Clinical efficacy and safety of switching from eculizumab to ravulizumab in adult patients with aHUS- real-world data.

BACKGROUND: The complement factor 5 (C5)-inhibitor eculizumab has been established as standard-of-care for the treatment of atypical hemolytic uremic syndrome (aHUS). In 2021, the long-acting C5-inhibitor ravulizumab was approved, extending intervals of intravenous treatment from two to eight weeks resulting in improvement of quality of life for patients and lowering direct and indirect therapy associated costs. METHODS: This multicenter, retrospective data analysis of 32 adult patients with aHUS (including 10 kidney transplant recipients) treated with eculizumab for at least three months and switched to ravulizumab aims to evaluate the safety and efficacy of switching medication in the real-world setting. Hematologic parameters, kidney function, concurrent therapy and aHUS associated events were evaluated three months before and until up to 12 months after switching to ravulizumab. RESULTS: Mean age (range) at ravulizumab initiation was 41 years (19-78 years) and 59% of the patients were female. Genetic analysis was available for all patients with 72% showing a pathogenic variant. Median time (range) on eculizumab before switching was 20 months (3-120 months). No new events of TMA or worsening of renal function were reported during up to 12 months of follow-up during ravulizumab treatment. CONCLUSIONS: This is the largest, non-industry derived, multi-center retrospective analysis of adult patients with aHUS switching C5-inhibitor treatment from eculizumab to ravulizumab in the real-world setting. Switching to ravulizumab was safe and efficient resulting in sustained hematological stability and preservation of renal function.

Feasibility Analysis of Ultrasound-Guided Placement of Tunneled Hemodialysis Catheters.

Introduction: Radiographic fluoroscopy is the current standard for placement of tunneled central venous catheters (CVCs) for hemodialysis. Radiographic fluoroscopy requires structural and personnel infrastructure and exposes the patient to ionizing radiation. Here, we investigate the feasibility of solely ultrasound-guided placement of tunneled central venous dialysis catheters (USCVCs). Methods: We evaluated prospectively collected single-center data regarding safety and catheter function of 134 consecutive patients who underwent USCVC implantation between 2020 and 2021. We used the inset guidewire to visualize the position of the catheter tip. In the case of inadequate visibility by ultrasound, we used intracardiac electrocardiography (ECG) recording or agitated saline. A total of 1844 catheter days were assessed. The optimal CVC position was defined as being within the upper right atrium (URA) and middle to deep right atrium. Results: Of the 134 USCVCs, 87% were placed on the right side. The primary success rate for optimal tip position and catheter function was 98%. Of the USCVCs, 97% were placed solely by ultrasound. Regarding positioning, 6% were in the vena cava superior zone, 70% in the URA and 24% in the middle to deep right atrium, resulting in a rate of 94% with optimal positioning. Effective blood flow averaged 292 ± 39 ml/min. There were no immediate procedure-associated complications. Conclusion: Placement of CVC for hemodialysis solely by ultrasound is an effective alternative to fluoroscopy-assisted placement.

[Treatment response and complications of older patients with ANCA(antineutrophil cytoplasmatic antibody)-associated vasculitis]. / Therapieansprechen und Komplikationen von älteren Patienten mit ANCA(antineutrophile cytoplasmatische Antikörper)-assoziierten Vaskulitiden.

BACKGROUND: ANCA (antineutrophil cytoplasmatic antibody)-associated vasculitis (AAV) mainly affects elderley people but adjusted therapy concepts for this patient group are lacking. AIM: The aim of this study was therefore to analyze differences in course and outcome of patients with AAV with respect to age. MATERIALS AND METHODS: 62 patients were analyzed for treatment response, of whom 53 (85%) experienced adverse events (AE and SAE) that could be evaluated. Older (> 65 yrs.) versus younger (< 65 yrs.) patients were compared. Treatment response was assessed at 6 months, complications were assessed over 18 months. RESULTS: Treatment response was not seen to differ by age groups. In multiple logistic regression, pulmonary involvement (OR = 6,9; CI = 1,7-27,8, p < 0,01) and ΔGFR [ml/min] (OR = 0,93; CI = 0,89-0,97, p < 0,01) were predictors of SAE. 14 patients had more than 1 SAE. Again, pulmonary involvement (28,2% vs. 78,6%, p < 0,01) was a risk factor and older patients (78,6% vs. 43,6%, p = 0,025) were more frequently affected. Patients with multiple SAEs received glucocorticoids of more than 5 mg/d for longer periods of time (171 ± 65 days vs. 120 ± 70 days, p = 0,03). DISCUSSION: No differences were found between older and younger patients with regard to treatment response. Multiple SAEs occurred more frequently in elderly patients. There was a correlation between pulmonary manifestation and duration of glucocorticoid therapy with a complicated course. The most frequent SAEs were infections requiring hospitalisation. CONCLUSION: Therapy for elderly patients should be individualized with the goal of a fast reduction of glucocorticoids. Special monitoring is indicated for elderly patients, especially those with pulmonary involvement.

[Frailty in renal diseases]. / "Frailty" bei nephrologischen Erkrankungen.

The term frailty describes a complex syndrome of reduced resistance to stress factors as a consequence of age-related degeneration in various organ systems.In the general population frailty is associated with poor clinical outcomes, including an increased risk of falls, hospitalization, functional impairment and mortality. Frailty occurs earlier and its prevalence is higher in patients with chronic kidney disease (CKD) compared to the general population. Frail patients with CKD, on dialysis or not, have reduced quality of life and increased hospitalization and mortality rates, regardless of age, sex or comorbidities.The identification of frailty in patients with CKD can lead to the detection of important and potentially modifiable risk factors. Early nephrological evaluation coupled with an interdisciplinary approach including primary care physicians, geriatricians, physiotherapists, occupational therapists and nutritionists, is fundamental in the prevention of frailty as well as in the management of frail patients with CKD.Several instruments have been developed to screen for and assess the degree of frailty; however, there is currently no recommendation as to which should be used in nephrology and how to manage frail patients with CKD. In this article we suggest an approach based on a multidimensional, interdisciplinary evaluation aimed at the early identification and management of frail CKD patients independent of the clinical setting of admission; however, more important than the method used is the need to identify and follow-up on frail CKD patients.

Eculizumab in chemotherapy-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare but severe complication of tumors and their chemotherapeutic treatment. We report on two patients with chemotherapy-induced TMA who were successfully treated with a short course of the terminal complement inhibitor eculizumab. Both patients quickly achieved remission of microangiopathic hemolytic anemia and recovery of renal function. After withdrawal of eculizumab, remission was stable over an observation period of 47 months and 15 months, respectively. Our data show that eculizumab is effective in treating chemotherapy-induced TMA. Discontinuation of eculizumab is feasible once the complement-activating condition is controlled and the trigger is eliminated. Additional studies need to determine the optimal duration of complement-directed therapies and validate effective monitoring strategies after discontinuation of such therapy.

Survey among nephrologists in Germany: current practice and management of pregnant women on dialysis
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BACKGROUND: To assess the experience and practice patterns of nephrologists in Germany with regard to the care of pregnant women on dialysis. METHODS: The 26-item internet survey sent by email asked for demographic information, subjective proficiency, maternal and fetal complications, treatment approaches and goals. RESULTS: Of the 2,015 surveys sent out, 200 (10%) were available for evaluation. 38% of respondents never provided care, whereas 62% treated at least one pregnant patient on dialysis. In 306 total reported cases of pregnant women on dialysis, 58% became pregnant while on maintenance dialysis, and 42% developed dialysis-dependent renal failure in the course of pregnancy. For women on peritoneal dialysis (PD), only 22% of the nephrologists would continue PD until delivery, while 78% would convert to hemodialysis either immediately or shortly before delivery. 40% of the respondents reported complications in either mother or child. 45% of the respondents routinely provided prenatal counseling, and 2/3 of the nephrologists did not routinely perform fetal monitoring. While we found a significant difference in self-reported proficiency between nephrologists having and those not having treated pregnant women on dialysis, only 40% of all physicians felt confident in treating pregnant women on dialysis. CONCLUSIONS: Our survey demonstrates that the practice of nephrologists in treating pregnant women on dialysis differs significantly. These findings highlight the need for European guidelines to standardize the care of pregnant dialysis patients.
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