CiteULike: jyuh's Miller

28-Way vertebrate alignment and conservation track in the UCSC Genome Browser

Webb Miller — 2007-11-06T09:14:22-00:00

Genome Res. (5 November 2007), gr.6761107.

This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006 assembly) at http://genome.ucsc.edu, downloaded in bulk by anonymous FTP from http://hgdownload.cse.ucsc.edu/goldenPath/hg18/multiz28way, or analyzed with the Galaxy server at http://g2.bx.psu.edu. This article illustrates the power of this resource for exploring vertebrate and mammalian evolution, using three examples. First, we present several vignettes involving insertions and deletions within protein-coding regions, including a look at some human-specific indels. Then we study the extent to which start codons and stop codons in the human sequence are conserved in other species, showing that start codons are in general more poorly conserved than stop codons. Finally, an investigation of the phylogenetic depth of conservation for several classes of functional elements in the human genome reveals striking differences in the rates and modes of decay in alignability. Each functional class has a distinctive period of stringent constraint, followed by decays that allow (for the case of regulatory regions) or reject (for coding regions and ultraconserved elements) insertions and deletions. 10.1101/gr.6761107

Aligning goals, assessments, and activities: an approach to teaching PCR and gel electrophoresis.

AR Phillips — 2008-07-17T08:17:13-00:00

CBE life sciences education, Vol. 7, No. 1. (2008), pp. 96-106.

Polymerase chain reaction (PCR) and gel electrophoresis have become common techniques used in undergraduate molecular and cell biology labs. Although students enjoy learning these techniques, they often cannot fully comprehend and analyze the outcomes of their experiments because of a disconnect between concepts taught in lecture and experiments done in lab. Here we report the development and implementation of novel exercises that integrate the biological concepts of DNA structure and replication with the techniques of PCR and gel electrophoresis. Learning goals were defined based on concepts taught throughout the cell biology lab course and learning objectives specific to the PCR and gel electrophoresis lab. Exercises developed to promote critical thinking and target the underlying concepts of PCR, primer design, gel analysis, and troubleshooting were incorporated into an existing lab unit based on the detection of genetically modified organisms. Evaluative assessments for each exercise were aligned with the learning goals and used to measure student learning achievements. Our analysis found that the exercises were effective in enhancing student understanding of these concepts as shown by student performance across all learning goals. The new materials were particularly helpful in acquiring relevant knowledge, fostering critical-thinking skills, and uncovering prevalent misconceptions.

Hepatitis C inflection in dialysis patients: a link to poor clinical outcome?

Kalantar-Zadeh — 2007-07-02T14:10:15-00:00

International Urology and Nephrology, Vol. 39, No. 1. (March 2007), pp. 247-259.

Diagnostic discordance for hepatitis C virus infection in hemodialysis patients.

K Kalantar-Zadeh — 2008-07-06T16:21:36-00:00

American journal of kidney diseases : the official journal of the National Kidney Foundation, Vol. 46, No. 2. (August 2005), pp. 290-300.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with an increase in proinflammatory cytokine levels. Similar changes are seen in maintenance hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS), which is associated with poor clinical outcomes in this population. We hypothesized that HCV transcription-mediated amplification (TMA), a sensitive qualitative molecular test for HCV RNA, may identify maintenance hemodialysis patients with HCV infection not detected by means of antibody enzyme immunoassay (EIA), particularly in those with MICS. METHODS: We evaluated HCV status in 314 maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories, Berkeley, CA). Results: Twenty-five patients (8%) were EIA positive (EIA+)/TMA+; 4 patients (1%), EIA+/TMA negative (TMA-), and 22 patients (7%), EIA-/TMA+. In the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+ patients had lower albumin levels and higher tumor necrosis factor alpha and serum glutamic oxaloacetic transaminase levels than TMA- patients. EIA+/TMA+ patients were more likely than EIA-/TMA+ or EIA-/TMA- patients to have hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients, EIA- patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor alpha and interleukin 6. CONCLUSION: Maintenance hemodialysis patients infected with HCV according to TMA have clinical features suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity for the identification of HCV infection, which may be caused by the confounding effect of MICS or other demographic or clinical factors. These apparently false-negative HCV antibody test results are seen in persons with a longer time on hemodialysis therapy, mirroring observations in other populations with serious progressive conditions, such as human immunodeficiency virus infection.

CellML and associated tools and techniques.

Alan Garny — 2008-07-05T00:25:36-00:00

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences (25 June 2008)

We have, in the last few years, witnessed the development and availability of an ever increasing number of computer models that describe complex biological structures and processes. The multi-scale and multi-physics nature of these models makes their development particularly challenging, not only from a biological or biophysical viewpoint but also from a mathematical and computational perspective. In addition, the issue of sharing and reusing such models has proved to be particularly problematic, with the published models often lacking information that is required to accurately reproduce the published results.The International Union of Physiological Sciences Physiome Project was launched in 1997 with the aim of tackling the aforementioned issues by providing a framework for the modelling of the human body. As part of this initiative, the specifications of the CellML mark-up language were released in 2001.Now, more than 7 years later, the time has come to assess the situation, in particular with regard to the tools and techniques that are now available to the modelling community. Thus, after introducing CellML, we review and discuss existing editors, validators, online repository, code generators and simulation environments, as well as the CellML Application Program Interface. We also address possible future directions including the need for additional mark-up languages.

Survival benefit of nephrologic care in patients with diabetes mellitus and chronic kidney disease.

CL Tseng — 2008-07-03T13:25:43-00:00

Archives of internal medicine, Vol. 168, No. 1. (14 January 2008), pp. 55-62.

BACKGROUND: The association of nephrologic care and survival in patients with diabetes mellitus and chronic kidney disease is unknown. METHODS: Using data from 1997 to 2000, we conducted a retrospective cohort study of Veterans Health Administration clinic users having diabetes mellitus and stage 3 or 4 chronic kidney disease. The baseline period was 12 months and median follow-up was 19.3 months. Degree of consistency of visits to a nephrologist, defined as the number of calendar quarters in which there was 1 visit or more (range, 0-4 quarters), and covariates were calculated from the baseline period. The outcome measure was dialysis-free death. RESULTS: Of 39,031 patients, 70.0%, 22.4%, and 7.6% had early stage 3, late stage 3, and stage 4 chronic kidney disease, respectively, and 3.1%, 9.5%, and 28.2%, respectively, visited a nephrologist. Dialysis-free mortality rates were 9.6, 14.1, and 19.4, respectively, per 100 person-years. More calendar quarters with visits to a nephrologist were associated with lower mortality: adjusted hazard ratios were 0.80 (95% confidence interval, 0.67-0.97), 0.68 (95% confidence interval, 0.55-0.86), and 0.45 (95% confidence interval, 0.32-0.63), respectively, when the groups having 2, 3, and 4 visits were compared with those who had no visits. One visit only was not associated with a difference in mortality when compared with no visits (adjusted hazard ratio,1.02; 95% confidence interval, 0.89-1.16). CONCLUSIONS: The consistency of outpatient nephrologic care was independently associated in a graded fashion with lower risk of deaths in patients with diabetes and moderately severe to severe chronic kidney disease. However, only a minority of patients had any visits to a nephrologist.

Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms.

J Clausell-Tormos — 2008-07-02T08:02:36-00:00

Chemistry & biology, Vol. 15, No. 5. (May 2008), pp. 427-437.

High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

Gamma-tocopherol and docosahexaenoic acid decrease inflammation in dialysis patients.

J Himmelfarb — 2008-07-01T02:40:37-00:00

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, Vol. 17, No. 5. (September 2007), pp. 296-304.

OBJECTIVE: Increased cardiovascular risk in hemodialysis patients may be related to augmented oxidative stress and inflammation, for which no proven beneficial therapies are available. STUDY DESIGN: We examined the effects of gamma tocopherol and docosahexaenoic acid (DHA) administration on inflammation and oxidative stress markers in hemodialysis patients in a randomized, double-blinded, placebo-controlled, clinical trial. Active treatment consisted of capsules containing gamma tocopherol (308 mg) and DHA (800 mg). SETTING: Outpatient dialysis center. PATIENTS: Seventy maintenance hemodialysis patients. MAIN OUTCOME MEASURES: Plasma concentrations of interleukin-6 (IL-6) and protein carbonyl content were determined by enzyme-linked immunosorbant assay. C-reactive protein was measured by nephelometry. The F(2) isoprostanes were measured by gas chromatography-mass spectrometry. Erythrocyte DHA content was measured by gas chromatography. RESULTS: Sixty-three patients were enrolled, and 57 completed the study. No serious adverse events were attributed to either active treatment or placebo. In the treatment group, but not in the placebo group, there were significant decreases in IL-6 (21.4 +/- 3.5 to 16.8 +/- 3.7 pg/mL), white blood cell (WBC) count (7.4 +/- 0.3 to 6.9 +/- 0.4 10(3)/microL), and neutrophil fraction of WBCs (4.8 +/- 0.3 to 4.4 +/- 0.3 10(3)/microL), at P < .05 for all. There were no significant changes in plasma concentrations of CRP, F(2) isoprostanes, or carbonyls in either group. CONCLUSION: Thus, gamma tocopherol and DHA are well-tolerated and reduce selected biomarkers of inflammation in hemodialysis patients. Larger randomized, clinical trials will be required to determine if gamma tocopherol and DHA can reduce cardiovascular complications in hemodialysis patients.

Cardioprotective medication use in hemodialysis patients.

LM Miller — 2008-06-28T05:16:46-00:00

The Canadian journal of cardiology, Vol. 22, No. 9. (July 2006), pp. 755-760.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with renal failure, accounting for more than 50% of deaths in end-stage renal disease. Risk factor modification with the use of cardioprotective medications such as angiotensin-converting enzyme inhibitors (ACEIs), beta-adrenergic antagonists (beta-blockers), acetylsalicylic acid (ASA) and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce mortality in the general population. OBJECTIVE: To determine the extent of use of these medications in a hemodialysis population. METHODS: This was a cross-sectional study of a cohort of 185 prevalent hemodialysis patients. The inclusion criterion was dialysis dependence and there were no exclusion criteria. Data collection was by chart review. Contraindications to individual medication classes were not obtained. RESULTS: There were 185 patients enrolled, the mean age was 63.42+/-15.1 years and 126 (68.1%) were male. Sixty-six (35.7%) patients had diabetes and 89 (48.1%) patients had established coronary artery disease (CAD). Forty-six (24.9%) patients were on ACEIs or angiotensin II receptor blockers, 59 (31.9%) were on beta-blockers, 70 (37.8%) were on ASA and 84 (45.4%) were on statins. Although these medications were used in fewer than 60% of patients, those with CAD were more likely to be prescribed an ACEI or an angiotensin II receptor blocker (P=0.026), a beta-blocker (P<0.001), ASA (P<0.001) or a statin (P=0.001) than those without CAD. There were no differences in the use of these medications between diabetic and nondiabetic patients. CONCLUSIONS: Many hemodialysis patients are not prescribed cardioprotective medications. Given the high cardiovascular mortality in this high-risk population, more attention to reducing cardiovascular risk is warranted.

Weighted estimating equations for longitudinal studies with death and non-monotone missing time-dependent covariates and outcomes.

M Shardell — 2008-06-23T07:15:26-00:00

Statistics in medicine, Vol. 27, No. 7. (30 March 2008), pp. 1008-1025.

We propose a marginal modeling approach to estimate the association between a time-dependent covariate and an outcome in longitudinal studies where some study participants die during follow-up and both variables have non-monotone response patterns. The proposed method is an extension of weighted estimating equations that allows the outcome and covariate to have different missing-data patterns. We present methods for both random and non-random missing-data mechanisms. A study of functional recovery in a cohort of elderly female hip-fracture patients motivates the approach.

Pharmacologic management of adult depression.

SM Adams — 2008-06-17T02:21:47-00:00

American family physician, Vol. 77, No. 6. (15 March 2008), pp. 785-792.

Major depression is a common and treatable disease. Many patients benefit from pharmacologic treatment and, because there is little variation in antidepressant effectiveness, medication choices should be made based on patient characteristics, safety, and anticipated side effects. Most patients respond favorably to treatment, but many do not have complete symptom relief. Changing medications or augmenting with a second medication is helpful for some partial or nonresponders. All antidepressants are capable of producing harmful side effects, and some are particularly prone to dangerous drug-drug interactions. The risk of suicide is always a concern in depression and this risk is not necessarily reduced by the use of antidepressants. Some persons may have an increase in suicidal thoughts with antidepressant treatment. Close follow-up is required when initiating therapy and adjusting dosages.

Facility variation in utilization of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with diabetes mellitus and chronic kidney disease.

A Tiwari — 2008-05-20T02:51:04-00:00

The American journal of managed care, Vol. 13, No. 2. (February 2007), pp. 73-79.

OBJECTIVE: To evaluate facility-level variation in prescription rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) medications for patients with diabetes mellitus (DM) and chronic kidney disease (CKD). STUDY DESIGN: Retrospective database analysis from 143 Veterans Health Administration facilities. METHODS: Subjects with DM aged 18 to 75 years were identified as having stage 2-4 CKD using estimated glomerular filtration rate (eGFR) based on an index eGFR in 1999 and a subsequent eGFR 90-365 days later. Whether ACEI/ARB medications were prescribed within 1 year after the index eGFR was determined. Variation in facility-level rates was evaluated separately for subjects age <65 years and 65 to 75 years from facilities with more than 50 subjects per age group. RESULTS: A total of 103 853 subjects had stage 2 CKD; 51 728, stage 3; and 3233, stage 4. However, 25% of facilities had fewer than 50 patients age <65 years with either stage 3 or 4 CKD. The median (range) facility-level prescription rates of ACEI/ARB for stage 2 and combined stage 3-4 CKD were 58.5% (44.3%-71.2%) and 73.3% (51.7%-84.6%), respectively, for subjects age <65 years; and 56.5% (38.1%-71.4%) and 68.4% (51.6%-80.1%), respectively, for subjects aged 65 to 75 years. Spearman rank correlation between facility rankings by age group was 0.72 for stage 2 (139 facilities) and 0.49 for stage 3-4 (111 facilities) (P < .001). CONCLUSION: Although ascertainment of prescription rates of ACEI/ARB to CKD patients is feasible using electronic health records, small sample size at the healthcare-system level preclude their utility for public reporting.

ACCF/ASE/ACEP/ASNC/SCAI/SCCT/SCMR 2007 appropriateness criteria for transthoracic and transesophageal echocardiography: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American Society of Echocardiography, American College of Emergency Physicians, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance endorsed by the American College of Chest Physicians and the Society of Critical Care Medicine.

PS Douglas — 2008-05-12T01:55:10-00:00

Journal of the American College of Cardiology, Vol. 50, No. 2. (10 July 2007), pp. 187-204.

ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology).

2008-05-12T01:55:54-00:00

Circulation, Vol. 114, No. 23. (5 December 2006), pp. 2534-2570.

ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias--executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society.

C Blomström-Lundqvist — 2008-05-12T01:58:25-00:00

Journal of the American College of Cardiology, Vol. 42, No. 8. (15 October 2003), pp. 1493-1531.

Inhibition of oral carcinogenesis by citrus flavonoids.

EG Miller — 2008-05-10T04:40:56-00:00

Nutrition and cancer, Vol. 60, No. 1. (b 2008), pp. 69-74.

Six citrus flavonoids were tested for antineoplastic activity. The hamster cheek pouch model was utilized, and the solutions of the flavonoids (2.0-2.5%) and the solution of the carcinogen, 7,12-dimethylbenz[a]anthracene (0.5%), were applied topically to the pouches. The pouches of the positive controls were treated with the solvent used to dissolve the flavonoids and the solution of the carcinogen. The data show that 4 flavonoids (hesperetin, neohesperidin, tangeretin, and nobiletin) were inactive. The results with naringin and naringenin show that both of these flavonoids significantly lowered tumor number [5.00 (control group), 2.53 (naringin group), and 3.25 (naringenin group)]. Naringin also significantly reduced tumor burden [269 mm(3)(control group) and 77.1 mm(3)(naringin group)]. The data suggest that naringin and naringenin, 2 flavonoids found in high concentrations in grapefruit, may be able to inhibit the development of cancer.

Tractable Cre-lox system for stochastic alteration of genes in mice

Ashleigh Miller — 2008-02-29T01:36:32-00:00

Nature Methods, Vol. 5, No. 3. (10 February 2008), pp. 227-229.

Amplification of complex gene libraries by emulsion PCR

Richard Williams — 2006-06-24T00:10:07-00:00

Nature Methods, Vol. 3, No. 7., pp. 545-550.

Fluorescent probes for nitric oxide and hydrogen peroxide in cell signaling.

EW Miller — 2008-05-07T08:10:51-00:00

Current opinion in chemical biology, Vol. 11, No. 6. (December 2007), pp. 620-625.

Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) have emerged as essential small molecules for cellular signal transduction owing largely to their ability to mediate oxidative posttranslational modifications (PTMs). Inventing new ways to track these small, diffusible, and reactive species with spatial and temporal resolution is a key challenge in elucidating their chemistry in living systems. Recent progress in the development of fluorescent probes that respond selectively to NO and H(2)O(2) produced at cell signaling levels offers a promising approach to interrogating their physiological production, accumulation, trafficking, and function.

Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes

David Cherney — 2005-09-13T13:28:37-00:00

Kidney International, Vol. 68, No. 4. (October 2005), pp. 1722-1728.

Enteric infections, diarrhea, and their impact on function and development.

William A Petri — 2008-05-02T10:28:19-00:00

The Journal of clinical investigation, Vol. 118, No. 4. (1 April 2008), pp. 1277-1290.

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.

Evaluation and validation of candidate endogenous control genes in real-time quantitative PCR studies of breast cancer

Roisin Mcneill — 2007-11-28T02:44:14-00:00

BMC Molecular Biology, Vol. 8 (27 November 2007), 107.

Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

Fulvio Lauretani — 2008-05-01T09:44:09-00:00

Clin Chem, Vol. 54, No. 3. (1 March 2008), pp. 475-481.

Background: Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods: We performed a cross-sectional and prospective analysis of 931 adults, [≥]65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results: At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion: High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. 10.1373/clinchem.2007.095521

Metabolic syndrome, proteinuria, and the risk of progressive CKD in hypertensive African Americans.

J Lea — 2008-04-29T02:53:45-00:00

American journal of kidney diseases : the official journal of the National Kidney Foundation, Vol. 51, No. 5. (May 2008), pp. 732-740.

BACKGROUND: Chronic kidney disease (CKD) is more likely to progress to kidney failure (end-stage renal disease) in African Americans, although the reasons for this are unclear. Metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease and recently was linked to incident CKD. The purpose of this study is to examine whether metabolic syndrome is associated with kidney disease progression in hypertensive African Americans. DESIGN & PARTICIPANTS: The current study design is a secondary analysis of the African-American Study of Hypertension and Kidney Disease, a randomized controlled trial of blood pressure goal and agents in hypertensive African Americans with CKD. PREDICTORS: Metabolic syndrome was defined according to the modified National Cholesterol Education Program guidelines. OUTCOMES: Decrease in glomerular filtration rate of 50% or 25 mL/min/1.73 m(2), end-stage renal disease (initiation of dialysis therapy or transplantation), death, or a composite outcome of all 3. RESULTS: 842 subjects were included in this analysis, and 41.7% met criteria for metabolic syndrome. Subjects meeting criteria for metabolic syndrome had greater levels of proteinuria. Cox regression analyses adjusted for age, sex, glomerular filtration rate, and other significant covariates except for proteinuria indicated a 31% increased risk, with a 95% confidence interval of 1.03 to 1.7 (P = 0.03) for time to reach the composite outcome in those with metabolic syndrome. Adjusting for proteinuria, the effect was abated to 16% (95% confidence interval, 0.9 to 1.5), no longer remained significant (P = 0.2), and was unchanged by adjusting randomized treatment group (blood pressure goal or antihypertensive drug). LIMITATIONS: Lack of waist circumference as a better surrogate of abdominal obesity. CONCLUSIONS: In summary, metabolic syndrome is associated with proteinuria in hypertensive African Americans, but is not independently associated with CKD progression.

Receptor tyrosine kinases: mechanisms of activation and signaling

Stevan Hubbard — 2007-03-15T09:30:25-00:00

Current Opinion in Cell Biology, Vol. 19, No. 2. (April 2007), pp. 117-123.

Receptor tyrosine kinases (RTKs) are essential components of signal transduction pathways that mediate cell-to-cell communication. These single-pass transmembrane receptors, which bind polypeptide ligands -- mainly growth factors -- play key roles in processes such as cellular growth, differentiation, metabolism and motility. Recent progress has been achieved towards an understanding of the precise (and varied) mechanisms by which RTKs are activated by ligand binding and by which signals are propagated from the activated receptors to downstream targets in the cell.

The Other Side of the Maillard Reaction

Ram Nagaraj — 2008-04-24T08:38:49-00:00

Annals of the New York Academy of Sciences, Vol. 1126, No. 1. (2008), pp. 107-112.

The Maillard reaction plays an important role in eye lens aging and cataract formation. Methylglyoxal (MGO) is a metabolic dicarbonyl compound present in the lens. It reacts with arginine residues in lens proteins to form advanced glycation end products (AGEs), such as hydroimidazolones and argpyrimidine. alpha-Crystallin, comprising alphaA- and alphaB-crystallin, is a major protein of the lens and it functions as a chaperone protein. We have found that upon reaction with MGO, human alphaA-crystallin becomes a more effective chaperone. Modification of specific arginine residues to AGEs appears to be the reason. Mutation of these arginine residues to alanine mirrors the effect of MGO, suggesting neutralization of the positive charge on arginine residues as a cause for improved chaperone function. Reaction with MGO also blocks the loss of the chaperone function of alphaA-crystallin caused by nonenzymatic glycation by ascorbate and ribose. These findings suggest that low levels of MGO might help the lens remain transparent during aging.

Comparison of methods for measuring albumin in peritoneal dialysis and hemodialysis patients.

R Joseph — 2008-04-18T04:55:31-00:00

American journal of kidney diseases : the official journal of the National Kidney Foundation, Vol. 27, No. 4. (April 1996), pp. 566-572.

Serum albumin levels have been used extensively as an indicator of morbidity in patients with end-stage renal disease. Recent evidence suggests that albumin levels vary considerably in hemodialysis patients depending on the laboratory method used, but formulas for comparing albumin values by different methods have not been developed. We prospectively evaluated the effects of measuring albumin by three different methods on paired plasma and serum from 23 patients on continuous ambulatory peritoneal dialysis (CAPD) and 53 patients on chronic maintenance hemodialysis. Plasma and serum gave virtually identical results independent of method used. In CAPD patients, bromcresol green and nephelometry gave nearly identical albumin measurements through the entire range of plasma levels. In contrast, bromcresol purple gave values that were 9.9 percent +/- 1.3 percent lower (P < 0.05). Hemodialysis patients showed a similar pattern with close agreement between bromcresol green and nephelometry, but bromcresol purple gave lower albumin levels by 19.1 percent +/- 1.2 percent (P < 0.05). The discrepancy in albumin in CAPD patients was significantly less than in the hemodialysis patients (P < 0.05), suggesting that there were fewer interfering substances in the blood of CAPD patients than in hemodialysis patients. Linear regression analysis was used to develop simple formulas for comparing albumin values obtained by the different methods in CAPD and hemodialysis patients. These studies show that values for albumin in blood vary significantly by method of analysis in CAPD and hemodialysis patients. By the use of these formulas, it becomes possible to compare albumin values between centers using different methods for the purpose of quality management.

Reference materials and commutability.

HW Vesper — 2008-04-13T09:40:07-00:00

The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists, Vol. 28, No. 4. (November 2007), pp. 139-147.

Maintaining accurate laboratory measurements over time is crucial for assuring appropriate patient care and disease management. Accurate results over time and location are achieved by standardising measurements and establishing traceability to a reference system. Reference materials are key components of such reference systems and for establishing traceability. Commutability of reference materials is a critical property to ensure they are fit for use.Commutability is defined as the equivalence of the mathematical relationships between the results of different measurement procedures for a reference material and for representative samples from healthy and diseased individuals. This material characteristic is of special importance for measurement procedures that are optimised for measuring analytes directly in patient samples. The commutability of a reference material is measurement procedure specific and its assessment requires special experimental designs.This review explains the importance of commutability and summarises different experimental approaches described in the literature that have been used to assess the commutability of reference materials in clinical chemistry.

Glomerular Filtration Rate, Albuminuria, and Risk of Cardiovascular and All-Cause Mortality in the US Population.

Brad C Astor — 2008-04-06T13:54:52-00:00

American journal of epidemiology (2 April 2008)

Decreased glomerular filtration rate (GFR) and albuminuria are used in combination to define chronic kidney disease, but their separate and combined effects on cardiovascular and all-cause mortality have not been studied in the general population. The linked mortality file of the Third National Health and Nutrition Examination Survey includes data from 13 years of follow-up (1988-2000) for 14,586 US adults. The authors estimated GFR from standardized serum creatinine levels. Albuminuria was defined by the urinary albumin:creatinine ratio. Incidence rate ratios (IRRs) were adjusted for major cardiovascular disease risk factors and C-reactive protein. Lower estimated GFR was associated with higher risks of cardiovascular and all-cause mortality overall and within every albuminuria category. Likewise, increasing albuminuria was associated with higher risk of estimated GFR overall and within every category. When estimated GFR and albuminuria were examined simultaneously, a 10-ml/minute/1.73 m(2) lower estimated GFR (among persons with estimated GFR <60 ml/minute/1.73 m(2)) was associated with an IRR of 1.29 (95% confidence interval: 1.06, 1.55) for cardiovascular mortality and a doubling of albuminuria was associated with an IRR of 1.06 (95% confidence interval: 1.04, 1.08) for cardiovascular mortality. The authors conclude that moderately decreased estimated GFR and albuminuria independently predict cardiovascular and all-cause mortality in the general population. These data support recent recommendations defining chronic kidney disease and stratifying subsequent risks based on both decreased GFR and albuminuria.

Approaches to working in high-dimensional data spaces: gene expression microarrays

Y Wang — 2008-02-20T01:20:16-00:00

British Journal of Cancer, Vol. aop, No. current. (19 February 2008)

Regulation of renal ion transport by the calcium-sensing receptor: an update.

C Huang — 2008-03-23T13:50:38-00:00

Curr Opin Nephrol Hypertens, Vol. 16, No. 5. (September 2007), pp. 437-443.

PURPOSE OF REVIEW: Extracellular calcium has profound effects on renal tubular transport, presumably via the calcium-sensing receptor, which is expressed in all nephron segments, but its effects in specific segments and the mechanism of regulation of transport are not fully understood. RECENT FINDINGS: Recognition that activating calcium-sensing receptor mutations result in a Bartter-like syndrome demonstrate that the transport effects of extracellular calcium are mediated by the calcium-sensing receptor. Its presence in the gills and solute and water-transporting organs of fish coupled with appropriate calcium-sensing receptor kinetics indicate that the calcium-sensing receptor was originally involved in the regulation of sodium chloride, calcium and magnesium transport. Based on its physiological effects on tubular transport and biochemical and genetic data, the calcium-sensing receptor appears to act by mechanisms that distinguish it from other G protein-coupled receptors. SUMMARY: The calcium-sensing receptor mediates the effects of extracellular calcium on the kidney, is an essential control point in the regulation of calcium balance and possibly the physiological regulation of sodium chloride balance. The thick ascending limb of Henle and distal convoluted tubule appear to be the nephron segments most responsible for the effects of the calcium-sensing receptor, although its mechanisms of action are not fully established.

Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction.

KA Hruska — 2008-03-22T03:23:27-00:00

Am J Physiol Renal Physiol, Vol. 279, No. 1. (July 2000)

Morphometry: Unilateral ureteral obstruction (UUO) is a model of renal injury characterized by progressive tubulointerstitial fibrosis and renal damage, while relatively sparing the glomerulus and not producing hypertension or abnormalities in lipid metabolism. Tubulointerstitial fibrosis is a major component of several kidney diseases associated with the progression to end-stage renal failure. Here we report that when a critical renal developmental morphogen, osteogenic protein-1 (OP-1; 100 or 300 microg/kg body wt), is administered at the time of UUO and every other day thereafter, interstitial inflammation and fibrogenesis are prevented, leading to preservation of renal function during the first 5 days after obstruction. Compared with angiotensin-converting enzyme inhibition with enalapril treatment, OP-1 was more effective in preventing tubulointerstitial fibrosis and in preserving renal function. The mechanism of OP-1- induced renal protection was associated with prevention of tubular atrophy, an effect not shared with enalapril, and was related to preservation of tubular epithelial integrity. OP-1 blocked the stimulation of epithelial cell apoptosis produced by UUO, which promoted maintenance of tubular epithelial integrity. OP-1 preserved renal blood flow (RBF) during UUO, but enalapril also stimulated RBF. Thus OP-1 treatment inhibited tubular epithelial disruption stimulated by the renal injury of UUO, preventing tubular atrophy and diminishing the activation of tubulointerstitial inflammation and fibrosis and preserving renal function.

YPED: a web-accessible database system for protein expression analysis.

MA Shifman — 2008-03-13T16:14:40-00:00

J Proteome Res, Vol. 6, No. 10. (October 2007), pp. 4019-4024.

We have developed an integrated web-accessible software system called the Yale Protein Expression Database (YPED) to address the need for storage, retrieval, and integrated analysis of large amounts of data from high throughput proteomic technologies. YPED is an open source system which integrates gel analysis results with protein identifications from DIGE experiments. The system associates the DIGE gel spots and image, analyzed with DeCyder, with mass spectrometric protein identifications from selected gel spots. Following in gel trypsin digestion, proteins in spots of interest are analyzed using MALDI-TOF/TOF on an AB 4700 or, more recently, on an AB 4800 with protein identifications performed by Mascot in conjunction with the AB GPS Explorer system. In addition to DIGE, YPED currently handles protein identifications from MudPIT, iTRAQ, and ICAT experiments. Sample descriptions are compatible with the evolving MIAPE standards. Tandem MS/MS results from MudPIT, and ICAT analyses are validated with the Trans-Proteomic Pipeline and then stored in the database for viewing and linking to the identified proteins. Researchers can view, subset, and download their data through a secure Web interface that includes a table containing proteins identified, a sample summary, the sample description, and a clickable gel image for DIGE samples. Tools are available to facilitate sample comparison and the viewing of phosphoproteins. A summary report with PANTHER Classification System annotations is also available to aid in biological interpretation of the results. The source code is open-source and is available from http://yped.med.yale.edu/yped_dist.

Bayesian hypothesis testing-use in interpretation of measurements.

G Miller — 2008-03-09T01:22:22-00:00

Health Phys, Vol. 94, No. 3. (March 2008), pp. 248-254.

Bayesian hypothesis testing may be used to qualitatively interpret a dataset as indicating something "detected" or not. Hypothesis testing is shown to be equivalent to testing the posterior distribution for positive true amounts by redefining the prior to be a mixture of the original prior and a delta-function component at 0 representing the null hypothesis that nothing is truly present. The hypothesis-testing interpretation of the data is based on the posterior probability of the usual modeling hypothesis relative to the null hypothesis. Real numerical examples are given and discussed, including the distribution of the non-null hypothesis probability over 4,000 internal dosimetry cases. Currently used comparable methods based on classical statistics are discussed.

Human Proteinpedia enables sharing of human protein data

Suresh Mathivanan — 2008-02-08T00:40:35-00:00

Nature Biotechnology, Vol. 26, No. 2., pp. 164-167.

Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium.

Y Zhou — 2008-03-04T04:25:41-00:00

Toxicol Sci, Vol. 101, No. 1. (January 2008), pp. 159-170.

Sensitive biomarkers are needed to detect kidney injury at the earliest stages. The objective of this study was to determine whether the appearance of kidney injury molecule-1 (Kim-1) protein ectodomain in urine and kidney injury molecule-1/hepatitis A viral cellular receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be more predictive of renal injury after exposure to nephrotoxicants when compared to traditionally used biomarkers. Male Sprague-Dawley rats were injected with a range of doses of gentamicin, mercury (Hg; HgCl2), or chromium (Cr; K2Cr2O7). The results showed that increases in urinary Kim-1 and kidney Kim-1/Havcr1 gene expression paralleled the degree of severity of renal histopathology and were detected at lower doses of nephrotoxicants when compared to blood urea nitrogen (BUN), serum creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG). In a time course study, urinary Kim-1 was elevated within 24 h after exposure to gentamicin (100 mg/kg), Hg (0.25 mg/kg), or Cr (5 mg/kg) and remained elevated through 72 h. NAG responses were nephrotoxicant dependent with elevations occurring early (gentamicin), late (Cr), or no change (Hg). At 72 h, after treatment with any of the three nephrotoxicants, there was increased Kim-1 immunoreactivity and necrosis involving approximately 50% of the proximal tubules; however, only urinary Kim-1 was significantly increased, while BUN, serum creatinine, and NAG were not different from controls. In rats treated with the hepatotoxicant galactosamine (1.1 mg/kg), serum alanine aminotransferase was increased, but no increase in urinary Kim-1 was observed. Urinary Kim-1 and kidney Kim-1/Havcr1 expression appear to be sensitive and tissue-specific biomarkers that will improve detection of early acute kidney injury following exposure to nephrotoxic chemicals and drugs.

EFFECT OF GENDER AND SEX HORMONES ON VASCULAR OXIDATIVE STRESS

Miller — 2007-08-21T04:36:33-00:00

Clinical and Experimental Pharmacology and Physiology, Vol. 34, No. 10. (October 2007), pp. 1037-1043.

The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes

David Cherney — 2008-03-03T02:21:41-00:00

Diabetes, Vol. 57, No. 3. (1 March 2008), pp. 688-695.

OBJECTIVEStudies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. We hypothesized that COX2 inhibition would alleviate the hyperfiltration state and would abrogate the hyperglycemia-mediated rise in glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODSRenal function was assessed during clamped euglycemia and hyperglycemia on 2 consecutive days before and then again after 14 days of COX2 inhibition using 200 mg celecoxib once daily by mouth. For analysis, the cohort was then divided into two groups based on the baseline GFR: 9 subjects exhibited hyperfiltration (GFR [≥]135 ml/min per 1.73 m2), and 12 subjects exhibited normofiltration (GFR <135 ml/min per 1.73 m2). RESULTSUnder euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the hyperfiltration group (150 +/- 5 to 139 +/- 5 ml/min per 1.73 m2) but increased GFR in the normofiltration group (118 +/- 5 to 138 +/- 5 ml/min per 1.73 m2). COX2 inhibition did not blunt the hyperglycemia-associated rise in GFR in the normofiltration group and was instead associated with an augmented rise in GFR. CONCLUSIONSIn summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 diabetes. The renal response to COX2 inhibition emphasizes that hyperfiltration and normofiltration are distinct physiological states. 10.2337/db07-1230

Exon level integration of proteomics and microarray data

Danny Bitton — 2008-02-26T02:14:31-00:00

BMC Bioinformatics, Vol. 9 (25 February 2008), 118.

Interrogation of the plasma proteome with differential scanning calorimetry.

NC Garbett — 2008-02-21T08:30:53-00:00

Clin Chem, Vol. 53, No. 11. (November 2007), pp. 2012-2014.

Calorimetry outside the box: a new window into the plasma proteome.

NC Garbett — 2008-02-21T08:28:42-00:00

Biophys J, Vol. 94, No. 4. (15 February 2008), pp. 1377-1383.

Differential scanning calorimetry provides a new window into the plasma proteome. Plasma from normal individuals yields a characteristic, reproducible thermogram that appears to represent the weighted sum of denaturation profiles of the most abundant constituent plasma proteins. Plasma from diseased individuals yields dramatically different signature thermograms. Thermograms from individuals suffering from rheumatoid arthritis, systemic lupus, and Lyme disease were measured. Each disease appears to have a distinctive and characteristic thermogram. The difference in thermograms between normal and diseased individuals is not caused by radical changes in the concentrations of the most abundant plasma proteins but rather appears to result from interaction of as yet unknown biomarkers with the major plasma proteins. These results signal a novel use for calorimetry as a diagnostic tool.

Myths and misconceptions of Wernicke's encephalopathy: what every emergency physician should know.

MW Donnino — 2008-02-19T10:39:25-00:00

Ann Emerg Med, Vol. 50, No. 6. (December 2007), pp. 715-721.

First described in 1881, Wernicke's encephalopathy continues to be an unrecognized and often misunderstood disease. The cause of Wernicke's encephalopathy is thiamine deficiency as a result of any nutritionally deficient state, though many physicians erroneously consider this disease to be confined only to alcoholics. Unfortunately, the syndrome is most often recognized only on autopsy, especially among nonalcoholics. Despite advances in magnetic resonance imaging, Wernicke's encephalopathy remains primarily a clinical diagnosis. The common clinical findings include mental status changes, ocular dysfunction, and gait ataxia. Additional signs may be present, or 1 or more of the common findings may be absent. Treatment mandates timely intravenous thiamine therapy, for which the optimum dosage remains controversial. This review traces the history of Wernicke's encephalopathy from the first description to our current understanding of the disease and includes many of the misconceptions, myths, and controversies that surround this disease. Emergency physicians need to be well versed in the varied presentation of Wernicke's encephalopathy because most of these patients will present to the emergency department and are oftentimes unrecognized. Further, physician knowledge of this disease is vital because the failure to diagnose results in severe neurologic morbidity and possible mortality, but the treatment is safe and effective.

Screening for carotid artery stenosis: an update of the evidence for the U.S. Preventive Services Task Force.

T Wolff — 2008-02-19T04:04:32-00:00

Ann Intern Med, Vol. 147, No. 12. (18 December 2007), pp. 860-870.

BACKGROUND: Cerebrovascular disease is the third leading cause of death in the United States. The proportion of all strokes attributable to previously asymptomatic carotid artery stenosis (CAS) is low. In 1996, the U.S. Preventive Services Task Force concluded that evidence was insufficient to recommend for or against screening of asymptomatic persons for CAS by using physical examination or carotid ultrasonography. PURPOSE: To examine the evidence of benefits and harms of screening asymptomatic patients with duplex ultrasonography and treatment with carotid endarterectomy for CAS. DATA SOURCES: MEDLINE and Cochrane Library (search dates January 1994 to April 2007), recent systematic reviews, reference lists of retrieved articles, and suggestions from experts. STUDY SELECTION: English-language randomized, controlled trials (RCTs) of screening for CAS; RCTs of carotid endarterectomy versus medical treatment; systematic reviews of screening tests; and observational studies of harms from carotid endarterectomy were selected to answer the following questions: Is there direct evidence that screening with ultrasonography for asymptomatic CAS reduces strokes? What is the accuracy of ultrasonography to detect CAS? Does intervention with carotid endarterectomy reduce morbidity or mortality? Does screening or carotid endarterectomy result in harm? DATA EXTRACTION: All studies were reviewed, abstracted, and rated for quality by using predefined Task Force criteria. DATA SYNTHESIS: No RCTs of screening for CAS have been done. According to systematic reviews, the sensitivity of ultrasonography is approximately 94% and the specificity is approximately 92%. Treatment of CAS in selected patients by selected surgeons could lead to an approximately 5-percentage point absolute reduction in strokes over 5 years. Thirty-day stroke and death rates from carotid endarterectomy vary from 2.7% to 4.7% in RCTs; higher rates have been reported in observational studies (up to 6.7%). LIMITATIONS: Evidence is inadequate to stratify people into categories of risk for clinically important CAS. The RCTs of carotid endarterectomy versus medical treatment were conducted in selected populations with selected surgeons. CONCLUSION: The actual stroke reduction from screening asymptomatic patients and treatment with carotid endarterectomy is unknown; the benefit is limited by a low overall prevalence of treatable disease in the general asymptomatic population and harms from treatment.

Calorimetric analysis of the plasma proteome.

NC Garbett — 2008-02-13T03:13:22-00:00

Semin Nephrol, Vol. 27, No. 6. (November 2007), pp. 621-626.

The plasma proteome is a complex mixture of more than 3,000 proteins that has routinely been exploited by physicians for clinical diagnostic assays. More recently, the low-abundance region of the proteome has been examined for potential biomarkers of disease. A calorimetric assay has been developed that exploits a new physical basis with which to interrogate the plasma proteome. This article provides a brief overview of the use of the plasma proteome in clinical diagnosis and biomarker discovery and then introduces the new calorimetric assay. Some initial results are reported that indicate the potential clinical utility of the assay.

Automated method for the isolation of collecting ducts

Lance Miller — 2008-01-31T02:22:05-00:00

Am J Physiol Renal Physiol, Vol. 291, No. 1. (1 July 2006), pp. F236-245.

The structural and functional heterogeneity of the collecting duct present a tremendous experimental challenge requiring manual microdissection, which is time-consuming, labor intensive, and not amenable to high throughput. To overcome these limitations, we developed a novel approach combining the use of transgenic mice expressing green fluorescent protein (GFP) in the collecting duct with large-particle-based flow cytometry to isolate pure populations of tubular fragments from the whole collecting duct (CD), or inner medullary (IMCD), outer medullary (OMCD), or connecting segment/cortical collecting duct (CNT/CCD). Kidneys were enzymatically dispersed into tubular fragments and sorted based on tubular length and GFP intensity using large-particle-based flow cytometry or a complex object parametric analyzer and sorter (COPAS). A LIVE/DEAD assay demonstrates that the tubules were >90% viable. Tubules were collected as a function of fluorescent intensity and analyzed by epifluorescence and phase microscopy for count accuracy, GFP positivity, average tubule length, and time required to collect 100 tubules. Similarly, mRNA and protein from sorted tubules were analyzed for expression of tubule segment-specific genes using quantitative real-time RT-PCR and immunoblotting. The purity and yield of sorted tubules were related to sort stringency. Four to six replicates of 100 collecting ducts (9.68 +/- 0.44-14.5 +/- 0.66 cm or 9.2 +/- 0.7 mg tubular protein) were routinely obtained from a single mouse in under 1 h. In conclusion, large-particle-based flow cytometry is fast, reproducible, and generates sufficient amounts of highly pure and viable collecting ducts from single or replicate animals for gene expression and proteomic analysis. 10.1152/ajprenal.00273.2005

Clinical characteristics and mortality in hepatitis C-positive haemodialysis patients: a population based study.

K Kalantar-Zadeh — 2008-01-30T07:27:05-00:00

Nephrol Dial Transplant, Vol. 20, No. 8. (August 2005), pp. 1662-1669.

BACKGROUND: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood. METHODS: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001. RESULTS: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals. In a multivariate logistic regression model that adjusts for case-mix and available surrogates of malnutrition-inflammation complex syndrome (MICS), the following were independent predictors of HCV infection: younger age, male gender, Black race, Hispanic ethnicity, higher haemoglobin, lower serum albumin, higher total iron binding capacity, higher creatinine, and higher serum glutamic oxaloacetic transaminase (SGOT). Among receiver operating characteristics of commonly measured laboratory values in this population, the SGOT had the highest area. An SGOT > or =25 u/l had an adjusted odds ratio of 4.96 (95% confidence interval: 3.75-6.57) for HCV antibody positivity (sensitivity 50%, specificity 87%). HCV EIA positivity among MHD patients younger than 65 years was associated with 40-80% higher hazard ratio of all-cause and cardiovascular death during the 2 year follow-up (July 2001 to June 2003) after adjustment for case-mix and measures of MICS. CONCLUSION: HCV infection, as diagnosed by EIA, has distinct racial, age and laboratory predilections in MHD patients. HCV positivity among MHD patients younger than 65 years is associated with significantly higher cardiovascular mortality. More diligent HCV detection and treatment may improve cardiovascular survival in MHD patients.

Hepatitis C virus and death risk in hemodialysis patients.

K Kalantar-Zadeh — 2008-01-30T07:22:56-00:00

J Am Soc Nephrol, Vol. 18, No. 5. (May 2007), pp. 1584-1593.

In maintenance hemodialysis (MHD) patients, hepatitis C virus (HCV) infection is common and may be associated with poor clinical outcomes. It was hypothesized that HCV infection would be associated with high all-cause and cardiovascular mortality in these patients after controlling for demographic and clinical characteristics, including surrogates of malnutrition-inflammation complex syndrome. A national database of 13,664 MHD patients who underwent HCV antibody serology testing at least once during a 3-yr interval (July 2001 through June 2004) was analyzed. Measurements included third-generation HCV enzyme immunoassay and routine laboratory measurements. The HCV enzyme immunoassay was reported positive in 1590 (12%) patients. In logistic regression models that included case mix and available surrogates of malnutrition-inflammation complex syndrome, HCV infection was associated with younger age, male gender, black race, Hispanic ethnicity, Medicaid insurance, longer dialysis vintage (duration), unmarried status, HIV infection, and smoking history. In proportional-hazards regressions, the mortality hazard ratio that was associated with HCV infection was 1.25 (95% confidence interval 1.12 to 1.39; P < 0.001). Mortality hazards were higher among incident (dialysis duration <6 mo) than prevalent HD patients. Subgroup analyses indicated that HCV was associated with higher all-cause and cardiovascular mortality across almost all clinical, demographic, and laboratory groups of patients. Hence, in MHD patients, HCV infection exhibits distinct demographic, clinical, and laboratory patterns, including associations with higher dialysis treatment vintage, and is associated with higher mortality. More diligent efforts to prevent and treat HCV infection may improve outcomes in MHD patients.