Weiling Wang

Outcomes Associated With Intradialytic Oral Nutritional Supplements in Patients Undergoing Maintenance Hemodialysis: A Quality Improvement Report

BACKGROUND Insufficient clinical data exist to determine whether provision of oral nutritional supplements during dialysis can improve survival in hypoalbuminemic maintenance hemodialysis patients. STUDY DESIGN Retrospective matched-cohort study. SETTING & PARTICIPANTS All oral nutritional supplement program-eligible in-center maintenance hemodialysis patients with albumin level ≤3.5 g/dL in quarter 4 of 2009 without oral nutritional supplements in the prior 90 days at Fresenius Medical Care, North America facilities. QUALITY IMPROVEMENT PLAN Monitored intradialytic oral nutritional supplements were provided to eligible maintenance hemodialysis patients upon physician order, to continue for a year or until serum albumin level was ≥4.0 g/dL. OUTCOME Mortality (including deaths and withdrawals), followed up until December 31, 2010. MEASUREMENTS Both an intention-to-treat (ITT) and an as-treated analysis was performed using a 1:1 geographic region and propensity score-matched study population (using case-mix, laboratory test, access type, 30-day prior hospitalization, and incident patient status) comparing patients treated with intradialytic oral nutritional supplements with usual-care patients. Cox models were constructed, unadjusted and adjusted for facility standardized mortality ratio and case-mix and laboratory variables. RESULTS The ITT and as-treated analyses both showed lower mortality in the oral nutritional supplement group. The conservative ITT models with 5,227 matched pairs had 40% of controls subsequently receiving oral nutritional supplements after January 1, 2010 (because many physicians delayed participation), with comparative death rates of 30.1% versus 30.4%. The corresponding as-treated (excluding crossovers) death rates for 4,289 matched pairs were 30.9% versus 37.3%. The unadjusted ITT mortality HR for oral nutritional supplement use was 0.95 (95% CI, 0.88-1.01), and the adjusted HR was 0.91 (95% CI, 0.85-0.98); the corresponding as-treated HRs were 0.71 (95% CI, 0.66-0.76) and 0.66 (95% CI, 0.61-0.71) before and after adjustment, respectively. LIMITATIONS Limited capture of oral nutritional supplement intake outside the facility and potential residual confounding from unmeasured variables, such as dietary intake. CONCLUSIONS Maintenance hemodialysis patients with albumin levels ≤3.5 g/dL who received monitored intradialytic oral nutritional supplements showed survival significantly better than similar matched patient controls, with the as-treated analysis highlighting the potentially large effect of this strategy in clinical practice.

Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy

BACKGROUND AND OBJECTIVE Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. RESULTS Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. CONCLUSIONS Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study.

Hemodialysis Access Usage Patterns in the Incident Dialysis Year and Associated Catheter-Related Complications

BACKGROUND Hemodialysis (HD) access is considered a critical and actionable determinant of morbidity, with a growing literature suggesting that initial HD access type is an important marker of long-term outcomes. Accordingly, we examined HD access during the incident dialysis period, focusing on infection risk and successful fistula creation during the first dialysis year. STUDY DESIGN Longitudinal cohort. SETTING & PARTICIPANTS All US adults admitted to Fresenius Medical Care North America facilities within 15 days of first maintenance dialysis session between January 1 and December 31, 2007. PREDICTOR Vascular access type at HD therapy initiation. OUTCOMES Vascular access type at 90 days and at the end of the first year on HD therapy, bloodstream infection within the first year by access type, and catheter complication rate. RESULTS Of 25,003 incident dialysis patients studied, 19,622 (78.5%) initiated dialysis with a catheter; 4,151 (16.6%), with a fistula; and 1,230 (4.9%), with a graft. At 90 days, 14,105 (69.7%) had a catheter, 4,432 (21.9%) had a fistula, and 1,705 (8.4%) had a graft. Functioning fistulas and grafts at dialysis therapy initiation had first-year failure rates of 10% and 15%, respectively. Grafts were seldom replaced by fistulas (3%), whereas 7,064 (47.6%) of all patients who initiated with a catheter alone still had only a catheter at 1 year. Overall, 3,327 (13.3%) patients had at least one positive blood culture during follow-up, with the risk being similar between the fistula and graft groups, but approximately 3-fold higher in patients with a catheter (P<0.001 for either comparison). Nearly 1 in 3 catheters (32.5%) will require tissue plasminogen activator use by a median of 41 days, with 59% requiring more than one tissue plasminogen activator administration. LIMITATIONS Potential underestimation of bacteremia because follow-up blood culture results did not include samples sent to local laboratories. CONCLUSIONS In a large and representative population of incident US dialysis patients, catheter use remains very high during the first year of HD care and is associated with high mechanical complication and bloodstream infection rates.

Outcomes Associated with In-Center Nocturnal Hemodialysis from a Large Multicenter Program

BACKGROUND AND OBJECTIVES The objective of this study was to evaluate epidemiology and outcomes of a large in-center nocturnal hemodialysis (INHD) program. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This case-control study compared patients who were on thrice-weekly INHD from 56 Fresenius Medical Care, North America facilities with conventional hemodialysis patients from 244 facilities within the surrounding geographic area. All INHD cases and conventional hemodialysis control subjects who were active as of January 1, 2007, were followed until December 31, 2007, for evaluation of mortality and hospitalization. RESULTS As of January 1, 2007, 655 patients had been on INHD for 51 +/- 73 d. Patients were younger, there were more male and black patients, and vintage was longer, but they had less diabetes compared with 15,334 control subjects. Unadjusted hazard ratio was 0.59 for mortality and 0.76 for hospitalization. After adjustment for case mix and access type, only hospitalization remained significant. Fewer INHD patients were hospitalized (48 versus 59%) with a normalized rate of 9.6 versus 13.5 hospital days per patient-year. INHD patients had greater interdialytic weight gains but lower BP. At baseline, hemoglobin values were similar, whereas albumin and phosphorus values favored INHD. Mean equilibrated Kt/V was higher in INHD patients related to longer treatment time, despite lower blood and dialysate flow rates. CONCLUSIONS Patients who were on INHD exhibited excellent quality indicators, with better survival and lower hospitalization rates. The relative contributions of patient selection versus effect of therapy on outcomes remain to be elucidated in prospective clinical trials.

Choice of Vascular Access among Incident Hemodialysis Patients: A Decision and Cost-Utility Analysis

BACKGROUND AND OBJECTIVES Arteriovenous fistulas (AVFs) are widely accepted as the preferred hemodialysis vascular access type. However, supporting data have failed to consider morbidity and mortality incurred during failed creation attempts and may therefore overstate potential advantages. This study compares survival, quality-adjusted survival, and costs among incident hemodialysis patients after attempted placement of AVFs or arteriovenous grafts (AVGs). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Analogous Markov models were created, one each for AVF and AVG. Patients entered consideration at the time of first access creation, contemporaneous with dialysis initiation. Subsequent outcomes were determined probabilistically; transition probabilities, utilities, and costs were gathered from published sources. To ensure comparability between AVFs and AVGs, the timing and likelihood of access maturation were measured in a contemporary cohort of incident hemodialysis patients. RESULTS Mean (SD) overall survival was 39.2 (0.8) and 36.7 (1.0) months for AVFs and AVGs, respectively: difference (95% confidence interval [CI]) 2.6 (1.8, 3.3) months. Quality-adjusted survival was 36.1 (0.8) and 32.5 (0.9) quality-adjusted life months (QALMs) for AVFs and AVGs, respectively: difference (95% CI) 3.6 (2.8, 4.3) QALMs. The incremental cost-effectiveness ratio (95% CI) for AVFs relative to AVGs was

Change in Vascular Access and Hospitalization Risk in Long-Term Hemodialysis Patients

446 (-6023, 6994) per quality-adjusted life year saved. CONCLUSIONS AVFs are associated with greater overall and quality-adjusted survival than AVGs. Observed differences were much less pronounced than might be expected from existing literature, suggesting that prospective identification of patients at high risk for AVF maturational failure might enable improvements in health outcomes via individualization of access planning.

Hemodialysis Facility–Based Quality-of-Care Indicators and Facility-Specific Patient Outcomes

BACKGROUND AND OBJECTIVES Conversion from central venous catheters to a graft or a fistula is associated with lower mortality risk in long-term hemodialysis (HD) patients; however, a similar association with hospitalization risk remains to be elucidated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a prospective observational study all maintenance in-center HD patients who were treated in Fresenius Medical Care, North America legacy facilities; were alive on January 1, 2007; and had baseline laboratory data from December 2006. Access conversion (particularly from a catheter to a fistula or a graft) during the 4-month period from January 1 through April 30, 2007, was linked using Cox models to hospitalization risk during the succeeding 1-year follow-up period (until April 30, 2008). RESULTS The cohort (N = 79,545) on January 1, 2007 had 43% fistulas, 29% catheters, and 27% grafts. By April 30, 2007, 70,852 patients were still on HD, and among 19,792 catheters initially, only 10.3% (2045 patients) converted to either a graft or a fistula. With catheters as reference, patients who converted to grafts/fistulas had similar adjusted hazard ratios (0.69) as patients on fistulas (0.71), while patients with fistulas/grafts who converted to catheters did worse (1.22), all P < 0.0001. CONCLUSIONS Catheters remain associated with the greatest hospitalization risk. Conversion from a catheter to either graft or fistula had significantly lower hospitalization risk relative to keeping the catheter. Prospective studies are needed to determine whether programs that reduce catheters will decrease hospitalization risk in HD patients.

High Hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients

BACKGROUND We evaluated whether incremental achievement of up to 8 facility quality goals was associated with improvement in facility-specific mortality and hospitalization rates. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS 1,085 Fresenius Medical Care, North America facilities providing hemodialysis (HD) for 25 or more patients during January 2006. MEASUREMENTS The facility average for the period up to December 31, 2006, was used to determine achievement of each goal for equilibrated Kt/V, missed HD treatments, hemoglobin level, bicarbonate level, albumin level, phosphorus level, fistulae, and HD catheters. Linear regression models were used to relate facility-wide achievement of goals with facility-specific hospital days and standardized mortality ratios. RESULTS Most facilities (64%) achieved 2 to 4 of 8 goals, with only 8% meeting more than 5 quality goals. Achieving more than 5 goals averaged 3.5 fewer hospital days/patient-year and 20% lower standardized mortality ratios (all P < 0.001). The incremental number of goals met also was associated with improvement in facility mortality (P < 0.001) and hospital days (P < 0.001). Catheter and albumin level goals were achieved least (6% and 9% of facilities, respectively), but they had the best outcomes. Facilities achieving more than 5 goals had older patients (64.0 versus 61.5 years; P < 0.001), fewer African American patients (16% versus 38%; P < 0.001), and fewer women (44% versus 46%; P = 0.003) compared with the average. LIMITATIONS Observational design with residual confounding from unmeasured patient-, facility-, and treatment-related factors. CONCLUSIONS Achieving more facility quality goals was significantly associated with better facility-based measurements of patient outcomes. Although these results do not establish a causal relationship, findings agree with the present practice of monitoring facility performance for continuous quality improvement.

Incident diabetic foot ulcers and mortality in hemodialysis patients

While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end‐stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time‐lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD.

Effects of a Nationwide Predialysis Educational Program on Modality Choice, Vascular Access, and Patient Outcomes

Rates of non-traumatic lower limb amputations are approximately 4.3/100 person-years among end-stage renal disease patients, reaching as high as 13.8/100 person-years in the diabetic subpopulation. Generally, foot ulcers precede 84% of amputations with half occurring in diabetic patients. Worse, diabetic dialysis patients develop foot ulcers at fivefold higher rate than even diabetic chronic kidney disease patients. Since foot ulceration is a significant risk factor for limb loss, prevention, along with timely diagnosis and treatment, may translate into a reduced amputation rate. Historically, a chiropodist at a dialysis unit providing weekly foot assessment, foot care education and triaged specialist referrals, effected a trend toward fewer amputations, with a lower risk of death or time to first amputation. Our group demonstrated that implementation of a monthly foot-check program in dialysis units was associated with a reduction of major lower limb amputations in diabetic hemodialysis (HD) patients. However, that study design did not evaluate a potential mechanism for the association and did not track mortality. Therefore, we further evaluated the association between the development of ulcers, amputation and mortality, in a cohort receiving monthly foot-checks from a subset of facilities in the above-mentioned study with electronic capture of foot examination findings.