cohort). All these data are consistent with a role for both genetic and environmental determinants of inflammation (white adipose tissue mass) in the development of AE in renal transplanted patients.

The COX-2 gene promoter polymorphism -765 delays CD4 T-cell reconstitution after lymphocyte depletion with antithymocyte globulins.

Polyclonal antithymocyte globulins (ATG) induce persistent changes in T-lymphocyte subsets characterized by low CD4 T. The mechanisms remain partly unknown. Prostaglandin E(2) (PGE(2)) is involved in lymphocyte homeostasis. Whether PGE(2) may be involved in persistent CD4 T-cell lymphopenia after ATG is unknown. We examined the association between this polymorphism and CD4 T-cell count in 159 renal transplant recipients (RTR) who received ATG. Analysis of these patients identified 6 CC (3.8%), 32 GC (22.6%), and 117 GG (73.6%) genotypes. Patients with the GG genotype had significantly higher serum PGE(2) concentrations, leading us to compare C carriers with GG patients. Carriers of the C allele had lower CD4 T cell count 1 year (235 ± 96 vs 323 ± 227/mm(3); p = 0.022) and 2 years posttransplant (325 ± 79 vs 422 ± 231/mm(3); p = 0.024). In multivariate analysis, the C allele (p = 0.029) conferred an increased risk of posttransplant CD4 T-cell lymphocytopenia. Pretransplant T-cell receptor excision circle levels were lower in C carriers. COX-2 gene promoter polymorphism at position -765 (G → C) is associated with persistent CD4 T-cell lymphopenia after ATG in RTR. This effect is likely to be mediated by the actions of PGE(2) on thymus function and viability.

Thymic function, anti-thymocytes globulins, and cancer after renal transplantation.

BACKGROUND: Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment. PATIENTS AND METHODS: The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG. RESULTS: Mean follow-up was 7.5±2.6years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4(+) and CD4(+) CD45RA(+) CD45RO(-) T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127(+)CD4(+)CD25(+)Foxp3(+)). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p<0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (T1 [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p<0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% CI, 0.16 to 0.97, for one log (TREC/10(6) PBMC); p=0.046). CONCLUSIONS: Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered.

Protective effect of intra-peritoneal epinephrine on postoperative renal function after cisplatin-based intra-peritoneal intra-operative chemotherapy.

OBJECTIVES: Intra-operative cisplatin-based intra-peritoneal chemotherapy (IPC) may alter renal function in patients with advanced ovarian cancer. The aim of this study was to describe postoperative alteration of renal function after cisplatin-based IPC and to identify risk factors for moderate to severe acute renal failure. STUDY DESIGN: This prospective observational study was carried out on 77 consecutive patients who underwent cisplatin-based IPC procedures, with (n=23) or without (n=54) intra-peritoneal epinephrine, for advanced ovarian cancer. Postoperative renal function was assessed using serial serum creatinine measurements and was based on serum creatinine changes from pre-operative values, according to the risk, injury, failure, loss, end-stage kidney disease (RIFLE) classification. Patients were divided into two groups according to postoperative renal function: patients with renal injury or failure (IF group) or patients with no renal alteration or renal risk (NR group). Clinical variables were compared between the IF and NR groups using univariate and multivariate analysis. RESULTS: Postoperative acute change in renal function was observed in 34 (44.2%) patients (unimodal distribution), among whom 23 patients (29.8%) constituted the IF group. In univariate analysis, the absence of epinephrine in the IPC bath, a higher duration of severe hypotension, a lower postoperative blood protein level, and a lower volume of intra-operative diuresis were significantly associated with the occurrence of renal injury or failure. In multivariate analysis, the absence of epinephrine was the only factor associated with the occurrence of moderate to severe acute renal failure (odds ratio [95% confidence interval]=4.49 [1.36-14.80]). CONCLUSIONS: Transient acute renal dysfunction after cisplatin-based IPC associated with cytoreductive surgery is frequent and intra-peritoneal epinephrine plays a protective role.

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.

Significant increase in 1-year posttransplant renal arterial index predicts graft loss.

BACKGROUND AND OBJECTIVES: Conflicting data have been reported concerning the use of kidney graft arterial resistance index (RI) measured by Doppler to predict death-censored graft loss. We hypothesized that changes in RI values could carry better information than a single measure of RI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four hundred twenty-five renal transplant recipients were included in the study. We tested whether changes in renal arterial resistance index between 4 and 12 months after transplant (ΔRI(4→12)) were predictive of graft loss. RESULTS: Neither 4-month nor 1-year RI predicted graft loss. The area under the receiver operating characteristics curve of ΔRI(4→12) for graft loss was 0.75. A ΔRI(4→12) ≥10% had the best sensitivity and specificity. One year after transplant, 22% of the study population had ΔRI(4→12) ≥10%. Fifty-five patients (12.9%) experienced graft loss during follow-up. The annual incidence of graft loss was higher in patients with ΔRI(4→12) ≥10% (3.5 versus 1.3%; P = 0.009). In multivariate analysis, patients with ΔRI(4→12) ≥10% had an increased risk of graft loss (hazard ratio, 6.21; 95% confidence interval, 1.99 to 22.15; P = 0.002). CONCLUSIONS: A variation in RI ≥10% in the first year after transplant is an independent risk factor for death-censored graft loss in renal transplant recipients.

Thymoglobulin induction and sirolimus versus tacrolimus in kidney transplant recipients receiving mycophenolate mofetil and steroids.

BACKGROUND: To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. METHODS: De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. RESULTS: GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P<0.05). At month 12, patient survival and incidence of biopsy-proven rejection were not different between groups (95.8% vs. 97.1%, and 16.9% vs. 12.9%, respectively). However, proportion of graft loss was higher with SRL at months 6 and 12 (11.3% vs. 0.0%, P=0.004; 14.1% vs. 4.3%, P=0.044, respectively). Adverse events and premature withdrawals were more frequent with SRL (P<0.001 and P<0.05, respectively), whereas cytomegalovirus infections were more frequent with tacrolimus (P<0.001). CONCLUSION: Patients treated with induction plus SRL, mycophenolate mofetil, and corticosteroids may obtain good renal function but have a higher risk of adverse events, drug withdrawal, and graft loss.