Anti-SARS-CoV-2 spike protein and neutralizing antibodies at 1 and 3 months after three doses of SARS-CoV-2 vaccine in a large cohort of solid organ transplant patients.

The immunogenicity of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccine was improved by the administration of a third dose. The aim of our retrospective study was to assess the evolution of binding and neutralizing antibody concentration until 3 months after the third dose in a large cohort of solid organ transplant (SOT) patients (n = 872). At 1 month after the third dose, anti-SARS-CoV-2 antibodies were detected by means of enzyme-linked immunosorbent assay tests in 578 patients (66.3%). In a subgroup of patients, 70% (180 out of 257) had anti-SARS-CoV-2 antibody concentrations ranging from 1.2 to 18 411 binding antibody units (BAU)/ml and 48.5% (115 out of 239) had a neutralizing antibodies titer that can confer clinical protection against SARS-CoV-2. Three-hundred ninety-three patients out of the 416 (94.5%) who were seropositive at month 1 and were tested at 3 months after vaccination remained seropositive. Between months 1 and 3 after vaccination, binding and neutralizing antibodies concentrations decreased significantly. The proportion of protected patients against the SARS-CoV-2 also slightly decreased. In conclusion, this study shows that although two-third of SOT develop anti-SARS-CoV-2 antibodies after three doses, one-third of them remain weak or non-protected. It is important to measure anti-SARS-CoV-2 antibodies to define the strategy that can optimize SOT protection against SARS-CoV-2.

Expression of Exhaustion Markers on CD8+ T-Cell Patterns Predict Outcomes in Septic Patients Admitted to the ICU.

RATIONALE: There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. DESIGN: Observational prospective study. SETTING: Two ICUs in a teaching hospital (France). PATIENTS: Eighty patients with sepsis admitted to the ICU. INTERVENTIONS: Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). MEASUREMENTS AND MAIN RESULTS: Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. CONCLUSIONS: Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.

Outcome of Liver Transplant Patients With Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies.

After liver transplantation (LT), the role of preformed donor-specific anti-human leukocyte antigen antibodies (pDSAs) remains incompletely understood. We conducted a retrospective, case-control analysis to determine the impact of pDSAs after LT in 3 French transplant centers (Bordeaux, Lyon, and Toulouse). Among the 1788 LTs performed during the study period, 142 (7.9%) had at least 1 pDSA. The patient survival rate was not different between patients who received an LT with pDSAs and the matched-control group. A liver biopsy was performed 1 year after transplantation in 87 recipients. The metavir fibrosis score did not differ between both groups (1 ± 0.8 versus 0 ± 0.8; P = 0.80). However, undergoing a retransplantation (hazard ratio [HR] = 2.6, 95% confidence interval [CI], 1.02-6.77; P = 0.05) and receiving induction therapy with polyclonal antibodies (HR = 2.5; 95% CI, 1.33-4.74; P = 0.01) were associated with a higher risk of mortality. Nonetheless, high mean fluorescence intensity (MFI) donor-specific antibodies (ie, >10,000 with One Lambda assay or >5000 with Immucor assay) were associated with an increased risk of acute rejection (HR = 2.0; 95% CI, 1.12-3.49; P = 0.02). Acute antibody-mediated rejection was diagnosed in 10 patients: 8 recipients were alive 34 (1-125) months after rejection. The use of polyclonal antibodies or rituximab as an induction therapy did not reduce the risk of acute rejection, but it increased the risk of infectious complications. In conclusion, high MFI pDSAs increase the risk of graft rejection after LT, but they do not reduce medium-term and longterm patient survival. The use of a T or B cell-depleting agent did not reduce the risk of acute rejection.

Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections.

OBJECTIVES: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients. METHODS: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors. RESULTS: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load.

No evidence of occult hepatitis C or E virus infections in liver-transplant patients with sustained virological response after therapy with direct acting agents.

BACKGROUND AND AIMS: It has been recently suggested that occult hepatitis C virus (HCV) infection and hepatitis E virus (HEV) reactivation might occur after direct acting antiviral agent-induced (DAA-induced) sustained virological response (SVR). The aim of our study was to identify occult HCV and HEV infection in a cohort of organ transplant patients who had achieved SVR and had persistent elevation in liver-enzyme levels. PATIENTS AND METHOD: Sixty-six liver and/or kidney transplant patients were treated with DAAs. All but one achieved SVR12. Twenty-nine (8-39) months post-SVR12, 8 of the 65 patients (12.3%) who achieved SVR12 had persistently elevated liver enzyme levels. In 1 patient, this was related to hepatitis B virus reactivation. In the 7 remaining patients, blood samples (n = 7), liver biopsies (n = 4), and peripheral blood mononuclear cells (PBMCs) (n = 7) were collected simultaneously in order to identify occult HCV or HEV infection. RESULTS: Hepatitis C virus RNA and HEV RNA were not detected in serum, liver tissues, or PBMCs. No HEV reactivation was observed after HCV clearance in patients who had anti-HEV IgG. CONCLUSION: Our study suggests that there is no occult HCV or HEV infection in transplant patients after successful treatment of HCV infection with DAAs, even in patients with a persistent elevation of liver enzyme levels. However, due to the small number of patients included in our study, this finding should be confirmed in a larger cohort.

Outcomes of kidney transplant recipients admitted to the intensive care unit: a retrospective study of 200 patients.

BACKGROUND: Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors. METHODS: Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7-68]; time from transplantation 41 months [IQR 5-119]). Survival curves were compared using the Log-rank test. RESULTS: Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function. CONCLUSIONS: Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.

Heparin-Free Prolonged Intermittent Hemodialysis Using Calcium-Free Citrate Dialysate in Critically Ill Patients.

OBJECTIVES: Critically ill patients who have a high risk of bleeding but require prolonged intermittent dialysis need a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit. We assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Critically ill patients who required renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 101 dialysis sessions were performed in 35 patients (mechanical ventilation n = 78; norepinephrine n = 13). Median duration of dialysis was 294 minutes (interquartile range, 240-300), and median ultrafiltration volume was 2.3 L (1-2.8). Urea and ß2-microglobulin reduction rates were 64.5% ± 0.4% and 48% ± 0.13%, respectively. Postfilter ionized calcium was 0.35 ± 0.17 and 0.38 ± 0.14 mmol/L at 1 and 3 hours, respectively, within the extracorporeal circuit. A major clotting event that led to premature termination of the session occurred in only three of 101 sessions. In these three cases, major catheter dysfunction occurred before clotting within the circuit. Prefilter ionized calcium remained within narrow ranges (before/after change +0.07 ± 0.006 mmol/L), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged. CONCLUSIONS: Dialysis anticoagulation with calcium-free citrate-containing dialysate and calcium reinjection according to ionic dialysance is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. It allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. Furthermore, sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe acute kidney disease.

Transfusion-acquired hepatitis E infection misdiagnosed as severe critical illness polyneuromyopathy in a heart transplant patient.

This is the case of a 56-year-old man who underwent heart transplantation. Within the first postoperative days, his respiratory and limb muscles weakened, which was attributed to critical illness polyneuromyopathy (CIPM). At day 70 post transplantation, he had increased liver enzyme levels and acute hepatitis E virus (HEV) infection was diagnosed. HEV RNA was found in the serum, stools, and cerebrospinal fluid. Results of further investigations suggested a possible HEV-related polyradiculoneuropathy. At transplantation, the patient was negative for immunoglobulin (Ig)G, IgM, and HEV RNA. A trace-back procedure identified the source of infection and concluded that HEV infection was contracted from blood transfusion 12 days prior to transplantation from an HEV RNA-positive donor. Tests of the organ donor for HEV were negative. Phylogenetic analysis revealed sequence homology between the HEV-3 strain of the patient and the HEV-3 strain of the blood donor. Despite ribavirin treatment, the patient died on day 153 post transplantation from multiorgan failure. In conclusion, patients with hepatitis or neuropathic illness who have received blood products should be screened for HEV.

Malignancies in hepatitis C virus-positive and -negative kidney transplant recipients: A case-controlled study.

BACKGROUND: Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication. PATIENTS AND METHODS: A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months. RESULTS: During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group. CONCLUSION: The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients.

Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

BACKGROUND AND AIM: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. METHOD: Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. RESULTS: Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). CONCLUSION: In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection.

Short- and long-term outcomes of AL amyloidosis patients admitted into intensive care units.

Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation.

BACKGROUND & AIMS: Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis. METHODS: Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study. RESULTS: GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed. CONCLUSION: Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation.

Successful treatment of fibrosing cholestatic hepatitis with pegylated interferon, ribavirin and sofosbuvir after a combined kidney-liver transplantation.

Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver-kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney-liver transplantation.

De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.

Pregnancy after kidney transplantation: outcome and anti-human leucocyte antigen alloimmunization risk.

BACKGROUND: Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization. METHODS: We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay. RESULTS: Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (<37 weeks). The median birth weight was 2720 (1040-3730) g. Nine newborns (15%) had low birth weights (<2.5 kg). At least one severe complication occurred in 56% of pregnancies. A high glomerular-filtration rate (GFR) before pregnancy was the sole independent protective factor that avoided a severe complication. Death-censored kidney-allograft survival was 80.4% at 6 years. De novo donor-specific anti-HLA antibodies were detected after only 5.9% of pregnancies: for two women, the father had the same HLA antigens as those from the deceased organ donor. The determination of the HLA of the father before pregnancy can better inform the woman about the possible impact of pregnancy on her kidney-allograft function. CONCLUSIONS: Despite many complications, the outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA alloimmunization was low.

Impact of molecular adsorbent recirculating system on renal recovery in type-1 hepatorenal syndrome patients with chronic liver failure.

BACKGROUND AND AIM: Liver transplantation remains the best option for treating type-1 hepatorenal syndrome (HRS1). The aim of this retrospective study was to determine whether the molecular adsorbent recirculation system (MARS) can improve renal function in HRS1 patients. METHODS: Thirty-two patients with chronic liver disease and HRS1 were treated by MARS sessions which were performed every other day. The endpoint was renal function improvement by 28 days after diagnosis of HRS1 that was defined as a serum-creatinine level of < 133 µmol/L. Partial renal recovery was defined as a 10% decrease in baseline serum-creatinine level. RESULTS: The mean number of MARS sessions required by each patient was 3.5 ± 1.5. The median time between admission and the start of MARS therapy was 3 (0-15) days. Of the total patients, 13 (40%) had improved renal function. Among these, nine (28%) had complete renal recovery. Among the patients that survived, only 40% (6/15) had improved renal function, and among the patients that died within the first month after the initiation of MARS, seven patients had a renal response. The 28-day survival rate was 47%. Seven patients received a liver transplant after diagnosis of HRS. Of these, four had complete or partial recovery after transplantation (57%) versus 9 of the 25 patients who did not undergo liver transplantation (36%), P = not significant. CONCLUSION: MARS therapy improved renal function in only very few patients with HRS1. Further controlled studies including large number of patients are required.

Do kidney histology lesions predict long-term kidney function after liver transplantation?

Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60±48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109±48 months after liver transplantation. eGFR decreased from 92±33 mL/min at transplantation to 63±19 mL/min after six months, to 57±17 mL/min at the kidney biopsy, to 54±24 mL/min at last follow-up (p<0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.

Alveolar and blood T lymphocyte profiles in Pneumocystis jirovecii-positive patients: effects of HIV status.

BACKGROUND: There are substantial differences in the risk evaluation, clinical presentation, and outcome of Pneumocystis pneumonia between human immunodeficiency virus (HIV)-positive and HIV-negative immunocompromised patients. To compare the host immune defenses against Pneumocystis jirovecii, the blood and alveolar lymphocyte profile was explored in these 2 populations. METHODS: The total, CD3(+), CD4(+), and CD8(+) T-lymphocyte counts were measured in the blood and alveoli of immunocompromised patients with a P. jirovecii DNA detected in their bronchoalveolar lavage samples, according to their HIV status. RESULTS: In blood and alveoli, the CD4(+) and CD8(+) T-lymphocyte counts were higher and lower, respectively, in the HIV-negative group. The threshold for initiating prophylaxis in HIV-positive persons, 200 CD4(+) T cells/µL, was not pertinent for HIV-negative patients. The P. jirovecii burden correlated with the blood CD4(+) T-cell counts in the HIV-positive but not in the HIV-negative group. Nevertheless, whatever the HIV status, a correlation was observed between alveolar CD4(+) T cells and the P. jirovecii burden. CONCLUSIONS: The T-lymphocyte profile was different between HIV-positive and HIV-negative patients with P. jirovecii, suggesting a distinct pathogenesis. Alveolar CD4(+) T cells could be critical to explain the development of Pneumocystis pneumonia but may also be important for evaluation of disease risk, mostly among HIV-negative immunocompromised patients.