Karthik K. Tennankore

Intensive Hemodialysis Associates with Improved Pregnancy Outcomes: A Canadian and United States Cohort Comparison

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.

Frailty and Mortality in Dialysis: Evaluation of a Clinical Frailty Scale

BACKGROUND AND OBJECTIVES Frailty is associated with poor outcomes for patients on dialysis; however, previous studies have not taken into account the severity of frailty as a predictor of outcomes. The purpose of this study was to assess if there was an association between the degree of frailty and mortality among patients on incident dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cohort study of incident chronic dialysis patients was conducted between January of 2009 and June of 2013 (last follow-up in December of 2013). On the basis of overall clinical impression, the Clinical Frailty Scale (CFS) score was determined for patients at the start of dialysis by their primary nephrologist. This simple scale allocates a single point to different states of frailty (1, very fit; 2, well; 3, managing well; 4, vulnerable; 5, mildly frail; 6, moderately frail; 7, severely frail or terminally ill) with an emphasis on function of the assessed individual. The primary outcome was time to death. Patients were censored at the time of transplantation. RESULTS The cohort consisted of 390 patients with completed CFS scores (mean age of 63±15 years old). Most were Caucasian (89%) and men (67%), and 30% of patients had ESRD caused by diabetic nephropathy. The median Charlson Comorbidity Index score was 4 (interquartile range =3-6), and the median CFS score was 4 (interquartile range =2-5). There were 96 deaths over 750 patient-years at risk. In an adjusted Cox survival analysis, the hazard ratio associated with each 1-point increase in the CFS was 1.22 (95% confidence interval, 1.04 to 1.43; P=0.02). CONCLUSIONS A higher severity of frailty (as defined by the CFS) at dialysis initiation is associated with higher mortality.

Survival and Hospitalization for Intensive Home Hemodialysis Compared with Kidney Transplantation

Canadian patients receiving intensive home hemodialysis (IHHD; ≥16 hours per week) have survival comparable to that of deceased donor kidney transplant recipients in the United States, but a comparison with Canadian kidney transplant recipients has not been conducted. We conducted a retrospective cohort study of consecutive, adult IHHD patients and kidney transplant recipients between 2000 and 2011 at a large Canadian tertiary care center. The primary outcome was time-to-treatment failure or death for IHHD patients compared with expanded criteria, standard criteria, and living donor recipients, and secondary outcomes included hospitalization rate. Treatment failure was defined as a permanent switch to an alternative dialysis modality for IHHD patients, and graft failure for transplant recipients. The cohort comprised 173 IHHD patients and 202 expanded criteria, 642 standard criteria, and 673 living donor recipients. There were 285 events in the primary analysis. Transplant recipients had a reduced risk of treatment failure/death compared with IHHD patients, with relative hazards of 0.45 (95% confidence interval [95% CI], 0.31 to 0.67) for living donor recipients, 0.39 (95% CI, 0.26 to 0.59) for standard criteria donor recipients, and 0.42 (95% CI, 0.26 to 0.67) for expanded criteria donor recipients. IHHD patients had a lower hospitalization rate in the first year of treatment compared with standard criteria donor recipients and in the first 3 months of treatment compared with living donor and expanded criteria donor recipients. In this cohort, kidney transplantation was associated with superior treatment and patient survival, but higher early rates of hospitalization, compared with IHHD.

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.

Determinants of training and technique failure in home hemodialysis.

Home hemodialysis (HHD) has clinical and economic advantages compared with in‐center conventional hemodialysis. Many health systems wish to broaden the population to which this modality can be successfully offered. However, determinants of successful HHD training and technique survival are unknown. We hypothesize that both medical and social factors play a role when patients fail to successfully adopt HHD.

Intensive home haemodialysis: benefits and barriers

Accumulating evidence of the benefits of intensive home haemodialysis has led to increased international interest in this modality as a viable option for renal replacement therapy. Until the late 1970s, haemodialysis was primarily performed at home; however, the development of in-centre and satellite dialysis units and the advent of peritoneal dialysis led to decreased numbers of patients being managed by home haemodialysis. Over the past decade, a move towards once again providing and supporting haemodialysis at home has emerged, due to a desire to offer a more convenient form of dialysis for the patient in a more cost-effective manner. This shift has generated clinical evidence indicating benefits both from receiving haemodialysis at home, and from the option to provide intensive dialysis treatment in this setting. With the development of new home haemodialysis programs, specific patient-related, physician-related and cost-related barriers to their introduction have been encountered, including patient fear of self-cannulation and lack of expert medical knowledge in the area. This Review discusses the benefits and barriers associated with intensive home haemodialysis.

Intensified home hemodialysis: clinical benefits, risks and target populations

Intensive home hemodialysis (IHHD) has emerged as an alternate treatment option for patients with end-stage renal disease and has several established and potential clinical benefits. These clinical advantages need to be tempered against a growing appreciation of the risks of IHHD, including a potentially higher rate of vascular access interventions. Identifying who might be an eligible and optimal candidate for IHHD is paramount to its expansion as an important form of renal replacement therapy. In the following review, we will provide a working definition of IHHD, discuss its major clinical benefits/risks and identify potential target populations to whom this therapy can be provided.

Adverse Technical Events in Home Hemodialysis

BACKGROUND There is a growing interest in home hemodialysis because of its clinical benefits. However, given that patients are responsible for performing a complex medical procedure at home, adverse-event reporting is important to ensure patient safety. The purpose of this study was to describe adverse technical events in a large cohort of home hemodialysis patients. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS All consecutive patients undergoing home hemodialysis at a large tertiary-care center from 1999 through 2011 (last follow-up, July 2012). OUTCOMES Overall rate of adverse technical events and number/rate of severe adverse events (defined as those requiring intervention). RESULTS The cohort consisted of 202 patients with total follow-up of 757 patient-years. The cohort underwent a median of 5 dialysis treatments per week and 8 hours per session. 22 first adverse events and 7 recurrent events were identified. Adverse event rates were 0.049 per arteriovenous fistula access-year, 0.015 per arteriovenous graft access-year, and 0.022 per dialysis catheter access-year. Event rates per 1,000 dialysis treatments were 0.208, 0.068, and 0.087 for arteriovenous fistula, arteriovenous graft, and dialysis catheter access, respectively. Most adverse events were related to needle dislodgement (n=18) or air embolism (n=6). 8 adverse events resulted in emergency department visits and 5 required hospital admission. The rate of severe adverse events was 0.009 per patient-year of home hemodialysis and 0.038 per 1,000 dialysis treatments. Interventions included 3 blood transfusions, 2 catheter changes, 1 use of intravenous fluids, and 1 need for urgent dialysis. Attempts were made to retrain or review the technique in all patients with a first adverse event. LIMITATIONS Events that were not severe may have been under-reported by patients. CONCLUSIONS Serious adverse technical events in home hemodialysis are relatively rare. Strategies to further prevent these events may include patient retraining and periodic vascular access technique audit.

Macrocytosis may be associated with mortality in chronic hemodialysis patients: a prospective study

BackgroundMacrocytosis occurs in chronic hemodialysis (CHD) patients; however, its significance is unknown. The purpose of this study was to establish the prevalence and distribution of macrocytosis, to identify its clinical associations and to determine if macrocytosis is associated with mortality in stable, chronic hemodialysis patients.MethodsWe conducted a single-centre prospective cohort study of 150 stable, adult CHD patients followed for nine months. Macrocytosis was defined as a mean corpuscular volume (MCV) > 97 fl. We analyzed MCV as a continuous variable, in tertiles and using a cutoff point of 102 fl.ResultsThe mean MCV was 99.1 ± 6.4 fl, (range 66-120 fl). MCV was normally distributed. 92 (61%) of patients had an MCV > 97 fl and 45 (30%) > 102 fl. Patients were not B12 or folate deficient in those with available data and three patients with an MCV > 102 fl had hypothyroidism. In a logistic regression analysis, an MCV > 102 fl was associated with a higher Charlson-Age Comorbidity Index (CACI) and higher ratios of darbepoetin alfa to hemoglobin (Hb), [(weekly darbepoetin alfa dose in micrograms per kg body weight / Hb in g/L)*1000]. There were 23 deaths at nine months in this study. Unadjusted MCV > 102 fl was associated with mortality (HR 3.24, 95% CI 1.42-7.39, P = 0.005). Adjusting for the CACI, an MCV > 102 fl was still associated with mortality (HR 2.47, 95% CI 1.07-5.71, P = 0.035).ConclusionsMacrocytosis may be associated with mortality in stable, chronic hemodialysis patients. Future studies will need to be conducted to confirm this finding.

Vascular Access Type and Patient and Technique Survival in Home Hemodialysis Patients: The Canadian Organ Replacement Register.

BACKGROUND While central venous catheter (CVC) use has expanded home hemodialysis (HHD) eligibility to many patients who may be unable to self-cannulate an arteriovenous (AV) access, the association between CVC use and mortality has not been directly examined among HHD patients. STUDY DESIGN Registry-based retrospective observational cohort study. SETTING & PARTICIPANTS Incident HHD patients in The Canadian Organ Replacement Register who had information for vascular access type (CVC vs AV access) within the first year of HHD therapy initiation. PREDICTOR Use of a CVC versus an AV access (AV fistula or graft) within the first year of HHD therapy initiation. OUTCOME The composite of all-cause mortality and technique failure (long-term transfer to an alternate dialysis modality). A Cox proportional hazards model was used to evaluate the adjusted composite outcome and each outcome separately. RESULTS 1,869 patients initiated HHD therapy in Canada in 1996 to 2012, of whom 1,217 had an access type recorded within the first year of HHD therapy initiation. Compared to CVC use (n=523) and during a median follow-up of 513 and 427 days for AV access and CVC patients, respectively, AV access use (n=694) was associated with lower risk for the composite event of death and technique failure (490 events; adjusted HR, 0.78; 95% CI, 0.64-0.94) and lower adjusted all-cause mortality (129 deaths; adjusted HR, 0.63; 95% CI, 0.43-0.91); the risk for technique failure was nominally lower, but this result was not statistically significant (361 events; adjusted HR, 0.84; 95% CI, 0.67-1.05). Results were robust to sensitivity analyses and after missing data imputation. LIMITATIONS Missing information for vascular access type (n=659[35% of patients]) and lack of information for longitudinal changes in vascular access type. CONCLUSIONS Compared to CVC use, AV access use was associated with superior survival. Minimizing CVC use and maximizing AV access use while addressing barriers to their placement and self-cannulation may improve HHD outcomes.