RESUMO
Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD ,estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks treatment with standard of care plus subcutaneous cotadutide up-titrated to100, 300, or 600 µg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once-weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 µg (-43.9% [95%confidence interval -54.7 to -30.6]) and 600 µg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 µg were comparable to semaglutide. Thus, our study shows that in patients with T2Dand CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.
RESUMO
RATIONALE: The evidence supporting the safety of restarting peritoneal dialysis (PD) immediately after abdominal surgery and interventions is scant. In particular, there are no reported cases characterizing periprocedural management of PD for patients undergoing endoscopic submucosal dissection for gastric intramucosal tumor removal. PRESENTING CONCERNS OF THE PATIENT: A 66-year-old female with end-stage kidney disease secondary to diabetic nephropathy, currently on nocturnal automatic PD, presented with new iron-deficiency anemia. Workup revealed an intramucosal gastric lesion proximal to the pylorus, without surrounding lymph node involvement. Endoscopic submucosal dissection was performed with en bloc endoscopic resection of a 5-cm, partially flat, partially sessile mass along the posterior wall and lesser curvature of the gastric antrum. Pathology revealed low-grade dysplasia without features of malignancy. There was no evidence of hemorrhage or leak post-dissection. DIAGNOSES: The clinical presentation was consistent with an uncomplicated endoscopic submucosal dissection. INTERVENTIONS: Peritoneal dialysis was held for 48 hours and restarted thereafter with no complications. The patient did not require bridging with hemodialysis. OUTCOMES: The patient had an uncomplicated post-endoscopic course, with no subsequent episodes of PD-associated peritonitis after at least 6-month follow-up. NOVEL FINDING: This is the first reported case of PD reinitiation after endoscopic submucosal dissection of a gastric tumor.
JUSTIFICATION: Les données probantes soutenant l'innocuité de la reprise de la dialyse péritonéale (DP) immédiatement après une procédure ou une chirurgie abdominale sont rares. Surtout, il n'existe aucun cas signalé caractérisant la prise en charge périprocédurale de la dialyse péritonéale chez les patients subissant une dissection sous-muqueuse endoscopique pour l'ablation d'une tumeur de la muqueuse gastrique. PRÉSENTATION DU CAS: Une patiente de 66 ans atteinte d'insuffisance rénale terminale consécutive à une néphropathie diabétique. La patiente était traitée par dialyse péritonéale nocturne automatique et présentait une anémie ferriprive. Le bilan a révélé une lésion gastrique intramucosale à proximité du pylore, sans atteinte des ganglions lymphatiques environnants. Une dissection sous-muqueuse endoscopique a été pratiquée, avec exérèse endoscopique en monobloc d'une tumeur de 5-cm, partiellement plate et partiellement sessile, le long de la paroi postérieure et de la petite courbure de l'antre pylorique. L'examen pathologique a révélé une dysplasie de bas grade sans caractères de malignité. Aucun signe d'hémorragie ou de fuite n'a été observé après l'intervention. DIAGNOSTIC: Le tableau clinique était typique d'une dissection sous-muqueuse endoscopique sans complication. INTERVENTION: La dialyse péritonéale a été interrompue pour 48 heures, puis redémarrée sans complication. La patiente n'a pas eu besoin d'hémodialyse entre temps. RÉSULTATS: Le parcours post-endoscopique de la patiente s'est avéré simple, aucun épisode subséquent de péritonite associée à la DP n'a été rapporté après au moins six mois de suivi. CONCLUSION: Il s'agit du premier cas rapporté de reprise d'une dialyse péritonéale après la dissection sous-muqueuse endoscopique d'une tumeur gastrique.