Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.

Antihypertensive medications and risk of death and hospitalizations in US hemodialysis patients: Evidence from a cohort study to inform hypertension treatment practices.

Antihypertensive medications are commonly prescribed to hemodialysis patients but the optimal regimens to prevent morbidity and mortality are unknown. The goal of our study was to compare the association of routinely prescribed antihypertensive regimens with outcomes in US hemodialysis patients.We used 2 datasets for our analysis. Our primary cohort (US Renal Data System [USRDS]) included adult patients initiating in-center hemodialysis from July 1, 2006 to June 30, 2008 (n = 33,005) with follow-up through December 31, 2009. Our secondary cohort included adult patients from Dialysis Clinic, Inc. (DCI), a national not-for-profit dialysis provider, initiating in-center hemodialysis from January 1, 2003 to June 30, 2008 (n = 11,291) with follow-up through December 31, 2008. We linked the USRDS cohort with Medicare part D prescriptions-fill data and the DCI cohort with USRDS data. Unique aspect of USRDS cohort was pharmacy prescription-fill data and for DCI cohort was detailed clinical data, including blood pressure, weight, and ultrafiltration. We classified prescribed antihypertensives into the following mutually exclusive regimens: ß-blockers, renin-angiotensin system blocking drugs-containing regimens without a ß-blocker (RAS), ß-blocker + RAS, and others. We used marginal structural models accounting for time-updated comorbidities to quantify each regimen's association with mortality (both cohorts) and cardiovascular hospitalization (DCI-Medicare Subcohort).In the USRDS and DCI cohorts there were 9655 (29%) and 3200 (28%) deaths, respectively. In both cohorts, RAS compared to ß-blockers regimens were associated with lower risk of death; (hazard ratio [HR]) (95% confidence interval [CI]) for all-cause mortality, (0.90 [0.82-0.97] in USRDS and 0.87 [0.76-0.98] in DCI) and cardiovascular mortality (0.84 [0.75-0.95] in USRDS and 0.88 [0.71-1.07] in DCI). There was no association between antihypertensive regimens and the risk of cardiovascular hospitalizations.In hemodialysis patients undergoing routine care, renin-angiotensin system blocking drugs-containing regimens were associated with a lower risk of death compared with ß-blockers-containing regimens but there was no association with cardiovascular hospitalizations. Pragmatic clinical trials are needed to specifically examine the effectiveness of these commonly used antihypertensive regimens in dialysis patients.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project.

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

Satisfaction with Care of Patients on Hemodialysis.

BACKGROUND AND OBJECTIVES: Little is known about patients receiving dialysis who respond to satisfaction and experience of care surveys and those who do not respond, nor is much known about the corollaries of satisfaction. This study examined factors predicting response to Dialysis Clinic, Inc. (DCI)'s patient satisfaction survey and factors associated with higher satisfaction among responders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: A total of 10,628 patients receiving in-center hemodialysis care at 201 DCI facilities between January 1, 2011, and December 31, 2011, aged ≥18 years, treated during the survey administration window, and at the facility for ≥3 months before survey administration. Primary outcome was response to at least one of the nine survey questions; secondary outcome was overall satisfaction with care. RESULTS: Response rate was 77.3%. In adjusted logistic regression (odds ratios with 95% confidence intervals), race other than black (white race, 1.23 [1.10 to 1.37]), missed treatments (1.16 [1.02 to 1.32]) or shortened treatments (≥5 treatments, 1.40 [1.22 to 1.60]), more hospital days (>3 days in the last 3 months, 1.89 [1.66 to 2.15]), and lower serum albumin (albumin level <3.5 g/dl, 1.4 [1.28 to 1.73]) all independently predicted nonresponse. In adjusted linear regression, the following were more satisfied with care: older patients (age ≥63 years, 1.84 [1.78 to 1.90]; age <63 years, 1.91 [1.86 to 1.97]; P<0.001), white patients (1.76 [1.71 to 1.81]) versus black patients (1.93 [1.88 to 1.99]) or those of other race (1.93 [1.83 to 2.03]) (P<0.001), patients with shorter duration of dialysis (≤2.5 years, 1.79 [1.73 to 1.84]; >2.5 years, 1.96 [1.91 to 2.02]; P<0.001), patients who had missed one or fewer treatments (1.83 [1.78 to 1.88]) versus those who had missed more than one treatment (1.92 [1.85 to 1.98]; P=0.002) and those who had shortened treatment (for one treatment or less, 1.84 [1.77 to 1.90]; for two to four treatments, 1.87 [1.81 to 1.93]; for five or more treatments, 1.92 [1.87 to 1.98]; P=0.004). CONCLUSIONS: Survey results represent healthier and more adherent patients on hemodialysis. Shorter survey administration windows were associated with higher response rates. Older, white patients with shorter dialysis vintage were more satisfied.

Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project.

The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p < 1.58 × 10(-7)) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p < 1.58 × 10(-6)) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions.

Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy.

Mortality is highest in the first months of maintenance hemodialysis (HD) therapy. In many Western countries, patients who transition to kidney replacement therapy usually begin thrice-weekly HD regardless of their level of residual kidney function (RKF). RKF is a major predictor of survival. RKF may decline more rapidly with thrice-weekly HD treatments, is associated with a reduced need for dialytic solute clearance, and is an important factor in the prescription of peritoneal dialysis. In this article, we review the concept of incremental HD, in which weekly dialysis dose, in particular HD treatment frequency, is based on a variety of clinical factors, such as RKF (including urine output > 0.5 L/d), volume status, cardiovascular symptoms, body size, potassium and phosphorus levels, nutritional status, hemoglobin level, comorbid conditions, hospitalizations, and health-related quality of life. These 10 clinical criteria may identify which patients might benefit from beginning maintenance HD therapy twice weekly. Periodic monitoring of these criteria will determine the timing for increasing dialysis dose and frequency. We recognize that twice-weekly HD represents a major paradigm shift for many clinicians and jurisdictions. Therefore, we propose conducting randomized controlled trials of twice-weekly versus thrice-weekly HD to assess the potential of twice-weekly HD to improve survival and health-related quality of life while simultaneously reducing costs, protecting fragile vascular accesses, and optimizing resource use during the first year of hemodialysis therapy. Such incremental and individualized HD therapy may prove to be the most appropriate approach for transitioning to dialytic therapy.

Troponin I and NT-proBNP and the association of systolic blood pressure with outcomes in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study.

BACKGROUND: There is uncertainty regarding treatment of hypertension in hemodialysis patients due to the observed J-shaped association between blood pressure (BP) and death. We hypothesized that this association reflects confounding by cardiovascular disease (CVD) and that stratification by CVD biomarkers, cardiac troponin I (cTnI) and N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), might change this association. STUDY DESIGN: National prospective cohort study. SETTING & PARTICIPANTS: 446 incident hemodialysis patients. PREDICTOR: Predialysis systolic BP. OUTCOMES: Mortality (all-cause and CVD) and first CVD event assessed using Cox regression adjusted for demographics, comorbid conditions, and clinical factors. MEASUREMENTS: Participants with cTnI level ≥0.1 ng/mL or NT-proBNP level ≥9,252 pg/mL were classified as the high-biomarker group; remaining participants were included in the low-biomarker group. RESULTS: Participants in the high-biomarker group (n=138 [31%]) were older (61 vs. 57 years) and had a higher prevalence of CVD (67% vs. 23%), but similar baseline BPs (152 vs. 153 mm Hg). There were 323 deaths (143 from CVD) and 271 CVD events. The high-biomarker group had a higher risk of mortality than the low-biomarker group (HR, 1.75; 95% CI, 1.37-2.24). The association between BP and outcomes differed between the 2 biomarker groups (P for interaction=0.01, 0.2, and 0.07 for all-cause mortality, CVD mortality, and first CVD event, respectively). In the low-biomarker group, BP was associated with greater risk of outcomes: HR per 10 mm Hg higher BP was 1.07 (95% CI, 1.01-1.14), 1.10 (95% CI, 0.96-1.25), and 1.04 (95% CI, 0.96-1.13) for all-cause mortality, CVD mortality, and first CVD event, respectively. Importantly, lower BP was not associated with increased risk of outcomes in stratified models, including for those in high biomarker group. LIMITATIONS: BP measurements not standardized. CONCLUSIONS: The observed J-shaped association between BP and outcomes in hemodialysis patients is due to confounding by subclinical CVD. A stratification approach based on cTnI and NT-proBNP levels has the potential to inform BP treatment in hemodialysis patients.

Hypertension in hemodialysis patients: an opinion-based update.

Hypertension is highly prevalent in hemodialysis patients but its management remains a matter of debate. In this review, we discuss the observational studies on the association of blood pressure with outcomes, measurement of blood pressure in hemodialysis patients and present an opinion-based approach to treating hypertension.

Predialysis systolic BP variability and outcomes in hemodialysis patients.

BP variability (BPV) is an important predictor of outcomes in the general population, but its association with clinical outcomes in hemodialysis patients is not clear. We identified 11,291 patients starting dialysis in 2003-2008 and followed them through December 31, 2008 (median=22 months). Predialysis systolic BPV was assessed over monthly intervals. Outcomes included factors associated with BPV, mortality (all-cause and cardiovascular), and first cardiovascular event (cardiovascular death or hospitalization). Patients' mean age was 62 years, 55% of patients were men, and 58% of patients were white. Modifiable factors associated with higher BPV included obesity, higher calcium-phosphate product levels, and lower hemoglobin concentration; factors associated with lower BPV included greater fluid removal, achievement of prescribed dry weight during dialysis, higher hemoglobin concentration, and antihypertensive regimens without ß-blockers or renin-angiotensin system blocking agents. In total, 3200 deaths occurred, including 1592 cardiovascular deaths. After adjustment for demographics, comorbidities, and clinical factors, higher predialysis BPV was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.18; 95% confidence interval [95% CI] per 1 SD increase in BPV, 1.13 to 1.22), cardiovascular mortality (HR, 1.18; 95% CI, 1.12 to 1.24), and first cardiovascular event (HR, 1.11; 95% CI, 1.07 to 1.15). Results were similar when BPV was categorized in tertiles and patients were stratified by baseline systolic BP. In summary, predialysis systolic BPV is an important, potentially modifiable risk factor for death and cardiovascular outcomes in incident hemodialysis patients. Studies of BP management in dialysis patients should focus on both absolute BP and BPV.

Oral intradialytic nutritional supplement use and mortality in hemodialysis patients.

BACKGROUND: Hemodialysis patients have high mortality rates, potentially reflecting underlying comorbid conditions and ongoing catabolism. Intradialytic oral nutritional supplements may reduce this risk. STUDY DESIGN: Retrospective propensity-matched cohort. SETTING & PARTICIPANTS: Maintenance hemodialysis patients treated at Dialysis Clinic Inc facilities who were initiated on a nutritional supplement protocol in September to October 2010 were matched using a propensity score to patients at facilities at which the protocol was not used. PREDICTORS: Prescription of the protocol, whereby hemodialysis patients with serum albumin levels ≤3.5g/dL would initiate oral protein supplementation during the dialysis procedure. Sensitivity analyses matched on actual supplement intake during the first 3 study months. Covariates included patient and facility characteristics, which were used to develop the propensity scores and adjust multivariable models. OUTCOMES: All-cause mortality, ascertained though March 2012. RESULTS: Of 6,453 eligible patients in 101 eligible hemodialysis facilities, the protocol was prescribed to 2,700, and 1,278 of these were propensity matched to controls. Mean age was 61 ± 15 (SD) years and median dialysis vintage was 34 months. There were 258 deaths among protocol assignees versus 310 among matched controls during a mean follow-up of 14 months. In matched analyses, protocol prescription was associated with a 29% reduction in the hazard of all-cause mortality (HR, 0.71; 95% CI, 0.58-0.86); adjustment had minimal impact on models. In time-dependent models incorporating change in albumin level, protocol status remained significant but was attenuated in models incorporating a 30-day lag. Similar results were seen in sensitivity analyses of 439 patients receiving supplements who were propensity-matched to controls, with 116 deaths among supplement users versus 140 among controls (HR, 0.79; 95% CI, 0.60-1.05), achieving statistical significance in adjusted models. LIMITATIONS: Observational design, potential residual confounding. CONCLUSIONS: Prescription of an oral nutritional supplement protocol and use of oral protein nutritional supplements during hemodialysis are associated with reduced mortality among in-center maintenance hemodialysis patients, an effect likely not mediated by change in serum albumin levels.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

OBJECTIVE: Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. METHODS: Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. CONCLUSION: The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

Heritability of serum sodium concentration: evidence for sex- and ethnic-specific effects.

Serum sodium concentration is the clinical index of systemic water balance. Although disordered water balance is common and morbid, little is known about genetic effects on serum sodium concentration at the population level. Prior studies addressed only participants of European descent and either failed to demonstrate significant heritability or showed only modest effect. We investigated heritability of serum sodium concentration in large cohorts reflecting a range of races/ethnicities, including the Framingham Heart Study (FHS, non-Hispanic Caucasian), the Heredity and Phenotype Intervention Heart Study (HAPI, Amish Caucasian), the Jackson Heart Study (JHS, African American), the Strong Heart Family Study (SHFS, American Indian), and the Genetics of Kidney Disease in Zuni Indians Study (GKDZI, American Indian). Serum sodium was transformed for the osmotic effect of glucose, and participants with markedly elevated glucose or reduced estimated glomerular filtration rate (eGFR) were excluded. Using a standard variance components method, incorporating covariates of age, glucose, and eGFR, we found heritability to be high in African American and American Indian populations and much more modest in non-Hispanic Caucasian populations. Estimates among females increased after stratification on sex and were suggestive among female participants in FHS (0.18 ± 0.12, P = 0.057) and male participants in JHS (0.24 ± 0.16, P = 0.067) and statistically significant among female participants in JHS (0.44 ± 0.09, P = 1 × 10 ⁻7), SHFS (0.59 ± 0.05, P = 9.4 × 10⁻46), and GKDZI (0.46 ± 0.15, P = 1.7 × 10⁻4), and male participants in HAPI (0.18 ± 0.12, P = 0.03) and SHFS (0.67 ± 0.07, P = 5.4 × 10⁻²6). Exclusion of diuretic users increased heritability among females and was significant in all cohorts where data were available. In aggregate, these data strongly support the heritability of systemic water balance and underscore sex and ethnicity-specific effects.

Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study.

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. METHODS: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. RESULTS: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. CONCLUSION: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.

Age, race, diabetes, blood pressure, and mortality among hemodialysis patients.

Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.

Heritability of measures of kidney disease among Zuni Indians: the Zuni Kidney Project.

BACKGROUND: The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. STUDY DESIGN: A community-based participatory research approach was used to recruit family members of individuals with kidney disease. SETTING & PARTICIPANTS: The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. PREDICTOR OUTCOMES & MEASUREMENTS: Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was >or=0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. RESULTS: Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. LIMITATIONS: Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. CONCLUSIONS: Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations.

Left ventricular diastolic function in patients on hemodialysis.

BACKGROUND: Previous studies have shown that the assessment of Doppler mitral flow velocity (DMFV) curves can be used to predict prognosis owing to left ventricular (LV) diastolic dysfunction in certain specific diseases. Our aim was to study whether the prognostic value of DMFV curves is affected by the many end-stage renal disease factors, such as chronic uremia and long-term hemodialysis (HD), which cause LV diastolic dysfunction and death. METHODS: Retrospective echo Doppler studies obtained 10 to 12 hours after HD in 90 patients (52 males; mean age, 56 years) were analyzed to determine changes in deceleration time (DT) of the early mitral filling wave (E) and the ratio of E to the atrial velocity (A). The study findings (n = 83) showed 2 groups of DT: long DT (DT > 240 milliseconds) and normal/short DT (DT

Increased CD36 expression signals monocyte activation among patients with type 2 diabetes.

OBJECTIVE: To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation. RESEARCH DESIGN AND METHODS: We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs-interleukin-6 (hsIL-6), and adiponectin were measured. RESULTS: Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups. CONCLUSIONS: Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

BACKGROUND: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. METHODS: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. RESULTS: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. CONCLUSIONS: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.