Pour qui, pourquoi et comment favoriser et préconiser l’hémodialyse à domicile : des leçons à tirer de l’expérience de l’Australie et la Nouvelle-Zélande

Avec la croissance continue du nombre de patients souffrant d’insuffisance rénale terminale dans le monde, dans un contexte de ressources limitées des soins de santé, beaucoup d’emphase est mise sur l’importance de favoriser les modalités de dialyse à domicile, soit la dialyse péritonéale et l’hémodialyse à domicile (HDD). Toutefois, l’HDD est encore très peu utilisée, notamment au Canada. Ce mémoire visait à identifier pour qui, pourquoi et comment il est possible de favoriser l'utilisation de l'HDD dans nos milieux cliniques en se basant sur l'expérience de l'Australie et la Nouvelle-Zélande (ANZ), où le recours à l’HDD est le plus haut dans le monde, afin d’en tirer des leçons qui pourraient être transposées au modèle canadien. Ceci pourrait favoriser l’amélioration des soins des patients et, dans un deuxième temps, réduire les besoins en ressources humaines et les coûts associés aux thérapies de remplacement rénal. Le registre Australia and New Zealand Dialysis & Transplantation (ANZDATA) a été utilisé pour évaluer divers aspects de l’HDD en ANZ de 1997 à 2017. Tout d’abord, la présence d’un effet de centre dans le recours à la dialyse à domicile a été identifiée, démontrant que des caractéristiques, tant au niveau des patients que des centres, étaient responsables de la variabilité dans le taux d’utilisation d’HDD notée entre les centres de dialyse. Ensuite, il a été démontré qu’il n’existait pas d’effet de centre dans la durée de traitement d’hémodialyse, tant à domicile qu’en centre, mais que la variabilité de cette durée était principalement due aux caractéristiques propres aux patients, ainsi qu’à des pratiques variant entre les états/pays, et ce, de manière beaucoup plus notable en HDD. En effet, une plus grande flexibilité est offerte par cette modalité, qui est beaucoup moins affectée par la limitation des ressources que l’hémodialyse en centre. Finalement, il a été démontré que l’HDD était potentiellement une alternative équivalente à la transplantation rénale au niveau de la survie des patients dans le cas d’un greffon reçu d’un donneur à critères étendus.With the continued growth in the number of patients with end-stage renal disease around the world, in a context of limited healthcare resources, much emphasis is being placed on the importance of promoting home dialysis modalities, namely peritoneal dialysis and home hemodialysis (HHD). However, HHD is still underutilized, especially in Canada. This thesis aimed to identify for whom, why and how it is possible to promote the use of HHD based on the experience of Australia and New Zealand (ANZ), where the use of HHD is the highest in the world, to draw lessons that could be transposed to the Canadian model. The Australia and New Zealand Dialysis & Transplantation (ANZDATA) registry was used to assess various aspects of HHD in ANZ from 1997 to 2017. First, the presence of a center effect in the use of home dialysis was identified, demonstrating that both patient- and center-level characteristics were responsible for the variability noted in the rate of HHD use between dialysis centers. We then showed that there was no center effect in the duration of hemodialysis treatment, neither at home nor in center, but that the variability of this duration was mainly due to the characteristics of the patients, as well as to varying practices between states/countries, and this, more notably in HHD. Indeed, greater flexibility is offered by this modality, which is much less affected by the limitation of resources than in-center hemodialysis. Finally, HHD was shown to be potentially an equivalent alternative to kidney transplantation in terms of patient survival in the case of a transplant received from an expanded criteria donor

Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region:Report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA)

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplant, and a 3-fold higher than global median prevalence of dialysis centers. Peritoneal dialysis prevalence was lower than global median, and transplantation data was missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease (CKD), such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was more commonly identified as a governmental priority than was CKD or acute kidney injury. In this generally affluent region, there is better access to kidney replacement therapy and CKD-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals

Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS) aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions.</p> <p>Results</p> <p>PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1.</p> <p>Conclusions</p> <p>This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose) metabolism.</p

Bcl-2–Modifying Factor Induces Renal Proximal Tubular Cell Apoptosis in Diabetic Mice

This study investigated the mechanisms underlying tubular apoptosis in diabetes by identifying proapoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RPTCs) in models of diabetes. Total RNAs isolated from renal proximal tubules (RPTs) of 20-week-old heterozygous db/m+, db/db, and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real-time quantitative PCR assays, immunohistochemistry, and mice rendered diabetic with streptozotocin were used to validate the proapoptotic gene expression in RPTs. Cultured rat RPTCs were used to confirm the apoptotic activity and regulation of proapoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were used to confirm enhanced proapoptotic gene expression in RPTs. Bcl-2–modifying factor (Bmf) was differentially upregulated (P < 0.01) in RPTs of db/db mice compared with db/m+ and db/db CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs coimmunoprecipated with Bcl-2, enhanced caspase-3 activity, and promoted apoptosis. High glucose (25 mmol/L) induced Bmf mRNA expression in RPTCs, whereas rotenone, catalase, diphenylene iodinium, and apocynin decreased it. Knockdown of Bmf with small interfering RNA reduced high glucose–induced apoptosis in RPTCs. More important, enhanced Bmf expression was detected in RPTs of kidneys from patients with diabetes. These data demonstrate differential upregulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes

CA-125 early dynamics to predict overall survival in women with newly diagnosed advanced ovarian cancer based on meta-analysis data

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients’ monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy

Expression of TRPC6 channels in human epithelial breast cancer cells

<p>Abstract</p> <p>Background</p> <p>TRP channels have been shown to be involved in tumour generation and malignant growth. However, the expression of these channels in breast cancer remains unclear. Here we studied the expression and function of endogenous TRPC6 channels in a breast cancer cell line (MCF-7), a human breast cancer epithelial primary culture (hBCE) and in normal and tumour breast tissues.</p> <p>Methods</p> <p>Molecular (Western blot and RT-PCR), and immunohistochemical techniques were used to investigate TRPC6 expression. To investigate the channel activity in both MCF-7 cells and hBCE we used electrophysiological technique (whole cell patch clamp configuration).</p> <p>Results</p> <p>A non selective cationic current was activated by the oleoyl-2-acetyl-sn-glycerol (OAG) in both hBCE and MCF-7 cells. OAG-inward current was inhibited by 2-APB, SK&F 96365 and La³⁺. TRPC6, but not TRPC7, was expressed both in hBCE and in MCF-7 cells. TRPC3 was only expressed in hBCE. Clinically, TRPC6 mRNA and protein were elevated in breast carcinoma specimens in comparison to normal breast tissue. Furthermore, we found that the overexpression of TRPC6 protein levels were not correlated with tumour grades, estrogen receptor expression or lymph node positive tumours.</p> <p>Conclusion</p> <p>Our results indicate that TRPC6 channels are strongly expressed and functional in breast cancer epithelial cells. Moreover, the overexpression of these channels appears without any correlation with tumour grade, ER expression and lymph node metastasis. Our findings support the idea that TRPC6 may have a role in breast carcinogenesis.</p

ISPD Catheter-related Infection Recommendations: 2023 Update

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested