Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Background: Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. Methods: A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. Results: The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. Conclusions: Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Greffes rénales HLA identiques avec donneur vivant apparente (l'expérience de l'hôpital Necker)

Cette étude rétrospective décrit l'évolution de 59 patients greffés avec un rein de donneur vivant HLA identique entre 1977 et 1998 à l'hôpital Necker. Leur particularité est de recevoir qu'une monothérapie d'entretien par l'azathioprine, précédée ou non d'une induction par l'OKT3 ou l'ATG (groupe sans induction, I (-), n = 21, groupe avec induction, I (+), n = 38. En effet, une bithérapie, voire une trithérapie d'entretien est souvent employée dans ces greffes famiuales HLA identiques, malgré leur faible risque immunologique. Les caractéristiques des donneurs et des receveurs ne différaient pas statistiquement d'un groupe à l'autre, à l'exception de l'a^ge des donneurs (25 ans (19-43) dans le groupe I (-), 32 ans (18-58) dans le groupe I (+)), de lâge des receveurs (28 ans (19-43) dans le groupe I (-), 33 ans (14-51) dans le groupe I (+)), du nombre de patients présentant des anticorps anti HLA (0 / 15 dans le groupe I (-), 8/ 38 dans le groupe I (+)) et de la durée du suivi ( 149 mois (8-250) dans le groupe I (-), 85 mois (2-216) dans le groupe I (+))...PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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Reversal of Arterial Stiffness and Maladaptative Arterial Remodeling After Kidney Transplantation

International audienceBackground Chronic kidney disease is characterized by stiffening, thinning, dilatation, and increased circumferential wall stress of large arteries, associated with increased cardiovascular risk. Kidney transplantation (KT) reverses many pathological features of chronic kidney disease and improves life expectancy; however, longitudinal studies exploring the impact of KT on recipient large arteries are scarce.Methods and Results This study was designed to appraise arterial changes following KT. Carotid‐femoral pulse wave velocity, carotid remodeling (circumferential wall stress and carotid internal diameter), and stiffness were measured in 161 consecutive recipients receiving either a living (n=49) or a deceased (n=112) donor allograft, at 3 and 12 months after transplantation. Mean pulse wave velocity decreased from 10.8 m/s (95% confidence interval, 10.5–11.2 m/s) (at month 3) to 10.1 m/s (95% confidence interval, 9.8–10.5 m/s) (at month 12) (P<0.001). After multivariate adjustment, pulse wave velocity reduction from month 3 to month 12 was significantly larger in the living donor allograft KT (P<0.001). Circumferential wall stress decreased, 70 kPa (95% confidence interval, 68–72 kPa) to 64 kPa (95% confidence interval, 62–67 kPa), as well as carotid internal diameter and carotid stiffness (P<0.001 for all). Reductions in circumferential wall stress, diameter, and stiffness were significantly larger in the living donor allograft KT (P<0.001). When deceased donor allograft patients were classified into standard and expanded criteria donors, changes in both pulse wave velocity and circumferential wall stress were blunted in expanded criteria donors. Changes were independent of graft function and blood pressure changes.Conclusions Large‐artery stiffness and maladaptive carotid artery remodeling of chronic kidney disease is partially reversed within 12 months of KT and appears unrelated to renal function. Improvements were independently associated with live organ donation. Our data suggest that expanded criteria donors may hamper vascular recovery

Aortic Stiffness of Kidney Transplant Recipients Correlates with Donor Age

Increased aortic stiffness is a major factor responsible for the high cardiovascular mortality in patients with end-stage renal disease, but the impact of kidney transplantation on recipient aortic stiffness remains poorly defined. The use of expanded-criteria kidney donors is associated with decreased recipient survival compared with the use of standard-criteria donors, although the underlying mechanisms are incompletely understood. It was hypothesized that donor characteristics may affect recipient aortic stiffness, which may contribute to cardiovascular mortality in these patients. Aortic stiffness was evaluated by measurement of carotid-femoral pulse wave velocity in 74 cadaveric kidney recipients at 3 and 12 mo after transplantation. At 3 mo, aortic stiffness was associated exclusively with recipient-related factors: Age, gender, and mean BP. At 12 mo, age of the donor kidney emerged as an additional determinant. The change in aortic stiffness between 3 and 12 mo strongly correlated with donor age; stiffness improved in recipients of young kidneys (first tertile of donor age) and worsened in recipients of older kidneys (upper tertile of donor age). At 12 mo, the carotid-femoral pulse wave velocity was >1 m/s higher in recipients of the oldest kidneys than in the recipients of younger kidneys. The association between donor age and aortic stiffness was independent of recipient age, gender, mean BP, pretransplantation dialysis duration, conventional cardiovascular risk factors, medication, posttransplantation events, and GFR. These results demonstrate that the impact of kidney transplantation on recipient aortic stiffness is dependent on donor age and suggest that ongoing damage to large arteries might contribute to the mechanism underlying the association of old-donor kidneys and increased cardiovascular mortality

Impact of post-transplant MICA antibodies on long-term graft outcomes: a multicenter analysis of 788 renal transplant patients

info:eu-repo/semantics/publishe

Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function

International audienceBackgroundChronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate–matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid–femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR).MethodsWe analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s).ResultsAt 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P < 0.001). It was especially associated with lower mGFR, older age, higher BMI, higher MBP, diabetes and higher serum parathyroid hormone levels. After adjustment, the odds ratio for the risk of high arterial stiffness in KTRs was 0.40 (95% confidence interval 0.23–0.68, P < 0.001).ConclusionsAortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se

Evaluation of Protocol Biopsy Utility 12 Months after Renal Transplantation: A Multicenter Observational Analysis

The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ≥30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ≥30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73 m² with SB and 54 (15) mL/min/1.73 m² with NSB (=0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73 m² at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, <0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed