Polyomavirus Bk Infection in Renal Transplant Recipients

peer reviewedBeside acute rejection or immunosuppressive therapy toxicity, infection by Polyomavirus BK, usually not aggressive in immunoactive patients, has emerged as an important factor affecting graft function in renal transplant recipients. Indeed, one of the most important complications of BK infection is nephropathy. Viral replication in the urinary tract as assessed by the presence of "decoy cells", or by a positive PCR for BK virus has been detected in up to half of the recipients but only 5% will present nephropathy which is usually the only sign. The most common risk factors for this emerging new cause are new immunosuppressive drugs and rejection episodes. The gold standard to diagnose BK nephropathy is immunohistochemical staining for large T antigen in graft biopsy specimens. Urine cytology examination and DNA BK PCR are used as a screening test. The prognosis in BK nephropathy has been considered to be poor. The early reduction of immunosuppression can improve the prognosis and perhaps also cidofovir or leflunomide use

HOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (Ktr)-VALIDITY OF DIFFERENT SCHEDULES OF SELF-MONITORING

Office blood pressure (OBP) coupled with 24-h ambulatory monitoring (24-h ABPM) or home self-monitoring (HBPM) allow a more accurate assessment of BP control in treated hypertensive patients and identification of different phenotypes of BP. ESH/ESC guidelines (2013) recommended 7 days of home measurements (3 days at least) but that duration is questioned. The present study examined if we can reduce, and to what extent, the 7-days schedule for home measurements in treated hypertensive kidney transplant recipients (ktr) while keeping a reliable assessment of their BP status

Increased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function

Administration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3, third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recip- ients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. Seven comparable KTx recipients were included as controls. Informed consent was obtained. No side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Ten months after KTx, 1 MSC patient had type B aortic dissection and STEMI. Four MSC patients had at least 1 opportunistic infection, whereas 3 controls had polyoma-BK viremia. At day 14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 46.5 ± 18.6 and 54.2 ± 16.3 ml/min, respectively (p, 0.42). Per-cause biopsies evidenced 1 bor- derline and 1 acute rejections in MSC group, whereas no AR was biopsy-proven in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches.MSC infusion was safe in all patients except one. Incidence of opportunist infections was similar in both groups. No difference in eGFR was found at 1-year post KTx. Putative immunization against MSC was observed in 3 patients

Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2.

peer reviewedGrupper et al. have reported on a positive humoral response post full vaccination with mRNA SARS-CoV2 BNT162b2 in only 51/136 (37.5%) kidney transplant recipients (KTRs) without prior exposure to the virus(1) . We have conducted an IRB-approved (B707201215598-2021/80) prospective small sample-size study comparing the humoral response to BNT162b2 in 40 consecutive individuals early exposed to the Belgian vaccination program, including 20 KTRs with (n=10, COVID-19(+)) versus without (n=10, COVID-19(-)) history of exposure to SARS-CoV-2 and 20 controls including 10 COVID-19(+) versus 10 COVID-19(-)

The Effect of Elective Ligation of the Arteriovenous Fistula on Cardiac and Renal Functions in Kidney Transplant Recipients.

peer reviewed[en] KEY POINTS: Surgical AVF ligation in KTRs is associated with a significant increase in diastolic BP while systolic BP remains stable. AVF closure in KTRs leads to an improvement of LV and LA morphology and a decrease in serum NT-proBNP levels. There is no significant effect of AVF ligation on kidney allograft function: The eGFR remains stable over time. BACKGROUND: Kidney transplantation is considered as the best kidney replacement therapy, and arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The systematic ligation of a functioning AVF in stable kidney transplant recipients (KTRs) remains debatable. METHODS: In this prospective study, we investigated the hemodynamic effect of the surgical closure of AVF in KTRs. Forty-three KTRs underwent an ambulatory BP monitoring before surgical closure of AVF (T0) and 12 months later (M12), as well as measurement of serum cardiac biomarkers (i.e., soluble suppression of tumorigenicity 2, N-terminal pro b-type natriuretic peptide [NT-proBNP], and galectin-3). Serum tests were also performed 6 months after AVF closure (M6). An echocardiographic examination was performed at each time point. All serum creatinine values were collected to compare the individual eGFR slopes before versus after AVF closure. The latest measure of the AVF flow before kidney transplantation was recorded. RESULTS: Diastolic BP significantly rose from T0 to M12: +4.4±7.3 mm Hg (P = 0.0003) for 24h, +3.8±7.4 mm Hg (P = 0.0018) during the day, and +6.3±9.9 mm Hg (P = 0.0002) during the night, leading to an increased proportion of KTRs with European Society of Hypertension (ESH)-defined arterial hypertension after AVF ligation. No change was observed for systolic BP. NT-proBNP significantly dropped between T0 and M6 (345 [190; 553] to 230 [118; 458] pg/ml, P = 0.0001) and then remained stable from M6 to M12 while suppression of tumorigenicity 2 and galectin-3 levels did not change from T0 to M12. We observed a significant decrease in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV mass, interventricular septum diameter, left atrial volume, and tricuspid annular plane systolic excursion from T0 to M6 and then a stability from M6 to M12. LV ejection fraction and eGFR slope remained stable during the whole study. These observations remained unchanged after adjustment for AVF flow. CONCLUSION: The closure of a patent AVF in KTRs is associated with elevation of diastolic BP, drop in serum NT-proBNP levels, reduction of left ventricular and atrial dimensions, and stability of eGFR slope

The uptake of [18F]-fluorodeoxyglucose by the renal allograft correlates with the acute Banff scores of cortex inflammation but not with the 1-year graft outcomes

peer reviewedIntroduction[18F]FDG PET/CT noninvasively disproves acute kidney allograft rejection (AR) in kidney transplant recipients (KTRs) with suspected AR. However, the correlation of biopsy-based Banff vs. PET/CT-based scores of acute inflammation remains unknown, as does the prognostic performance of [18F]FDG PET/CT at one year post suspected AR.MethodsFrom 2012 to 2019, 114 [18F]FDG-PET/CTs were prospectively performed in 105 adult KTRs who underwent per cause transplant biopsies. Ordinal logistic regression assessed the correlation between the extent of histological inflammation and the mean standardized [18F]FDG uptake values (mSUVmean). Functional outcomes of kidney allografts were evaluated at one year post per cause biopsy and correlated to mSUVmean.ResultsA significant correlation between mSUVmean and acute Banff score was found, with an adjusted R2 of 0.25. The mSUVmean was significantly different between subgroups of “total i”, with 2.30 ± 0.71 in score 3 vs. 1.68 ± 0.24 in score 0. Neither the function nor the survival of the graft at one year was statistically related to mSUVmean.Discussion[18F]FDG-PET/CT may help noninvasively assess the severity of kidney allograft inflammation in KTRs with suspected AR, but it does not predict graft outcomes at one year

Masked hypertension is associated with a high cardiovascular risk in hypertensive kidney transplant recipients

Objective: High blood pressure (BP) is a major risk factor for graft function in kidney transplant recipients (KTs) Our aim was to evaluate BP control in the office, but also in the ambulatory and home settings, in stable KTs, ali treated for hypertension, and to characterize patients with masked hypertension (MHT). Design and Method: Three BP measurement techniques were used in 70 late KT patients, (mean age 56.5 years; 43 males): ambulatory BP monitoring (ABPM-Spacelab 90207) office (OBP) and home BP monitoring (HBPM)- (OMRON M6). Carotid­ femoral pulse wave velocity was measured (Sphygmocor) as weil as a calcification score (arteries) and the systolic ankle brachial index (ABI) as recommended. The period since transplantation was 6.9±6.6 years, the mean GFR was 65.6±24±ml/min, Body Mass Index was 25.8±4.7 kg/m2 and the number of antihypertensive drug was 2.1±1 pills/d. Results: Uncontrolled hypertension (HTN) remained frequent in our treated population, 46 % were still hypertensive in the office, 39% using ABPM and 43% with HBPM. The proportion of MHT was 22% whatever the out-of-clinic method used, with more males, more overweight (BMI between, 25-30). lnterestingly when compared with controlled KTs (i.e both OBP and Daytime ABP controlled or both OBP and HBP controlled), using either ABPM or Home BP, patients with MHT had significantly higher PWV, a higher aortic augmentation pressure (AP), a higher calcification score and a higher ABI. However we did not find any significant impact of graft survival, immunosuppressive drugs, smoking habits, diabetes, or alcohol use. Conclusion: A high percentage of uncontrolled HTN was noted by OBP, but also by ABPM and HBPM despite antihypertensive treatment. MHT was frequently observed in KTs. This particular HT subtype, either defined by OBP vs ABPM or by OBP vs HBP, was significantly associated with major markers of arterial stiffness. So, MHT is associated with a high cardiovascular (cv) risk and therefore has to be manage to reduce incidence of cv events and graft loss