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Biomedical subjects

Kirsten L Johansen

Publications and source records attributed to Kirsten L Johansen.

At least 19 recordsLinked to original sources
PubMed2006

Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial.

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.

Absorptiometry, Photon↗
PubMed2006

An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease.

The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation-maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4%. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72% risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This "protective" haplotype may encompass loci with functional significance in the ACE gene.

Aged↗
PubMed2006

Targeting screening mammography according to life expectancy among women undergoing dialysis.

BACKGROUND: Screening guidelines recommend that mammography be targeted to women likely to live longer than 5 years. Because women undergoing dialysis have a reduced but variable life expectancy, their appropriate use of screening is controversial. Therefore, we conducted this study to describe national mammography rates among women undergoing dialysis with differing prognostic factors and to determine whether screening is targeted to healthier women who live longer. METHODS: Using the US Renal Data System, we identified 17,090 women aged 50 years or older who started dialysis in 1997. We tracked women for 5 years to ascertain their use of screening mammography or death. RESULTS: The 5-year survival rate was 25%. The biennial screening mammography rate was 25%, ranging from 12% for women aged 80 years or older to 69% for women who were ever on the transplant list. Women who were screened in the past year had a lower death rate than those who were not (hazards ratio, 0.55; 95% confidence interval, 0.51-0.59). Yet, 2198 women (13%) who died within 5 years underwent screening, and 2004 women (12%) who lived more than 5 years while receiving dialysis did not undergo screening. CONCLUSIONS: Screening mammography rates are appropriately low among women undergoing dialysis because the 5-year survival rate is low. Screening is being targeted to women who are healthier and live longer. However, targeting could be improved by increasing screening in the few women undergoing dialysis with substantial life expectancies while decreasing screening in most women undergoing dialysis who live less than 5 years.

Aged↗
PubMed2006

Effect of diabetes mellitus on muscle size and strength in patients receiving dialysis therapy.

BACKGROUND: Diabetes mellitus (DM) is a potential contributor to the muscle abnormalities and poor physical functioning of the dialysis population. METHODS: Thirty-three dialysis patients without DM (non-DM group) were compared with 25 dialysis patients with DM (DM group). Measures were made of cross-sectional area and composition of the leg muscles by using proton T1-weighted magnetic resonance imaging; body composition by means of dual-energy X-ray absorptiometry; leg muscle strength by means of isokinetic knee extension; isometric dorsiflexor maximum voluntary contraction by means of force plate; physical activity by means of 3-dimensional accelerometry; and functional capacity by using various functional tests. RESULTS: The DM group was older, weaker, more atrophic, and had a greater amount of intramuscular fat compared with the non-DM group. However, when the overall analysis was adjusted for age and sex, there were no differences between the 2 groups with respect to muscle cross-sectional area, leg strength, or physical activity. To further account for sex and age differences, a paired analysis was performed after matching patients by age (within 5 years) and sex (N = 16/group). In the matched analysis, only intramuscular fat and leg adipose tissue were different between the 2 groups. CONCLUSION: DM is associated with more fat within muscles of dialysis patients, but is unrelated to muscle size or strength. Demographic differences between the DM and non-DM groups on dialysis therapy likely are responsible for the general perception that patients with DM are more debilitated.

Diabetes Complications↗
PubMed2006

Association of body size with health status in patients beginning dialysis.

BACKGROUND: Greater weight-for-height has been associated with prolonged survival in patients with end-stage renal disease (ESRD) but not in the general population. The association between body size and health status has not been carefully evaluated. OBJECTIVES: We compared the self-reported health status of 2467 participants in the Dialysis Morbidity and Mortality Study Wave 2 by using body mass index (BMI; in kg/m2) to approximate body size and composition. DESIGN: BMI was categorized into 4 groups (<19, 19 to <25, 25 to <30, and > or = 30) corresponding to World Health Organization criteria for underweight, normal-weight, overweight, and obese status. We adjusted for demographic, clinical, and laboratory factors that may have confounded the association between body size and health status. RESULTS: Scores on the physical component summary and the physical functioning scale were significantly lower for obese subjects than for those with normal weight or moderately high BMI after adjustment for demographic factors, comorbidity, and laboratory markers of nutritional status. Mental component summary and symptom scores were unrelated to BMI. The underweight group scored lower on many Medical Outcomes Study 36-Item Short Form scales than did the normal-weight group. CONCLUSIONS: Whereas higher BMI has consistently been associated with enhanced dialysis-related survival, health status-particularly physical function-may be impaired by obesity. Additional longitudinal studies of body weight and composition are needed for a better understanding of the complex effects of obesity and undernutrition in persons with ESRD and advanced chronic kidney disease.

Body Composition↗
PubMed2005

Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients.

Dialysis patients have severe exercise limitations related to metabolic disturbances, but muscle fatigue has not been well studied in this population. We investigated the magnitude and mechanisms of fatigue of the ankle dorsiflexor muscles in patients on maintenance hemodialysis. Thirty-three dialysis patients and twelve healthy control subjects performed incremental isometric dorsiflexion exercise, beginning at 10% of their maximal voluntary contraction (MVC) and increasing by 10% every 2 min. Muscle fatigue (fall of MVC), completeness of voluntary activation, and metabolic responses to exercise were measured. Before exercise, dialysis subjects exhibited reduced strength and impaired peripheral activation (lower compound muscle activation potential amplitude) but no metabolic perturbation. During exercise, dialysis subjects demonstrated threefold greater fatigue than controls with evidence of central activation failure but no change in peripheral activation. All metabolic parameters were significantly more perturbed at end exercise in dialysis subjects than in controls, including lower phosphocreatine (PCr) and pH, and higher P(i), P(i)/PCr, and H(2)PO(4)(-). Oxidative potential was markedly lower in patients than in controls [62.5 (SD 27.2) vs. 134.6 (SD 31.7), P < 0.0001]. Muscle fatigue was negatively correlated with oxidative potential among dialysis subjects (r = -0.52, P = 0.04) but not controls. Changes in central activation ratio were also correlated with muscle fatigue in the dialysis subjects (r = 0.59, P = 0.001) but not the controls. This study provides new information regarding the excessive muscular fatigue of dialysis patients and demonstrates that the mechanisms of this fatigue include both intramuscular energy metabolism and central activation failure.

Ankle↗
PubMed2005

Interleukin-1 gene cluster polymorphisms predict risk of ESRD.

BACKGROUND: Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD). METHODS: Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated. RESULTS: A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04). CONCLUSION: Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.

Aged↗
PubMed2005

Exercise and chronic kidney disease: current recommendations.

Patients with chronic kidney disease (CKD) are inactive and have reduced physical functioning and performance. Aerobic exercise interventions have been shown to increase maximal oxygen consumption in selected patients. In addition, preliminary evidence, although mixed, suggests that aerobic exercise training can improve blood pressure control, lipid profiles and mental health in this population. A few larger studies are now available showing that aerobic training can also improve physical functioning and performance. The impact on survival or hospitalisation has not been determined. Resistance exercise training, although less studied, appears to increase muscle strength and size and may also improve functioning. There have been several reports of successful combined exercise interventions, but the designs have not allowed evaluation of the relative benefits of aerobic and resistance training on physical functioning. Despite the evidence that exercise is safe and beneficial in patients with CKD, dialysis patients remain inactive, and exercise assessment, counselling and training is not widely offered to patients with CKD. Studies of the barriers to patient participation in exercise and to provider assessment and recommendations are needed so that more widely generalisable interventions can be developed. However, in the interim, patients should be encouraged to participate in moderate physical activity to meet the US Surgeon General's recommendations. Patients who are weak can benefit from strength-training interventions. Resistance and aerobic exercise programmes should be initiated at relatively low intensity in patients with CKD and progressed as slowly as tolerated in order to avoid injury and discontinuation of exercise. For patients on haemodialysis, incorporation of exercise into the dialysis session may increase patient participation and tolerance of exercise.

Exercise↗
PubMed2004

Influence of race on kidney transplant outcomes within and outside the Department of Veterans Affairs.

Inferior outcomes after kidney transplantation among African Americans are poorly understood. It was hypothesized that unequal access to medical care among transplant recipients might contribute to worse posttransplantation outcomes among African Americans and that racial disparities in kidney transplant outcomes would be less pronounced among patients who receive health care within versus outside the Department of Veterans Affairs (VA), because eligible veterans who receive care within the VA are entitled to receive universal access to care, including coverage of prescription drugs. A study cohort of 79,361 patients who were undergoing their first kidney transplant in the United States between October 1, 1991, and October 31, 2000, was assembled, with follow-up data on graft survival obtained through October 31, 2001. After multivariable proportional hazards adjustment for a wide range of recipient and donor characteristics, African-American patients were at increased risk for graft failure compared with non-African-American patients (relative risk [RR] 1.31; 95% confidence interval [CI] 1.26 to 1.36). African-American race was associated with a similarly increased risk for graft failure among patients who were VA users (RR 1.31; 95% CI 1.11 to 1.54) and non-VA users (RR 1.31; 95% CI 1.26 to 1.36). In conclusion, racial disparities in kidney transplant outcomes seem to persist even in a universal access-to-care system such as the VA. Reasons for worse outcomes among African Americans require further investigation.

Adult↗
PubMed2004

Influence of renal insufficiency on limb loss and mortality after initial lower extremity surgical revascularization.

OBJECTIVE: Limb loss after lower extremity surgical revascularization occurs relatively frequently in patients receiving dialysis. The goal of the present study was to determine whether patients with milder degrees of renal insufficiency are also at risk for this complication. MATERIAL AND METHODS: This cohort study was carried out at the Department of Veterans Affairs (VA). The study sample consisted of 9932 patients undergoing an initial surgical revascularization procedure between October 1, 1995, and September 30, 2000, recorded by the VA National Surgical Quality Improvement Program (NSQIP). We examined the occurrence of major amputation within 1 year of lower extremity surgical revascularization by level of renal function. RESULTS: Eleven percent of study patients underwent major lower extremity amputation within 1 year of NSQIP-documented lower extremity revascularization surgery: 10% (739 of 7335) of patients with normal renal function, 11% (251 of 2210) of patients with moderately reduced renal function, 12% (24 of 205) of patients with severe renal insufficiency, and 29% (53 of 182) of patients receiving dialysis. After adjustment for demographic characteristics and comorbid conditions, only patients receiving dialysis were at significantly increased risk for amputation, compared with patients with normal renal function (odds ratio, 2.46; 95% confidence interval, 1.74-3.47; P<.001). Compared with all other veterans undergoing bypass procedures, patients receiving dialysis were more likely to have a wound infection; a diagnostic code for lower extremity gangrene, infection, or ischemic ulceration; an elevated white blood cell count; and preoperative sepsis at the time of initial revascularization. In addition, they were more likely to have a preoperative hospital stay longer than 1 week, undergo concurrent minor amputation, and undergo an outflow (vs inflow) procedure. CONCLUSION: Only patients receiving dialysis, and not patients with milder degrees of renal insufficiency, appear to be at higher risk for limb loss after revascularization, compared with patients with normal renal function. Further studies are needed to determine why patients receiving dialysis are at a singularly increased risk for limb loss after lower extremity revascularization and whether their more frequent presentation with limb-threatening infection at the time of revascularization reflects late presentation for surgery or a more rapid course of peripheral arterial disease in this patient group.

Aged↗
PubMed2004

Association of body size with outcomes among patients beginning dialysis.

BACKGROUND: Although obesity confers an increased risk of mortality in the general population, observational reports on the dialysis population have suggested that obesity is associated with improved survival. These reports have generally not examined extremely high values of body mass index (BMI; in kg/m(2)), survival >1 y, or alternative measures of adiposity. OBJECTIVE: We sought to clarify the relation between body size and outcomes among a large cohort of patients beginning dialysis. DESIGN: Data on 418 055 patients beginning dialysis between 1 April 1995 and 1 November 2000 were analyzed by using US Renal Data System data. BMI was divided into 8 categories in increments of 3 units, ranging from < 19 to > or =37, and the relation between survival and BMI was examined by using proportional hazards regression with adjustment for demographic, laboratory, and comorbidity data. RESULTS: High BMI was associated with increased survival in this cohort, even at extremely high BMI, after adjustment, and over a 2-y average follow-up time. This was true for whites, African Americans, and Hispanics but not for Asians. High BMI was also associated with a reduced risk of hospitalization and a lower rate of mortality in all mortality categories. Alternative estimates of adiposity, including the Benn index and estimated fat mass, yielded similar results, and adjustments for lean body mass did not substantially alter the findings. CONCLUSIONS: High BMI is not associated with increased mortality among patients beginning dialysis. This finding does not appear to be a function of lean body mass and, although modified by certain patient characteristics, it is a robust finding.

Body Mass Index↗
PubMed2004

Postoperative mortality after nontraumatic lower extremity amputation in patients with renal insufficiency.

Mortality rates after lower extremity amputation are extremely high among dialysis patients. However, the impact of milder degrees of renal insufficiency on death rates after lower extremity amputation has not been carefully examined. In this study, the authors used data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to measure the association between renal dysfunction and 30-d mortality after nontraumatic amputation adjusted for confounders. The study population consisted of 16,994 patients undergoing their first NSQIP recorded amputation from January 1, 1994 through September 30, 2001. Thirty-five percent of all cohort patients had at least moderate renal insufficiency, and 52% of all postoperative deaths occurred in this group. Postoperative mortality was 9% in patients with moderate renal insufficiency, 15% in patients with severe renal insufficiency, and 16% in dialysis patients, compared with 6% in patients with normal or mildly reduced renal function. Renal insufficiency remained associated with death after adjustment for confounders (adjusted odds ratio [OR] 3.36, 95% confidence interval [CI] 2.75 to 4.10 [dialysis patients]; OR 2.54, CI 2.06 to 3.14 [severe renal insufficiency]; and OR 1.52, CI 1.32 to 1.76 [moderate renal insufficiency]). In conclusion, even moderate renal insufficiency is independently associated with postoperative death after lower extremity amputation. This finding highlights the need for a targeted approach to improving the care of patients with renal insufficiency undergoing lower extremity amputation.

Aged↗
PubMed2004

Treatment of hypogonadism in men with chronic kidney disease.

Hypogonadism is common among men with chronic kidney disease, but few studies have directly assessed the effects of testosterone replacement in this population. Limited information suggests that androgen replacement may improve libido and sexual function among men who are frankly hypogonadal. However, the threshold for normal sexual function is in the lower end of the normal range. Increasing serum testosterone above this level does not appear to have beneficial effects on sexual functioning. On the other hand, at least among healthy men, the dose-response curve for anabolic effects of testosterone administration appears to extend to testosterone levels on the high end of the normal range or above. Small studies have suggested that androgen treatment has anabolic effects among end-stage renal disease patients, even in the absence of hypogonadism. Androgens have potential side effects, and some preinitiation and subsequent assessment and monitoring are recommended to minimize these adverse effects. Recommendations for healthy older men appear to be reasonable for patients with chronic kidney disease. More research is needed to measure the effects of androgen therapy on various symptoms of hypogonadism as well as on overall quality of life, physical functioning, and survival among patients with chronic kidney disease.

Androgens↗
PubMed2003

Time- and exercise-dependent gene regulation in human skeletal muscle.

BACKGROUND: Skeletal muscle remodeling is a critical component of an organism's response to environmental changes. Exercise causes structural changes in muscle and can induce phase shifts in circadian rhythms, fluctuations in physiology and behavior with a period of around 24 hours that are maintained by a core clock mechanism. Both exercise-induced remodeling and circadian rhythms rely on the transcriptional regulation of key genes. RESULTS: We used DNA microarrays to determine the effects of resistance exercise (RE) on gene regulation in biopsy samples of human quadriceps muscle obtained 6 and 18 hours after an acute bout of isotonic exercise with one leg. We also profiled diurnal gene regulation at the same time points (2000 and 0800 hours) in the non-exercised leg. Comparison of our results with published circadian gene profiles in mice identified 44 putative genes that were regulated in a circadian fashion. We then used quantitative PCR to validate the circadian expression of selected gene orthologs in mouse skeletal muscle. CONCLUSIONS: The coordinated regulation of the circadian clock genes Cry1, Per2, and Bmal1 6 hours after RE and diurnal genes 18 hours after RE in the exercised leg suggest that RE may directly modulate circadian rhythms in human skeletal muscle.

Animals↗
PubMed2003

Impact of surgeon and surgical center characteristics on choice of permanent vascular access.

BACKGROUND: The impact of the surgeon and surgical center characteristics on choice of autogenous arteriovenous (AV) fistula versus artificial AV graft as permanent vascular access for hemodialysis has not been studied. METHODS: We used national data from the Department of Veterans Affairs Veterans Health Administration to measure the association of surgeon and surgical center characteristics with choice of initial permanent vascular access among patients undergoing their first vascular access placement procedure between October 1, 2000 and September 30, 2001 (fiscal year 2001). Data were analyzed using a hierarchical logistic regression model clustered for surgical center and surgeon. RESULTS: The study population included 1114 patients, 74 Veterans Administration Medical Centers, and 182 surgeons. Seventy-two percent of patients received an AV fistula as their initial form of permanent vascular access. After adjusting for differences in patient, center, and surgeon characteristics, odds of AV fistula placement at high volume centers (>30 procedures per year) were more than three times greater than at low volume centers [odds ratio (OR) 3.26, 95% confidence interval (95% CI) 1.37 to 7.75, P = 0.008]. In addition, a strong clustering effect was present at the level of the surgeon (OR 1.55, 95% CI 1.19 to 2.03, P = 0.001) but not at the level of the surgical center, indicating an association with surgeon practice pattern. CONCLUSION: Barriers to AV fistula placement can exist at the levels of the surgeon and surgical center, respectively. Future strategies to improve AV fistula placement rates should target surgeons and surgical centers in addition to patients, nephrologists, and primary care providers.

Aged↗
PubMed2003

Muscle atrophy in patients receiving hemodialysis: effects on muscle strength, muscle quality, and physical function.

BACKGROUND: Dialysis patients are less active and have reduced functional capacity compared to individuals with normal renal function. Muscle atrophy and weakness may contribute to these problems. This investigation was undertaken to quantify the extent of atrophy in the lower extremity muscles, to determine whether defects in muscle specific strength (force per unit mass) or central nervous system (CNS) activation are present, and to assess the relationship between muscle size and physical performance in a group of patients on hemodialysis. METHODS: Thirty-eight dialysis subjects (aged 55 +/- 15 years) and nineteen healthy sedentary controls (aged 55 +/- 13 years) were enrolled. Magnetic resonance imaging of the lower leg was used to determine the total cross-sectional area (CSA) and the area of contractile and non-contractile tissue of the ankle dorsiflexor muscles. Isometric dorsiflexor strength was measured during a maximal voluntary contraction with and without superimposed tetanic stimulation (N = 22 for dialysis subjects, N = 12 for controls). Physical activity was measured by accelerometry, and gait speed was recorded as a measure of physical performance. RESULTS: Dialysis subjects were weaker, less active, and walked more slowly than controls. Total muscle compartment CSA was not significantly different between dialysis subjects and controls, but the contractile CSA was smaller in the dialysis patients even after adjustment for age, gender, and physical activity. Central activation and specific strength were normal. Gait speed was correlated with contractile CSA. CONCLUSIONS: Significant atrophy and increased non-contractile tissue are present in the muscle of patients on hemodialysis. The relationship between contractile area and strength is intact in this population. Muscle atrophy is associated with poor physical performance. Thus, interventions to increase physical activity or otherwise address atrophy may improve performance and quality of life.

Adult↗