James M. Zacharias

Impact of contraindications, barriers to self-care and support on incident peritoneal dialysis utilization

BACKGROUND Targets for peritoneal dialysis (PD) utilization may be difficult to achieve because many older patients have contraindications to PD or barriers to self-care. The objectives of this study were to determine the impact that contraindications and barriers to self-care have on incident PD use, and to determine whether family support increased PD utilization when home care support is available. METHODS Consecutive incident dialysis patients were assessed for PD eligibility, offered PD if eligible and followed up for PD use. All patients lived in regions where home care assistance was available. RESULTS The average patient age was 66 years. One hundred and ten (22%) of the 497 patients had absolute medical or social contraindications to PD. Of the remaining 387 patients who were potentially eligible for PD, 245 (63%) had at least one physical or cognitive barrier to self-care PD. Patients with barriers were older, weighed less and were more likely to be female, start dialysis as an inpatient and have a history of vascular disease, cardiac disease and cancer. Family support was associated with an increase in PD eligibility from 63% to 80% (P = 0.003) and PD choice from 40% to 57% (P = 0.03) in patients with barriers to self-care. Family support increased incidence PD utilization from 23% to 39% among patients with barriers to self-care (P = 0.009). When family support was available, 34% received family-assisted PD, 47% received home care-assisted PD, 12% received both family- and home care-assisted PD, and 7% performed only self-care PD. Incident PD use in an incident end-stage renal disease (ESRD) population was 30% (147 of the 497 patients). CONCLUSIONS Contraindications, barriers to self-care and the availability of family support are important drivers of PD utilization in the incident ESRD population even when home assistance is available. These factors should be considered when setting targets for PD.

Alteplase Versus Urokinase for Occluded Hemodialysis Catheters

BACKGROUND The use of central venous catheters as a source of vascular access in patients undergoing hemodialysis may be complicated by thrombosis. Frequently, thrombolytics are used in an attempt to reestablish blood flow through partially or completely occluded catheters. OBJECTIVE To compare the efficacy of alteplase (recombinant tissue plasminogen activator) versus urokinase in reestablishing adequate blood flow through partially or completely occluded vascular catheters. METHODS Part 1 of the study prospectively investigated the effect of alteplase in reestablishing adequate blood flow through partially or completely occluded vascular catheters in 30 hemodialysis patients. Part 2 of the trial compared the efficacy of alteplase with that of urokinase in 14 of 30 patients who had also previously received urokinase. A 30-minute push-protocol was used to administer thrombolytics in both parts of the study. The primary endpoint was the proportion of patients with partially or completely occluded catheters achieving post-thrombolytic blood flow of ≥200 mL/min. RESULTS Part 1 showed a large proportion of partially or completely occluded catheters achieving post-alteplase blood flows ≥200 mL/min (70/76, 92.1% vs. 34/40, 85%, respectively). In Part 2 of the study, the proportion of partially occluded catheters achieving post-thrombolytic blood flows ≥200 mL/min was not significantly different between the alteplase and urokinase groups, (36/41, 87.8% vs. 21/28, 75%, respectively; p = 0.205). The proportion of completely occluded catheters achieving post-thrombolytic blood flows ≥200 mL/min was significantly better with alteplase compared with urokinase (15/17, 88.2% vs. 6/14, 42.8%, respectively; p = .018). CONCLUSIONS Alteplase, administered via the 30-minute push-protocol, is an effective thrombolytic for restoring hemodialysis catheter patency. In our study sample, alteplase was generally more effective than urokinase in restoring blood flow through catheters, especially those that were completely occluded.

Choosing peritoneal dialysis reduces the risk of invasive access interventions

BACKGROUND Patients choosing between hemodialysis (HD) and peritoneal dialysis (PD) should be well informed of the risks and benefits of each modality. Invasive access interventions are important outcomes because frequent interventions lower patients quality of life and consume limited resources. The objective of this study was to compare the risk of access interventions between the two modalities. METHODS Three hundred and sixty-nine incident chronic dialysis patients were prospectively enrolled at four Canadian centers that were eligible for both modalities, received at least 4 months of pre-dialysis care and started dialysis electively as an outpatient. Two hundred and twenty-four (61%) chose PD and 145 (39%) chose HD. Patients were followed for an average of 1.3 years (range 0.07-3.6 years). RESULTS In the PD group, there were fewer access interventions (2.5 versus 3.1 interventions per patient, adjusted odds ratio of 0.79 for PD versus HD, P = 0.005) and a lower intervention rate (2.3 versus 1.9 per patient-year, adjusted rate ratio of 0.81 for PD versus HD, P = 0.04). PD catheters were less likely to experience primary failure (4.6 versus 32%, P < 0.0001), showed a trend toward lower intervention rates during use (0.8 versus 1.2 per patient-year, P = 0.06), and had equal patency compared to fistulae (1-year patency of 84 versus 88%, P = 0.48). Patients managed exclusively with HD catheters (28% of the HD group) required 1.7 interventions per patient and an intervention rate of 1.9 per patient-year. CONCLUSION Patients who choose PD require fewer access interventions to maintain dialysis access than patients choosing HD.

Prevalence, risk factors and awareness of albuminuria on a Canadian First Nation: A community-based screening study

BackgroundBoth diabetic and non-diabetic end stage renal disease (ESRD) are more common among Canadian First Nations people than among the general Canadian population. The purpose of this research was to determine the prevalence of and risk factors for albuminuria in a Canadian First Nation population at high risk for ESRD and dialysis.MethodsData from a community-based screening study of 483 residents of a Plains Ojibway First Nation in Manitoba was used. Participants provided random urine samples. Proteinuria was defined as any dipstick positive for protein (≥1 g/L) or those with ACR in the macroalbuminuric range (≥30 mg/mmol) on at least one sample. Microalbuminuria was defined as ACR ≥2 mg/mmol for males and ≥2.8 mg/mmol for females. Other measures included fasting glucose, haemoglobin A1c, triglycerides, cholesterol, blood pressure, height, weight and waist and hip circumferences.ResultsTwenty percent of study participants had albuminuria, (5% proteinuria and 15% microalbuminuria). Of participants with diabetes, 42% (56/132) had albuminuria compared to 26% (7/27) among those with impaired fasting glucose and 10% (30/303) among those with normal glucose tolerance. Only 5.3% of those with albuminuria were aware of any degree of renal disease. In a multivariate logistic regression, independent associations with albuminuria were male gender [p = 0.002], increasing fasting glucose [p <0.0001], years diagnosed with diabetes [p = 0.03], increasing systolic blood pressure [p = 0.009], and increasing body mass index (BMI) [p = 0.04].ConclusionsThe independent association between BMI and albuminuria has not been previously reported among indigenous populations. There is a high prevalence of albuminuria in this Canadian First Nation population; the high proportion of patients with diabetes and undiagnosed kidney disease demonstrates the need for screening, education and intervention to halt the progression and development of albuminuria and ultimately ESRD and CVD.

Antigenic Heterogeneity of IgA Anti-GBM Disease: New Renal Targets of IgA Autoantibodies

Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of alpha 3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the alpha 3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patients IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the alpha 3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results.

Dignity and Distress towards the End of Life across Four Non-Cancer Populations

Objective The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations. Design A prospective, multi-site approach was used. Setting Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada. Participants Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly. Main Outcome Measure In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI). Results Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102). Depending on group designation, 35% to 58% died within one year of taking part in the study. While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4–11%), the number of PDI items reported as problematic was significantly different i.e. ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001]. Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress. Conclusion People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life. Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs.

Risk Factors for Infectious Spondylodiscitis in Patients Receiving Hemodialysis

A retrospective case-control and cohort analysis of hemodialysis patients was done to identify risk factors for spondylodiscitis. These risk factors included bacteremia, receipt of blood products, invasive procedures, and establishment of vascular access. The death rate was greater for case subjects than for control subjects (odds ratio, 2.7).

Bayesian pharmacokinetics of gentamicin in a haemodialysis population.

AbstractBackground: Aminoglycosides are commonly used in the haemodialysis population. Standard pharmacokinetic approaches require multiple sampling to describe the parameters of drug distribution and elimination in the intra- and interdialytic periods. Objective: To characterise the pharmacokinetics of gentamicin in a haemodialysis population by using Bayesian pharmacokinetic methods and only two plasma concentrations. Design and participants: Prospective case series of 13 adult (aged 36–70 years) haemodialysis patients (Fresenius F80 dialysers were used) receiving gentamicin. Methods: Patients with suspected or confirmed Gram-negative infections were given gentamicin. At 48 hours after receiving the dose (at the next haemodialysis session), patients provided two blood samples, one immediately before the dialysis session and another 1 hour after haemodialysis. Data on dosage, timing and plasma concentrations for all subjects were analysed with PASTRX version 10.6 and Bayesian pharmacokinetic analysis. Volume of distribution (Vd), interdialytic elimination rate constant (kinter), interdialytic elimination half-life (t½β, inter) and interdialytic clearance (CLinter) were determined from a single predialysis plasma concentration. Elimination rate constant (kdinal), elimination half-life (t½β, dial) and clearance (CLdial) during 3.5–4 hours of dialysis were also determined from the pre- and post-plasma concentrations. Results: Pharmacokinetic parameters (mean ± SD) were: Vd 0.288 ± 0.002 L/kg, kinter 0.015 ± 0.004h−1, t½β, inter 48 ± 11h, CLinter 5.9 ± 2.4 mL/min, kdial 0.25 ±0.05 h−1, t½β, dial 3.0 ± 1.0h and CLdial 91 ± 24 mL/min. Conclusion: The rate of elimination of gentamicin was 17-fold greater (95% CI 13.7–20.7) on haemodialysis with a Fresenius F80 than off haemodialysis. All of the pharmacokinetic parameters of interest were determined using Bayesian pharmacokinetic procedures and only two plasma gentamicin concentrations.

Impact of Modality Choice on Rates of Hospitalization in Patients Eligible for Both Peritoneal Dialysis and Hemodialysis

♦ Background: Hospitalization rates are a relevant consideration when choosing or recommending a dialysis modality. Previous comparisons of peritoneal dialysis (PD) and hemodialysis (HD) have not been restricted to individuals who were eligible for both therapies. ♦ Methods: We conducted a multicenter prospective cohort study of people 18 years of age and older who were eligible for both PD and HD, and who started outpatient dialysis between 2007 and 2010 in four Canadian dialysis programs. Zero-inflated negative binomial models, adjusted for baseline patient characteristics, were used to examine the association between modality choice and rates of hospitalization. ♦ Results: The study enrolled 314 patients. A trend in the HD group toward higher rates of hospitalization, observed in the primary analysis, became significant when modality was treated as a time-varying exposure or when the population was restricted to elective outpatient starts in patients with at least 4 months of pre-dialysis care. Cardiovascular disease, infectious complications, and elective surgery were the most common reasons for hospital admission; only 23% of hospital stays were directly related to complications of dialysis or kidney disease. ♦ Conclusions: Efforts to promote PD utilization are unlikely to result in increased rates of hospitalization, and efforts to reduce hospital admissions should focus on potentially avoidable causes of cardiovascular disease and infectious complications.

UPPER EXTREMITY COMPLICATIONS IN PATIENTS WITH CHRONIC RENAL FAILURE RECEIVING HAEMODIALYSIS

Limited data are available about disability associated with upper extremity complications in patients who receive haemodialysis for end-stage renal disease. In this study of 123 patients receiving haemodialysis, the mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 31 ± 22 points, indicating markedly greater disability than in a normal population. Dupuytrens contracture was the most frequent deformity. Brachial, radial and ulnar pulses were present in most upper limbs, but 14 (14%) of 102 patients had poor arterial perfusion pressures. Diabetic patients had residual or complete loss of protective sensation more frequently than nondiabetic patients. Motor testing with the index finger abduction and fifth finger flexion tests showed a significantly greater frequency of weakness in diabetic than nondiabetic patients. In summary, upper extremity disability was noted in haemodialysis patients, including loss of protective sensation and motor strength, both in diabetic and nondiabetic subjects.