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Clinical Investigation [chapter]

Susan L. Furth, Jeffrey J. Fadrowski
2009 Pediatric Nephrology  
Purpose: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe
more » ... e reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. Material and Methods: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 (RTOG) acute and/or late tissue radiation side effects by reaction severity. DNA from the peripheral blood of patients was isolated. All 66 exons and adjacent intron regions of the ATM gene were PCR-amplified and examined for mutations by a combination of agarose gel electrophoresis, single-stranded conformational polymorphism (SSCP) analysis, and exon-scanning direct sequencing. Results: Only 2 of the patients revealed altogether four heteroallelic sequence variants. The latter included two single-base deletions in different introns, a single-base change causing an amino acid substitution in an exon, and a large insertion in another intron. Both the single-base deletions and the single-base change represent known polymorphisms. The large insertion was an Alu repeat, shown not to give rise to altered gene product. Conclusions: Despite high technical efforts, no unequivocal ATM mutation was detected. Nevertheless, extension of similar studies to larger and differently composed cohorts of patients suffering severe adverse effects of radiotherapy, and application of new technologies for mutation detection may be worthwhile to assess the definite prevalence of significant ATM mutations within the group of radiotherapy patients with adverse reactions. To date, it must be recognized that our present results do not suggest that heterozygous ATM mutations are involved in clinically observed radiosensitivity but, rather, invoke different genetic predisposition or so far unknown exogenous factors.
doi:10.1007/978-3-540-76341-3_17 fatcat:572zuekhkvei3acdz7qkxmxyw4

Anemia in children with chronic kidney disease

Meredith A. Atkinson, Susan L. Furth
2011 Nature Reviews Nephrology  
controlled trial conducted in adult patients with CKD found that early initiation of erythropoietin therapy in those with mild anemia seemed to delay the initiation of renal replacement therapy. 20 Furth  ... 
doi:10.1038/nrneph.2011.115 pmid:21894183 pmcid:PMC5739031 fatcat:lfwt2cm3rveqtgxjdofh2xugtq

Acute kidney injury: a not-so-silent disease

Edward D. Siew, Susan L. Furth
2014 Kidney International  
Author manuscript; available in PMC 2014 September 01. and Furth Page 5 Kidney Int. Author manuscript; available in PMC 2014 September 01.  ... 
doi:10.1038/ki.2013.389 pmid:24583979 pmcid:PMC4000542 fatcat:pe2l7g64azesdn6aeks6a2w74u

Obesidad y enfermedad renal: consecuencias ocultas de la epidemia

Csaba P. Kovesdy, Susan Furth, Carmine Zoccali
2017 Nefrología  
doi:10.1016/j.nefro.2017.02.005 pmid:28434624 fatcat:oxxyt6e6rzccjfwa3tlbcbezui

The TAKE-IT study: aims, design, and methods

Bethany J Foster, Ahna Pai, Huaqing Zhao, Susan Furth
2014 BMC Nephrology  
Effective interventions to improve immunosuppressive medication adherence among adolescent and young adult kidney transplant recipients are desperately needed. This paper describes the aims, design, and methods of the Teen Adherence in Kidney transplant, Effectiveness of Intervention Trial (TAKE-IT) study.
doi:10.1186/1471-2369-15-139 pmid:25176317 pmcid:PMC4236658 fatcat:plbhsth4vnbovau5qr4yqknlpq

Obesity and Kidney Disease

Csaba P. Kovesdy, Susan L. Furth, Carmine Zoccali
2017 Canadian Journal of Kidney Health and Disease  
doi:10.1177/2054358117698669 pmid:28540059 pmcid:PMC5433675 fatcat:6y3pqqbfdbarhfkgfb4g4kylma

Arterial Stiffness in Children: Pediatric Measurement and Considerations

Jonathan D. Savant, Susan L. Furth, Kevin E.C. Meyers
2015 Pulse  
Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. Methods: There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for
more » ... tric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). Conclusions: The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure.
doi:10.1159/000374095 pmid:26587447 pmcid:PMC4646130 fatcat:2aerbxlnqjeurns7sksm2xke7y

Childhood Kidney Disease: A Troubling Prognosis?

Darcy K. Weidemann, Bradley A. Warady, Susan L. Furth
2018 American Journal of Kidney Diseases  
Warady, and Susan L.  ...  Furth T he 11th annual World Kidney Day was celebrated on March 10, 2016, across the globe in an effort to better inform the general public, policymakers, and the medical community about the importance  ... 
doi:10.1053/j.ajkd.2018.04.015 pmid:29921452 fatcat:lnlo7egj65fxhivlzrgcibezbm

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

Csaba P. Kovesdy, Susan L. Furth, Carmine Zoccali
2017 Kidney Diseases  
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The
more » ... in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesityrelated glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.
doi:10.1159/000452965 pmid:28785562 pmcid:PMC5527180 fatcat:zhuypepgcbg2bc4sqeqciht5pa

The Role of Prolactin in Mammary Carcinoma

Charles V. Clevenger, Priscilla A. Furth, Susan E. Hankinson, Linda A. Schuler
2003 Endocrine reviews  
The contribution of prolactin (PRL) to the pathogenesis and progression of human breast cancer at the cellular, transgenic, and epidemiological levels is increasingly appreciated. Acting at the endocrine and autocrine/paracrine levels, PRL functions to stimulate the growth and motility of human breast cancer cells. The actions of this ligand are mediated by at least six recognized PRL receptor isoforms found on, or secreted by, human breast epithelium. The PRL/PRL receptor complex associates
more » ... h and activates several signaling net-works that are shared with other members of the cytokine receptor superfamily. Coupled with the recently identified intranuclear function of PRL, these networks are integrated into the in vitro and in vivo actions induced by ligand. These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer. (Endocrine Reviews 24: 1-27, 2003)
doi:10.1210/er.2001-0036 pmid:12588805 pmcid:PMC1698952 fatcat:3lmn6tvlrfghlkf3ugrknixgue

Kidney Stone Recurrence among Children and Adolescents

Gregory E. Tasian, Abdo E. Kabarriti, Angela Kalmus, Susan L. Furth
2017 Journal of Urology  
Furth was supported by K24DK78737 from the National Institutes of Health/ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).  ... 
doi:10.1016/j.juro.2016.07.090 pmid:27521691 pmcid:PMC5161588 fatcat:bnc2wakh3reu3nbaerxxfe377m

Blood Pressure Control and Progression of CKD in Children

Susan Furth
2010 American Journal of Kidney Diseases  
Hypertension both accelerates and is exacerbated by progression of chronic kidney disease (CKD). In children with CKD, hypertension is common and often undertreated. A report by the North American Pediatric Renal Transplant Cooperative Study in 2002 showed that nearly half of the children enrolled in the Chronic Renal Insufficiency arm of the registry had hypertension based upon a casual blood pressure at the time of enrollment.(1) Hypertensive children with CKD developed either end-stage renal
more » ... disease or loss of glomerular filtration rate (GFR) > 10 ml/min/1.73m 2 significantly more often than normotensive children with CKD. In a recent cross-sectional analysis of baseline blood pressure in almost 400 children in the CKiD (Chronic Kidney Disease in Children) cohort study, hypertension was common and frequently not adequately controlled.(2) The overall prevalence of systolic or diastolic hypertension was over 50%, with 13% of participants having uncontrolled hypertension. After multivariable adjustment, both nephrotic-range proteinuria and non-use of an agent to block the renin angiotensin system (RAS; angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker) were associated with having uncontrolled hypertension. More aggressive treatment of hypertension is a clear opportunity to improve the treatment of children with CKD. Although substantial randomized controlled trial data in adults with CKD demonstrate that drugs blocking the renin-angiotensin II-aldosterone system, especially ACE inhibitors, both decrease proteinuria and slow CKD progression more than conventional antihypertensive therapy (3-6), little direct evidence has been available to support the generalization of these findings to children with CKD. Furthermore, although studies in adults have suggested that lower blood pressure targets may further slow CKD progression (7), this has not previously been shown in children. A recent study by the ESCAPE (Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients) trial group, published in 2009 in the New England Journal of Medicine, addresses both of these gaps in the current literature on slowing progression of CKD in children. (8) pediatric nephrology units across Europe collaborated to randomize 468 children aged 3 -18 years with estimated GFR by the Schwartz formula of 15 -80 ml/min/ 1.73m 2 in order to assess the long-term effect on kidney disease progression of intensified blood pressure control among children who were receiving a fixed high dose of an ACE
doi:10.1053/j.ajkd.2010.03.007 pmid:20417000 pmcid:PMC2878764 fatcat:jm2whdp62zfdtax7b3smqre4ve

Defining new surrogate markers for CKD progression

H. William Schnaper, Susan L. Furth, Lynne P. Yao
2014 Pediatric nephrology (Berlin, West)  
At a recent meeting of international experts on clinical aspects of progressive chronic kidney disease (CKD), an extensive analysis of extant clinical trials was used to develop more effective and economical surrogate markers for CKD outcomes in adults. This article describes the reasons for this undertaking, the methods and conclusions of the meeting, and the relevance of these findings to pediatric nephrology.
doi:10.1007/s00467-014-2995-0 pmid:25370779 pmcid:PMC4282962 fatcat:jyvly5wyqfg5ro44qnhhkhreta

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

Csaba P. Kovesdy, Susan Furth, Carmine Zoccali
2017 Nephrology - Open Journal  
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in
more » ... rular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the "World Kidney Day" promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.
doi:10.17140/npoj-3-e007 fatcat:idwt3oykrbh2pgbxexyzpfkpry

Society for Pediatric Research 2012 Presidential Address: SPR strategic plan priorities 2012

Susan L. Furth
2012 Pediatric Research  
Special Article Furth What can an organization such as the SPR do to counter some of these threats to the core values of our membership? What are the strengths that we can leverage?  ... 
doi:10.1038/pr.2012.121 pmid:23190623 fatcat:7zk3ifmrobfbtfaacgs56lruoe
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