Infectious Complications Associated to Buttonhole Cannulation of Native Arteriovenous Fistulas: A 22-year follow-up.

BACKGROUND AND HYPOTHESIS: Buttonhole cannulation of native arteriovenous fistulas (AVFs) appears associated with an increased infectious risk. We previously reported a dramatic increase in the incidence of infectious events after shift to buttonhole in an in-center hemodialysis unit, largely reduced after staff (re)education regarding strict respect of the procedure. We assessed the evolution over the following 12-years period in our center. METHODS: In this prospective follow-up of a previous, pre (rope-ladder)-post (buttonhole) comparison (2001-2010), all in-center hemodialysis patients with a native AVF were included from July 1st, 2010 to December 31st, 2022. Primary and secondary outcomes were infectious events (unexplained bacteraemia due to skin bacteria and/or local AVF infection) and complicated infectious events (metastatic infection, AVF surgery, death). Overall, the impact of several quality improvement strategies was tested according to the events rate over 6 periods: 1: Rope-ladder in all; 2: switch to buttonhole; 3: buttonhole in all, before workshops; 4: buttonhole in all, after workshops; 5: buttonhole withdrawal in problematic AVFs; 6: additional procedural changes. RESULTS: This extended observation period allowed adding 195,180 AVF-days to our previous report. Overall, 381,661 AVF-days (366 AVFs, 345 patients) were analysed. After an increase of the infectious events rate in 2012, the shift to rope-ladder in problematic AVFs during Period 5 did not have a significant impact. The incidence of infectious events decrease significantly during Period 6 compared to Periods 3, 4 and 5 [IRR 0.24 (95%CI 0.09-0.52) p=0.0001, IRR 0.22 (95%CI 0.09-0.47) p<0.0001, and IRR 0.29 (95%CI 0.11-0.66) p=0.001, respectively] and became eventually for the first time comparable to Period 1 [IRR 0.59 (95%CI 0.21-1.62) p=0.27]. CONCLUSION: The constant observance of reinforced hygiene protocols by trained staff and central coordination succeeded in significantly mitigating the infectious risk associated with buttonhole.

Dynamics of spreading of SARS-CoV-2 in a Belgian hemodialysis facility: The importance of the analysis of viral strains.

In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.

Circulating Proprotein Convertase Subtilisin/Kexin type 9 level independently predicts incident cardiovascular events and all-cause mortality in hemodialysis black Africans patients.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of mortality in patients with end-stage kidney disease (ESKD). The aim of the present study was to determine whether Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) could be an independent predictor of CV events and all-cause mortality in black African haemodialysis patients. METHODS: We carried out a prospective cohort study of all consecutive hemodialysis (HD) patients between August 2016 and July 2020, admitted in six hemodialysis centers of Kinshasa, Democratic Republic of Congo. Independent determinants of plasma PCSK-9 measured by ELISA were sought using multiple linear regression analysis. Kaplan-Meier's method described the incidence of CV events while competitive and proportional risk models looked for independent risk factors for death at the .05 significance level. RESULTS: Out of 207 HD patients, 91 (43.9%) died; 116 (56.1%) have survived. PCSK9 level was significantly higher in deceased patients compared to survivors: 28.0 (24.0-31.0) ng/l vs 9.6 (8.6-11.6) ng/ml (p <  0.001). Patients with plasma PCSK9 levels in tertile 3 had a higher incidence of CV events and mortality compared to patients with plasma PCSK9 levels in tertile 2 or tertile 1 (p <  0.001). Tertile 3 negatively influence survival rates (26.6%) compared to tertile 2 (54.7%) and tertile 1 (85.3%). Patients in tertile 3 and tertile 2 had a 4-fold higher risk of death than patients in tertile 1. After adjustment for all parameters, competitive risk analysis showed that mortality was 2 times higher in patients with stroke. Similarly, serum albumin < 3.5 g/dL or PCSK9 in tertile 3 were respectively associated with 2 or 6 times higher rates of deaths. CONCLUSION: Elevated plasma PCSK9 level is an independent major predictor of incident CV events and all-cause mortality in black African HD patients.

Central diabetes insipidus induced by temozolomide: A report of two cases.

INTRODUCTION: Central diabetes insipidus is a heterogeneous condition characterized by decreased release of antidiuretic hormone by the neurohypophysis resulting in a urine concentration deficit with variable degrees of polyuria. The most common causes include idiopathic diabetes insipidus, tumors or infiltrative diseases, neurosurgery and trauma. Temozolomide is an oral DNA-alkylating agent capable of crossing the blood-brain barrier and used as chemotherapy primarily to treat glioblastoma and other brain cancers. CASES: Two men (aged 38 and 54 years) suddenly developed polyuria and polydispsia approximately four weeks after the initiation of temozolomide for a glioblastoma. Plasma and urine parameters demonstrated the presence of a urinary concentration defect. MANAGEMENT: The clinical and laboratory abnormalities completely resolved with intranasal desmopressin therapy, allowing the continuation of temozolomide. The disorder did not relapse after cessation of temozolomide and desmopressin and relapsed in one patient after rechallenge with temozolomide. DISCUSSION: Our report highlights the importance of a quick recognition of this exceptional complication, in order to initiate promptly treatment with desmopressin and to maintain therapy with temozolomide.

Antibiotic locks for the treatment of catheter-related blood stream infection: Still more hope than data.

Antibiotic lock therapy (ALT), in conjunction with systemic antibiotics, is recommended by scientific societies as a treatment of uncomplicated catheter-related bloodstream infections (CRBSI) in hemodynamically stable hemodialysis patients for whom catheter salvage is the goal. The rationale for this strategy is the eradication of intraluminal biofilms by the highly concentrated antibiotic used in the lock. However, the available evidence supporting this recommendation is scanty, and only includes small, short-term, observational studies (most of them single-arm), with different definitions of CRBSI cure and variable follow-up periods. Furthermore, the ability of an antibiotic to eradicate a biofilm is not predicted by its inherent spectrum of antibacterial activity, since sessile microorganisms in their biofilm display other mechanisms of resistance to antibiotics than their planktonic counter-parts. Additionally, penetration of some antibiotics frequently used into biofilms produced by common microorganisms appears to be low. In this editorial we provide a critical view on the available evidence regarding the efficacy of ALT on the treatment of CRBSI in hemodialysis patients, as well as the microbiological issues and technical challenges of this strategy.

Superior vena cava stenosis in haemodialysis patients with a tunnelled cuffed catheter: prevalence and risk factors.

Background: Although superior vena cava (SVC) stenosis may be a life-threatening complication of haemodialysis (HD) catheters, its prevalence and risk factors in HD patients are unknown. Our aim was to assess the prevalence and risk factors for SVC stenosis in HD patients with a tunnelled cuffed catheter (TCC) and to describe its clinical presentation. Methods: In this single-centre, retrospective cohort study, all in-centre chronic HD patients carrying a TCC (1 January 2008-31 December 2012) were included (n = 117 patients, 214 TCC, 80 911 catheter-days). SVC stenosis was defined as a diameter reduction >50% on phlebography or computed tomography. Imaging was triggered by clinical SVC stenosis syndrome or vascular access (VA)-related concerns. We recorded demographics, conditions potentially influencing catheter permeability (medications, carriage of thoracic devices), number of TCCs, total duration of TCC carriage, previous arteriovenous VA and last (in use at time of stenosis detection) TCC details (location, diameter and length). VAs created while a TCC was still used were also recorded. Results: An SVC stenosis was found in 11 patients (9.4%, 0.14/1000 catheter-days), which represents almost one-quarter of patients undergoing imaging, whatever the cause (11/45). Only two presented with clinically obvious SVC stenosis. The number of TCCs per patient was 2.64 ± 1.8 in the SVC stenosis group versus 1.75 ± 0.94 in the negative group (P = 0.13). On multivariate analysis (Poisson), diabetes {incidence rate ratio [IRR] 4.63 [confidence interval (CI) 1.2-17.8]; P = 0.02} and total duration of TCC carriage [IRR 1.47 (CI 1.2-1.8) per year; P = 0.001] were associated with SVC stenosis, whereas age had a slightly protective effect [IRR 0.96 (CI 0.91-1.01); P = 0.01]. Limitations are the retrospective design, detection and survivor bias. Conclusion: SVC stenosis is not a rare condition, is mostly asymptomatic in the absence of a peripheral VA, is strongly associated with diabetes and is promoted by long TCC carriage. Age is slightly protective.

Dialysis-related Amyloidosis: Is It Gone or Should It Be?

The prevalence and severity of dialysis-related amyloidosis (DRA) appear to have decreased significantly over the last two decades, although recent, large-scale epidemiological studies show that DRA continues to occur. Recent experimental findings have documented a direct cellular toxicity of ß2microglobulin (ß2m) fibrils but the mechanisms of ß2m fibrillogenesis remain incompletely understood. Although a high plasma concentration of ß2m is still considered as a prerequisite for developing DRA, other factors have been clearly incriminated such as older age at dialysis onset and longer dialysis vintage, or suspected effects such as proinflammatory effects of bioincompatible dialysis techniques. Improved dialysis technology has definitely played a role in delaying the onset of the disease, although the respective contributions of high-flux biocompatible membranes, use of convective mode, and ultrapure dialysate remain imperfectly defined. Importantly, DRA still does exist and no current dialytic modality seems able to fully prevent it. Awaiting further progress in the understanding of DRA pathogenesis, the use of biocompatible high-flux membranes and ultrapure dialysate is strongly recommended in order to minimize or delay its onset. Convective regimens may provide an additional benefit.

Moderator's View: Buttonhole cannulation of arteriovenous fistulae: great caution is warranted.

Potential advantages of buttonhole (BH) cannulation over the standard rope-ladder technique have been claimed on the basis of small sized, potentially biased observational studies with a relatively short follow-up. On the contrary, randomized controlled trials (RCTs) show inconclusive or conflicting results. The uncertain benefit must thus be weighed against a definite increase in the infectious risk with the BH technique, which may not be completely abolished by preventative strategies. Awaiting the results of long-term studies (>2-3 years follow-up), the widespread use of the BH technique is not warranted, especially in busy in-centre haemodialysis (HD) settings with many rotating nurses. In our experience, the BH technique has been implemented safely in a self-care HD unit, presumably because of the limited number of cannulators and, in the case of self-cannulating patients, direct supervision by a small team of nurses. Units (and patients) willing to use the BH technique should be aware that BH is an extremely demanding technique and requires constant and strict adherence to the protocol. Regular monitoring of infection rates is recommended. Additional RCTs are clearly warranted, together with large-sized observational studies with multivariable adjustment.

Con: Frequent haemodialysis for all chronic haemodialysis patients.

Frequent haemodialysis (HD) regimens have been proposed with the aim to improve survival and other important patient outcomes. They indeed avoid the long interdialytic interval and have been associated with some proven benefits, i.e. an improvement in blood pressure and phosphataemia control, a reduction in left ventricular mass and lower ultrafiltration rates. However, the actual impact of frequent HD regimens on survival is, at best, inconclusive and, at worse, harmful, and remains uncertain regarding nutritional status and anaemia control. Moreover, the higher rates of vascular access complications and more rapid development of anuria with frequent HD regimens are worrying. Frequent HD also considerably increases the burden for patients and their caregivers, logistics and costs, especially with in-centre frequent schedules. In our opinion, before increasing HD frequency, a number of underused strategies summarized in our review and able to improve patient tolerance and/or HD dose should be tested first, taking into account patient's characteristics and life expectancy. Frequent HD schedules should be reserved for selected cases, only after all other available options have failed.

Paradoxical response to furosemide in uromodulin-associated kidney disease.

Mutations in the UMOD gene coding for uromodulin cause autosomal dominant tubulointerstitial kidney disease. Uromodulin is known to regulate transport processes in the thick ascending limb, but it remains unknown whether UMOD mutations are associated with functional tubular alterations in the early phase of the disease. The responses to furosemide and to a water deprivation test were compared in a 32-year-old female patient carrying the pathogenic UMOD mutation p.C217G and her unaffected 31-year-old sister. A single dose of furosemide induced an intense headache with exaggerated decrease in blood pressure (Δsyst: 30 versus 20 mmHg; Δdiast: 18 versus 5 mmHg) and body weight (Δ2.6 kg versus Δ0.9 kg over 3 h) in the proband versus unaffected sib. The diuretic response and the fall in urine osmolality were also more important and detected earlier in the affected sib. Water deprivation led to increased plasma osmolality and urine concentration in both siblings; however, the response to desmopressin was attenuated in the affected sib. These data reveal that mutations of uromodulin cause specific transport alterations, including exaggerated response to furosemide and a failure to maximally concentrate urine, in the early phase of the disease.