Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS.

BACKGROUND: Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients. METHODS: We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months. RESULTS: Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was -0.60%, -0.12%, -0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%. CONCLUSIONS: Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.

Employee attitudes about moving toward a smoke-free campus at a Veterans Affairs hospital.

BACKGROUND: Although Veterans Affairs (VA) hospitals have been smoke-free inside of buildings since 1991, smoke-free campuses have not been initiated. The purpose of this article is to describe staff attitudes regarding making the VA hospital a smoke-free campus except for the mandated smoking shelters. METHODS: In 2008, a cross-sectional, anonymous survey was conducted with a convenience sample of employees at a Midwestern VA (N = 397). RESULTS: Descriptive statistics showed that the vast number of employees were in support of a smoke-free campus (76%), relocating the smoking shelters (62%), and offering employees assistance to quit smoking (71%). Multivariate analyses showed that those who were nonsmokers, older, women, and higher educated were the greatest supporters of policies to support a smoke-free environment (p < .05). Write-in comments were generally favorable but also revealed employee resistance related to freedom, personal choice, and potential loss in productivity as smokers go further away from the building to smoke. CONCLUSIONS: VA hospitals have unique challenges in implementing smoke-free campus policies.

Enhanced training in vascular access creation predicts arteriovenous fistula placement and patency in hemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study.

OBJECTIVE: To investigate whether intensity of surgical training influences type of vascular access placed and fistula survival. SUMMARY BACKGROUND DATA: Wide variations in fistula placement and survival occur internationally. Underlying explanations are not well understood. METHODS: Prospective data from 12 countries in the Dialysis Outcomes and Practice Patterns Study were analyzed; outcomes of interest were type of vascular access in use (fistula vs. graft) in hemodialysis patients at study entry and time from placement until primary and secondary access failures, as predicted by surgical training. Logistic and Cox regression models were adjusted for patient characteristics and time on hemodialysis. RESULTS: During training, US surgeons created fewer fistulae (US mean = 16 vs. 39-426 in other countries) and noted less emphasis on vascular access placement compared with surgeons elsewhere. Significant predictors of fistula versus graft placement in hemodialysis patients included number of fistulae placed during training (adjusted odds ratio [AOR] = 2.2 for fistula placement, per 2 times greater number of fistulae placed during training, P < 0.0001) and degree of emphasis on vascular access creation during training (AOR = 2.4 for fistula placement, for much-to-extreme emphasis vs. no emphasis, P = 0.0008). Risk of primary fistula failure was 34% lower (relative risk = 0.66, P = 0.002) when placed by surgeons who created > or = 25 (vs. < 25) fistulae during training. CONCLUSIONS: Surgical training is key to both fistula placement and survival, yet US surgical programs seem to place less emphasis on fistula creation than those in other countries. Enhancing surgical training in fistula creation would help meet targets of the Fistula First Initiative.

Mortality among hemodialysis patients in Europe, Japan, and the United States: case-mix effects.

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study is well suited to identify case-mix effects, given its extensive data set. The data set was used to examine the influence of case-mix variables on mortality and the extent to which these variables account for differences in mortality across regions, as well as the prevalence and incidence of hepatitis B and hepatitis C. METHODS: Demographic and comorbid disease features were determined for 8,615 patients internationally; mortality was recorded for this cohort, plus replacement patients (total n = 16,720), from 1996 to 2002. Mortality was associated with increasing age, nonblack race, coronary artery disease, congestive heart failure, other cardiac disease, diabetes mellitus, peripheral vascular disease, cerebrovascular disease, absence of hypertension, lung disease, cancer, human immunodeficiency virus infection, gastrointestinal bleeding, neurologic disease, psychiatric disease, cellulitis/gangrene, hepatitis C, and smoking. RESULTS: US patients were slightly older than those in Europe or Japan and had the highest prevalence of diabetes, coronary artery disease, congestive heart failure, peripheral vascular disease, and cerebrovascular disease. CONCLUSION: Upon adjusting for case-mix to assess mortality across facilities, it was found that regional differences in mortality (highest in the United States and lowest in Japan) and differences across facilities within nations remain after such corrections. It is likely that practice patterns account for some of this variation. Prevalence of hepatitis B virus (HBV) across facilities increased as the number of dialyzing patients per facility increased; risk of HBV seroconversion decreased among facilities using protocols for treatment of patients with HBV infection. Greater employment of staff with at least 2 years of formal nursing training was associated with lower prevalence of hepatitis C virus infection and lower seroconversion risk.

Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.

BACKGROUND: Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients. We assessed the prevalence of depressive symptoms and physician-diagnosed depression, their variations by country, and associations with treatment by antidepressants among hemodialysis patients. We also assessed whether depressive symptoms were independently associated with mortality, hospitalization, and dialysis withdrawal. METHODS: The sample was represented by 9382 hemodialysis patients randomly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index (CES-D), using > or =10 CES-D score as the cut-off value. RESULTS: Overall prevalence of physician-diagnosed depression was 13.9%, and percentage of CES-D score > or =10 43.0%. While the smallest prevalence of physician-diagnosed depression was observed in Japan (2.0%) and France (10.6%), the percentage of CES-D score > or =10 in these counties was similar to the whole sample. Patients on antidepressants also varied by country, 34.9% and 17.3% among those with physician-diagnosed depression and CES-D scores > or =10, respectively. In Cox models adjusted for several comorbidities, CES-D scores > or =10 were associated with significantly higher relative risks (RR) of death (RR = 1.42; 95% CI = 1.29 to 1.57), hospitalization (RR = 1.12; 95% CI = 1.03 to 1.22), and dialysis withdrawal (RR = 1.55; 95% CI = 1.29 to 1.85). CONCLUSION: The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients. CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization. Interventions should target these patients with the goal to improve survival and reduce hospitalizations.

Analgesic prescription patterns among hemodialysis patients in the DOPPS: potential for underprescription.

BACKGROUND: Dialysis patients require special consideration regarding analgesics, given their altered pharmacokinetic and pharmacodynamic profiles and increased potential for adverse reactions. METHODS: Analgesic prescription patterns were investigated using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), with 3749 patients in 142 United States facilities studied between May 1996 and September 2001. RESULTS: The proportion of patients prescribed any analgesic decreased from 30.2% to 24.3%; narcotic prescriptions decreased from 18.0% to 14.9%. The most commonly prescribed narcotics were propoxyphene/acetaminophen combinations (47.2%). Combinations containing acetaminophen were prescribed concurrently for 84.1% of patients on narcotics. About one half of prescriptions for narcotics, acetaminophen, and cyclooxygenase-2 (COX-2) agents were for 12 months or more; one half of prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs) were for 8 months or more. The proportion of patients prescribed analgesics varied by facility (mean +/- SD = 27.9%+/- 18.9% for all analgesics, range 0% to 89.3%). Analgesic prescription was more likely among the elderly, women, and patients with cardiovascular disease (other than coronary artery disease or congestive heart failure), lung and psychiatric disease, cancer (other than skin), and recurrent cellulitis. Patients prescribed laxatives were almost twice as likely to be on a narcotic (odds ratio = 1.95, P < 0.0001). Analgesic prescription did not correlate with loss of residual renal function or hospitalization for a gastrointestinal disorder. Three-quarters of patients reporting moderate to very severe pain were not prescribed analgesics. Furthermore, 74% of patients with pain that interfered with work had no analgesic prescription. CONCLUSION: Dialysis patients and providers may benefit from both refinement of existing guidelines and a renewed understanding regarding appropriate prescription of analgesics.

An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.

BACKGROUND: Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats. METHODS: To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks. RESULTS: From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms. CONCLUSION: Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.

Vascular access use in Europe and the United States: results from the DOPPS.

BACKGROUND: A direct broad-based comparison of vascular access use and survival in Europe (EUR) and the United States (US) has not been performed previously. Case series reports suggest that vascular access practices differ substantially in the US and EUR. We report on a representative study (DOPPS) which has used the same data collection protocol for> 6400 hemodialysis (HD) patients to compare vascular access use at 145 US dialysis units and 101 units in five EUR countries (France, Germany, Italy, Spain, and the United Kingdom). METHODS: Logistic analysis evaluated factors associated with native arteriovenous fistula (AVF) versus graft use or permanent access versus catheter use for prevalent and incident HD patients. Times to failure for AVF and graft were analyzed using Cox proportional hazards regression. RESULTS: AVF was used by 80% of EUR and 24% of US prevalent patients, and was significantly associated with younger age, male gender, lower body mass index, non-diabetic status, lack of peripheral vascular disease, and no angina. After adjusting for these factors, AVF versus graft use was still much higher in EUR than US (AOR=21, P < 0.0001). AVF use within facilities varied from 0 to 87% (median 21%) in the US, and 39 to 100% (median 83%) in EUR. For patients who were new to HD, access use was: 66% AVF in EUR versus 15% in US (AOR=39, P < 0.0001), 31% catheters in EUR vs. 60% in US, and 2% grafts in EUR vs. 24% in US. In addition, 25% of EUR and 46% of US incident patients did not have a permanent access placed prior to starting HD. In EUR, 84% of new HD patients had seen a nephrologist for> 30 days prior to ESRD compared with 74% in the US (P < 0.0001); pre-ESRD care was associated with increased odds of AVF versus graft use (AOR=1.9, P=0.01). New HD patients had a 1.8-fold greater odds (P=0.002) of starting HD with a permanent access if a facility's typical time from referral to access placement was < or =2 weeks. AVF use when compared to grafts was substantially lower (AOR=0.61, P=0.04) when surgery trainees assisted or performed access placements. When used as a patient's first access, AVF survival was superior to grafts regarding time to first failure (RR=0.53, P=0.0002), and AVF survival was longer in EUR compared with the US (RR=0.49, P=0.0005). AVF and grafts each displayed better survival if used when initiating HD compared with being used after patients began dialysis with a catheter. CONCLUSION: Large differences in vascular access use exist between EUR and the US, even after adjustment for patient characteristics. The results strongly suggest that a facility's preferences and approaches to vascular access practice are major determinants of vascular access use.