Journal of applied physiology (Bethesda, Md. : 1985), 2003
Respiratory muscle weakness is common in children with neuromuscular disease (NMD). We hypothesiz... more Respiratory muscle weakness is common in children with neuromuscular disease (NMD). We hypothesized that weakness puts them at risk for respiratory muscle fatigue, a harbinger of chronic respiratory failure. We therefore measured a noninvasive index of respiratory muscle fatigue, the tension-time index of the respiratory muscles (TT(mus)), in 11 children with NMD and 13 control subjects. Spirometric flow rates and maximal inspiratory pressure were significantly lower in the NMD group than in controls (43 +/- 23 vs. 99 +/- 21 cmH2O, P < 0.001). The mean TT(mus) was significantly higher in the NMD group than in controls (0.205 +/- 0.117 vs. 0.054 +/- 0.021, P < 0.001). The increase in TT(mus) was primarily due to an increase in the ratio of average mean inspiratory pressure to maximal inspiratory pressure, indicating decreased respiratory muscle strength reserve. We found a significant correlation between TT(mus) and the residual volume-to-total lung capacity ratio (r = 0.504, P...
Journal of the American Society of Nephrology : JASN, Jan 4, 2015
Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft fai... more Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adju...
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 6, 2015
In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately aff... more In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. Longitudinal cohort study. 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-β-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR). Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to...
Current opinion in nephrology and hypertension, Jan 28, 2015
The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated... more The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated, with small clinical trials exploring surrogate outcomes and larger epidemiologic studies generating treatment hypotheses requiring further study. The present review focuses on major aspects of nutrition and outcomes in hemodialysis patients: protein and calorie intake and nutritional vitamin D supplementation. Building on data from small studies, two large, quasi-experimental cohort studies showed significant mortality benefits associated with oral nutritional supplements provided during dialysis, suggesting potential options for ameliorating the protein-energy wasting that is common in dialysis patients and associated with poor outcomes. Multiple cohort studies suggest, both in the general population and in dialysis, that higher 25(OH) vitamin D levels are associated with improved outcomes; however, no major mortality trials exist in dialysis, and the smaller, surrogate studies conduc...
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 25, 2015
An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recogn... more An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney...
Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferri... more Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Maintenance dialysis patients with serum phosphorus levels ≥6.0mg/dL after washout of prior phosphate binders. 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Open-label study, few peritoneal dialysis patients. Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
With its rising incidence and prevalence, chronic kidney disease (CKD) is a major public health c... more With its rising incidence and prevalence, chronic kidney disease (CKD) is a major public health concern, both in the United States and worldwide. Recent worldwide initiatives have attempted to garner attention for CKD by emphasizing that the condition is "common, harmful, and treatable." In the United States, as many as 26 million adults may have CKD, an increase from approximately 10% of the US adult population between 1988 and 1994 to >13% just one decade later. Similar rates have been seen worldwide, with a CKD prevalence of 13% in Beijing, China and 16% in Australia. In the United States, the dramatic rise in the prevalence of CKD likely reflects similar increases in obesity and its sequelae-namely, diabetes, hypertension, and cardiovascular disease. The prevalence of CKD, as well as its associated costs, is expected to continue to increase.
Clinical Journal of the American Society of Nephrology, 2014
Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kid... more Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race. Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested. Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50). African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015
Cognitive impairment is common in hemodialysis patients and is associated with significant morbid... more Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important. Longitudinal cohort. Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients. Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1. Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors. Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Ea...
Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) an... more Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) and is associated with worse survival. Prior data suggest a relationship between vascular disease and cognitive impairment in individuals with CKD. Clinicians should be aware of the high rates of cognitive impairment that occur in all stages of CKD, which, although sometimes subtle, may impact comprehension and decision making and may herald future, more debilitating impairment.
Journal of the American Society of Nephrology, 2004
Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among ... more Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.
Journal of the American Society of Nephrology, 2005
Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney dis... more Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney disease (CKD). Because anemia may potentiate the adverse effects of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes in CKD was examined. Data from four community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were calibrated indirectly across studies, and GFR was estimated using the Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15 and 60 ml/min per 1.73 m(2). LVH was based on electrocardiogram criteria. Anemia was defined as hematocrit &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;36% in women and 39% in men. The primary outcome was a composite of myocardial infarction, stroke, and death; a secondary cardiac outcome included only myocardial infarction and fatal coronary heart disease. Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median follow-up was 102 mo. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively), whereas anemia was associated with increased risk for the only composite outcome (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was associated with an increased risk for both study outcomes compared with individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92 [95% CI, 2.05 to 7.48]; P = 0.02 and 0.01 for interaction term, respectively). The combination of anemia and LVH in CKD identifies a high-risk population.
Journal of applied physiology (Bethesda, Md. : 1985), 2003
Respiratory muscle weakness is common in children with neuromuscular disease (NMD). We hypothesiz... more Respiratory muscle weakness is common in children with neuromuscular disease (NMD). We hypothesized that weakness puts them at risk for respiratory muscle fatigue, a harbinger of chronic respiratory failure. We therefore measured a noninvasive index of respiratory muscle fatigue, the tension-time index of the respiratory muscles (TT(mus)), in 11 children with NMD and 13 control subjects. Spirometric flow rates and maximal inspiratory pressure were significantly lower in the NMD group than in controls (43 +/- 23 vs. 99 +/- 21 cmH2O, P < 0.001). The mean TT(mus) was significantly higher in the NMD group than in controls (0.205 +/- 0.117 vs. 0.054 +/- 0.021, P < 0.001). The increase in TT(mus) was primarily due to an increase in the ratio of average mean inspiratory pressure to maximal inspiratory pressure, indicating decreased respiratory muscle strength reserve. We found a significant correlation between TT(mus) and the residual volume-to-total lung capacity ratio (r = 0.504, P...
Journal of the American Society of Nephrology : JASN, Jan 4, 2015
Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft fai... more Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adju...
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 6, 2015
In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately aff... more In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. Longitudinal cohort study. 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-β-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR). Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to...
Current opinion in nephrology and hypertension, Jan 28, 2015
The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated... more The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated, with small clinical trials exploring surrogate outcomes and larger epidemiologic studies generating treatment hypotheses requiring further study. The present review focuses on major aspects of nutrition and outcomes in hemodialysis patients: protein and calorie intake and nutritional vitamin D supplementation. Building on data from small studies, two large, quasi-experimental cohort studies showed significant mortality benefits associated with oral nutritional supplements provided during dialysis, suggesting potential options for ameliorating the protein-energy wasting that is common in dialysis patients and associated with poor outcomes. Multiple cohort studies suggest, both in the general population and in dialysis, that higher 25(OH) vitamin D levels are associated with improved outcomes; however, no major mortality trials exist in dialysis, and the smaller, surrogate studies conduc...
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 25, 2015
An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recogn... more An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney...
Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferri... more Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Maintenance dialysis patients with serum phosphorus levels ≥6.0mg/dL after washout of prior phosphate binders. 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Open-label study, few peritoneal dialysis patients. Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
With its rising incidence and prevalence, chronic kidney disease (CKD) is a major public health c... more With its rising incidence and prevalence, chronic kidney disease (CKD) is a major public health concern, both in the United States and worldwide. Recent worldwide initiatives have attempted to garner attention for CKD by emphasizing that the condition is "common, harmful, and treatable." In the United States, as many as 26 million adults may have CKD, an increase from approximately 10% of the US adult population between 1988 and 1994 to >13% just one decade later. Similar rates have been seen worldwide, with a CKD prevalence of 13% in Beijing, China and 16% in Australia. In the United States, the dramatic rise in the prevalence of CKD likely reflects similar increases in obesity and its sequelae-namely, diabetes, hypertension, and cardiovascular disease. The prevalence of CKD, as well as its associated costs, is expected to continue to increase.
Clinical Journal of the American Society of Nephrology, 2014
Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kid... more Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race. Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested. Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50). African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015
Cognitive impairment is common in hemodialysis patients and is associated with significant morbid... more Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important. Longitudinal cohort. Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients. Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1. Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors. Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Ea...
Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) an... more Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) and is associated with worse survival. Prior data suggest a relationship between vascular disease and cognitive impairment in individuals with CKD. Clinicians should be aware of the high rates of cognitive impairment that occur in all stages of CKD, which, although sometimes subtle, may impact comprehension and decision making and may herald future, more debilitating impairment.
Journal of the American Society of Nephrology, 2004
Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among ... more Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.
Journal of the American Society of Nephrology, 2005
Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney dis... more Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney disease (CKD). Because anemia may potentiate the adverse effects of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes in CKD was examined. Data from four community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were calibrated indirectly across studies, and GFR was estimated using the Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15 and 60 ml/min per 1.73 m(2). LVH was based on electrocardiogram criteria. Anemia was defined as hematocrit &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;36% in women and 39% in men. The primary outcome was a composite of myocardial infarction, stroke, and death; a secondary cardiac outcome included only myocardial infarction and fatal coronary heart disease. Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median follow-up was 102 mo. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively), whereas anemia was associated with increased risk for the only composite outcome (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was associated with an increased risk for both study outcomes compared with individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92 [95% CI, 2.05 to 7.48]; P = 0.02 and 0.01 for interaction term, respectively). The combination of anemia and LVH in CKD identifies a high-risk population.
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