Type of PKD1 Mutation Influences Renal Outcome in ADPKD LE GALL, Emilie Cornec; AUDREZET, Marie-Pierre; GUILLODO, Marie-Paule ...
Journal of the American Society of Nephrology,
06/2013, Volume:
24, Issue:
6
Journal Article
Peer reviewed
Open access
Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD ...is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.
The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed ...a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.
Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to ...plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004–12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10‐year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.
This French nationwide retrospective study shows that rituximab may be useful to treat recurrent focal segmental glomerulosclerosis in adult kidney transplant recipients after conventional treatment failure or to facilitate plasmapheresis discontinuation more rapidly after achieving remission.
The objective of this observational cross-sectional study was to describe the cleanliness of various equipment used for colostrum harvest and calf feeding procedures on dairy farms in Québec, Canada. ...The study was performed on 42 commercial dairy herds also enrolled in another study aiming to determine the transfer of passive immunity over a 14-mo period. Information on colostrum quality (using Brix value) and cleanliness (total aerobic and total coliform count) were recorded as well as various practices focused on colostrum-feeding equipment and preweaning period using a standard questionnaire. During the study period, colostrum and milk-feeding equipment cleanliness was assessed using direct surface swabbing with Hygiena Ultrasnap swabs. A total of 155 swab samples were obtained from 6 pieces of equipment. Adenosine triphosphate collected from the swabbed surface reacts with the luciferase solution present in the swab by bioluminescence, which is proportional to the quantity of ATP present and quantified as relative light units (RLU). The description of feed equipment cleanliness (defined as the maximal RLU found for a specific herd, dichotomized as <1,000 RLU vs. ≥1,000 RLU) was compared with the herds' descriptive characteristics, focusing on the first 2 components of a multiple correspondence analysis. The median (range) RLU for buckets used for colostrum harvest, bucket or bottle used for feeding, tube feeders, milking colostrum line, and internal surface of the nipples were 41 RLU (3–1,625 RLU), 78 RLU (<1–3,765 RLU), 29 RLU (<1–2,177 RLU), 83 RLU (<1–9,968 RLU), and 1,101 RLU (2–9,546 RLU), respectively. The first 2 components of multiple correspondence analysis explained 24.7% of data variances and were related to the farms' hygiene and health (13.0%) and feeding practices (11.7% of data variance). The maximal dichotomized luminometry value (<1,000 RLU or ≥1,000 RLU) was associated with hygiene and health dimension. This study gave promising results concerning the potential application of ATP luminometry for calf rearing practices assessment.
The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was necessary to achieve adequate ...drug exposure and improve kidney function.
Purpose
Therapeutic drug monitoring of tacrolimus using trough concentration (C
min
) is mandatory to ensure drug efficacy and safety in solid organ transplantation. However, C
min
is just a proxy ...for the area under the curve of drug concentrations (AUC) which is the best pharmacokinetic parameter for exposure evaluation. Some studies suggest that patients may present discrepancies between these two parameters. AUC is now easily available through mini-invasive microsampling approach. The aim of this study is to evaluate the relationship between AUC and C
min
in patients benefiting from a complete pharmacokinetic profile using a microsampling approach.
Methods
Fifty-one transplant recipients benefited from a complete pharmacokinetic profile using a microsampling approach, and their 24-h AUC were calculated using the trapezoidal method. The correlation with C
min
was then explored. In parallel, we estimated AUC using the sole C
min
and regression equations according to the post-transplantation days and the galenic form.
Results
Weak correlations were found between 24-h AUC observed and the corresponding C
min
(
R
2
= 0.60) and between AUC observed and expected using the sole C
min
(
R
2
= 0.62). Therapeutic drug monitoring of tacrolimus using C
min
leads to over- or under-estimate drug exposure in 40.3% of patients.
Conclusion
Tacrolimus C
min
appears to be an imperfect reflection of drug exposure. Evaluating AUC using a microsampling approach offers a mini-invasive strategy to monitor tacrolimus treatment in transplant recipients.
Studies generally focus on one type of chronic condition and the effect of medical cannabis (MC) on symptoms; little is known about the perceptions and engagement of patients living with chronic ...conditions regarding the use of MC.
This scoping review aims to explore: (1) what are the dimensions addressed in studies on MC that deal with patients' perceptions of MC? and (2) how have patients been engaged in developing these studies and their methodologies? Through these objectives, we have identified areas for improving future research.
We searched five databases and applied exclusion criteria to select relevant articles. A thematic analysis approach was used to identify the main themes: (1) reasons to use, to stop using or not to use MC, (2) effects of MC on patients themselves and empowerment, (3) perspective and knowledge about MC, and (4) discussion with relatives and healthcare professionals.
Of 53 articles, the main interest when assessing the perceptions of MC is to identify the reasons to use MC (n = 39), while few articles focused on the reasons leading to stop using MC (n = 13). The majority (85%) appraise the effects of MC as perceived by patients. Less than one third assessed patients' sense of empowerment. Articles determining the beliefs surrounding and knowledge of MC (n = 41) generally addressed the concerns about or the comfort level with respect to using MC. Only six articles assessed patients' stereotypes regarding cannabis. Concerns about stigma constituted the main topic while assessing relationships with relatives. Some articles included patients in the research, but none of them had co-created the data collection tool with patients.
Our review outlined that few studies considered chronic diseases as a whole and that few patients are involved in the co-construction of data collection tools as well. There is an evidence gap concerning the results in terms of methodological quality when engaging patients in their design. Future research should evaluate why cannabis' effectiveness varies between patients, and how access affects the decision to use or not to use MC, particularly regarding the relationship between patients and healthcare providers. Future research should consider age and gender while assessing perceptions and should take into consideration the legislation status of cannabis as these factors could in fact shape perception. To reduce stigma and stereotypes about MC users, better quality and accessible information on MC should be disseminated.
Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE ...(VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 13.7 years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 0.60-1.48; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 0.07-0.86, P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).
There have been few prospective studies on the natural history of nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective of this study was to prospectively evaluate the ...rate of and risk factors for NA in a French cohort of KTRs.
A total of 312 KTRs from eight French transplantation centers were included in this prospective, noninterventional cohort study. A computer-learning software package (the Organ Transplant Information System) was made available to all patients.
Using the four-item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively. Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple treatment regimens including a small number of doses per day and a small number of tablets per day were associated with NA at M3 and M12, respectively. Other factors predictive of NA included failure to use the Organ Transplant Information System software package at M6 and patient reports of adverse events at M12 and M24. Importantly, we observed that physicians underestimated the prevalence of adverse events when compared to patient self-reporting.
Our observed rate of medication NA in France is consistent with rates reported in previous studies. We found variability in NA risk factors over time as well as an unexpected risk factor (simple treatment regimens). These findings will be useful in developing effective adherence-promoting interventions.
Background Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments ...to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD) on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. Methods A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l’Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7 days. The main outcome will be the difference in this score at 4 weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Discussion Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. Clinical trial registration ClinicalTrials.Gov , NCT05092191.
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