Correlates and outcomes of warfarin initiation in kidney transplant recipients newly diagnosed with atrial fibrillation.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
2015; 30 (2): 321-329
Comparison of longer-term outcomes after kidney transplantation between Hispanic and non-Hispanic whites in the United States.
American journal of transplantation
2015; 15 (2): 499-507
In the kidney transplant population with atrial fibrillation (AF), evidence regarding the effectiveness and safety of warfarin treatment is lacking. We used fee-for-service Medicare claims to identify kidney transplant recipients with newly diagnosed AF from the United States Renal Data System. Warfarin use within 30 days of AF diagnosis was ascertained from Medicare Part D prescription claims (2007-11) or using a validated algorithm (1997-2011). The study end points were (i) the composite of death, stroke or gastrointestinal bleed, (ii) death and (iii) death-censored graft failure. Warfarin user and non-user groups were balanced using inverse probability of treatment weighting and hazard ratios were (HRs) estimated using Cox regression. Among 718 subjects with an indication for anticoagulation, 24% initiated warfarin treatment within 30 days of AF diagnosis. Age was the only independent correlate of warfarin use [odds ratio = 1.02 per year; 95% confidence interval (95% CI) 1.01-1.04]. In the larger cohort of 6492 patients with AF, warfarin use [(23.5%) versus non-use (76.5%)] was associated with small and non-significant reductions in the composite of death, stroke or gastrointestinal bleed (HR = 0.92; 95% CI 0.83-1.02), death (HR = 0.92; 95% CI 0.82-1.02) and death-censored graft failure (HR = 0.90; 95% CI 0.76-1.08). Our study suggests the need for clinical trials of warfarin use in the kidney transplant population with AF.
View details for DOI 10.1093/ndt/gfu323
View details for PubMedID 25335507
Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis.
Journal of the American Heart Association
2014; 3 (5)
Little is known about the longer-term kidney transplant outcomes in the rapidly growing Hispanic population. Using the United States Renal Data System, we identified 105 250 Caucasian patients who received a first kidney transplant between January 1, 1996 and December 31, 2010. We tested for differences between Hispanic and non-Hispanic patients in the outcomes of (1) mortality, (2) all-cause graft failure, and (3) graft failure excluding death with a functioning graft. We used Cox regression to estimate (with 95% confidence intervals) multivariable-adjusted cause-specific hazard ratios (aHRCS ) for mortality and all-cause graft failure and subdistribution hazard ratios (aHRSD ) accounting for death as a competing risk for graft failure excluding death with a functioning graft. Both mortality [aHRCS = 0.69 (0.65-0.73)] and all-cause graft failure [aHRCS = 0.79 (0.75-0.83)] were lower in Hispanics. The association between Hispanic ethnicity and graft failure excluding death was modified by age (p < 0.003). Compared with non-Hispanic whites, graft failure excluding death with a functioning graft did not differ in Hispanics aged 18-39 years [aHRSD = 0.96 (0.89-1.05)] or aged 40-59 years [aHRSD = 1.08 (1.00-1.16)], but was 13% lower in those aged ≥60 years [aHRSD = 0.87 (0.78-0.98)]. In conclusion, once accounting for differences in overall survival, better graft survival was found in older Hispanic patients, but among not those aged <60 years.
View details for DOI 10.1111/ajt.13043
View details for PubMedID 25556854
Prognostic stratification in older adults commencing dialysis.
journals of gerontology. Series A, Biological sciences and medical sciences
2014; 69 (8): 1033-1039
Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (PCI) with stenting in patients on dialysis. We conducted 3-, 6-, and 12-month landmark analyses to test the hypothesis that thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued thienopyridine use.Using the US Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing PCI with stenting between July 2007 and December 2010. Ninety-nine percent of all thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug-eluting stents (DES) had evidence of thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare-metal stent (BMS), 70%, 34%, and 26% of patients had evidence of thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a DES, there was a suggestion of higher risks of death or myocardial infarction associated with thienopyridine discontinuation in the 3-, 6-, and 12-months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a BMS, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with thienopyridine discontinuation in the 3- and 6-month landmark analyses.The majority of patients on dialysis who undergo PCI discontinue thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer-term thienopyridine use may be of benefit to patients on dialysis who undergo PCI with DES.
View details for DOI 10.1161/JAHA.114.001356
View details for PubMedID 25336465
Addressing Missing Data in Clinical Studies of Kidney Diseases
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2014; 9 (7): 1328-1335
Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ≥67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ≥9 or an hospice eligibility criteria ≥3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.
View details for DOI 10.1093/gerona/glt289
View details for PubMedID 24482541
Correlates and variance decomposition analysis of heparin dosing for maintenance hemodialysis in older US patients
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
2014; 23 (5): 515-525
Missing data constitute a problem present in all studies of medical research. The most common approach to handling missing data-complete case analysis-relies on assumptions about missing data that rarely hold in practice. The implications of this approach are biased and inefficient descriptions of relationships of interest. Here, various approaches for handling missing data in clinical studies are described. In particular, this work promotes the use of multiple imputation methods that rely on assumptions about missingness that are more flexible than those assumptions relied on by the most common method in use. Furthermore, multiple imputation methods are becoming increasingly more accessible in mainstream statistical software packages, making them both a sound and practical choice. The use of multiple imputation methods is illustrated with examples pertinent to kidney research, and concrete guidance on their use is provided.
View details for DOI 10.2215/CJN.10141013
View details for Web of Science ID 000338615300024
View details for PubMedID 24509298
Temporal Trends in the Incidence, Treatment and Outcomes of Hip Fracture After First Kidney Transplantation in the United States
AMERICAN JOURNAL OF TRANSPLANTATION
2014; 14 (4): 943-951
Heparin is commonly used to anticoagulate the hemodialysis (HD) circuit. Despite the bleeding risk, no American standards exist for its administration. We identified correlates and quantified sources of variance in heparin dosing for HD.We performed a cross-sectional study of patients aged 67 years or older who underwent HD with heparin on one of two randomly chosen days in 2008 at a national chain of dialysis facilities. Using a mixed effects model with random intercept for facility and fixed patient and facility characteristics, we examined heparin dosing at patient and facility levels.The median heparin dose among the 17 722 patients treated in 1366 facilities was 4000 (25th-75th percentile: 2625-6000) units. In multivariable-adjusted analyses, higher weight, longer session duration, catheter use, and dialyzer reuse were significantly associated with higher heparin dose. Dose also varied considerably among census divisions. Of the overall variance in dose, 21% was due to between-facility differences, independent of facilities' case mix, geography, size, or rurality; 79% was due to differences at the patient level. The patient and facility characteristics in our model explained only 25% of the variance at the patient level.Despite the lack of standards for heparin administration, we noted patterns of use, including weight-based and time-dependent dosing. Most of the variance was at the patient level; however, only a quarter of it could be explained. The high amount of unexplained variance suggests that factors other than clinical need are driving heparin dosing and that there is likely room for more judicious dosing of heparin. Copyright © 2014 John Wiley & Sons, Ltd.
View details for DOI 10.1002/pds.3595
View details for Web of Science ID 000333948300008
View details for PubMedID 24677688
Multivessel coronary revascularization and outcomes in kidney transplant recipients
2013; 26 (11): 1080-1087
It is currently unknown whether any secular trends exist in the incidence and outcomes of hip fracture in kidney transplant recipients (KTR). We identified first-time KTR (1997-2010) who had >1 year of Medicare coverage and no recorded history of hip fracture. New hip fractures were identified from corresponding diagnosis and surgical procedure codes. Outcomes studied included time to hip fracture, type of surgery received and 30-day mortality. Of 69 740 KTR transplanted in 1997-2010, 597 experienced a hip fracture event during 155 341 person-years of follow-up for an incidence rate of 3.8 per 1000 person-years. While unadjusted hip fracture incidence did not change, strong confounding by case mix was present. Using year of transplantation as a continuous variable, the hazard ratio (HR) for hip fracture in 2010 compared with 1997, adjusted for demographic, dialysis, comorbid and most transplant-related factors, was 0.56 (95% confidence interval [CI]: 0.41-0.77). Adjusting for baseline immunosuppression modestly attenuated the HR (0.68; 95% CI: 0.47-0.99). The 30-day mortality was 2.2 (95% CI: 1.3-3.7) per 100 events. In summary, hip fractures remain an important complication after kidney transplantation. Since 1997, case-mix adjusted posttransplant hip fracture rates have declined substantially. Changes in immunosuppressive therapy appear to be partly responsible for these favorable findings.
View details for DOI 10.1111/ajt.12652
View details for Web of Science ID 000333318800025
View details for PubMedID 24712332
Outcomes After Kidney Transplantation of Patients Previously Diagnosed With Atrial Fibrillation
AMERICAN JOURNAL OF TRANSPLANTATION
2013; 13 (6): 1566-1575
Coronary artery disease is a major cause of morbidity and mortality in the kidney transplant population. We compared the long-term outcomes of coronary artery bypass graft (CABG) surgery with percutaneous coronary intervention (PCI) for multivessel coronary disease in a contemporary cohort of US kidney transplant recipients. From the U.S. Renal Data System, we identified all adult kidney transplant patients with ≥6 months of Medicare A+B undergoing first recorded multivessel coronary revascularization from 1997 to 2009. The associations of CABG versus PCI with death and the composite of death or myocardial infarction (MI) were compared using proportional hazards regression. Of the 2272 patients included in the study, 1594 underwent CABG and 678 underwent PCI. The estimated 5-year survival rate was 55% [95% confidence interval (CI) 53% to 57%] following coronary revascularization, with no significant association between revascularization type and death [adjusted hazard ratio (aHR) = 1.08; CI 0.94-1.23] or the composite of death or MI (aHR = 1.07; CI 0.96-1.18). Separate propensity score-matched analyses yielded similar results. In this analysis of kidney transplant recipients undergoing multivessel coronary revascularization, we found no difference between CABG and PCI in terms of survival or the composite of death and MI.
View details for DOI 10.1111/tri.12168
View details for Web of Science ID 000325980200010
View details for PubMedID 23957580
Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study
Trends in the incidence of intestinal perforation in US dialysis patients (1992-2005)
JOURNAL OF NEPHROLOGY
2013; 26 (2): 281-288
Little is known about the prevalence and outcomes of patients with atrial fibrillation/flutter (AF) who receive a kidney transplant. We identified all patients who had >1 year of uninterrupted Medicare A+B coverage before receiving their first kidney transplant (1997-2009). The presence of pretransplant AF was ascertained from diagnosis codes in Medicare physician claims. We studied the posttransplant outcomes of death, all-cause graft failure, death-censored graft failure and stroke using multivariable Cox regression. Of 62 706 eligible first kidney transplant recipients studied, 3794 (6.4%) were diagnosed with AF prior to kidney transplant. Over a mean follow up of 4.9 years, 40.6% of AF patients and 24.9% without AF died. All-cause and death-censored graft failure were 46.8% and 16.5%, respectively, in the AF group and 36.4% and 19.5%, respectively, in those without AF. Ischemic stroke occurred in 2.8% of patients with and 1.6% of patients without AF. In patients with AF, multivariable-adjusted hazard ratios (95% confidence intervals) for death, graft failure, death-censored graft failure and ischemic stroke were 1.46 (1.38-1.54), 1.41 (1.34-1.48), 1.26 (1.15-1.37) and 1.36 (1.10-1.68), respectively. Pre-existing AF is associated with poor posttransplant outcomes. Special attention should be paid to AF in pretransplant evaluation, counseling and risk stratification of kidney transplant candidates.
View details for DOI 10.1111/ajt.12197
View details for Web of Science ID 000319706900024
Trends in acute kidney injury, associated use of dialysis, and mortality after cardiac surgery, 1999 to 2008.
Annals of thoracic surgery
2013; 95 (1): 20-28
Little is known about the incidence of intestinal perforation in patients undergoing dialysis. Concerns exist that sevelamer hydrochloride may increase the risk of intestinal perforation. We examined long-term trends for the incidence of intestinal perforation among US dialysis patients.We studied all dialysis patients (1992-2005) who had Medicare as primary payer. We used ICD-9 diagnosis code 569.83 to ascertain events of intestinal perforation. We studied (a) all perforations and (b) perforations that did not appear to be associated with specific causative conditions (specific diseases or iatrogenic procedures within 7 days of perforation). We used Poisson regression to model the annual number of intestinal perforations and tested for any changes in levels and temporal trends of incidence rates before versus after January 1, 1999.Overall, 1,060,132 patients contributed 2.7 million patient-years. We observed 12,355 events of intestinal perforation and 7,814 spontaneous perforations. The corresponding incidence rates were 4.6 (total) and 2.9 (spontaneous perforation) episodes per 1,000 person-years, respectively. For both outcome definitions, 30-day mortality was 42%. Unadjusted and adjusted incidence rates were not materially different over time. Formal tests for any changes in the level or slope of incidence comparing time periods before and after January 1, 1999, indicated no evidence for any changes in the incidence of intestinal perforation over time.In US dialysis patients, incidence of intestinal perforation was low, but associated with high short-term mortality. We did not detect any significant changes in the incidence of intestinal perforation before versus after approval of sevelamer hydrochloride in late 1998.
View details for DOI 10.5301/jn.5000104
View details for Web of Science ID 000319644600006
View details for PubMedID 22419235
Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study.
2013; 14: 97-?
The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.
View details for DOI 10.1016/j.athoracsur.2012.05.131
View details for PubMedID 23272825
Multivessel Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in ESRD
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2012; 23 (12): 2042-2049
Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis.Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events.From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68).We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.
View details for DOI 10.1186/1471-2369-14-97
View details for PubMedID 23621917
Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2012; 23 (3): 495-506
Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.
View details for DOI 10.1681/ASN.2012060554
View details for Web of Science ID 000311819000017
View details for PubMedID 23204445
Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.
View details for DOI 10.1681/ASN.2011070658
View details for Web of Science ID 000301206900017
View details for PubMedID 22266666