Melissa Soohoo

Association between vascular access creation and deceleration of estimated glomerular filtration rate decline in late-stage chronic kidney disease patients transitioning to end-stage renal disease

Background Prior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors. Methods We examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes. Results Of the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models. Conclusions The creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients.

Cervical HPV Infection in Female Sex Workers: A Global Perspective

Introduction: Approximately 291 million women worldwide are HPV DNA carriers. Studies have indicated that having multiple sexual partners may lead to higher HPV transmission. Thus female sex workers (FSWs) may be at greater risk of infection compared to the general population. Herein we review publications with data on FSW cervical HPV test results. We also examine variations of HPV prevalence and risk behaviors by region. Knowledge of prevalent HPV types in FSWs may lead to improved prevention measures and assist in understanding vaccination in high-risk groups. Methods: We conducted a review of the literature by searching PUBMED using the terms “prostitution” or “female sex workers”, “human papillomavirus” or “HPV”, and “prevalence” or “PCR” to find articles. We excluded studies without HPV testing or HPV type specific results, or unconventional HPV testing. Results: A total of 35 peer-reviewed publications were included in our review. High risk HPV types 16 and 18 ranged from 1.1-38.9‰ in prevalence. In addition to high-risk HPV types, newer studies reported non-carcinogenic HPV types also of high prevalence. The most prevalent HPV types reported among FSWs included HPV 6 (11.5%), 16 (38.9%), 18 (23.1%), 31 (28.4%), 52 (32.7%), and 58 (26.0%). Conclusions: Female sex workers have an overall high prevalence of HPV infection of high-risk types as evident through various testing methods. FSWs are thought to be at increased risk of cervical cancer because of high HPV exposure. This highlights the need for HPV and cervical prevention campaigns tailored to FSWs.

Transition of care from pre-dialysis prelude to renal replacement therapy: the blueprints of emerging research in advanced chronic kidney disease

Abstract In patients with advanced (estimated glomerular filtration rate <25 mL/min/1.73 m2) non‐dialysis‐dependent chronic kidney disease (CKD) the optimal transition of care to renal replacement therapy (RRT), i.e. dialysis or transplantation, is not known. Mortality and hospitalization risk are extremely high upon transition and in the first months following the transition to dialysis. Major knowledge gaps persist pertaining to differential or individualized transitions across different demographics and clinical measures during the ‘prelude’ period prior to the transition, particularly in several key areas: (i) the best timing for RRT transition; (ii) the optimal RRT type (dialysis versus transplant), and in the case of dialysis, the best modality (hemodialysis versus peritoneal dialysis), format (in‐center versus home), frequency (infrequent versus thrice‐weekly versus more frequent) and vascular access preparation; (iii) the post‐RRT impact of pre‐RRT prelude conditions and events such as blood pressure and glycemic control, acute kidney injury episodes, and management of CKD‐specific conditions such as anemia and mineral disorders; and (iv) the impact of the above prelude conditions on end‐of‐life care and RRT decision‐making versus conservative management of CKD. Given the enormous changes occurring in the global CKD healthcare landscape, as well as the high costs of transitioning to dialysis therapy with persistently poor outcomes, there is an urgent need to answer these important questions. This review describes the key concepts and questions related to the emerging field of ‘Transition of Care in CKD’, systematically defines six main categories of CKD transition, and reviews approaches to data linkage and novel prelude analyses along with clinical applications of these studies.

Longitudinal associations among renal urea clearance–corrected normalized protein catabolic rate, serum albumin, and mortality in patients on hemodialysis

BACKGROUND AND OBJECTIVES There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). RESULTS Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (Ptrend<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (Ptrend<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. CONCLUSIONS Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.

Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis

BACKGROUND The inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated. METHODS We examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation. RESULTS The patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to <27.5 kg/m(2)), a BMI of <18 kg/m(2) was associated with a 3.2-fold higher death risk [hazard ratio (HR) 3.17 (95% CI 3.05-3.29)], and mortality risks declined with increasing BMI with the greatest survival advantage of 31% lower risk [HR 0.69 (95% CI 0.64-0.75)] observed with a BMI of 40 to <45 kg/m(2). CONCLUSIONS The linear inverse relationship between BMI and mortality is robust across models including MSM analyses that more completely account for time-varying confounders and biases.

Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United States

Home dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n =: 162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.

Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients

BACKGROUND AND OBJECTIVES Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy. RESULTS During the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups. CONCLUSIONS Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD.

Extended-hours hemodialysis is associated with lower mortality risk in patients with end-stage renal disease.

Extended-hours hemodialysis offers substantially longer treatment time compared to conventional hemodialysis schedules and is associated with improved fluid and electrolyte control and favorable cardiac remodeling. However, whether extended-hours hemodialysis improves survival remains unclear. Therefore, we determined the association between extended-hours compared to conventional hemodialysis and the risk of all-cause mortality in a nationally representative cohort of patients initiating maintenance dialysis in the United States from 2007 to 2011. Survival analyses using causal inference modeling with marginal structural models were performed to compare mortality risk among 1206 individuals undergoing thrice weekly extended-hours hemodialysis or 111,707 patients receiving conventional hemodialysis treatments. The average treatment time per session for extended-hours hemodialysis was 399 minutes compared to 211 minutes for conventional therapy. The crude mortality rate with extended-hours hemodialysis was 6.4 deaths per 100 patient-years compared with 14.7 deaths per 100 patient-years for conventional hemodialysis. In the primary analysis, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk of death compared to those who were treated with a conventional regimen (95% confidence interval: 7% to 51%). Additional analyses accounting for analytical assumptions regarding exposure and outcome, facility-level confounders, and prior modality history were similar. Thus, in this large nationally representative cohort, treatment with extended-hours hemodialysis was associated with a lower risk for mortality compared to treatment with conventional in-center therapy. Adequately powered randomized clinical trials comparing extended-hours to conventional hemodialysis are required to confirm these findings.

Changes in Markers of Mineral and Bone Disorders and Mortality in Incident Hemodialysis Patients.

Background: Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival. Methods: We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (CaAlb), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011. Results: Across all MBD markers (Phos, CaAlb, iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up. Conclusions: There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population.

Association of body weight changes with mortality in incident hemodialysis patients.

Background. Incident hemodialysis patients may experience rapid weight loss in the first few months of starting dialysis. However, trends in weight changes over time and their associations with survival have not yet been characterized in this population. Methods. In a large contemporary US cohort of 58 106 patients who initiated hemodialysis during 1 January 2007–31 December 2011 and survived the first year of dialysis, we observed trends in weight changes during the first year of treatment and then examined the association of post‐dialysis weight changes with all‐cause mortality. Results. Patients’ post‐dialysis weights rapidly decreased and reached a nadir at the 5th month of dialysis with an average decline of 2% from baseline, whereas obese patients (body mass index ≥30 kg/m2) did not reach a nadir and lost ˜3.8% of their weight by the 12th month. Compared with the reference group (−2 to 2% changes in weight), the death hazard ratios (HRs) of patients with −6 to −2% and greater than or equal to −6% weight loss during the first 5 months were 1.08 (95% confidence interval, 1.02–1.14) and 1.14 (1.07–1.22), respectively. Moreover, the death HRs with 2–6% and ≥6% weight gain during the 5th to 12th months were 0.91 (0.85–0.97) and 0.92 (0.86–0.99), respectively. Conclusions. In patients who survive the first year of hemodialysis, a decline in post‐dialysis weight is observed and reaches a nadir at the 5th month. An incrementally larger weight loss during the first 12 months is associated with higher death risk, whereas weight gain is associated with greater survival during the 5th to 12th month but not in the first 5 months of dialysis therapy.