Deborah Adey - Academia.edu (original) (raw)

Papers by Deborah Adey

American Journal of Kidney Diseases, 2019

Kidney transplantation is associated with improvement in quality of life and mortality as compare... more Kidney transplantation is associated with improvement in quality of life and mortality as compared to remaining on dialysis. It is therefore the optimal treatment for kidney failure for most patients. While transplantation nephrologists typically care for the patient in the first 6 months posttransplantation, general nephrologists and internists often care for kidney transplant recipients after this period. Medical management of the kidney transplant recipient can be challenging, and primary care physicians and nephrologists may be unfamiliar with the medical nuances of caring for these patients. This includes drug interactions, which are common and can result in drug toxicities, rejection, and graft injury. Infections and malignancies related to long-term immunosuppression may pose diagnostic and treatment challenges. In this article, we review the mechanisms of immunosuppression, types of rejection, complications of recurrent disease, common infectious diseases, and the nonrenal complications commonly encountered in the kidney transplant recipient.

Human Immunology, 2004

Background: Hepatitis C Virus infection is the leading cause of liver transplantation in the Unit... more Background: Hepatitis C Virus infection is the leading cause of liver transplantation in the United States. The potential for viral recurrence post-transplantation compounds the clinical management of these transplant recipient. Because symptoms of viral resurgence and allograft rejection appear similar, a method is needed to assist with distinguishing between the two. The FDA cleared Cylex® ImmuKnow™ assay for detecting cellmediated immunity in an immunosuppressed population was used to guide therapy decisions for managing HCVϩ liver recipients. Methods: We showed previously that HCVϩ liver recipients were significantly more immunosuppressed than HCV(-) liver recipients. This finding led to exploring the adjustment of immunosuppressant therapy in HCV-infected patients by lowering the amount Prograf® monotherapy. Based on initial testing using the Cylex assay, 32 HCVϩ patients were followed longitudinally for 1 year after adjusting the dosage of Prograf based on a patients immune response. The analysis included comparison of Cylex ImmuKnow results to HCV viral load, Liver Function tests, biopsies and immunosuppressant drug levels. Results: Case studies of three HCVϩ liver recipients are described that illustrate different immune response profiles for recipients undergoing HCV recurrence versus recipients experiencing a cellular rejection. Conclusions: The Cylex® ImmuKnow™ assay provides physicians with a new tool to manage transplant patients immunosuppressant therapy and especially the 'always difficult' liver transplant recipient with recurrent hepatitis C. Partial support of data analysis by Cylex Inc.

Clinical Transplantation, 2012

Background-Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CV... more Background-Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor lowering medications in contemporary KTRs. Methods-The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4,107 KTRs with elevated homocysteine and stable graft function an average of 5 years post-transplant. Results-CVD risk factors were common (hypertension or use of blood pressure lowering medication in 92%, borderline or elevated LDL or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation blood pressure (BP) guidelines (BP < 130/80 mm Hg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mm Hg or higher) was present in 44% of those taking anti-hypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an anti-platelet agent. Conclusion-There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.

American Journal of Kidney Diseases, 2011

Transplant International, 2010

Success of renal transplantation, as a viable alternative to dialysis, has been tempered by long-... more Success of renal transplantation, as a viable alternative to dialysis, has been tempered by long-standing racial disparities. Ethnic minorities have less access to transplantation, are less likely to be listed for transplantation, and experience a higher rate of graft failure. Reasons for the existing racial disparities at various stages of the transplantation process are complex and multi-factorial. They include a combination of behavioral, social, environmental, and occupational factors, as well as potential intended or unintended discrimination within the healthcare system. Immunologic factors such as human leukocyte antigen matching, composition of the organ donor pool, and patient immune response, all of which affect post-transplantation graft rejection rates and patient survival, also contribute to health disparities between ethnic groups.

Clinical Journal of the American Society of Nephrology, 2014

Background and objectives BK virus reactivation in kidney transplant recipients can lead to progr... more Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

American Journal of Physiology-Endocrinology and Metabolism, 1997

A decline in muscle mass and contractile function are prominent features of the sarcopenia of old... more A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synthesis of this protein decreases in sarcopenia. The fractional synthesis rate of myosin heavy chain was measured simultaneously with rates of mixed muscle and sarcoplasmic proteins from the increment of [13C]leucine in these proteins purified from serial needle biopsy samples taken from 24 subjects (age: from 20 to 92 yr) during a primed continuous infusion ofl-[1-13C]leucine. A decline in synthesis rate of mixed muscle protein ( P < 0.01) and whole body protein ( P < 0.01) was observed from young to middle age with no further change with advancing age. An age-related decline of myosin heavy-chain synthesis rate was also observed ( P < 0.01), with progressive decline occurring from young, through middle, to old age. However, sarcoplasmic protein synthesis did not decline with age. M...

American Journal of Physiology-Endocrinology and Metabolism, 2001

Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin ... more Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain (MHC) occurs in age-related muscle wasting and weakness. To determine the molecular mechanism of this lower synthesis of MHC, we measured transcript levels of isoforms of MHC (MHCI, MHCIIa, and MHCIIx) in muscle biopsy samples of 7 young (20–27 yr), 12 middle-aged (47–60 yr), and 14 older (>65 yr) people. We further determined the effect of 3 mo of resistance exercise training (exercise) vs. nonintervention (control) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate (FSR) of MHC in 39 people aged 46–79 yr. MHCI mRNA levels did not significantly change with age, but MHCIIa decreased 38% ( P < 0.05) from young to middle age and further decreased 50% ( P < 0.05) from middle to old age. MHCIIx decreased 84% ( P < 0.05) from young to middle age and 48% from middle to old age ( P < 0.05). Exercise increased FSR of MHC by 47% ( P...

American Journal of Physiology-Endocrinology and Metabolism, 2001

Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin ... more Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain (MHC) occurs in age-related muscle wasting and weakness. To determine the molecular mechanism of this lower synthesis of MHC, we measured transcript levels of isoforms of MHC (MHCI, MHCIIa, and MHCIIx) in muscle biopsy samples of 7 young (20–27 yr), 12 middle-aged (47–60 yr), and 14 older (>65 yr) people. We further determined the effect of 3 mo of resistance exercise training (exercise) vs. nonintervention (control) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate (FSR) of MHC in 39 people aged 46–79 yr. MHCI mRNA levels did not significantly change with age, but MHCIIa decreased 38% ( P < 0.05) from young to middle age and further decreased 50% ( P < 0.05) from middle to old age. MHCIIx decreased 84% ( P < 0.05) from young to middle age and 48% from middle to old age ( P < 0.05). Exercise increased FSR of MHC by 47% ( P...

American Journal of Physiology-Endocrinology and Metabolism, 2000

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanis... more Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion ofl[1-13C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) ( P < 0.05), muscle cytochrome c-oxidase activity (42%) ( P < 0.007), and citrate synthase (27%) ( P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of...

American Journal of Physiology-Endocrinology and Metabolism, 2000

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanis... more Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion ofl[1-13C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) ( P < 0.05), muscle cytochrome c-oxidase activity (42%) ( P < 0.007), and citrate synthase (27%) ( P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of...

Clinical nephrology, 2018

Few quantitative assessments have assessed disaster preparation in kidney transplant patients. Th... more Few quantitative assessments have assessed disaster preparation in kidney transplant patients. This is a survey-based assessment of disaster preparedness of 200 patients at the University of California San Francisco, USA. Patients answered questionnaires assessing their level of preparedness as well as barriers to preparation. Preparedness was scored based on response to 7 questions. Univariate analyses compared participant characteristics extracted from the medical chart against three tertiles of preparedness: low (scores 0 - 2), medium (scores 3 - 4), and high (scores 5 - 7). California counties were coded and mapped by average preparedness scores. Only 30% of patients were highly prepared for disasters. Participants were prepared with available medication for 2 weeks (78.5%) and least prepared in having a medical ID bracelet (13%). Significant minorities of patients (40% of patients or more) were unprepared with lists of medications, important phone numbers and disaster kits. Pre...

Proceedings of the National Academy of Sciences, 1996

A progressive decline in muscle performance in the rapidly expanding aging population is causing ... more A progressive decline in muscle performance in the rapidly expanding aging population is causing a dramatic increase in disability and health care costs. A decrease in muscle endurance capacity due to mitochondrial decay likely contributes to this decline in muscle performance. We developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using needle biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and function of skeletal muscle. The fractional rate of muscle mitochondrial protein synthesis in young humans (24 ± 1 year) was 0.081 ± 0.004%·h −1 , and this rate declined to 0.047 ± 0.005%·h −1 by middle age (54 ± 1 year; P < 0.01). No further decline in the rate of mitochondrial protein synthesis (0.051 ± 0.004%·h −1 ) occurred with advancing age (73 ± 2 years). The mitochondrial synthesis rate was about 95% higher than that of m...

Medicine & Science in Sports & Exercise, 2003

Kidney International, 2003

Health-related fitness and quality of life following steroid with-Patients presenting for renal t... more Health-related fitness and quality of life following steroid with-Patients presenting for renal transplantation are limdrawal in renal transplant recipients. ited in their exercise capacity [1-12]. Although exercise Background. Exercise capacity increases significantly soon capacity improves dramatically soon after successful after transplantation; however, over time it does not further transplantation [7, 13], patients who remain inactive have improve and patients remain low compared to normal levels. markedly reduced exercise capacity at 1 year posttrans-The limitations to exercise following transplantation have not been identified, but may be related to immunosuppression ther-plant [14, 15]. Kempeneers et al [16] reported that exerapy regimens that include prednisone. cise capacity is limited following transplantation by skel-Methods. We studied health-related fitness measures (caretal muscle myopathy, which is not fully corrected with diorespiratory fitness, muscle strength, and body composition) exercise training. Although there are many possible facand quality of life in renal transplant recipients randomized tors contributing to limitations to exercise in patients into two groups: those using standard maintenance immunowith end-stage renal disease (ESRD) treated with dialsuppression, including prednisone therapy (N ϭ 14); and those undergoing rapid withdrawal of steroids using Simulect [inysis [4, 10, 11, 17, 18], cause for persistent limitation terleukin-2 (IL-2) receptor inhibitor] (N ϭ 9). Testing was following transplant has not been clearly identified. The done at 3 and 12 months following transplant and the 12-month effects of immunosuppression, specifically glucocortidata were compared to 15 normal sedentary controls. coids, on muscle function and structure is well docu-Results. Compared to those maintained on steroids, the stemented by Horber et al [19, 20]. It is unclear whether roid withdrawal group showed greater gains in VO 2peak (P ϭ 0.05) and quadriceps peak torque (P ϭ 0.05) and greater gains the absence of steroids from maintenance immunosupin the vitality score and the Physical Composite Scale on the pressive regimens improve exercise capacity, muscle struc-SF-36 questionnaire (P Ͻ 0.05). At 1 year, all patients had ture, or muscle function. significantly lower exercise capacity compared to the sedentary Glucocorticoids cause proximal muscle weakness and controls (P ϭ 0.01). No differences were observed in body atrophy. Ultrastructural abnormalities in skeletal muscle composition, with both patient groups increasing in body weight (primarily body fat) over time. At 12 months, all patients include reduced myofibrillar mass, mitochondrial volwere not different in body fat percentage compared to the ume, and decreased capillary number. Lower extremities sedentary controls. typically are the first affected, demonstrating the first Conclusion. We conclude that prednisone is not the cause signs of weakness during climbing stairs and rising from for increased body fat following transplantation; however, it chairs. Quadriceps strength is markedly reduced in both may contribute to lower spontaneous improvements in exercise kidney and heart transplant recipients [16, 20, 21] and capacity possibly by limiting increases in muscle strength. The low exercise capacity in all transplant recipients studied at 1 reported to be 80% [20] and 69% [22] of untrained sedyear suggests a need for exercise training to optimize physical entary control subjects. The atrophy of skeletal muscle functioning following transplant. with administration of glucocorticoids is related to increased amino acid efflux and decreased rates of protein synthesis. Additionally, glucocorticoids may also reduce

Journal of Clinical Investigation, 1996

Despite the strong association between protein catabolic conditions and hyperglucagonemia, and en... more Despite the strong association between protein catabolic conditions and hyperglucagonemia, and enhanced glucagon secretion by amino acids (AA), glucagon's effects on protein metabolism remain less clear than on glucose metabolism. To clearly define glucagon's catabolic effect on protein metabolism during AA load, we studied the effects of glucagon on circulating AA and protein dynamics in six healthy subjects. Five protocols were performed in each subject using somatostatin to inhibit the secretion of insulin, glucagon, and growth hormone (GH) and selectively replacing these hormones in different protocols. Total AA concentration was the highest when glucagon, insulin, and GH were low. Selective increase of glucagon levels prevented this increment in AA. Addition of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endogenous leucine flux, reflecting proteolysis, decreased while leucine oxidation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated this effect. Addition of GH and insulin partially reversed the inhibitory effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA load and, by reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA. These data provide further support for a catabolic role of glucagon at physiological concentrations.

Clinical Journal of the American Society of Nephrology, 2007

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of mor... more Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in dialysis patients and kidney transplant recipients. Evaluation of patients with chronic HCV infection is warranted to determine stage of disease and the need for HCV therapy. Although combination therapy with interferon (IFN) plus ribavirin is the standard of care for chronic HCV infection, IFN monotherapy is recommended in dialysis patients because ribavirin is contraindicated in the presence of renal failure. The goals of pretransplantation HCV therapy are to decrease the risk for progression of HCV-associated liver disease, stabilize renal function in patients with HCV-related glomerulopathy, and prevent development of HCV-associated renal disease after transplantation. Posttransplantation HCV therapy is generally not recommended because of concerns regarding risk for precipitating acute rejection; however, antiviral therapy may be indicated to treat HCV-related glomerulopathy or prevent progression of chronic hepatitis C in patients with more advanced stages of fibrosis. When treatment is required, restored renal function allows use of combination therapy with IFN and ribavirin. Limitations of current HCV therapy include lack of tolerability and suboptimal response rates. New antiviral agents that can be used in dialysis patients (e.g., ribavirin alternatives) and in the posttransplantation setting (e.g., IFN alternatives) are needed to improve outcomes in these populations.

Clinical Journal of the American Society of Nephrology, 2013

American Journal of Kidney Diseases, 2019

Kidney transplantation is associated with improvement in quality of life and mortality as compare... more Kidney transplantation is associated with improvement in quality of life and mortality as compared to remaining on dialysis. It is therefore the optimal treatment for kidney failure for most patients. While transplantation nephrologists typically care for the patient in the first 6 months posttransplantation, general nephrologists and internists often care for kidney transplant recipients after this period. Medical management of the kidney transplant recipient can be challenging, and primary care physicians and nephrologists may be unfamiliar with the medical nuances of caring for these patients. This includes drug interactions, which are common and can result in drug toxicities, rejection, and graft injury. Infections and malignancies related to long-term immunosuppression may pose diagnostic and treatment challenges. In this article, we review the mechanisms of immunosuppression, types of rejection, complications of recurrent disease, common infectious diseases, and the nonrenal complications commonly encountered in the kidney transplant recipient.

Human Immunology, 2004

Background: Hepatitis C Virus infection is the leading cause of liver transplantation in the Unit... more Background: Hepatitis C Virus infection is the leading cause of liver transplantation in the United States. The potential for viral recurrence post-transplantation compounds the clinical management of these transplant recipient. Because symptoms of viral resurgence and allograft rejection appear similar, a method is needed to assist with distinguishing between the two. The FDA cleared Cylex® ImmuKnow™ assay for detecting cellmediated immunity in an immunosuppressed population was used to guide therapy decisions for managing HCVϩ liver recipients. Methods: We showed previously that HCVϩ liver recipients were significantly more immunosuppressed than HCV(-) liver recipients. This finding led to exploring the adjustment of immunosuppressant therapy in HCV-infected patients by lowering the amount Prograf® monotherapy. Based on initial testing using the Cylex assay, 32 HCVϩ patients were followed longitudinally for 1 year after adjusting the dosage of Prograf based on a patients immune response. The analysis included comparison of Cylex ImmuKnow results to HCV viral load, Liver Function tests, biopsies and immunosuppressant drug levels. Results: Case studies of three HCVϩ liver recipients are described that illustrate different immune response profiles for recipients undergoing HCV recurrence versus recipients experiencing a cellular rejection. Conclusions: The Cylex® ImmuKnow™ assay provides physicians with a new tool to manage transplant patients immunosuppressant therapy and especially the 'always difficult' liver transplant recipient with recurrent hepatitis C. Partial support of data analysis by Cylex Inc.

Clinical Transplantation, 2012

Background-Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CV... more Background-Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor lowering medications in contemporary KTRs. Methods-The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4,107 KTRs with elevated homocysteine and stable graft function an average of 5 years post-transplant. Results-CVD risk factors were common (hypertension or use of blood pressure lowering medication in 92%, borderline or elevated LDL or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation blood pressure (BP) guidelines (BP < 130/80 mm Hg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mm Hg or higher) was present in 44% of those taking anti-hypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an anti-platelet agent. Conclusion-There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.

American Journal of Kidney Diseases, 2011

Transplant International, 2010

Success of renal transplantation, as a viable alternative to dialysis, has been tempered by long-... more Success of renal transplantation, as a viable alternative to dialysis, has been tempered by long-standing racial disparities. Ethnic minorities have less access to transplantation, are less likely to be listed for transplantation, and experience a higher rate of graft failure. Reasons for the existing racial disparities at various stages of the transplantation process are complex and multi-factorial. They include a combination of behavioral, social, environmental, and occupational factors, as well as potential intended or unintended discrimination within the healthcare system. Immunologic factors such as human leukocyte antigen matching, composition of the organ donor pool, and patient immune response, all of which affect post-transplantation graft rejection rates and patient survival, also contribute to health disparities between ethnic groups.

Clinical Journal of the American Society of Nephrology, 2014

Background and objectives BK virus reactivation in kidney transplant recipients can lead to progr... more Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

American Journal of Physiology-Endocrinology and Metabolism, 1997

A decline in muscle mass and contractile function are prominent features of the sarcopenia of old... more A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synthesis of this protein decreases in sarcopenia. The fractional synthesis rate of myosin heavy chain was measured simultaneously with rates of mixed muscle and sarcoplasmic proteins from the increment of [13C]leucine in these proteins purified from serial needle biopsy samples taken from 24 subjects (age: from 20 to 92 yr) during a primed continuous infusion ofl-[1-13C]leucine. A decline in synthesis rate of mixed muscle protein ( P < 0.01) and whole body protein ( P < 0.01) was observed from young to middle age with no further change with advancing age. An age-related decline of myosin heavy-chain synthesis rate was also observed ( P < 0.01), with progressive decline occurring from young, through middle, to old age. However, sarcoplasmic protein synthesis did not decline with age. M...

American Journal of Physiology-Endocrinology and Metabolism, 2001

Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin ... more Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain (MHC) occurs in age-related muscle wasting and weakness. To determine the molecular mechanism of this lower synthesis of MHC, we measured transcript levels of isoforms of MHC (MHCI, MHCIIa, and MHCIIx) in muscle biopsy samples of 7 young (20–27 yr), 12 middle-aged (47–60 yr), and 14 older (>65 yr) people. We further determined the effect of 3 mo of resistance exercise training (exercise) vs. nonintervention (control) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate (FSR) of MHC in 39 people aged 46–79 yr. MHCI mRNA levels did not significantly change with age, but MHCIIa decreased 38% ( P < 0.05) from young to middle age and further decreased 50% ( P < 0.05) from middle to old age. MHCIIx decreased 84% ( P < 0.05) from young to middle age and 48% from middle to old age ( P < 0.05). Exercise increased FSR of MHC by 47% ( P...

American Journal of Physiology-Endocrinology and Metabolism, 2001

Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin ... more Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain (MHC) occurs in age-related muscle wasting and weakness. To determine the molecular mechanism of this lower synthesis of MHC, we measured transcript levels of isoforms of MHC (MHCI, MHCIIa, and MHCIIx) in muscle biopsy samples of 7 young (20–27 yr), 12 middle-aged (47–60 yr), and 14 older (>65 yr) people. We further determined the effect of 3 mo of resistance exercise training (exercise) vs. nonintervention (control) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate (FSR) of MHC in 39 people aged 46–79 yr. MHCI mRNA levels did not significantly change with age, but MHCIIa decreased 38% ( P < 0.05) from young to middle age and further decreased 50% ( P < 0.05) from middle to old age. MHCIIx decreased 84% ( P < 0.05) from young to middle age and 48% from middle to old age ( P < 0.05). Exercise increased FSR of MHC by 47% ( P...

American Journal of Physiology-Endocrinology and Metabolism, 2000

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanis... more Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion ofl[1-13C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) ( P < 0.05), muscle cytochrome c-oxidase activity (42%) ( P < 0.007), and citrate synthase (27%) ( P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of...

American Journal of Physiology-Endocrinology and Metabolism, 2000

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanis... more Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion ofl[1-13C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) ( P < 0.05), muscle cytochrome c-oxidase activity (42%) ( P < 0.007), and citrate synthase (27%) ( P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of...

Clinical nephrology, 2018

Few quantitative assessments have assessed disaster preparation in kidney transplant patients. Th... more Few quantitative assessments have assessed disaster preparation in kidney transplant patients. This is a survey-based assessment of disaster preparedness of 200 patients at the University of California San Francisco, USA. Patients answered questionnaires assessing their level of preparedness as well as barriers to preparation. Preparedness was scored based on response to 7 questions. Univariate analyses compared participant characteristics extracted from the medical chart against three tertiles of preparedness: low (scores 0 - 2), medium (scores 3 - 4), and high (scores 5 - 7). California counties were coded and mapped by average preparedness scores. Only 30% of patients were highly prepared for disasters. Participants were prepared with available medication for 2 weeks (78.5%) and least prepared in having a medical ID bracelet (13%). Significant minorities of patients (40% of patients or more) were unprepared with lists of medications, important phone numbers and disaster kits. Pre...

Proceedings of the National Academy of Sciences, 1996

A progressive decline in muscle performance in the rapidly expanding aging population is causing ... more A progressive decline in muscle performance in the rapidly expanding aging population is causing a dramatic increase in disability and health care costs. A decrease in muscle endurance capacity due to mitochondrial decay likely contributes to this decline in muscle performance. We developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using needle biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and function of skeletal muscle. The fractional rate of muscle mitochondrial protein synthesis in young humans (24 ± 1 year) was 0.081 ± 0.004%·h −1 , and this rate declined to 0.047 ± 0.005%·h −1 by middle age (54 ± 1 year; P < 0.01). No further decline in the rate of mitochondrial protein synthesis (0.051 ± 0.004%·h −1 ) occurred with advancing age (73 ± 2 years). The mitochondrial synthesis rate was about 95% higher than that of m...

Medicine & Science in Sports & Exercise, 2003

Kidney International, 2003

Health-related fitness and quality of life following steroid with-Patients presenting for renal t... more Health-related fitness and quality of life following steroid with-Patients presenting for renal transplantation are limdrawal in renal transplant recipients. ited in their exercise capacity [1-12]. Although exercise Background. Exercise capacity increases significantly soon capacity improves dramatically soon after successful after transplantation; however, over time it does not further transplantation [7, 13], patients who remain inactive have improve and patients remain low compared to normal levels. markedly reduced exercise capacity at 1 year posttrans-The limitations to exercise following transplantation have not been identified, but may be related to immunosuppression ther-plant [14, 15]. Kempeneers et al [16] reported that exerapy regimens that include prednisone. cise capacity is limited following transplantation by skel-Methods. We studied health-related fitness measures (caretal muscle myopathy, which is not fully corrected with diorespiratory fitness, muscle strength, and body composition) exercise training. Although there are many possible facand quality of life in renal transplant recipients randomized tors contributing to limitations to exercise in patients into two groups: those using standard maintenance immunowith end-stage renal disease (ESRD) treated with dialsuppression, including prednisone therapy (N ϭ 14); and those undergoing rapid withdrawal of steroids using Simulect [inysis [4, 10, 11, 17, 18], cause for persistent limitation terleukin-2 (IL-2) receptor inhibitor] (N ϭ 9). Testing was following transplant has not been clearly identified. The done at 3 and 12 months following transplant and the 12-month effects of immunosuppression, specifically glucocortidata were compared to 15 normal sedentary controls. coids, on muscle function and structure is well docu-Results. Compared to those maintained on steroids, the stemented by Horber et al [19, 20]. It is unclear whether roid withdrawal group showed greater gains in VO 2peak (P ϭ 0.05) and quadriceps peak torque (P ϭ 0.05) and greater gains the absence of steroids from maintenance immunosupin the vitality score and the Physical Composite Scale on the pressive regimens improve exercise capacity, muscle struc-SF-36 questionnaire (P Ͻ 0.05). At 1 year, all patients had ture, or muscle function. significantly lower exercise capacity compared to the sedentary Glucocorticoids cause proximal muscle weakness and controls (P ϭ 0.01). No differences were observed in body atrophy. Ultrastructural abnormalities in skeletal muscle composition, with both patient groups increasing in body weight (primarily body fat) over time. At 12 months, all patients include reduced myofibrillar mass, mitochondrial volwere not different in body fat percentage compared to the ume, and decreased capillary number. Lower extremities sedentary controls. typically are the first affected, demonstrating the first Conclusion. We conclude that prednisone is not the cause signs of weakness during climbing stairs and rising from for increased body fat following transplantation; however, it chairs. Quadriceps strength is markedly reduced in both may contribute to lower spontaneous improvements in exercise kidney and heart transplant recipients [16, 20, 21] and capacity possibly by limiting increases in muscle strength. The low exercise capacity in all transplant recipients studied at 1 reported to be 80% [20] and 69% [22] of untrained sedyear suggests a need for exercise training to optimize physical entary control subjects. The atrophy of skeletal muscle functioning following transplant. with administration of glucocorticoids is related to increased amino acid efflux and decreased rates of protein synthesis. Additionally, glucocorticoids may also reduce

Journal of Clinical Investigation, 1996

Despite the strong association between protein catabolic conditions and hyperglucagonemia, and en... more Despite the strong association between protein catabolic conditions and hyperglucagonemia, and enhanced glucagon secretion by amino acids (AA), glucagon's effects on protein metabolism remain less clear than on glucose metabolism. To clearly define glucagon's catabolic effect on protein metabolism during AA load, we studied the effects of glucagon on circulating AA and protein dynamics in six healthy subjects. Five protocols were performed in each subject using somatostatin to inhibit the secretion of insulin, glucagon, and growth hormone (GH) and selectively replacing these hormones in different protocols. Total AA concentration was the highest when glucagon, insulin, and GH were low. Selective increase of glucagon levels prevented this increment in AA. Addition of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endogenous leucine flux, reflecting proteolysis, decreased while leucine oxidation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated this effect. Addition of GH and insulin partially reversed the inhibitory effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA load and, by reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA. These data provide further support for a catabolic role of glucagon at physiological concentrations.

Clinical Journal of the American Society of Nephrology, 2007

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of mor... more Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in dialysis patients and kidney transplant recipients. Evaluation of patients with chronic HCV infection is warranted to determine stage of disease and the need for HCV therapy. Although combination therapy with interferon (IFN) plus ribavirin is the standard of care for chronic HCV infection, IFN monotherapy is recommended in dialysis patients because ribavirin is contraindicated in the presence of renal failure. The goals of pretransplantation HCV therapy are to decrease the risk for progression of HCV-associated liver disease, stabilize renal function in patients with HCV-related glomerulopathy, and prevent development of HCV-associated renal disease after transplantation. Posttransplantation HCV therapy is generally not recommended because of concerns regarding risk for precipitating acute rejection; however, antiviral therapy may be indicated to treat HCV-related glomerulopathy or prevent progression of chronic hepatitis C in patients with more advanced stages of fibrosis. When treatment is required, restored renal function allows use of combination therapy with IFN and ribavirin. Limitations of current HCV therapy include lack of tolerability and suboptimal response rates. New antiviral agents that can be used in dialysis patients (e.g., ribavirin alternatives) and in the posttransplantation setting (e.g., IFN alternatives) are needed to improve outcomes in these populations.

Clinical Journal of the American Society of Nephrology, 2013