Annie-Claire Nadeau-Fredette

Lymphopenia and Treatment-Related Infectious Complications in ANCA-Associated Vasculitis

BACKGROUND AND OBJECTIVES ANCA-associated vasculitis (AAV) is treated with potent immunosuppressive regimens. This study sought to determine risk factors associated with infections during first-intention therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This retrospective study involved two separate cohorts of consecutive cases of AAV seen from 2004 to 2011 at two university hospitals. The following were assessed: vasculitis severity; therapy; and periods with no, moderate (lymphocyte count, 0.3-1.0× 10(9)/L), or severe (lymphocyte count ≤ 0.3×10(9)/L) lymphopenia and neutropenia (neutrophil count ≤ 1.5×10(9)/L). RESULTS One hundred patients had a mean age of 57±15 years and a Birmingham vasculitis activity score of 7.7±3.6. Therapy consisted of pulse methylprednisolone (59%), cyclophosphamide (85%), methotrexate (6%), and plasmapheresis (25%) in addition to oral corticosteroids. During follow-up, 53% of patients experienced infection and 28% were hospitalized for infection (severe infection). Only 18% experienced neutropenia, but 72% and 36% presented moderate and severe lymphopenia for a total duration of <0.1%, 73%, and 8% of the treatment follow-up, respectively. Lower initial estimated GFR, longer duration of corticosteroid use, and presence of lymphopenia were risk factors of infections. The rate was 2.23 events/person-year in the presence of severe lymphopenia compared with 0.41 and 0.19 during periods with moderate or no lymphopenia (P<0.001). Similarly, the rate of severe infections was 1.00 event/person-year with severe lymphopenia and 0.08 and 0.10 with moderate and no lymphopenia (P<0.001). This association remained independent of other risk factors. CONCLUSIONS Lymphopenia is frequent during the treatment of AAV, and its severity is associated with the risk of infectious complications.

End-Stage Renal Disease and Pregnancy

Pregnancy in patients with ESRD is rare and remains especially challenging. Because endocrine abnormalities and sexual dysfunction decrease fertility, conception rates have been remarkably low in this patient population. Moreover, when pregnancy does occur, hypertension, preeclampsia, anemia, intrauterine growth restriction, preterm delivery, stillbirth, and other complications can decrease the rate of a successful outcome. However, recent experiences with intensive hemodialysis managed by a multidisciplinary team are encouraging with respect to better overall outcomes for mothers and infants. In this article, we discuss the main causes of decreased fertility in dialysis-dependent women, review outcomes and complications of pregnancy among dialysis patients with a special focus on recent intensive hemodialysis data, and summarize the current best strategy to manage pregnant women on dialysis.

An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry)

BACKGROUND AND OBJECTIVES Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile-stratified model, and propensity score-matched model. RESULTS The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank P<0.001). Using multivariable Cox proportional hazards analysis, home hemodialysis was associated with superior patient survival (hazard ratio for overall death, 0.47; 95% confidence interval, 0.38 to 0.59) as well as better on-treatment survival (hazard ratio for on-treatment death, 0.34; 95% confidence interval, 0.26 to 0.45), composite patient and technique survival (hazard ratio for death or technique failure, 0.34; 95% confidence interval, 0.29 to 0.40), and death-censored technique survival (hazard ratio for technique failure, 0.34; 95% confidence interval, 0.28 to 0.41). Similar results were obtained with the propensity score models as well as sensitivity analyses using competing risks models and different definitions for technique failure and lag period after modality switch, during which events were attributed to the initial modality. CONCLUSIONS Home hemodialysis was associated with superior patient and technique survival compared with peritoneal dialysis.

Arteriovenous fistula for the 80 years and older patients on hemodialysis: is it worth it?

Over the last years, the proportion of patients older than 80 years with end‐stage renal disease has been constantly growing. Arteriovenous fistula (AVF) is known as the best vascular access for hemodialysis, but evidence for its added value is lacking for elderly. We retrospectively identified new vascular access (AVF and central venous catheter) created or installed between June 2005 and June 2008 in patients 80 years and older and in patients between 50 and 60 years. For every new AVF, we calculated primary failure, primary and secondary patency durations. Fifty‐five and 57 patients had a new vascular access in the >80 years old and 50 to 60 years old groups. Among these, 25 and 41 were new AVF in the older and younger groups. Primary failure was more frequent in elderly than in the younger (40% vs. 17%, P = 0.04). Primary patency was not significantly different in both groups (P = 0.06). Secondary patency was shorter in elderly (P = 0.005). Among the older group, the presence of an AVF was not associated with a difference in mortality (46% vs. 60%, P = 0.28), whereas there was a lower mortality in the younger group with AVF (12% vs. 43% P = 0.008). These results indicate lower patency duration in very elderly patients compared to middle‐aged patients. Without leading to the exclusion of patients over 80 years old for AVF creation, it might reinforce the need of a careful selection and evaluation in this population prior to referral.

Fluid Management and Use of Diuretics in Acute Kidney Injury

Critically ill adult patients at risk for or with acute kidney injury (AKI) require careful attention to their hemodynamic status because hypotension and hypovolemia may contribute to or worsen kidney injury. Increasing evidence suggests that isotonic crystalloids should be used instead of colloids for initial expansion of intravascular volume in patients at risk for AKI or with AKI, such as those with sepsis, septic shock, or trauma. The timing and amount of volume to be administered to prevent AKI and other organ damage is still debated, but an aggressive fluid repletion in the early setting is probably beneficial. However, fluid overload has also been associated with increased mortality and reduced rate of kidney recovery in observational studies in critically ill patients with AKI. Diuretics may prevent or treat fluid overload and may also affect kidney function. The efficacy of these procedures in critically ill AKI patients need to be confirmed with randomized controlled trials. This review focuses on early volume resuscitation, overall fluid management, and use of diuretics in critically ill adult patients at risk for or with AKI and their effect on mortality and kidney function in this setting.

Ten-year experience with fungal peritonitis in peritoneal dialysis patients: antifungal susceptibility patterns in a North-American center

OBJECTIVE To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hôpital Maisonneuve-Rosemont, from August 1996 to July 2006. METHODS Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method. RESULTS Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived. CONCLUSIONS In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates.

Center-specific factors associated with peritonitis risk—a multi-center registry analysis

♦ Background: Previous studies have reported significant variation in peritonitis rates across dialysis centers. Limited evidence is available to explain this variability. The aim of this study was to assess center-level predictors of peritonitis and their relationship with peritonitis rate variations. ♦ Methods: All incident peritoneal dialysis (PD) patients treated in Australia between October 2003 and December 2013 were included. Data were accessed through the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was peritonitis rate, evaluated in a mixed effects negative binomial regression model. Peritonitis-free survival was assessed as a secondary outcome in a Cox proportional hazards model. ♦ Results: Overall, 8,711 incident PD patients from 51 dialysis centers were included in the study. Center-level predictors of lower peritonitis rates included smaller center size, high proportion of PD, low peritoneal equilibration test use at PD start, and low proportion of hospitalization for peritonitis. In contrast, a low proportion of automated PD exposure, high icodextrin exposure and low or high use of antifungal prophylaxis at the time of peritonitis were associated with a higher peritonitis rate. Similar results were obtained for peritonitis-free survival. Overall, accounting for center-level characteristics appreciably decreased peritonitis variability among dialysis centers (p = 0.02). ♦ Conclusion: This study identified specific center-level characteristics associated with the variation in peritonitis risk. Whether these factors are directly related to peritonitis risk or surrogate markers for other center characteristics is uncertain and should be validated in further studies.

Con: Buttonhole cannulation of arteriovenous fistulae

Successful cannulation of arteriovenous fistulas (AVFs) using a safe and effective technique that minimizes patient harm is a crucial aspect of haemodialysis treatment. Although the current standard of care for many years has been the rope-ladder technique (using sharp needles to cannulate rotating sites across the entire AVF), a number of enthusiasts have recently advocated for the alternative method of buttonhole cannulation (using blunt needles to repeatedly cannulate the same site via a healed track) on the basis of putative, as yet unproven benefits. In this article, we review all available observational studies, randomized controlled trials, and systematic reviews and meta-analyses that have compared the clinical outcomes of buttonhole and rope-ladder cannulation of AVFs. These studies clearly and consistently demonstrated that buttonhole cannulation causes significant and serious infectious harm to haemodialysis patients, especially in the home setting. No strategies or treatments have been proven to effectively mitigate this hazard of buttonhole cannulation. Moreover, buttonhole cannulation is associated with a higher rate of abandonment and has not been shown to have any proven benefit compared with the rope-ladder method. Specifically, buttonhole cannulation has not been shown to reduce cannulation-related pain, improve vascular access survival, reduce vascular access interventions, reduce haematoma formation, improve haemostasis or reduce aneurysm formation. Consequently, rope-ladder cannulation should remain the standard of care and buttonhole cannulation should only be used in rare circumstances (e.g. short segment AVFs where the only alternative is a haemodialysis catheter).

Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis

BACKGROUND AND OBJECTIVES Technique failure is a major limitation of peritoneal dialysis. Our study aimed to identify center- and patient-level predictors of peritoneal dialysis technique failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients on incident peritoneal dialysis in Australia from 2004 to 2014 were included in the study using data from the Australia and New Zealand Dialysis and Transplant Registry. Center- and patient-level characteristics associated with technique failure were evaluated using Cox shared frailty models. Death-censored technique failure and cause-specific technique failure were analyzed as secondary outcomes. RESULTS The study included 9362 patients from 51 centers in Australia. The technique failure rate was 0.35 (95% confidence interval, 0.34 to 0.36) episodes per patient-year, with a sevenfold variation across centers that was mainly associated with center-level characteristics. Technique failure was significantly less likely in centers with larger proportions of patients treated with peritoneal dialysis (>29%; adjusted hazard ratio, 0.83; 95% confidence interval, 0.73 to 0.94) and more likely in smaller centers (<16 new patients per year; adjusted hazard ratio, 1.10; 95% confidence interval, 1.00 to 1.21) and centers with lower proportions of patients achieving target baseline serum phosphate levels (<40%; adjusted hazard ratio, 1.15; 95% confidence interval, 1.03 to 1.29). Similar results were observed for death-censored technique failure, except that center target phosphate achievement was not significantly associated. Technique failure due to infection, social reasons, mechanical causes, or death was variably associated with center size, proportion of patients on peritoneal dialysis, and/or target phosphate achievement, automated peritoneal dialysis exposure, icodextrin use, and antifungal use. The variation of hazards of technique failure across centers was reduced by 28% after adjusting for patient-specific factors and an additional 53% after adding center-specific factors. CONCLUSIONS Technique failure varies widely across centers in Australia. A significant proportion of this variation is related to potentially modifiable center characteristics, including peritoneal dialysis center size, proportion of patients on peritoneal dialysis, and proportion of patients on peritoneal dialysis achieving target phosphate level.

Central and Brachial Blood Pressures, Statins, and Low-Density Lipoprotein CholesterolNovelty and Significance: A Mediation Analysis

Central blood pressure may be a better predictor of cardiovascular disease than brachial pressure. Although statins reduce brachial pressure, their impact on central pressure remains unknown. Furthermore, whether this effect is mediated through a decrease in low-density lipoprotein cholesterol (LDL-c) is unknown. This study aims to characterize the association of statins and LDL-c with central and brachial blood pressures and to quantify their respective effects. Of the 20 004 CARTaGENE participants, 16 507 had available central blood pressure, LDL-c, and Framingham risk score. Multivariate analyses were used to evaluate the association between central pressure and LDL-c in subjects with or without statins. The impact of LDL-c on the association between statin and pressure parameters was determined through mediation analyses. LDL-c was positively associated with systolic and diastolic central pressure in nonusers (&bgr;=0.077 and 0.106; P<0.001) and in participants with statins for primary (&bgr;=0.086 and 0.114; P<0.001) and secondary prevention (&bgr;=0.120 and 0.194; P<0.003). Statins as primary prevention were associated with lower central systolic, diastolic, and pulse pressures (−3.0, −1.6, and −1.3 mm Hg; P<0.001). Mediation analyses showed that LDL-c reduction contributed to 15% of central systolic and 44% of central diastolic pressure changes associated with statins and attenuated 22% of the effects on central pulse pressure. Similar results were found with brachial pressure components. In conclusion, reduction of LDL-c was associated with only a fraction of the lower blood pressures in statin user and seemed to be mostly associated with improvement of steady (diastolic) pressure, whereas non–LDL-c–mediated pathways were mostly associated with changes in pulsatile pressure components.