Supplementary Material for: Insights from Screening a Racially and Ethnically Diverse Population for Chronic Kidney Disease

<p><b><i>Background:</i></b> The value of chronic kidney disease (CKD) screening in the general population remains unclear but may be beneficial in populations with high disease prevalence. We examined risk factors for albuminuria among participants in a state-wide CKD screening program in Hawaii. <b><i>Methods:</i></b> The National Kidney Foundation of Hawaii Kidney Early Detection Screening (NKFH-KEDS) program held 19 CKD screening events from 2006 to 2012. Participants rotated through 5 stations during which sociodemographic, blood glucose, urine albumin-to-creatinine ratio (ACR), and spot urine albumin data were collected. Multivariate logistic regression analyses (adjusted for age, sex, race/ethnicity, body mass index [BMI]) were used to identify clinical predictors of abnormal ACR (≥30 μg/mg) and abnormal spot urine albumin (>20 mg/L) levels. <b><i>Results:</i></b> Among 1,190 NKFH-KEDS participants who met eligibility criteria, 13 and 49% had abnormal ACR and urine albumin levels, respectively. In multivariate logistic regression analyses, participants of older age (>65 years), Asian and Pacific Islander race/ethnicity, BMI ≥30 kg/m², and with hypertension had higher risk of abnormal ACR. Being of older age; Asian, Pacific Islander, and Mixed race/ethnicity; and having diabetes was associated with higher risk of abnormal urine albumin levels in adjusted analyses. <b><i>Conclusions:</i></b> NKFH-KEDS participants of older age; Asian and Pacific Islander race/ethnicity; and with obesity, hypertension, and diabetes had higher risk of kidney damage defined by elevated ACR and urine albumin levels. Further studies are needed to determine whether targeted screening programs can result in timely identification of CKD and implementation of interventions that reduce cardiovascular disease, death, and progression to end-stage renal disease.</p

Supplementary Material for: The Relationship Between Ultraviolet Light Exposure and Mortality in Dialysis Patients

<b><i>Background:</i></b> Emerging data suggest that reduced exposure to ultraviolet (UV) radiation is associated with increased mortality in the general population. To date, the association between UV exposure and mortality in dialysis patients has not been examined. <b><i>Methods:</i></b> We examined the association between UV index, a proxy of UV exposure, and all-cause mortality among 47,286 US dialysis patients (entry period 2001-2006, with follow-up through 2009) from a large national dialysis organization using multivariable Cox regression. The UV index was ascertained by linking individual patients' residential zip codes to National Oceanic and Atmospheric Administration data, and was categorized as low (0-<3), moderate (3-<5), moderate-high (5-<6), high (6-<7), and very-high (≥7). In secondary analyses, we examined the UV index-mortality association within subgroups of age (<65 vs. ≥65 years old), sex, and race (white vs. non-white). <b><i>Results:</i></b> The study population's mean ± SD age was 60 ± 16 and included 46% women and 56% diabetics. Compared to patients residing in moderate-high UV index regions, those residing in high and very-high UV index regions had a lower mortality risk: adjusted HRs 0.84 (95% CI) 0.81-0.88 and 0.83 (95% CI) 0.75-0.91, respectively. A similar inverse association between UV index and mortality was observed across all subgroups, although there was more pronounced reduction in mortality among whites vs. non-whites. <b><i>Conclusion:</i></b> These data suggest that dialysis patients residing in higher UV index regions have lower all-cause mortality compared to those living in moderate-high UV regions. Further studies are needed to determine the mechanisms underlying the UV index-mortality association

PowerPoint Slides for: Insights from Screening a Racially and Ethnically Diverse Population for Chronic Kidney Disease

<p><b><i>Background:</i></b> The value of chronic kidney disease (CKD) screening in the general population remains unclear but may be beneficial in populations with high disease prevalence. We examined risk factors for albuminuria among participants in a state-wide CKD screening program in Hawaii. <b><i>Methods:</i></b> The National Kidney Foundation of Hawaii Kidney Early Detection Screening (NKFH-KEDS) program held 19 CKD screening events from 2006 to 2012. Participants rotated through 5 stations during which sociodemographic, blood glucose, urine albumin-to-creatinine ratio (ACR), and spot urine albumin data were collected. Multivariate logistic regression analyses (adjusted for age, sex, race/ethnicity, body mass index [BMI]) were used to identify clinical predictors of abnormal ACR (≥30 μg/mg) and abnormal spot urine albumin (>20 mg/L) levels. <b><i>Results:</i></b> Among 1,190 NKFH-KEDS participants who met eligibility criteria, 13 and 49% had abnormal ACR and urine albumin levels, respectively. In multivariate logistic regression analyses, participants of older age (>65 years), Asian and Pacific Islander race/ethnicity, BMI ≥30 kg/m², and with hypertension had higher risk of abnormal ACR. Being of older age; Asian, Pacific Islander, and Mixed race/ethnicity; and having diabetes was associated with higher risk of abnormal urine albumin levels in adjusted analyses. <b><i>Conclusions:</i></b> NKFH-KEDS participants of older age; Asian and Pacific Islander race/ethnicity; and with obesity, hypertension, and diabetes had higher risk of kidney damage defined by elevated ACR and urine albumin levels. Further studies are needed to determine whether targeted screening programs can result in timely identification of CKD and implementation of interventions that reduce cardiovascular disease, death, and progression to end-stage renal disease.</p

Supplementary Material for: Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort

<b><i>Background:</i></b> Studies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations. <b><i>Methods:</i></b> We evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011–2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the ­overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models. <b><i>Results:</i></b> In baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01–2.88) and 0.95 (0.64–1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51–5.46) and 0.74 (0.27–2.07), respectively (<i>p</i> interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications. <b><i>Conclusion:</i></b> Low (1 mEq/L) dialysate potassium ­concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population

Supplementary Material for: Lymphocyte Cell Ratios and Mortality among Incident Hemodialysis Patients

<b><i>Background:</i></b> Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously suggested as oncologic prognostication markers. These are associated with malnutrition and inflammation, and hence, may provide benefit in predicting mortality among hemodialysis patients. <b><i>Methods:</i></b> Among 108,548 incident hemodialysis patients in a large U.S. dialysis organization (2007–2011), we compared the mortality predictability of NLR and PLR with baseline and time-varying covariate Cox models using the receiver operating characteristic curve (AUROC), net reclassification index (NRI), and adjusted R². <b><i>Results:</i></b> During the median follow-up period of 1.4 years, 28,618 patients died. Median (IQR) NLR and PLR at baseline were 3.64 (2.68–5.00) and 179 (136–248) respectively. NLR was associated with higher mortality, which appeared stronger in the time-varying versus baseline model. PLR exhibited a J-shaped association with mortality in both models. NLR provided better mortality prediction in addition to demographics, comorbidities, and serum albumin; ΔAUROC and NRI for 1-year mortality (95% CI) were 0.010 (0.009–0.012) and 6.4% (5.5–7.3%) respectively. Additionally, adjusted R² (95% CI) for the Cox model increased from 0.269 (0.262–0.276) to 0.283 (0.276–0.290) in the non-time-varying model and from 0.467 (0.461–0.472) to 0.505 (0.500–0.512) in the time-varying model. There was little to no benefit of adding PLR to predict mortality. <b><i>Conclusions:</i></b> High NLR in incident hemodialysis patients predicted mortality, especially in the short-term period. NLR, but not PLR, added modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostication approaches

Supplementary Material for: Body Mass Index and Mortality in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> A higher body mass index (BMI) seems to be linked to survival advantage in maintenance hemodialysis patients. However, it is uncertain if this ‘obesity survival paradox' is also observed in kidney transplant recipients. Hence, we systematically reviewed the literature on the impact of pre-transplantation BMI on all-cause mortality in this population. <b><i>Methods:</i></b> We searched MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane CENTRAL for relevant studies up to July 2013. Two investigators independently selected the studies using predefined criteria, abstracted the data from the included studies, and independently assessed each study's quality using the Newcastle-Ottawa Quality Assessment Scale. In addition to the qualitative synthesis, we quantitatively pooled the results of the studies with clinical, methodological, and statistical homogeneity. <b><i>Results:</i></b> We screened 7,123 records, from which we included 11 studies (with a total of 305,392 participants) in this systematic review and 4 studies in the meta-analyses. In the only study that included children, obesity was linked to higher mortality in children of 6-12 years old. For adults, our meta-analyses indicated that compared to normal BMI, underweight [Hazard Ratio (HR): 1.09; 95% Confidence Interval (CI): 1.02-1.20], overweight (HR: 1.07; 95% CI: 1.04-1.12), and obese (HR: 1.20; 95% CI: 1.14-1.23) levels of BMI were associated with higher mortality. <b><i>Conclusion:</i></b> The presence of the obesity survival paradox is unlikely in kidney transplant recipients since both extremes of pre-transplantation BMI are linked to higher mortality in this population

Supplementary Material for: Changes in Markers of Mineral and Bone Disorders and Mortality in Incident Hemodialysis Patients

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

Supplementary Material for: Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients

<p><b><i>Background:</i></b> Higher serum ferritin levels may be influenced by iron use and inflammation, and are associated with higher mortality in hemodialysis (HD) patients. We hypothesized that a major rise in serum ferritin is associated with a higher risk of mortality, irrespective of baseline serum ferritin in incident HD patients. <b><i>Methods:</i></b> In a cohort of 93,979 incident HD patients between 2007 and 2011, we examined the association of change in serum ferritin from the baseline patient quarter (first 91 days from dialysis start) to the subsequent quarter with mortality. Multivariable adjustments were done for case-mix and markers of the malnutrition, and inflammation complex and intravenous iron dose. Change in serum ferritin was stratified into 5 groups: <-400, -400 to <-100, -100 to <100, 100 to <400, and ≥400 ng/mL/quarter. <b><i>Results:</i></b> The median change in serum ferritin was 89 ng/mL/quarter (interquartile range -55 to 266 ng/mL/quarter). Compared to stable serum ferritin (-100 to <100 ng/mL/quarter), a major rise (≥400 ng/mL/quarter) was associated with higher all-cause mortality (hazard ratio [95% CI] 1.07 [0.99-1.15], 1.17 [1.09-1.24], 1.26 [1.12-1.41], and 1.49 [1.27-1.76] according to baseline serum ferritin: <200, 200 to <500, 500 to <800, and ≥800 ng/mL in adjusted models, respectively. The mortality risk associated with a rise in serum ferritin was robust, irrespective of intravenous iron use. <b><i>Conclusions:</i></b> During the first 6-months after HD initiation, a major rise in serum ferritin in those with a baseline ferritin ≥200 ng/mL and even a slight rise in serum ferritin in those with a baseline ferritin ≥800 ng/mL are associated with higher mortality.</p

Supplementary Material for: Impact of Age, Race and Ethnicity on Dialysis Patient Survival and Kidney Transplantation Disparities

<b><i>Background:</i></b> Prior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups. <b><i>Methods:</i></b> The associations between race/ethnicity with all-cause mortality and kidney transplantation were separately examined among 130,909 adult dialysis patients from a large national dialysis organization (entry period 2001-2006, follow-up through 2009) within 7 age categories using Cox proportional hazard models adjusted for case-mix and malnutrition and inflammatory surrogates.<b><i> Results:</i></b> African-Americans had similar mortality versus whites in younger age groups (18-40 years), but decreased mortality in older age groups (>40 years). In contrast, Hispanics had lower mortality versus whites across all ages. In sensitivity analyses using competing risk regression to account for differential kidney transplantation rates across racial/ethnic groups, the African-American survival advantage was limited to >60-years age categories. African-Americans and Hispanics were less likely to undergo kidney transplantation from all donor types versus whites across all ages, and these disparities were even more pronounced for living donor kidney transplantation (LDKT). <b><i>Conclusions:</i></b> Hispanic dialysis patients have greater survival versus whites across all ages; in African-Americans, this survival advantage is limited to patients >40 years of age. Minorities are less likely to undergo kidney transplantation, particularly LDKT, across all ages

Supplementary Material for: Association of Body Mass Index with Clinical Outcomes in Non-Dialysis-Dependent Chronic Kidney Disease: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Previous studies have not shown a consistent link between body mass index (BMI) and outcomes such as mortality and kidney disease progression in non-dialysis-dependent chronic kidney disease (CKD) patients. Therefore, we aimed to complete a systematic review and meta-analysis study on this subject. <b><i>Methods:</i></b> We searched MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL), and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa quality assessment scale. We meta-analyzed the results based on the BMI classification system by the WHO. <b><i>Results:</i></b> We included 10 studies (with a total sample size of 484,906) in the systematic review and 4 studies in the meta-analyses. The study results were generally heterogeneous. However, following reanalysis of the largest reported study and our meta-analyses, we observed that in stage 3-5 CKD, being underweight was associated with a higher risk of death while being overweight or obese class I was associated with a lower risk of death; however, obesity classes II and III were not associated with risk of death. In addition, reanalysis of the largest available study showed that a higher BMI was associated with an incrementally higher risk of kidney disease progression; however, this association was attenuated in our pooled results. For earlier stages of CKD, we could not complete meta-analyses as the studies were sparse and had heterogeneous BMI classifications and/or referent BMI groups. <b><i>Conclusion:</i></b> Among the group of patients with stage 3-5 CKD, we found a differential association between obesity classes I-III and mortality compared to the general population, indicating an obesity paradox in the CKD population