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

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

Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function.

Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.

Factors associated with changes in echocardiographic parameters following kidney transplantation.

BACKGROUND: Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes. METHODS: One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared. RESULTS: A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m2 post-KT vs. 30.9 mL/m2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT. DISCUSSION/CONCLUSION: Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling.

Evaluation of Subclinical Fluid Overload Using Lung Ultrasound and Estimated Plasma Volume in the Postoperative Period Following Kidney Transplantation.

AIM: B-lines count measured with lung ultrasound (LUS) quantifies extravascular lung water and is validated in the setting of acute cardiac failure or chronic dialysis. Patients are often kept in moderately overhydrated states during the early postoperative period following kidney transplantation (KT). We described congestion changes during the early postoperative period following KT and the feasibility of LUS in this setting. METHODS: LUS (28 scanning-points method) and inferior vena cava (IVC) measurements were routinely performed in 36 patients after KT. Estimated plasma volume (ePV) was calculated from hemoglobin and hematocrit levels. RESULTS: No patient had >15 B-lines during the hospital stay. B-lines slightly increased until Day 4 after KT (Day 1, 1.7 ± 1.7; Day 4, 2.5 ± 2.5) and decreased up to Day 10 (1.4 ± 2.2; P vs Day 4 <.05). More B-lines were observed in patients aged older than 60 (P = .01 at Day 4) whereas IVC diameter and ePV were similar. In patients older than 60, B-lines had weak correlation with body weight variation (r = 0.64; P < .05), IVC diameters (r = 0.59 at Day 4 and r = 0.58 at Day 10; P < .05) but a strong correlation with ePV (r = 0.93 at Day 14; P < .05). B-line changes from Day 1 to Day 10 correlated with IVC diameter changes (r = 0.62; P < .05). CONCLUSION: LUS identifies subtle congestion changes during the early postoperative period following KT. The hyperhydration strategy usually followed during this period does not result in overt pulmonary congestion as assessed by LUS, even in older recipients.

Temporal Trend and Time-Varying Effect of Preemptive Second Kidney Transplantation on Graft Survival: A 30-Year Single-Center Cohort Study.

BACKGROUND: There are discrepancies regarding the impact of preemptive 2nd kidney transplantation (PSKT) on graft survival. The present study aimed to determine whether the association between PSKT and outcome varies over time and whether this association is era dependent. METHODS: A total of 266 patients underwent SKT (244 non-PSKT, 22 PSKT) in our center from 1985 to 2015. Association between PSKT and graft survival (allograft failure from any cause including death) was assessed with the use of Cox models. RESULTS: During a median follow-up of 6.7 years, 116 events were recorded: 72 returns to dialysis and 44 deaths before return to dialysis. Survival curves diverged up to 5 years (5-year survivals: PSKT, 94.1 ± 5.7%; non-PSKT, 76.8 ± 2.9%) but they converged thereafter (12-year survivals: PSKT, 50.9 ± 15.2%; non-PSKT, 55.5 ± 3.9%). After adjustment for age and living-donor status, PSKT tended to be associated with better graft survival (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.02-1.27; P = .08) within the first 5 years of SKT but tended to be associated with worse outcome thereafter (HR, 2.36; 95% CI, 0.97-5.72; P = .06; P for interaction with time = .04). In addition, a significant interaction was identified between PSKT and SKT year (P for interaction = .04). In the multivariable model, the estimated HR for PSKT was 2.54 (95% CI, 0.88-7.35; P = .08) in 1990 as opposed to 0.16 (95% CI, 0.02-1.17; P = .07) in 2012. CONCLUSIONS: The effect of PSKT on graft survival varies over time and according to year of the procedure. Although the benefit observed within the first 5 years of SKT appears to fade over time, overall graft survival seemingly improved in more recent years.

Long-term follow-up of corticosteroid refractory acute GVHD treated with an Inolimomab-based algorithm: a single center experience.

Acute corticosteroid refractory GVHD (aGVHD) remains a challenging problem after allogeneic hematopoietic SCT. Even though immunosuppressive therapies may achieve a response, unsatisfactory aGVHD control and toxicity of high cumulative doses of corticosteroids are frequent, notably with an increased infection rate. We report long-term follow-up of 33 consecutive patients who developed corticosteroid refractory aGVHD in our institution, treated homogeneously according to a unique algorithm combining an induction treatment (Inolimomab, 0.3 mg/kg per day), an associated immunosuppression (Mycophenolate Mofetil) and a predefined management of partial responses (PR) by the switch from Cyclosporin to Tacrolimus, together with an intensive infectious monitoring and supportive care. In this cohort, 17 patients (52%) achieved a complete response (CR) and 14 patients (42%) a PR, which converted to CR for 12 patients after Tacrolimus introduction. Transplant related mortality (TRM) was 15.5% and 29.7% at 1 and 3 years, respectively. OS was 54.5% at 3 years. Multivariate analysis identified CR after Inolimomab therapy as the unique prognostic factor on OS. Among the 30 evaluable patients, 19 (63%) developed extensive chronic GVHD. This Inolimomab-based algorithm allows for an efficient control of corticosteroid refractory aGVHD in a high proportion of patients with low toxicity, and deserves further investigation.