Technologie voor een gezonde toekomst

Rede uitgesproken door prof.dr. J.I. Rotmans bij de aanvaarding van het ambt van hoogleraar met als leeropdracht Interne Geneeskunde, in het bijzonder technische innovaties voor nierpatiënten aan de Universiteit van Leiden op 24 maart 2023Rede uitgesproken door prof.dr. J.I. Rotmans bij de aanvaarding van het ambt van hoogleraar met als leeropdracht Interne Geneeskunde, in het bijzonder technische innovaties voor nierpatiënten aan de Universiteit van Leiden op 24 maart 2023LUMC / Geneeskund

A Randomized Trial of Liposomal Prednisolone (LIPMAT) to Enhance Radiocephalic Fistula Maturation: A Pilot Study

INTRODUCTION: Maturation failure of radiocephalic arteriovenous fistulas (RCAVF) is a significant clinical issue. Vascular inflammation after AVF surgery is associated with non-maturation.OBJECTIVE: To evaluate whether liposomal prednisolone improves RCAVF maturation in end-stage renal disease (ESRD) patients.DESIGN: The LIPMAT-study was a multi-center, double-blind, 1:1 randomized, placebo-controlled trial.MATERIALS AND METHODS: Subjects were enrolled after RCAVF creation and treated with placebo or 150 mg of liposomal prednisolone at days 1 and 15 after AVF surgery. The primary end point was the juxta-anastomotic diameter of the cephalic vein at 6 weeks after surgery. Secondary end points were the diameter of the cephalic vein, brachial and radial artery at 6 weeks and 3 months after surgery as well as AVF flow and functional use for hemodialysis. Adverse events were compared to assess safety.RESULTS: 29 subjects were included of which 13 received placebo and 16 received liposomal prednisolone. The juxta-anastomitic cephalic vein diameter at 6 weeks was 3.9 mm (95% confidence interval 2.7 – 5.8 mm) in the placebo group and 3.7 mm (95% confidence interval 3.0 – 5.3 mm) in the liposomal prednisolone group (p=0.88). No significant differences in secondary end point parameters were observed. Treatment of end-stage renal disease patients with liposomal prednisolone was not associated with significant side effects.CONCLUSION: Liposomal prednisolone treatment of ESRD patients was safe, but did not result in enhanced RCAVF maturation. Vascular Surger

Recent advances in liposomal-based anti-inflammatory therapy

Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects. Nonetheless, few liposomal formulations seem to reach the clinic. The current review provides an overview of the more recent innovations in liposomal treatment of rheumatoid arthritis, psoriasis, vascular inflammation, and transplantation. Cutting edge developments include the liposomal delivery of gene and RNA therapeutics and the use of hybrid systems where several liposomal bilayer features, or several drugs, are combined in a single formulation. The majority of the articles reviewed here focus on preclinical animal studies where proof-of-principle of an improved efficacy-safety ratio is observed when using liposomal formulations. A few clinical studies are included as well, which brings us to a discussion about the challenges of clinical translation of liposomal nanomedicines in the field of inflammatory diseases.Nephrolog

A novel technique to restore access in patients with central venous occlusion using the Surfacer(R) Inside-Out(R) Access Catheter System

Exhausted central venous access is a potentially life-threatening situation for patients dependent on haemodialysis. If standard guidewire recanalisation fails, unconventional venous access or central venous needle recanalisation can be considered but are often associated with higher rates of complications and/or dysfunction. Here, we report about two patients treated successfully with the Surfacer(R) Inside-Out(R) Access Catheter System (Bluegrass Vascular Technologies, San Antonio, TX, USA) to achieve transmediastinal central venous access.Cardiovascular Aspects of Radiolog

Practice variation in the treatment of patients with renal hyperparathyroidism: a survey-based study in the Netherlands

Background Renal hyperparathyroidism is a disease entity that is complex and poorly understood. Although there are guidelines regarding how to manage this patient group, evidence is scarce. Therefore, this survey-based study aims to map the physicians' attitude in terms of preference for management of renal hyperparathyroidism and the influence of patient and respondent factors. Methods A survey was sent to Dutch societies of nephrology, endocrinology, and surgeons with interest in endocrine surgery. The survey consisted of eight case vignettes of renal hyperparathyroidism patients who were on hemodialysis and suitable for kidney transplantation, and varied in one of three patient variables import for decision making: age (40 vs. 65 years), parathyroid hormone (40 vs. 90 pmol/L), and serum calcium level (2.25 vs. 2.8 mmol/L). For each case, respondents could choose between maintaining conservative treatment (active vitamin D metabolites), calcimimetics, or subtotal parathyroidectomy as their treatment of choice. Categorical multilevel logistic models were used to investigate the association of patient and respondent variables with treatment preference. The influence of patient variables was determined independently of each other and by means of logistic regression the probabilities of treatment choice were calculated. Results In total, 115 surveys were included in the analysis. In 6 out of 8 cases, less than two-thirds of respondents agreed on the most favoured treatment. Among patient characteristics, the main disincentive for respondents not to choose conservative therapy was an elevated serum calcium level (subtotal parathyroidectomy vs conservative OR 93.1, 95%-CI: 48.39-179.07 and calcimimetics vs conservative OR 31.2 95%-CI: 18.58-52.30). Additionally, the most significant treatment differences were found between medical specialties and the experience of the respondents, expressed as the amount of cases the physician was involved in during the past year. Conclusions Elevated serum calcium levels were widely recognized and the prime reason for respondents to abandon conservative treatment. However, considerable disagreement in treatment preferences remained throughout the cases, demonstrating the current literature available being inconclusive in guiding physicians. Therefore, a high-quality trial comparing subtotal parathyroidectomy to medical treatment is needed to determine optimal treatment.Diabetes mellitus: pathophysiological changes and therap

Prognostic Implications of Left Ventricular Global Longitudinal Strain in Predialysis and Dialysis Patients

Nephrolog

Left Ventricular Mechanical Dispersion and Global Longitudinal Strain and Ventricular Arrhythmias in Predialysis and Dialysis Patients

Cardiolog

The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease

AimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.Methods and resultsTen patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 & PLUSMN; 17 to 97 & PLUSMN; 23 & mu;mol/L, p = 0.036, and 72 & PLUSMN; 14 vs. 66 & PLUSMN; 16 ml/min/1.73m(2), p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.ConclusionDapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population

The best solution down the line: an observational study on taurolidine- versus citrate-based lock solutions for central venous catheters in hemodialysis patients

Introduction To prevent infection and thrombosis of central venous catheters (CVCs) in hemodialysis patients, different CVC lock solutions are available. Taurolidine-based solutions and citrate in different concentrations are frequently used, but no definite conclusions with regard to superiority have been drawn. Methods In this retrospective, observational, multicenter study, we aimed to assess the risk for removal of CVC due to infection or catheter malfunction in hemodialysis patients with CVC access for different lock solutions: taurolidine, high-concentrated citrate (46.7%) and low-concentrated citrate (4 or 30%). A multivariable Cox-regression model was used to calculate hazard ratio's (HR). Results We identified 1514 patients (median age 65 years, 59% male). In 96 (6%) taurolidine-based lock solutions were used. In 1418 (94%) citrate-based lock solutions were used (high-concentrated 73%, low-concentrated 20%). Taurolidine-based lock solutions were associated with a significantly lower hazard for removal of CVC due to infection or malfunction combined (HR 0.34, 95% CI 0.19-0.64), and for removal of CVC due to infection or malfunction separately (HR 0.36, 95% CI 0.15-0.88 and HR0.33, 95% CI 0.14-0.79). High-concentrated citrate lock solutions were not associated with a decreased hazard for our outcomes, compared to low-concentrated citrate lock solutions. Conclusion Removal of CVC due to infection or catheter malfunction occurred less often with taurolidine-based lock solutions. We present the largest cohort comparing taurolidine- and citrate-based lock solutions yet. However, due to the retrospective observational nature of this study, conclusions with regard to superiority should be drawn with caution.Clinical epidemiolog

Comparative effectiveness of renin-angiotensin system inhibitors and calcium channel blockers in individuals with advanced CKD: a nationwide observational cohort study

Rationale & Objective: It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy.Study Design: Observational study in the Swedish Renal Registry, 2007 to 2017.Settings & Participants: 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates < 30 mL/min/1.73 m(2) (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60 mL/min/1.73 m(2)) were evaluated.Exposures: RAS inhibitor versus CCB therapy initiation.Outcome: Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke).Analytical Approach: HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates.Results: Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs.Limitations: Potential confounding by indication.Conclusions: Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.Clinical epidemiolog