Use of T1 mapping in cardiac MRI for the follow-up of Fabry disease in a pediatric population.

Background: Fabry disease (FD) is a rare X-linked lysosomal disorder caused by pathogenic variants in the alpha-galactosidase-A gene (GLA). Life threatening complications in adulthood include chronic kidney failure, strokes and the cardiac involvement which is the leading cause of mortality. Usually, it presents with hypertrophic cardiomyopathy, together with arrhythmia and conduction abnormalities. An early indicator is decreased T1 value on cardiac magnetic resonance (CMR). Enzyme replacement therapy (ERT) is effective on some extra-cardiac symptoms but its effect on cardiac lesions depends on the level of initial myocardial lesions. CMR is routinely used to monitor cardiac involvement in FD due to its capacity for tissular characterization. However, there is a lack of data on the pediatric population to understand how to integrate CMR into early therapeutic decisions. Method: Monocentric longitudinal study carried out at Montpellier University Hospital from 2016 to 2022. All pediatric patients with FD were evaluated over time with clinical, biological, and cardiac imaging (CMR, echocardiography). Results: Out of the six patients included, (3 males), five were treated with ERT during the study. Low T1 values were observed in 4 patients. The normalization of T1 values was observed after 4 years of ERT in 3 patients. Conclusion: Due to the lack of strong clinical and biological markers of FD in pediatric patients, initiation and follow-up of ERT efficacy remain challenging. CMR with T1-mapping, a noninvasive method, could play a role in the evaluation of early cardiac impairment in young patients at diagnosis and during follow-up with or without ERT.

Measuring intradialyser transmembrane and hydrostatic pressures: pitfalls and relevance in haemodialysis and haemodiafiltration.

BACKGROUND: Post-dilutional haemodiafiltration (HDF) with high convection volumes (HCVs) could improve survival. HCV-HDF requires a significant pressure to be applied to the dialyser membrane. The aim of this study was to assess the pressure applied to the dialysers in HCV-HDF, evaluate the influence of transmembrane pressure (TMP) calculation methods on TMP values and check how they relate to the safety limits proposed by guidelines. METHODS: Nine stable dialysis patients were treated with post-dilutional HCV-HDF with three different convection volumes [including haemodialysis (HD)]. The pressures at blood inlet (Bi), blood outlet (Bo) and dialysate outlet (Do) were continuously recorded. TMP was calculated using two pressures (TMP2: Bo, Do) or three pressures (TMP3: Bo, Do, Bi). Dialysis parameters were analysed at the start of the session and at the end of treatment or at the first occurrence of a manual intervention to decrease convection due to TMP alarms. RESULTS: During HD sessions, TMP2 and TMP3 remained stable. During HCV-HDF, TMP2 remained stable while TMP3 clearly increased. For the same condition, TMP3 could be 3-fold greater than TMP2. This shows that the TMP limit of 300 mmHg as recommended by guidelines could have different effects according to the TMP calculation method. In HCV-HDF, the pressure at the Bi increased over time and exceeded the safety limits of 600 mmHg provided by the manufacturer, even when respecting TMP safety limits. CONCLUSIONS: This study draws our attention to the dangers of using a two-pressure points TMP calculation, particularly when performing HCV-HDF.

Correction: Consequences of increasing convection onto patient care and protein removal in hemodialysis.

[This corrects the article DOI: 10.1371/journal.pone.0171179.].

Geographical Variations in Blood Pressure Level and Seasonality in Hemodialysis Patients.

Seasons and climate influence the regulation of blood pressure (BP) in the general population and in hemodialysis patients. It is unknown whether this phenomenon varies across the world. Our objective was to estimate BP seasonality in hemodialysis patients from different geographical locations. Patients from 7 European countries (Spain, Italy, France, Belgium, Germany, United Kingdom, and Sweden) participating in the DOPPS (Dialysis Outcomes and Practice Patterns Study) on years 2005 to 2011 were studied. Factors influencing pre- and postdialysis systolic BP and diastolic BP levels were analyzed by mixed models. There were 9655 patients (median age, 68; 59% male) from 263 facilities, seen every 4 months during a median duration of 1.3 years. Pre- and postdialysis systolic BP increased by a mean estimate of 5.1 mm Hg (95% confidence interval [CI], 3.7-6.4 mm Hg) and 4.4 mm Hg (95% CI, 2.9-5.9 mm Hg) for each 10° increase in latitude (1111 km to the North). In the longitudinal analysis, predialysis systolic BP was lower in summer and higher in winter (difference, 1.7 mm Hg; 95% CI, 1.3-2.2 mm Hg), with greater differences in southern locations (Pinteraction=0.04). Predialysis systolic BP was inversely associated with outdoor temperature (-0.8 mm Hg/7.2°C; 95% CI, -1.0 to -0.5 mm Hg/7.2°C), with steeper slopes in southern locations (Pinteraction=0.005). Results were similar for predialysis diastolic BP. In conclusion, there is a geographical and seasonal gradient of BP in European hemodialysis patients. There is a need to consider these effects when evaluating and treating BP in this population and potentially in others.

Consequences of increasing convection onto patient care and protein removal in hemodialysis.

INTRODUCTION: Recent randomised controlled trials suggest that on-line hemodiafiltration (OL-HDF) improves survival, provided that it reaches high convective volumes. However, there is scant information on the feasibility and the consequences of modifying convection volumes in clinics. METHODS: Twelve stable dialysis patients were treated with high-flux 1.8 m2 polysulphone dialyzers and 4 levels of convection flows (QUF) based on GKD-UF monitoring of the system, for 1 week each. The consequences on dialysis delivery (transmembrane pressure (TMP), number of alarms, % of achieved prescribed convection) and efficacy (mass removal of low and high molecular weight compounds) were analysed. RESULTS: TMP increased exponentially with QUF (p<0.001 for N >56,000 monitoring values). Beyond 21 L/session, this resulted into frequent TMP alarms requiring nursing staff interventions (mean ± SEM: 10.3 ± 2.2 alarms per session, p<0.001 compared to lower convection volumes). Optimal convection volumes as assessed by GKD-UF-max were 20.6 ± 0.4 L/session, whilst 4 supplementary litres were obtained in the maximum situation (24.5 ± 0.6 L/session) but the proportion of sessions achieving the prescribed convection volume decreased from 94% to only 33% (p<0.001). Convection increased high molecular weight compound removal and shifted the membrane cut-off towards the higher molecular weight range. CONCLUSIONS: Reaching high convection volumes as recommended by the recent RCTs (> 20L) is feasible by setting an HDF system at its optimal conditions based upon the GKD-UF monitoring. Prescribing higher convection volumes resulted in instability of the system, provoked alarms, was bothersome for the nursing staff and the patients, rarely achieved the prescribed convection volumes and increased removal of high molecular weight compounds, notably albumin.

Dosing of Enteric-Coated Mycophenolate Sodium Under Routine Conditions: An Observational, Multicenter Study in Kidney Transplantation.

BACKGROUND Dosing of enteric-coated mycophenolate sodium (EC-MPS) should be adjusted to reflect concomitant immunosuppression, but it is largely undocumented whether such modifications are carried out during routine clinical practice. MATERIAL AND METHODS MyLIFE was an observational study of adult kidney-only or kidney-pancreas transplant patients starting -EC-MPS at 33 French transplant centers. Data were collected at first EC-MPS dose and 6 months later. The primary objective was to describe initial EC-MPS dosing according to concomitant immunosuppression. RESULTS There were 461 patients analyzed (174 started EC-MPS by month 1 post-transplant ['de novo'] and 287 started EC-MPS >1 month post-transplant ['maintenance']), receiving cyclosporine (CsA) (n=76), tacrolimus (n=363), or a mammalian target of rapamycin (mTOR) inhibitor (n=22). Mean (SD) starting dose was 1130 (511) mg/day, 1006 (441) mg/day, and 769 (300) mg/day in the CsA, tacrolimus, and mTOR inhibitor groups, respectively (p=0.003). In the de novo subpopulation, the starting dose was 1440 mg/day in 66.7% (14/21) of CsA-treated patients and 71.9% (110/153) of tacrolimus-treated patients, with an intensified dose of 2160 mg/day in 28.6% (6/21) and 8.5% (13/153), respectively. There was a non-significant trend to a higher rate of biopsy-proven acute rejection in patients receiving CsA versus tacrolimus or an mTOR inhibitor (p=0.082). Adverse events with a suspected relation to EC-MPS occurred in 21.0%, 23.1%, and 9.1% of the CsA, tacrolimus, and mTOR inhibitor subpopulations, respectively. CONCLUSIONS EC-MPS is usually initiated at the dose recommended for de novo CsA-treated kidney transplant patients, then titrated downwards as required. An early intensified regimen is not used frequently. The EC-MPS dose is modified in <20% of de novo patients to account for concomitant tacrolimus therapy instead of CsA administration.

Markers of bone remodeling are associated with arterial stiffness in renal transplanted subjects.

BACKGROUND: Bone-vessel interaction in chronic renal failure remains poorly understood and could be driven by bone remodeling factors including osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), parathormone and vitamin D. Only few data are available in renal transplantation. The aim of this study was to investigate the relationship between bone remodeling factors and large artery function in renal transplant patients. METHODS: 89 renal transplant patients were enrolled in this cross-sectional study. Carotid to femoral pulse wave velocity (PWV) and central augmentation index (AIx) were determined as an estimation of large artery function. Blood samples were collected for measurement of vascular risk markers. Independent predictors were identified by multivariate linear regression through backward feature selection using Akaike's information criteria. RESULTS: At multivariate analysis, age (p < 0.001) and systolic arterial pressure (p = 0.003) were significantly associated with PWV but not AIx. In addition, both elevated blood concentrations of 1.25(OH)2 vitamin D (p = 0.013) and OPG (p = 0.047) were still significantly related to high PWV. CONCLUSIONS: These results underline that age and mean arterial pressure are the main determinants of PWV following renal transplantation. Among bone remodeling biomarkers, plasma OPG and active vitamin D were the strongest determinants of arterial stiffness.

Prevalence and risk factors of noncontrolled and resistant arterial hypertension in renal transplant recipients.

BACKGROUND: Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg. METHODS: We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT. RESULTS: Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components. CONCLUSION: Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation.

[Toxoplasma infection, a rare but life-threatening complication after kidney transplantation: report of two cases]. / La toxoplasmose, une complication exceptionnelle mais grave chez le transplanté rénal : à propos de deux observations.

Toxoplasma infection is uncommon after renal transplantation. As a result, Toxoplasma gondii is often missed from the list of microbial agents which may be responsible of an infectious complication after renal transplantation. However, establishing this diagnosis is very important because toxoplasmosis can be life-threatening in an immunocompromised host, particularly when the diagnosis is too delayed. Here we report two cases of severe toxoplasmosis after renal transplantation. In the first case, primary infection transmitted by a cat developed in a seronegative recipient five years after renal transplantation. In the second case, reactivation of latent infection developed in a seropositive recipient 9 months after transplantation. In both cases, systematic screening for Toxoplasma gondii using polymerase chain reaction (PCR) in biological fluids was essential to suggest the diagnosis. Both recipients rapidly recovered after institution of antiparasitic therapy.

Early high pulse pressure is associated with graft dysfunction and predicts poor kidney allograft survival.

BACKGROUND: Pulse pressure (PP), which reflects the pulsatile component of the blood pressure (BP), is known as a major predictor of cardiovascular events and death. In the elderly and type 2 diabetic patients, PP is associated with low glomerular filtration rate and albuminuria. Because kidney allograft survival is closely related to BP levels, we investigated the impact of early high PP, systolic, diastolic, and mean arterial BP on kidney allograft survival. METHODS: Renal hemodynamic and function studies using isotopic methods were prospectively performed in 493 renal transplant patients at 3 months posttransplantation to determine the impact of the different BP components on allograft survival using a proportional hazard model. RESULTS: After a median follow-up of 6.3 years, 91 allografts were lost. High PP was associated with high systolic, diastolic, and mean arterial pressure, heart rate, recipient age, glycemia, and low glomerular filtration rate. Moreover, PP emerged as the strongest BP component influencing overall and death-censored kidney allograft survival. CONCLUSION: High PP is an early marker of poor allograft outcome that could be corrected by therapeutic intervention.

Does reduction in immunosuppression in viremic patients prevent BK virus nephropathy in de novo renal transplant recipients? A prospective study.

BACKGROUND: BK virus nephropathy (BKVN) is a severe complication of renal transplantation, resulting in graft loss in >50% of cases. Because patients with BKV viremia are at high risk for developing BKVN, the aim of our study was to analyze whether early reduction of immunosuppression (IS) could prevent BKVN in viremic patients. METHODS: BKV viruria was prospectively screened every 3 months by real-time polymerase chain reaction during the first year after transplantation in 123 consecutive renal transplant recipients. Plasma viral load was measured by polymerase chain reaction whenever viruria was positive; in viremic patients a graft biopsy was systematically performed and IS was reduced. RESULTS: Viruria, viremia, and BKVN occurred in 48.8%, 10.5%, and 2.4% of patients, respectively. In the 13 patients with positive viremia, initial graft biopsy showed BKVN in two. After reduction of IS in patients without BKVN, viremia disappeared in 8 of 11, decreased in 2 of 11, and increased in one patient who eventually developed BKVN. In contrast, viremia remained positive in one patient with BKVN and disappeared in the second but renal function deteriorated in both of them. Initial viral load was higher in patients who developed BKVN. CONCLUSION: Reduction of IS is probably an effective therapeutic option to clear viremia and prevent BKVN in viremic renal transplant patients.