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1.  Serum Fructosamine and Glycated Albumin and Risk of Mortality and Clinical Outcomes in Hemodialysis Patients 
Diabetes Care  2013;36(6):1522-1533.
OBJECTIVE
Assays for serum total glycated proteins (fructosamine) and the more specific glycated albumin may be useful indicators of hyperglycemia in dialysis patients, either as substitutes or adjuncts to standard markers such as hemoglobin A1c, as they are not affected by erythrocyte turnover. However, their relationship with long-term outcomes in dialysis patients is not well described.
RESEARCH DESIGN AND METHODS
We measured fructosamine and glycated albumin in baseline samples from 503 incident hemodialysis participants of a national prospective cohort study, with enrollment from 1995–1998 and median follow-up of 3.5 years. Outcomes were all-cause and cardiovascular disease (CVD) mortality and morbidity (first CVD event and first sepsis hospitalization) analyzed using Cox regression adjusted for demographic and clinical characteristics, and comorbidities.
RESULTS
Mean age was 58 years, 64% were white, 54% were male, and 57% had diabetes. There were 354 deaths (159 from CVD), 302 CVD events, and 118 sepsis hospitalizations over follow-up. Both fructosamine and glycated albumin were associated with all-cause mortality; adjusted HR per doubling of the biomarker was 1.96 (95% CI 1.38–2.79) for fructosamine and 1.40 (1.09–1.80) for glycated albumin. Both markers were also associated with CVD mortality [fructosamine 2.13 (1.28–3.54); glycated albumin 1.55 (1.09–2.21)]. Higher values of both markers were associated with trends toward a higher risk of hospitalization with sepsis [fructosamine 1.75 (1.01–3.02); glycated albumin 1.39 (0.94–2.06)].
CONCLUSIONS
Serum fructosamine and glycated albumin are risk factors for mortality and morbidity in hemodialysis patients.
doi:10.2337/dc12-1896
PMCID: PMC3661814  PMID: 23250799
2.  Frailty as a Novel Predictor of Mortality and Hospitalization in Hemodialysis Patients of All Ages 
Objectives
To quantify the prevalence of frailty in adult patients of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization.
Design
Prospective cohort study.
Setting
Single hemodialysis center in Baltimore, Maryland.
Participants
146 prevalent hemodialysis patients enrolled between January 2009 and March 2010 and followed through August 2012.
Measurements
Frailty, comorbidity, and disability on enrollment into the study and subsequent mortality and hospitalizations.
Results
At enrollment, 50.0% of older (age≥65) and 35.4% of younger (age<65) hemodialysis patients were frail; 35.9% and 29.3% were intermediately frail, respectively. The 3-year mortality was 16.2% for non frail, 34.4% for intermediately frail, and 40.2% for frail participants. Intermediate frailty and frailty were associated with a 2.68-fold (95% CI: 1.02-7.07, P=0.046) and 2.60-fold (95%CI: 1.04-6.49, P=0.041) higher risk of death independent of age, sex, comorbidity, and disability. In the year after enrollment, median number of hospitalizations was 1 (IQR 0-3). The proportion with 2 or more hospitalizations was 28.2% for non frail, 25.5% for intermediately frail, and 42.6% for frail participants. While intermediate frailty was not associated with the number of hospitalizations (RR=0.76, 95%CI:0.49-1.16, P=0.21), frailty was associated with a 1.43-fold (95%CI:1.00-2.03, P=0.049) higher number of hospitalizations independent of age, sex, comorbidity, and disability. The association of frailty with mortality and hospitalizations did not differ between older and younger participants (Interaction P=0.64 and P=0.14, respectively).
Conclusions
Adults of all ages undergoing hemodialysis have a very high prevalence of frailty, more than 5-fold higher than community dwelling older adults. In this population, regardless of age, frailtyis a strong, independent predictor of mortality and number of hospitalizations.
doi:10.1111/jgs.12266
PMCID: PMC3938084  PMID: 23711111
Frailty; hemodialysis; mortality; hospitalization
3.  Incidental findings on cardiac computed tomography in incident hemodialysis patients: the predictors of arrhythmic and cardiovascular events in end-stage renal disease (PACE) study 
BMC Nephrology  2014;15:68.
Background
This is the first study that has examined non-cardiac incidental findings in research cardiac computed tomography (CT) of hemodialysis patients and their relationship with patient characteristics.
Methods
We performed a cross-sectional analysis in the Predictors of Arrhythmic and Cardiovascular Events in End-Stage Renal Disease (PACE) study, a prospective cohort study on incident hemodialysis patients. Non-cardiac structures in the cardiac CT scan were reviewed and evaluated. The type and frequencies of non-cardiac incidental CT findings were summarized. Univariate and multivariate logistic regression were performed to analyze the associations between gender, older age, obesity, history of cardiovascular disease (CVD), smoking status, history of chronic pulmonary disease and history of cancer with presence of any incidental CT findings and, separately, pulmonary nodules.
Results
Among the 260 participants, a total of 229 non-cardiac incidental findings were observed in 145 participants (55.8% of all participants). Of these findings, pulmonary nodules were the most common incidental finding (24.2% of all findings), and 41.3% of them requiring further follow-up imaging per radiology recommendation. Vascular and gastrointestinal findings occurred in 11.8% and 15.3% of participants, respectively. Participants 65 years or older had a higher odds of any incidental findings (Odds Ratio (OR) =2.55; 95% Confidence Intervals (CI) 1.30, 4.99) and pulmonary nodules (OR = 4.80; 95% CI 2.51, 9.18). Prior history of CVD was independently and significantly associated with any incidental findings (OR = 2.00; 95% CI 1.19, 3.40); but not with the presence of pulmonary nodules.
Conclusions
We demonstrate that the prevalence of incidental findings by cardiac CT scanning is extremely high among patients on hemodialysis. Further investigations to follow-up on the high occurrence of incidental findings during our research study and potentially clinical studies raises important practical, ethical and medico-legal issues that need to be carefully considered in research projects using imaging studies.
doi:10.1186/1471-2369-15-68
PMCID: PMC4019788  PMID: 24885570
Incidental findings; Cardiac; Computed tomography; Hemodialysis; Prevalence; Pulmonary nodule
4.  Effectiveness of Educational and Social Worker Interventions to Activate Patients’ Discussion and Pursuit of Preemptive Living Donor Kidney Transplantation: A Randomized Controlled Trial 
Background
Many patients with chronic kidney disease (CKD) have difficulties becoming actively engaged in the pursuit of pre-emptive living donor kidney transplantation.
Study Design
The Talking About Live Kidney Donation (TALK) study was a randomized controlled trial of the effectiveness of educational and social worker interventions designed to encourage early discussions and active pursuit of pre-emptive LKT among patients with progressive CKD.
Setting & Participants
We recruited participants with progressive CKD from academically affiliated nephrology practices in Baltimore, Maryland.
Intervention
Participants randomly received 1) “Usual Care” (routine care with their nephrologists), 2) “TALK Education” intervention (video and booklet), or the 3) “TALK Social Worker” intervention (video and booklet plus patient and family social worker visits).
Outcomes
We followed participants for 6 months to assess their self-reported achievement of behaviors reflecting their discussions about LKT and/or pursuit of LKT (discussions with family; discussions with physicians; initiating recipient evaluation; completing recipient evaluation; identifying a potential living donor).
Measurements
We assessed outcomes via questionnaire at 1, 3, and 6-month follow up.
Results
Participants receiving Usual Care with their nephrologists (n=44), TALK Education (n=43), and the TALK Social Worker (n=43) were similar at baseline. TALK Study interventions improved participants’ LKT discussion and pursuit behaviors, with the Social Worker leading to greater patient activation (participants’ predicted probability (95% confidence interval) of achieving LKT discussions, evaluations, or donor identification over 6 months in Usual Care, TALK Education, and TALK Social Worker groups: 30% (20%–46%), 42% (33% –54%), and 58% (41% –83%), respectively (p=0.03).
Limitations
Our population was well educated and mostly insured, potentially limiting generalizability of our findings.
Conclusions
TALK interventions improved discussion and active pursuit of LKT among patients with progressive CKD and may improve their utilization of pre-emptive LKT.
doi:10.1053/j.ajkd.2012.08.039
PMCID: PMC3710736  PMID: 23089512
5.  African American and Non-African American Patients’ and Families’ Decision Making About Renal Replacement Therapies 
Qualitative health research  2012;22(7):997-1006.
We conducted focus group meetings of African American and non-African American patients with end-stage renal disease (six groups) and their family members (six groups), stratified by race/ethnicity and treatment. We elicited differences in participants’ experiences with shared decision making about initiating renal replacement therapy (RRT; that is, hemodialysis, peritoneal dialysis, or a kidney transplant). Patients were often very sick when initiating RRT, and had little, if any, time to make a decision about what type of RRT to initiate. They also lacked sufficient information about alternative treatment options prior to initiation. Family members played supportive roles and shared in decision making when possible. Reports were similar for African American and non-African American participants. Our findings suggest that a greater emphasis on the improved engagement of patients and their families in shared decision making about RRT initiation is needed for both ethnic/racial minorities and nonminorities.
doi:10.1177/1049732312443427
PMCID: PMC3927418  PMID: 22645225
African Americans; communication; medical; decision making; illness and disease; chronic; illness and disease; experiences; minorities; nephrology
6.  Perceptions and use of the national kidney foundation KDOQI guidelines: a survey of U.S. renal healthcare providers 
BMC Nephrology  2013;14:230.
Background
The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) developed guidelines to care for patients with chronic kidney disease (CKD). While these are disseminated through the NKF’s website and publications, the guidelines’ usage remains suboptimal. The KDOQI Educational Committee was formed to identify barriers to guideline implementation, determine provider and patient educational needs and develop tools to improve care of patients with CKD.
Methods
An online survey was conducted from May to September 2010 to evaluate renal providers’ familiarity, current use of and attitudes toward the guidelines and tools to implement the guidelines.
Results
Most responders reported using the guidelines often and felt that they could be easily implemented into clinical practice; however, approximately one-half identified at least one barrier. Physicians and physician extenders most commonly cited the lack of evidence supporting KDOQI guidelines while allied health professionals most commonly listed patient non-adherence, unrealistic guideline goals and provider time-constraints. Providers thought that the guidelines included too much detail and identified the lack of a quick resource as a barrier to clinical implementation. Most were unaware of the Clinical Action Plans.
Conclusions
Perceived barriers differed between renal clinicians and allied health professionals; educational and implementation tools tailored for different providers are needed.
doi:10.1186/1471-2369-14-230
PMCID: PMC4016578  PMID: 24152744
KDOQI; Chronic kidney disease; Guidelines; Survey
7.  Predictors of high sensitivity cardiac troponin T in chronic kidney disease patients: a cross-sectional study in the chronic renal insufficiency cohort (CRIC) 
BMC Nephrology  2013;14:229.
Background
Cardiac troponin T is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Serum levels of high sensitivity cardiac troponin T (hs-TnT) reflect subclinical myocardial injury in ambulatory patients. We sought to determine the distribution and predictors of hs-TnT in CKD patients without overt cardiovascular disease (CVD).
Methods
We studied 2464 participants within the multi-ethnic Chronic Renal Insufficiency Cohort (CRIC) who did not have self-reported CVD. We considered renal and non-renal factors as potential determinants of hs-TnT, including demographics, comorbidities, left ventricular (LV) mass, serologic factors, estimated glomerular filtration rate (eGFR) and albumin to creatinine ratio.
Results
Hs-TnT was detectable in 81% of subjects, and the median (IQR) hs-TnT was 9.4 pg/ml (4.3-18.3). Analysis was performed using Tobit regression, adjusting for renal and non-renal factors. After adjustment, lower eGFR was associated with higher expected hs-TnT; participants with eGFR < 30 ml/min/1.73 m2 had 3-fold higher expected hs-TnT compared to subjects with eGFR > 60. Older age, male gender, black race, LV mass, diabetes and higher blood pressure all had strong, independent associations with higher expected hs-TnT.
Conclusions
Knowledge of the determinants of hs-TnT in this cohort may guide further research on the pathology of heart disease in patients with CKD and help to stratify sub-groups of CKD patients at higher cardiovascular risk.
doi:10.1186/1471-2369-14-229
PMCID: PMC4016297  PMID: 24148285
Troponin T; Chronic kidney disease; Cardiovascular disease
8.  Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study 
BMC Nephrology  2013;14:224.
Background
Patients undergoing hemodialysis are at high risk of falls, with subsequent complications including fractures, loss of independence, hospitalization, and institutionalization. Factors associated with falls are poorly understood in this population. We hypothesized that insights derived from studies of the elderly might apply to adults of all ages undergoing hemodialysis; we focused on frailty, a phenotype of physiological decline strongly associated with falls in the elderly.
Methods
In this prospective, longitudinal study of 95 patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with future falls was explored using adjusted Poisson regression. Frailty was classified using the criteria established by Fried et al., as a combination of five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed.
Results
Over a median 6.7-month period of longitudinal follow-up, 28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and older) experienced a fall. After adjusting for age, sex, race, comorbidity, disability, number of medications, marital status, and education, frailty independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of falls. This relationship between frailty and falls did not differ for younger and older adults (P=0.57).
Conclusions
Frailty, a validated construct in the elderly, was a strong and independent predictor of falls in adults undergoing hemodialysis, regardless of age. Our results may aid in identifying frail hemodialysis patients who could be targeted for multidimensional fall prevention strategies.
doi:10.1186/1471-2369-14-224
PMCID: PMC3852906  PMID: 24131569
Hemodialysis; Falls; Frailty
9.  Associations of Multiple Metals with Kidney Outcomes in Lead Workers 
Objectives
Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal co-exposure on kidney function. Therefore, we evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers.
Methods
Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures, and ln-urine N-acetyl-β-D-glucosaminidase (NAG).
Results
In 684 participants, median urine thallium and antimony were 0.39 and 0.36 μg/g creatinine, respectively. After adjustment for lead dose, urine creatinine, and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate (eGFR); associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based eGFR = 5.2 mL/min/1.73 m2; 95% confidence interval = 2.4, 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium.
Conclusions
Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.
doi:10.1136/oemed-2012-100765
PMCID: PMC3542392  PMID: 22843435
antimony; cadmium; creatinine; kidney function; thallium
10.  U.S. Centers for Disease Control and Prevention launches new chronic kidney disease surveillance system website 
BMC Nephrology  2013;14:196.
The burden of chronic kidney disease (CKD) is substantial and is associated with poor health outcomes including increase hospitalizations and premature deaths, as well as considerable health care cost. In recognition of this mounting public health problem, the U.S. Centers for Disease Control and Prevention and their collaborators created a national CKD surveillance system. This commentary introduces the national CKD surveillance system and discusses some of its potential uses.
doi:10.1186/1471-2369-14-196
PMCID: PMC3847207  PMID: 24034342
Chronic kidney disease; Centers for Disease Control and Prevention; Epidemiology; Surveillance; Website
11.  Estimating GFR Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study 
Background
Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies.
Study Design
Cross-sectional study of 1,433 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study (i.e., the GFR subcohort) to derive an internal GFR estimating equation using a split sample approach.
Setting & Participants
Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black.
Index Test
CRIC GFR estimating equation
Reference Test or Outcome
Urinary 125I-iothalamate clearance testing (measured GFR)
Other Measurements
Laboratory measures including serum creatinine and cystatin C, and anthropometrics
Results
In the validation dataset, the model that included serum creatinine, serum cystatin C, age, gender, and race was the most parsimonious and similarly predictive of mGFR compared to a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, the root mean square errors for the separate model were 0.207 vs. 0.202, respectively. The performance of the CRIC GFR estimating equation was most accurate among the subgroups of younger participants, men, non-blacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m2, those with higher 24-hour urine creatinine excretion, those with lower levels of high-sensitivity C-reactive protein, and those with higher mGFR.
Limitations
Urinary clearance of 125I-iothalamate is an imperfect measure of true GFR; cystatin C is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors.
Conclusions
The CRIC GFR estimating equation predicts measured GFR accurately in the CRIC cohort using serum creatinine and cystatin C, age, gender, and race. Its performance was best among younger and healthier participants.
doi:10.1053/j.ajkd.2012.04.012
PMCID: PMC3565578  PMID: 22658574
glomerular filtration rate (GFR); kidney function; GFR estimation
12.  Access to Health Care Among Adults Evaluated for CKD: Findings From the Kidney Early Evaluation Program (KEEP) 
Background
Data are scant regarding access to health care in patients with chronic kidney disease (CKD). We performed descriptive analyses using data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP), a nationwide health screening program for adults at high risk of CKD.
Methods
From 2000–2010, a total of 122,502 adults without end-stage renal disease completed KEEP screenings; 27,927 (22.8%) met criteria for CKD (10,082, stages 1–2; 16,684, stage 3; and 1,161, stages 4–5). CKD awareness, self-rated health status, frequency of physician visits, difficulty obtaining medical care, types of caregivers, insurance status, and medication coverage and estimated costs were assessed.
Results
Participants with CKD were more likely to report fair/poor health status than those without CKD. Health care utilization increased at later CKD stages; ~95% of participants at stages 3–5 had visited a physician during the preceding year compared with 83.7% of participants without CKD. More Hispanic and African American than white participants at all CKD stages reported not having a physician. Approximately 40% of participants younger than 65 years reported fair/poor health status at stages 4–5 compared with ~30% who were 65 years and older. Younger participants at all stages were more likely to report extreme or somewhat/moderate difficulty obtaining medical care. Comorbid conditions (diabetes, hypertension, and prior cardiovascular events) were associated with increased utilization of care. Utilization of nephrology care was poor at all CKD stages; <6% of participants at stage 3 and <30% at stages 4–5 reported ever seeing a nephrologist.
Conclusions
Lack of health insurance and perceived difficulty obtaining medical care with lower health care utilization, both of which are consistent with inadequate access to health care, are more likely for KEEP participants who are younger than 65 years, nonwhite, and without previously diagnosed comorbid conditions. Nephrology care is infrequent in elderly participants with advanced CKD who are nonwhite, have comorbid disease, and have high-risk states for cardiovascular disease.
doi:10.1053/j.ajkd.2011.10.043
PMCID: PMC3694584  PMID: 22339901
Chronic kidney disease; health care access; health insurance; medication payment; socioeconomic status; educational status
13.  Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C 
Environmental research  2011;111(8):1236-1242.
Cadmium is a well known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs = 0.5; p less than 0.001). After adjustment, ln(urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln(urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient = 4.1 ml/min/1.73 m2; 95% confidence interval =1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.
doi:10.1016/j.envres.2011.07.012
PMCID: PMC3210933  PMID: 21871619
cadmium; cystatin C; kidney function; serum creatinine; urine creatinine
14.  Association of Residual Urine Output with Mortality, Quality of Life, and Inflammation in Incident Hemodialysis Patients: The CHOICE (Choices for Healthy Outcomes in Caring for End-Stage Renal Disease) Study 
Background
Residual kidney function (RKF) is associated with improved survival in peritoneal dialysis patients but its role in hemodialysis patients is less well known. Urine output may provide an estimate of RKF. The aim of our study was to determine the association of urine output with mortality, quality of life (QOL) and inflammation in incident hemodialysis patients.
Study Design
Nationally representative prospective cohort study
Setting & Participants
734 incident hemodialysis participants treated in 81 clinics; enrollment, 1995-1998, follow-up until December 2004.
Predictor
Urine output, defined as producing at least 250 mL (1 cup) of urine daily, ascertained by questionnaires at baseline and year 1.
Outcomes & Measurements
Primary outcomes were all-cause and cardiovascular (CVD) mortality, analyzed using Cox regression adjusted for demographic, clinical and treatment characteristics. Secondary outcomes were QOL, inflammation (CRP and interleukin-6 [IL-6] levels) and erythropoietin (EPO) requirements.
Results
617/734 (84%) participants reported urine output at baseline and 163/579 (28%) at year 1. Baseline urine output was not associated with survival. Urine output at year 1, indicating preserved RKF, was independently associated with lower all-cause mortality (Hazard Ratio [HR], 0.70; 95% Confidence Interval [CI], 0.52-0.93; p=0.02) and a trend towards lower CVD mortality (HR, 0.69; 95% CI, 0.45-1.05; p=0.09). Participants with urine output at baseline reported better QOL and had lower CRP (p=0.02) and IL-6 (p=0.03) levels. Importantly, EPO dose was 12,000 units/week lower in those with urine output at year 1 compared with those without (p=0.001).
Limitations
Urine volume was measured in only a subset of patients (42%) but was in agreement with self-report (p<0.001).
Conclusions
RKF in hemodialysis patients is associated with better survival and QOL, lower inflammation and significantly less EPO use. RKF should be monitored routinely in hemodialysis patients. Development of methods to assess and preserve RKF is important and may improve dialysis care.
doi:10.1053/j.ajkd.2010.03.020
PMCID: PMC2910835  PMID: 20605303
End-stage Renal Disease; Hemodialysis; Residual Kidney Function; Mortality; Quality of Life; Inflammation
15.  Associations of low-level urine cadmium with kidney function in lead workers 
Objectives
Low-level cadmium exposure, e.g., urinary cadmium < 2.0 μg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these lower levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead.
Methods
We evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-β-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead dose was assessed via blood and tibia lead, respectively.
Results
In 712 lead workers, mean (SD) blood and tibia lead, urine cadmium, and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) μg/dl, 26.6 (28.9) μg Pb/g bone mineral, 1.15 (0.66) μg/g creatinine, and 97.4 (19.2) ml/min/1.73m2, respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (β = 8.7 ml/min/1.73 m2; 95% CI = 5.4, 12.1) and ln-NAG but lower serum creatinine.
Conclusions
Potential explanations for these results include a normal physiologic response in which urine cadmium levels reflect renal filtration; the impact of adjustment for urine dilution with creatinine in models of kidney outcomes; and cadmium-related hyperfiltration.
doi:10.1136/oem.2010.056077
PMCID: PMC3053421  PMID: 20974743
cadmium; kidney function; lead exposure; urine creatinine
16.  Inpatient Hemodialysis Initiation: Reasons, Risk Factors and Outcomes 
Nephron. Clinical Practice  2009;114(1):c19-c28.
Background/Aims
Inpatient initiation of chronic hemodialysis is considered undesirable because of cost and possible harms of hospitalization. We examined the patient characteristics and outcomes associated with inpatient initiation.
Methods
In a prospective cohort study of incident dialysis patients, the independent association of inpatient hemodialysis initiation with patient outcomes was assessed in multivariable analyses with adjustment for patient characteristics and propensity for inpatient initiation.
Results
A total of 410 of 652 (63%) hemodialysis patients began as inpatients; uremia and volume overload were the most commonly documented reasons. Compared to outpatients, inpatients were more likely to be unmarried, report less social support, have multiple comorbidities and be referred to a nephrologist 4 months or less prior to initiation. Inpatient initiation was protective for subsequent all-cause hospitalization (incidence rate ratio (IRR) = 0.92, confidence interval (CI) 0.89–0.94); this was most pronounced among those who had the highest propensity for inpatient initiation (IRR = 0.66, CI 0.56–0.78), including those referred late to nephrology. Similar results were found for infectious hospitalization. Mortality [hazard ratio = 1.03, CI 0.82–1.30] and cardiovascular events were not significantly different for inpatients versus outpatients.
Conclusion
Inpatient hemodialysis initiation has a protective association with hospitalization among those patients referred late to nephrology, with multiple comorbidities and/or little social support.
doi:10.1159/000245066
PMCID: PMC2842162  PMID: 19816040
End-stage renal disease; Hospitalization; Late referral; Mortality; Social support
17.  Effect of primary care physicians' use of estimated glomerular filtration rate on the timing of their subspecialty referral decisions 
BMC Nephrology  2011;12:1.
Background
Primary care providers' suboptimal recognition of the severity of chronic kidney disease (CKD) may contribute to untimely referrals of patients with CKD to subspecialty care. It is unknown whether U.S. primary care physicians' use of estimated glomerular filtration rate (eGFR) rather than serum creatinine to estimate CKD severity could improve the timeliness of their subspecialty referral decisions.
Methods
We conducted a cross-sectional study of 154 United States primary care physicians to assess the effect of use of eGFR (versus creatinine) on the timing of their subspecialty referrals. Primary care physicians completed a questionnaire featuring questions regarding a hypothetical White or African American patient with progressing CKD. We asked primary care physicians to identify the serum creatinine and eGFR levels at which they would recommend patients like the hypothetical patient be referred for subspecialty evaluation. We assessed significant improvement in the timing [from eGFR < 30 to ≥ 30 mL/min/1.73m2) of their recommended referrals based on their use of creatinine versus eGFR.
Results
Primary care physicians recommended subspecialty referrals later (CKD more advanced) when using creatinine versus eGFR to assess kidney function [median eGFR 32 versus 55 mL/min/1.73m2, p < 0.001]. Forty percent of primary care physicians significantly improved the timing of their referrals when basing their recommendations on eGFR. Improved timing occurred more frequently among primary care physicians practicing in academic (versus non-academic) practices or presented with White (versus African American) hypothetical patients [adjusted percentage(95% CI): 70% (45-87) versus 37% (reference) and 57% (39-73) versus 25% (reference), respectively, both p ≤ 0.01).
Conclusions
Primary care physicians recommended subspecialty referrals earlier when using eGFR (versus creatinine) to assess kidney function. Enhanced use of eGFR by primary care physicians' could lead to more timely subspecialty care and improved clinical outcomes for patients with CKD.
doi:10.1186/1471-2369-12-1
PMCID: PMC3033812  PMID: 21235763
18.  Cerebrovascular Disease Incidence, Characteristics, and Outcomes in Patients Initiating Dialysis: The CHOICE (Choices for Healthy Outcomes in Caring for ESRD) Study 
Background
Stroke is the third most common cause of cardiovascular disease death in patients on dialysis; however, characteristics of cerebrovascular disease, including clinical subtypes and subsequent consequences, have not been well described.
Study Design
Prospective national cohort study, the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.
Settings & Participants
1,041 incident dialysis patients treated in 81 clinics, enrolled from 10/95–7/98, followed until 12/31/2004.
Predictor
Time from dialysis initiation.
Outcomes & Measurements
Cerebrovascular disease events were defined as non-fatal (hospitalized stroke, carotid endarterectomy) and fatal (stroke death) events after dialysis initiation. Stroke subtypes were classified using standardized criteria from the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system. Incidence of cerebrovascular event subtypes were analyzed using time-to-event analyses accounting for competing risk of death. Clinical outcomes after stroke were abstracted from medical records.
Results
A total of 165 participants experienced a cerebrovascular event with an overall incidence of 4.9 per 100 person-years. Ischemic stroke was the most common (76% of all 200 events) with cardioembolism subtype accounting for 28% of the 95 abstracted ischemic events. The median time from onset of symptoms to first stroke evaluation was 8.5 hours (25th and 75th percentiles 1, 42 hours), with only 56% of patients successfully escaping death, nursing home, or a skilled nursing facility.
Limitations
Relatively small sample size limits power to determine risk factors.
Conclusions
Cerebrovascular disease is common in dialysis patients, is identified late, and carries a significant risk of morbidity and mortality. Stroke etiologic subtypes on dialysis are multifactorial, suggesting risk factors may change the longer one has ESRD. Further studies are needed to address the poor prognosis through prevention, early identification, and treatment.
doi:10.1053/j.ajkd.2009.01.261
PMCID: PMC2744381  PMID: 19376618
Cerebrovascular disease; Stroke; Dialysis; Prognosis; Epidemiology
19.  Clinical testing patterns and cost implications of variation in the evaluation of chronic kidney disease among U.S. physicians 
Background
Clinical practice guidelines were established to improve the diagnosis and management of chronic kidney disease (CKD), but the extent, determinants, and cost implications of guideline adherence and variation in adherence have not been evaluated.
Study Design
Cross-sectional survey
Settings & Participants
Nationally representative sample of 301 U.S. primary care physicians and nephrologists
Predictor
Provider and patient characteristics
Outcomes & Measurements
Guideline adherence was assessed as present if physicians recommended at least 5 of 6 clinical tests prescribed by the National Kidney Foundation-Kidney Disease Outcomes and Quality Initiative (KDOQI) guidelines for a hypothetical patient with newly identified CKD. We also assessed patterns and cost of additional non-recommended tests for the initial clinical evaluation of CKD.
Results
Most of the 86 family medicine, 89 internal medicine, and 126 nephrology physicians practiced greater than 10 years (54%), were in non-academic practices (76%), spent greater than 80% of their time performing clinical duties (78%), and correctly estimated kidney function (73%). Overall, 35% of participants were guideline adherent. Compared to nephrologists, internal medicine and family physicians had lower odds of adherence for all recommended testing (Odds Ratio (OR) [95% CI]:0.6[0.3–1.1] and 0.3[0.1–0.6], respectively). Participants practicing greater than 10 years had lower odds of ordering all recommended testing compared to participants practicing less than 10 years (OR[95% CI]: 0.5[0.3–0.9]). Eighty-five percent of participants recommended additional tests, which resulted in a 23% increased total per patient cost of the clinical evaluation.
Limitations
Recommendations for a hypothetical case scenario may differ from that of actual patients.
Conclusions
Adherence to the recommended clinical testing for the diagnosis and management of CKD was poor and additional testing was associated with substantially increased cost of the clinical evaluation. Improved clarity, dissemination, and uptake of existing guidelines are needed to improve quality and decrease costs of care for patients with CKD.
doi:10.1053/j.ajkd.2008.12.044
PMCID: PMC2714476  PMID: 19371991
chronic kidney disease; primary care providers; guidelines; KDOQI; cost
20.  Association of Single-Nucleotide Polymorphisms in JAK3, STAT4, and STAT6 With New Cardiovascular Events in Incident Dialysis Patients 
Background
Increasing evidence supports a role for cell-mediated immunity in the pathogenesis of cardiovascular disease. Single nucleotide polymorphisms (SNPs) in JAK3, STAT4, and STAT6 of the Janus kinase–signal transducer and activator of transcription (Jak-Stat) signal transduction pathway were examined for association with time to new cardiovascular events in incident dialysis patients from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease study.
Study Design
Prospective cohort study.
Setting & Participants
764 White (n=518) and Black (n=246) participants from 79 dialysis centers.
Predictor
SNPs in JAK3, STAT4, and STAT6 selectedusing a pairwise approach to identify a maximally informative set of tag SNPs for populations of European and African descent.
Outcomes and Measurements
Cox proportional hazards models were used to estimate unadjusted and multivariable adjusted hazard ratios (HR) for incident cardiovascular disease events after dialysis initiation associated with each race-specific SNP.
Results
Two European tag SNPs (rs3212780 and rs3213409) were associated with new cardiovascular disease events in White patients in JAK3, with unadjusted HR 1.92 (p<0.001) and 1.82 (p=0.07), respectively. One dual-tag SNP (rs3212752) in JAK3 was associated with new cardiovascular events in White patients with unadjusted HR 2.09 (p<0.001) and in Black patients with HR 2.07 (p=0.007). SNP rs3213409 codes for a valine to isoleucine change at amino acid 722, a potentially functional mutation. SNPs in STAT4 and STAT6 were not associated with cardiovascular events after the initiation of dialysis.
Limitations
This study does not provide direct evidence for the mechanism of increased risk. Replication in independent cohorts is necessary.
Conclusions
Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients.
doi:10.1053/j.ajkd.2008.12.025
PMCID: PMC2744364  PMID: 19282076
dialysis; cardiovascular diseases; inflammation; genes
21.  Longitudinal associations between lead dose and renal function in lead workers 
Environmental research  2008;109(1):101-107.
Background
Existing research on the lead dose range associated with nephrotoxicity in the occupational setting is inconsistent and primarily cross-sectional in design.
Objective
To determine if lead dose predicts change in renal function in a large population of current and former lead workers.
Methods
Three evaluations were performed between 1997 and 2001. Lead dose was assessed with blood and tibia lead. Renal outcomes included blood urea nitrogen, serum creatinine, and calculated creatinine clearance. We used generalized estimating equations to model change in renal function between each evaluation in relation to tibia lead at the beginning of each follow-up period and concurrent change in blood lead, while adjusting for baseline lead dose and other covariates.
Results
At baseline, mean (SD) age and duration of occupational lead exposure were 42.0 (9.3) and 8.8 (6.3) years, respectively, in 537 current and former lead workers followed over a mean of 2.1 years. Mean (SD) blood and tibia lead were 31.3 (14.4) μg/dL and 35.0 (37.8) μg/g bone mineral, respectively. Women (25.9%) were older and more likely to be former lead workers than men. In males, serum creatinine decreased and calculated creatinine clearance increased over the course of the study. Mean blood lead was not significantly different between evaluations 1 and 3 in either sex, however, tibia lead decreased in women. Blood and tibia lead were significantly associated with change in renal function. In males, serum creatinine decreases and calculated creatinine clearance increases were greatest in participants whose blood lead declined.
Conclusions
Both acute and chronic occupational lead dose measures were associated with change in renal function measures prospectively.
doi:10.1016/j.envres.2008.09.005
PMCID: PMC2722941  PMID: 19038382
blood lead; renal function; lead exposure; longitudinal; tibia lead
22.  Racial differences in chronic kidney disease incidence and progression among individuals with HIV 
SUMMARY
This Practice Point commentary discusses the findings of Lucas et al.’s longitudinal cohort study of chronic kidney disease (CKD) in African American and white individuals with HIV. The study found that—compared with whites—African Americans had a slightly increased risk of incident CKD, but markedly increased rates of estimated glomerular filtration rate decline and progression to end-stage renal disease. This commentary details the clinical implications and limitations of these findings in the context of known racial differences in CKD prevalence and progression to end-stage renal disease in the general population and highlights the importance of screening high-risk HIV patients for kidney disease. CKD is common among HIV patients, and—as in the general population—has a more-aggressive course among African Americans than whites.
doi:10.1038/ncpneph0952
PMCID: PMC2648302  PMID: 18813233
chronic kidney disease; end-stage renal disease; HIV; racial differences; screening
23.  Association of Peritoneal Dialysis Clinic Size with Clinical Outcomes 
Objective
Very few studies have addressed the relationship between number of peritoneal dialysis (PD) patients treated at a clinic (PD clinic size) and clinical outcomes. In a national prospective cohort study of incident PD patients (n=236, from 26 clinics), we examined whether being treated at a larger PD clinic [≥50 PD patients (n=3 clinics) vs. <50 PD patients (n=23 clinics)] was associated with better patient outcomes, including fewer switches to hemodialysis, fewer cardiovascular events, lower cardiovascular mortality, and lower all-cause mortality.
Methods
Multivariable Cox models were used to assess relative hazards (RHs) for modality switches, cardiovascular events, cardiovascular deaths, and all-cause deaths by PD clinic size. All models were adjusted for demographics, comorbidities, laboratory values, and clinic years in operation.
Results
Being treated at a clinic with ≥50 patients was associated with fewer switches to hemodialysis (RH=0.13, 95% CI, 0.06-0.31) and fewer cardiovascular events (RH=0.62, 95% CI, 0.06-0.98). No associations of PD clinic size with cardiovascular or all-cause mortality were seen.
Conclusion
PD patients that are treated at clinics with greater numbers of PD patients may have better outcomes in terms of technique failure and cardiovascular morbidity. PD clinic size may act as a proxy of greater PD experience, more focus on the modality, and better PD practices at the clinic, resulting in better outcomes.
PMCID: PMC2686121  PMID: 19458300
peritoneal dialysis; clinic size; technique failure; cardiovascular morbidity; mortality
24.  Timing, causes, predictors and prognosis of switching from peritoneal dialysis to hemodialysis: a prospective study 
BMC Nephrology  2009;10:3.
Background
The use of peritoneal dialysis (PD) has declined in the United States over the past decade and technique failure is also reportedly higher in PD compared to hemodialysis (HD), but there are little data in the United States addressing the factors and outcomes associated with switching modalities from PD to HD.
Methods
In a prospective cohort study of 262 PD patients enrolled from 28 peritoneal dialysis clinics in 13 U.S. states, we examined potential predictors of switching from PD to HD (including demographics, clinical factors, and laboratory values) and the association of switching with mortality. Cox proportional hazards regression was used to assess relative hazards (RH) of switching and of mortality in PD patients who switched to HD.
Results
Among 262 PD patients, 24.8% switched to HD; with more than 70% switching within the first 2 years. Infectious peritonitis was the leading cause of switching. Patients of black race and with higher body mass index were significantly more likely to switch from PD to HD, RH (95% CI) of 5.01 (1.15–21.8) for black versus white and 1.09 (1.03–1.16) per 1 kg/m2 increase in BMI, respectively. There was no difference in survival between switchers and non-switchers, RH (95% CI) of 0.89 (0.41–1.93).
Conclusion
Switching from PD to HD occurs early and the rate is high, threatening long-term viability of PD programs. Several patient characteristics were associated with the risk of switching. However, there was no survival difference between switchers and non-switchers, reassuring providers and patients that PD technique failure is not necessarily associated with poor prognosis.
doi:10.1186/1471-2369-10-3
PMCID: PMC2649113  PMID: 19200383
25.  Attainment of clinical performance targets and improvement in clinical outcomes and resource use in hemodialysis care: a prospective cohort study 
Background
Clinical performance targets are intended to improve patient outcomes in chronic disease through quality improvement, but evidence of an association between multiple target attainment and patient outcomes in routine clinical practice is often lacking.
Methods
In a national prospective cohort study (ESRD Quality, or EQUAL), we examined whether attainment of multiple targets in 668 incident hemodialysis patients from 74 U.S. not-for-profit dialysis clinics was associated with better outcomes. We measured whether the following accepted clinical performance targets were met at 6 months after study enrollment: albumin (≥4.0 g/dl), hemoglobin (≥11 g/dl), calcium-phosphate product (<55 mg2/dl2), dialysis dose (Kt/V≥1.2), and vascular access type (fistula). Outcomes included mortality, hospital admissions, hospital days, and hospital costs.
Results
Attainment of each of the five targets was associated individually with better outcomes; e.g., patients who attained the albumin target had decreased mortality [relative hazard (RH) = 0.55, 95% confidence interval (CI), 0.41–0.75], hospital admissions [incidence rate ratio (IRR) = 0.67, 95% CI, 0.62–0.73], hospital days (IRR = 0.61, 95% CI, 0.58–0.63), and hospital costs (average annual cost reduction = $3,282, P = 0.002), relative to those who did not. Increasing numbers of targets attained were also associated, in a graded fashion, with decreased mortality (P = 0.030), fewer hospital admissions and days (P < 0.001 for both), and lower costs (P = 0.029); these trends remained statistically significant for all outcomes after adjustment (P < 0.001), except cost, which was marginally significant (P = 0.052).
Conclusion
Attainment of more clinical performance targets, regardless of which targets, was strongly associated with decreased mortality, hospital admissions, and resource use in hemodialysis patients.
doi:10.1186/1472-6963-7-5
PMCID: PMC1783649  PMID: 17212829

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