Thesis (M.S.)--Springfield College, 2003. / Includes bibliographical references.

Introdução: Devido ao fato dos antiinflamatórios serem amplamente utilizados no meio atlético, da suposta melhora de desempenho pelo efeito analgésico, independentemente da presença ou não de lesão, e, por fim, em razão dos extensos relatos de efeitos adversos associados a esta classe farmacológica, o objetivo da presente Tese Doutoral foi verificar a potencialidade do antiinflamatório não-esteroidal (AINE) Ibuprofeno em enquadrar-se como doping segundo o Código Mundial Antidoping da Agência Mundial Antidoping (WADA-COI), segundo critérios de ergogenia e risco à saúde em atleta em corrida de duração. Para tanto, foram realizados um estudo observacional e três ensaios clínicos, randomizados e duplo-cego. Materiais e Métodos: No primeiro trabalho (laboratorial), 14 atletas especialistas em provas de longa duração realizaram dois testes progressivos de corrida em esteira rolante com 72 horas de intervalo (modelo cruzado), sendo administrada em cada teste dose única e por via oral de 1,2g de AINE ou Placebo (lactose). Os resultados indicaram que o uso de AINE reduziu a percepção de esforço no segundo limiar ventilatório (p 0,01), todavia com diminuição da velocidade associada (p=0,01) e redução do VO2máx (p=0,04). No segundo estudo, 20 sujeitos (2x10 sujeitos) condicionados e saudáveis, após determinação da velocidade associada ao segundo limiar ventilatório, foram submetidos a um protocolo de tempo limite para exaustão (tlim) em corrida antes e 48h após indução de dano muscular com exercícios concêntricos e excêntricos (em dinamômetro isoscinético) nos grupos musculares do compartimento anterior e posterior da coxa. No segundo teste (pós-dano) um grupo recebeu, em dose única e por via oral, 1,2g de AINE e o outro grupo Placebo. Os resultados indicaram redução significativa do tlim em ambos os grupos (p 0,01), contudo sem atenuação de queda pelo AINE (p=0,55). No terceiro e último experimento, 14 atletas realizaram duas provas simuladas (PS) de 10 km em pista com sete dias de intervalo. Em cada dia os sujeitos receberam tratamento farmacológico idêntico aos estudos anteriores (modelo cruzado) tendo sido monitorados a filtragem glomerular (FG) pela técnica de clearance de 51CrEDTA, assim como o desempenho (tempo total de teste). Em ambas PSs foi observada redução significativa da FG (p 0,01), porém sem diferenciação entre as situações de uso de AINE e Placebo (p=0,235). O desempenho foi impactado negativamente pelo fármaco (p=0,02). Conclusões específicas: em corredores condicionados e atletas, a administração profilática de Ibuprofeno em dose única por via oral possui potencial chance de redução do desempenho por impactar possivelmente a distribuição volêmica ao tecido ativo (efeito associado à redução de hiperemia tecidual e à resposta cronotrópica frente ao exercício). Não restou assegurada sua eficácia analgésica sobre a atenuação do desconforto agudo (gerado pela corrida) ou tardio (gerado por dano prévio) no que tange a relação dor X desempenho. E por fim, a administração de dose única deste Ibuprofeno antes da corrida (nas condições de análise), não potencializa a condição de insuficiência renal aguda gerada pelo próprio exercício. Conclusão geral: O presente modelo experimental indica que o uso do antiinflamatório não-esteroidal Ibuprofeno não apresenta potencialidade de enquadrar-se como doping segundo Código Mundial Antidoping da WADA. / Introduction: Considering that anti-inflammatory drugs are widely used in the athletic community because of their supposed improvement of performance due to their analgesic action, either in the presence of lesion or not, and the numerous reports of the adverse effects associated with this pharmacological class, the aim of the present Doctoral Dissertation was to investigate the possibility of nonsteroidal anti-inflammatory ibuprofen being fit to be considered as doping according to the World Anti-Doping Code of the World Anti-Doping Agency (WADA-COI), by the criteria of ergogeny and risk to health in athletes in long duration run. To that purpose, three randomized, double blind clinical trials were performed. Materials and Methods: In the first trial (laboratory setting), 14 athletes experienced in long duration runs were submitted to 2 progressive tests of running on treadmill with a 72-hour interval between the tests (crossover design), with oral administration of a single dose of 1.2g NSAID or placebo (lactose) before each test. The results showed that the use of NSAID reduced the perceived exertion at the second ventilatory threshold (p 0.01), yet with decreased associated speed (p=0.01) and reduced VO2máx (p=0.04). In the second trial, 20 fit healthy subjects (2x10 subjects), after determination of the speed associated with the second ventilatory threshold, were submitted to a limit time protocol for exhaustion (tlim) in run before and 48h after inducing muscle damage with concentric and eccentric exercises (in isokinetic dynamometer) in the muscle groups of the anterior and posterior thigh compartment. In the second test (postdamage), one group was given a single oral dose of 1.2g NSAID and the other, placebo. The results showed a significant reduction in tlim in both groups (p 0.01), still without attenuation of fall by the NSAID (p=0.55). In the third and last test, 14 athletes performed two 10-km simulated runs (SRs) on track with a 7-day interval. On each day the runners received the same pharmacological treatment as in the previous trials (crossover design) and had their glomerular filtration rate (GFR) monitored by the 51CrEDTA clearance rate technique as well as their performance (total time of test). In both runs a significant reduction in the GFR (p 0.01) was observed, yet with no difference between the situations of using NSAID and placebo (p=0,235). Performance was negatively affected by the drug (p=0,02). Specific conclusions: In experienced, fit runners and athletes, prophylactic Ibuprofen administration in oral single dose is potentially able to reduce performance as it is likely to adversely affect volemic distribution to the active tissue (an effect associated with reduction in tissue hyperemia and chronotropic response resulting from exercise). Its analgesic efficacy on attenuating acute (caused by the run) or late (caused by previous damage) discomfort Is not guaranteed as the pain X performance relation is concerned. Finally, a single dose of Ibuprofen administered before the run (in the conditions investigated here) does not potentialize the acute renal failure condition caused by the exercise itself. General conclusion: The present experimental model indicates that the use of non-steroidal anti-inflammatory Ibuprofen cannot be considered as doping according to the World Anti-Doping Code of the WADA.

Introdução: Devido ao fato dos antiinflamatórios serem amplamente utilizados no meio atlético, da suposta melhora de desempenho pelo efeito analgésico, independentemente da presença ou não de lesão, e, por fim, em razão dos extensos relatos de efeitos adversos associados a esta classe farmacológica, o objetivo da presente Tese Doutoral foi verificar a potencialidade do antiinflamatório não-esteroidal (AINE) Ibuprofeno em enquadrar-se como doping segundo o Código Mundial Antidoping da Agência Mundial Antidoping (WADA-COI), segundo critérios de ergogenia e risco à saúde em atleta em corrida de duração. Para tanto, foram realizados um estudo observacional e três ensaios clínicos, randomizados e duplo-cego. Materiais e Métodos: No primeiro trabalho (laboratorial), 14 atletas especialistas em provas de longa duração realizaram dois testes progressivos de corrida em esteira rolante com 72 horas de intervalo (modelo cruzado), sendo administrada em cada teste dose única e por via oral de 1,2g de AINE ou Placebo (lactose). Os resultados indicaram que o uso de AINE reduziu a percepção de esforço no segundo limiar ventilatório (p 0,01), todavia com diminuição da velocidade associada (p=0,01) e redução do VO2máx (p=0,04). No segundo estudo, 20 sujeitos (2x10 sujeitos) condicionados e saudáveis, após determinação da velocidade associada ao segundo limiar ventilatório, foram submetidos a um protocolo de tempo limite para exaustão (tlim) em corrida antes e 48h após indução de dano muscular com exercícios concêntricos e excêntricos (em dinamômetro isoscinético) nos grupos musculares do compartimento anterior e posterior da coxa. No segundo teste (pós-dano) um grupo recebeu, em dose única e por via oral, 1,2g de AINE e o outro grupo Placebo. Os resultados indicaram redução significativa do tlim em ambos os grupos (p 0,01), contudo sem atenuação de queda pelo AINE (p=0,55). No terceiro e último experimento, 14 atletas realizaram duas provas simuladas (PS) de 10 km em pista com sete dias de intervalo. Em cada dia os sujeitos receberam tratamento farmacológico idêntico aos estudos anteriores (modelo cruzado) tendo sido monitorados a filtragem glomerular (FG) pela técnica de clearance de 51CrEDTA, assim como o desempenho (tempo total de teste). Em ambas PSs foi observada redução significativa da FG (p 0,01), porém sem diferenciação entre as situações de uso de AINE e Placebo (p=0,235). O desempenho foi impactado negativamente pelo fármaco (p=0,02). Conclusões específicas: em corredores condicionados e atletas, a administração profilática de Ibuprofeno em dose única por via oral possui potencial chance de redução do desempenho por impactar possivelmente a distribuição volêmica ao tecido ativo (efeito associado à redução de hiperemia tecidual e à resposta cronotrópica frente ao exercício). Não restou assegurada sua eficácia analgésica sobre a atenuação do desconforto agudo (gerado pela corrida) ou tardio (gerado por dano prévio) no que tange a relação dor X desempenho. E por fim, a administração de dose única deste Ibuprofeno antes da corrida (nas condições de análise), não potencializa a condição de insuficiência renal aguda gerada pelo próprio exercício. Conclusão geral: O presente modelo experimental indica que o uso do antiinflamatório não-esteroidal Ibuprofeno não apresenta potencialidade de enquadrar-se como doping segundo Código Mundial Antidoping da WADA. / Introduction: Considering that anti-inflammatory drugs are widely used in the athletic community because of their supposed improvement of performance due to their analgesic action, either in the presence of lesion or not, and the numerous reports of the adverse effects associated with this pharmacological class, the aim of the present Doctoral Dissertation was to investigate the possibility of nonsteroidal anti-inflammatory ibuprofen being fit to be considered as doping according to the World Anti-Doping Code of the World Anti-Doping Agency (WADA-COI), by the criteria of ergogeny and risk to health in athletes in long duration run. To that purpose, three randomized, double blind clinical trials were performed. Materials and Methods: In the first trial (laboratory setting), 14 athletes experienced in long duration runs were submitted to 2 progressive tests of running on treadmill with a 72-hour interval between the tests (crossover design), with oral administration of a single dose of 1.2g NSAID or placebo (lactose) before each test. The results showed that the use of NSAID reduced the perceived exertion at the second ventilatory threshold (p 0.01), yet with decreased associated speed (p=0.01) and reduced VO2máx (p=0.04). In the second trial, 20 fit healthy subjects (2x10 subjects), after determination of the speed associated with the second ventilatory threshold, were submitted to a limit time protocol for exhaustion (tlim) in run before and 48h after inducing muscle damage with concentric and eccentric exercises (in isokinetic dynamometer) in the muscle groups of the anterior and posterior thigh compartment. In the second test (postdamage), one group was given a single oral dose of 1.2g NSAID and the other, placebo. The results showed a significant reduction in tlim in both groups (p 0.01), still without attenuation of fall by the NSAID (p=0.55). In the third and last test, 14 athletes performed two 10-km simulated runs (SRs) on track with a 7-day interval. On each day the runners received the same pharmacological treatment as in the previous trials (crossover design) and had their glomerular filtration rate (GFR) monitored by the 51CrEDTA clearance rate technique as well as their performance (total time of test). In both runs a significant reduction in the GFR (p 0.01) was observed, yet with no difference between the situations of using NSAID and placebo (p=0,235). Performance was negatively affected by the drug (p=0,02). Specific conclusions: In experienced, fit runners and athletes, prophylactic Ibuprofen administration in oral single dose is potentially able to reduce performance as it is likely to adversely affect volemic distribution to the active tissue (an effect associated with reduction in tissue hyperemia and chronotropic response resulting from exercise). Its analgesic efficacy on attenuating acute (caused by the run) or late (caused by previous damage) discomfort Is not guaranteed as the pain X performance relation is concerned. Finally, a single dose of Ibuprofen administered before the run (in the conditions investigated here) does not potentialize the acute renal failure condition caused by the exercise itself. General conclusion: The present experimental model indicates that the use of non-steroidal anti-inflammatory Ibuprofen cannot be considered as doping according to the World Anti-Doping Code of the WADA.

abstract: Long term high fat diets (HFD) are correlated with the development of diabetes and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats. / Dissertation/Thesis / Masters Thesis Nutrition 2015

Introdução: Devido ao fato dos antiinflamatórios serem amplamente utilizados no meio atlético, da suposta melhora de desempenho pelo efeito analgésico, independentemente da presença ou não de lesão, e, por fim, em razão dos extensos relatos de efeitos adversos associados a esta classe farmacológica, o objetivo da presente Tese Doutoral foi verificar a potencialidade do antiinflamatório não-esteroidal (AINE) Ibuprofeno em enquadrar-se como doping segundo o Código Mundial Antidoping da Agência Mundial Antidoping (WADA-COI), segundo critérios de ergogenia e risco à saúde em atleta em corrida de duração. Para tanto, foram realizados um estudo observacional e três ensaios clínicos, randomizados e duplo-cego. Materiais e Métodos: No primeiro trabalho (laboratorial), 14 atletas especialistas em provas de longa duração realizaram dois testes progressivos de corrida em esteira rolante com 72 horas de intervalo (modelo cruzado), sendo administrada em cada teste dose única e por via oral de 1,2g de AINE ou Placebo (lactose). Os resultados indicaram que o uso de AINE reduziu a percepção de esforço no segundo limiar ventilatório (p 0,01), todavia com diminuição da velocidade associada (p=0,01) e redução do VO2máx (p=0,04). No segundo estudo, 20 sujeitos (2x10 sujeitos) condicionados e saudáveis, após determinação da velocidade associada ao segundo limiar ventilatório, foram submetidos a um protocolo de tempo limite para exaustão (tlim) em corrida antes e 48h após indução de dano muscular com exercícios concêntricos e excêntricos (em dinamômetro isoscinético) nos grupos musculares do compartimento anterior e posterior da coxa. No segundo teste (pós-dano) um grupo recebeu, em dose única e por via oral, 1,2g de AINE e o outro grupo Placebo. Os resultados indicaram redução significativa do tlim em ambos os grupos (p 0,01), contudo sem atenuação de queda pelo AINE (p=0,55). No terceiro e último experimento, 14 atletas realizaram duas provas simuladas (PS) de 10 km em pista com sete dias de intervalo. Em cada dia os sujeitos receberam tratamento farmacológico idêntico aos estudos anteriores (modelo cruzado) tendo sido monitorados a filtragem glomerular (FG) pela técnica de clearance de 51CrEDTA, assim como o desempenho (tempo total de teste). Em ambas PSs foi observada redução significativa da FG (p 0,01), porém sem diferenciação entre as situações de uso de AINE e Placebo (p=0,235). O desempenho foi impactado negativamente pelo fármaco (p=0,02). Conclusões específicas: em corredores condicionados e atletas, a administração profilática de Ibuprofeno em dose única por via oral possui potencial chance de redução do desempenho por impactar possivelmente a distribuição volêmica ao tecido ativo (efeito associado à redução de hiperemia tecidual e à resposta cronotrópica frente ao exercício). Não restou assegurada sua eficácia analgésica sobre a atenuação do desconforto agudo (gerado pela corrida) ou tardio (gerado por dano prévio) no que tange a relação dor X desempenho. E por fim, a administração de dose única deste Ibuprofeno antes da corrida (nas condições de análise), não potencializa a condição de insuficiência renal aguda gerada pelo próprio exercício. Conclusão geral: O presente modelo experimental indica que o uso do antiinflamatório não-esteroidal Ibuprofeno não apresenta potencialidade de enquadrar-se como doping segundo Código Mundial Antidoping da WADA. / Introduction: Considering that anti-inflammatory drugs are widely used in the athletic community because of their supposed improvement of performance due to their analgesic action, either in the presence of lesion or not, and the numerous reports of the adverse effects associated with this pharmacological class, the aim of the present Doctoral Dissertation was to investigate the possibility of nonsteroidal anti-inflammatory ibuprofen being fit to be considered as doping according to the World Anti-Doping Code of the World Anti-Doping Agency (WADA-COI), by the criteria of ergogeny and risk to health in athletes in long duration run. To that purpose, three randomized, double blind clinical trials were performed. Materials and Methods: In the first trial (laboratory setting), 14 athletes experienced in long duration runs were submitted to 2 progressive tests of running on treadmill with a 72-hour interval between the tests (crossover design), with oral administration of a single dose of 1.2g NSAID or placebo (lactose) before each test. The results showed that the use of NSAID reduced the perceived exertion at the second ventilatory threshold (p 0.01), yet with decreased associated speed (p=0.01) and reduced VO2máx (p=0.04). In the second trial, 20 fit healthy subjects (2x10 subjects), after determination of the speed associated with the second ventilatory threshold, were submitted to a limit time protocol for exhaustion (tlim) in run before and 48h after inducing muscle damage with concentric and eccentric exercises (in isokinetic dynamometer) in the muscle groups of the anterior and posterior thigh compartment. In the second test (postdamage), one group was given a single oral dose of 1.2g NSAID and the other, placebo. The results showed a significant reduction in tlim in both groups (p 0.01), still without attenuation of fall by the NSAID (p=0.55). In the third and last test, 14 athletes performed two 10-km simulated runs (SRs) on track with a 7-day interval. On each day the runners received the same pharmacological treatment as in the previous trials (crossover design) and had their glomerular filtration rate (GFR) monitored by the 51CrEDTA clearance rate technique as well as their performance (total time of test). In both runs a significant reduction in the GFR (p 0.01) was observed, yet with no difference between the situations of using NSAID and placebo (p=0,235). Performance was negatively affected by the drug (p=0,02). Specific conclusions: In experienced, fit runners and athletes, prophylactic Ibuprofen administration in oral single dose is potentially able to reduce performance as it is likely to adversely affect volemic distribution to the active tissue (an effect associated with reduction in tissue hyperemia and chronotropic response resulting from exercise). Its analgesic efficacy on attenuating acute (caused by the run) or late (caused by previous damage) discomfort Is not guaranteed as the pain X performance relation is concerned. Finally, a single dose of Ibuprofen administered before the run (in the conditions investigated here) does not potentialize the acute renal failure condition caused by the exercise itself. General conclusion: The present experimental model indicates that the use of non-steroidal anti-inflammatory Ibuprofen cannot be considered as doping according to the World Anti-Doping Code of the WADA.

Orientador: Jose Antonio Rocha Gontijo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T03:40:33Z (GMT). No. of bitstreams: 1 Zapparoli_Adriana_D.pdf: 1386561 bytes, checksum: e5de578f0bd743d6a6096a06e580fa00 (MD5) Previous issue date: 2008 / Resumo: A angiotensina II pode contribuir com o distúrbio do metabolismo renal de sódio presente em ratos espontaneamente hipertensos. Inicialmente, o estudo atentou à possibilidade de envolvimento da expressão do supressor de sinalização de citocinas (SOCS-3) (técnica de Western blotting) em hipotálamo de SHR durante o desenvolvimento hipertensivo (método indireto para medida de pressão arterial). Segundo, pós-estimulação aguda i.c.v com angiotensina II, avaliou a dipsogênese, o ritmo de filtração glomerular (técnica de clearance de creatinina), o manuseio tubular renal de sódio (técnica de clearance de lítio) e potássio em SHR e WKy. Os resultados obtidos confirmaram a estimulação central do receptor de angiotensina II e os seus efeitos dipsogênico e natriurético. A administração i.c.v de angiotensina II diminuiu o clearance de creatinina e, reciprocamente, aumentou a excreção tubular renal de sódio e de potássio nas duas linhagens, porém acentuadamente em WKy. Por outro lado, se comparada à diferença da expressão de JACK-2/SOCS-3 idade-dependente, a alteração da resposta funcional renal pós-estímulo intracerebroventricular com angiotensina II sugere uma disfunção das vias neurais existentes em animais SHR. As evidências supracitadas acrescentam à idéia existente na literatura que, a angiotensina II atuando no sistema nervoso central é um instrumento para regulação da homeostase do fluido corporal. Possivelmente, a resposta neural inapropriada resulte na inabilidade do manuseio hidrossalino e, conseqüentemente, colabore com o desenvolvimento da hipertensão arterial em SHR. Palavras-chave: Hipertensão arterial, SNC, angiotensina II; SOCS-3; SHR; função renal; natriurese; clearance de lítio / Abstract: There is a surprising lack of experimental data on the renal sodium handle mechanisms induced by i.c.v injection of AngII in hypertensive animals. Thus, we hypothesized that a presumable blunted response to centrally injected AngII may contribute to sodium metabolism disturbances observed in SHR. The study was performed after acute i.c.v AngII administration on tubular sodium handling, evaluated by lithium clearance, in conscious, unrestrained rats and their sham-operated appropriate WKy controls. The present series of experiments were also designed to investigate the possible involvement of SOCS-3 expression in AngII-induced control of water ingestion in SHR hypothalamus. Our results confirm earlier reports on the potent natriuretic effects of central AngII receptor stimulation. The i.c.v application of AngII significantly decreased CCr and reciprocally promotes increased absolute and fractional excretion rates of sodium and potassium in both WKy and SHR animals. The magnitude of the renal response to AngII was significantly greater in WKy rats than in SHR. The enhancement of renal function following the centrally applied AngII in WKy rats as compared with SHR associated with age-related difference in JACK-2/SOCS-3 expression suggest that a dysfunction in the angiotensin neural pathways exists in SHR. Our findings lend further support to the idea that AngII in CNS is an instrumental in the regulation of body fluid homeostasis. Speculatively, it seems interesting to suggest that perhaps one of the CNS inappropriate AngII pathway response defects may result in inability of renal tubules to handle the hydrosaline balance, consequently may contributing with development of arterial hypertension in genetically hypertensive rats from Kyoto. Keywords: Arterial hypertension; central nervous system; angiotensin II; SOCS-3, SHR, kidney function; natriuresis; lithium clearance / Doutorado / Doutor em Farmacologia

There is an epidemic of chronic kidney disease of unknown origin (CKDu) primarily affecting younger men in Central America, especially El Salvador and Nicaragua. The primary hypothesis has included heat stress and dehydration. Although medication usage is widely viewed as a likely contributor to kidney damage, the association with chronic kidney disease in Central America has not been fully explored. This study investigated medication usage, symptom presentation, and kidney function among 524 outdoor workers in agricultural and non-agricultural industries enrolled in the Mesoamerican Nephropathy Occupational Study (MANOS) led by Boston University researchers. An overview of the literature on the adverse effects of medication on renal function and thermoregulation, with a focus on medications considered in MANOS, was conducted. Medication usage and symptom presentation on both a short- and long-term timeframe were explored in relation to kidney function measured by estimated glomerular filtration rate. Long-term usage of NSAIDS and potassium supplements was significantly associated with kidney function. Neither short- or long-term uses of acetaminophen, the most commonly used medication, were associated with kidney function. While several self-reported health symptoms were significantly associated with lower kidney function in crude models, the associations’ significance levels lessened after adjusting for age, country, and industry. In contrast, symptoms of chistata (a local term for painful urination) and lower abdominal pain three months prior to data collection each significantly predicted higher kidney function. The results of this exploratory, cross-sectional study present an opportunity for further study on how medications and symptoms, related to both nephrotoxicity and heat stress, could be associated with kidney function.

Background: There is a 3-fold risk of developing end stage kidney disease in Non-Hispanic African Americans compared to Non-Hispanic White Americans (Centers for Disease Control and Prevention, 2017). Estimated glomerular filtration rate (eGFR), one of the fundamental algorithms for coordinating treatment for kidney disease which factors in age, race, gender, and levels of creatinine, may pose an issue in this vulnerable population. Currently African Americans receive a correction factor between 1.21 and 1.16 to their eGFR to adjusting the value higher, potentially impacting appropriate kidney disease classification, and delaying beneficial interventions (National Kidney Foundation, 2020). Methods: A systematic literature search of four databases was completed. Eligibility criteria included 1) published in a peer reviewed journal, 2) English language, 3) the use of race correction in calculating eGFR, and 4) a quantitative study design. A total of 47 articles were screened with 17 selected for final review. The Johns-Hopkins Nursing Evidence - Based Practice evidence guide was then used to rate the strength and quality of the evidence. Results: Early evidence of the unreliability of race based eGFR equations emerged in 2008, and the body of evidence continues to grow. Recent studies have found eGFR calculated with no race corrections correlate best with directly measured iothalmate GFR in black patients (Zelnick et al., 2021), and that a potential 1,066,026 Black Americans may be reclassified to a more severe stage of CKD (Bragg-Gresham et al., 2021). Use of the race correction in GFR equations has been poorly supported in studies conducted in Africa and Brazil. For those with HIV, an accurate eGFR is doubly important yet all eGFR equations have marked variability. Some medical facilities have successfully updated to calculating eGFR without the racial coefficient (Shi et al., 2021). Conclusion: Nurses should be aware of the implications of using race correction in eGFR equations, educate their patients on its use, and advocate for those near threshold targets to ensure equitable and timely access to appropriate kidney disease interventions.

Yes / Background: Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft–Gault) gives a more accurate estimate of kidney function. Aim: To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. Design and setting: A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. Method: The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft–Gault) was calculated using actual body weight and estimated ideal body weight. Results: Kidney function was too low for recommended prescribing in 4–40% of people aged ≥65 years, and in 24–80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3–28% of those aged ≥65 years, and for 13–58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Conclusion: Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft–Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced.

Orientador : Jose Antonio Rocha Gontijo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T14:12:40Z (GMT). No. of bitstreams: 1 Oliveira_PauloCesarde_D.pdf: 2188887 bytes, checksum: 309e674186fe399fd0cfec935fee1d78 (MD5) Previous issue date: 2009 / Resumo: No presente estudo, foi investigado os efeitos da administração intracerebroventricular (i.c.v) aguda de insulina sobre os mecanismos centrais responsáveis pela regulação da excreção tubular renal de sódio após injeção prévia de NG-nitro-1-arginine methylester (LNAME) em ratos não anestesiados. Ratos Wistar-Hannover Masculinos foram radomizados em cinco grupos: a) injeção i.c.v. de 0.15 M de NaCl em ratos (controle, N = 10), b) injeção i.c.v. de dose-resposta (1.26, 12.6 e 126 ng/3µL) em ratos (N = 10), c) Injeção i.c.v. de 60µg de L-NAME associada com NaCl (N = 10) ou d) com insulina 126ng (N = 10), e e) Injeção de insulina subcutânea em ratos (N = 5). A insulina injetada centralmente no ventrículo lateral direito de ratos promoveu uma elevação da excreção urinária de sódio (NaCl: 855.6 ± 85.1?%/min; 126 ng de insulina: 2055 ± 310.6?%/min; P = 0.005) e potássio (NaCl: 460.4 ± 100?%/min; 126ng insulina: 669.2 ± 60.8?%/min; P = 0.025). A excreção urinaria de sódio elevada observada após a microinjeção i.c.v. de 126 ng de insulina foi atenuada significativamente com administração prévia de L-NAME (126 ng insulina: 1935 ± 258.3?%/min; L-NAME + 126 ng de insulina do: 582.3 ± 69.6?%/min; P = 0.01). A natriurese induzida pela insulina i.c.v. ocorreu através da elevação da excreção tubular renal de sódio nos segmentos pós-proximais, a despeito de uma filtração glomerular inalterada. Embora o racional para a redução da excreção urinária de sódio induzida pela prévia administração i.c.v. de L-NAME seguida da administração de insulina i.c.v. permanece ainda desconhecida, podemos sugerir que um dos gatilhos responsáveis pela sinalização eferente da insulina no SNC possa ser de natureza nitrérgica / Abstract: In the present study, we investigated the effects of acute intracerebroventricular (icv) insulin administration on central mechanisms regulating urinary sodium excretion in simultaneously centrally NG-nitro-L-arginine methylester (L-NAME)-injected unanesthetized rats. Male Wistar-Hannover rats were randomly assigned to one of five groups: a) icv 0.15 M NaCl-injected rats (control, N = 10), b) icv dose-response (1.26, 12.6 and 126 ng/3 µL) insulin-injected rats (N = 10), c) rats icv injected with 60 µg L-NAME in combination with NaCl (N = 10) or d) with insulin (N = 10), and e) subcutaneously insulininjected rats (N = 5). Centrally administered insulin produced an increase in urinary output of sodium (NaCl: 855.6 ± 85.1 ?%/min; 126 ng insulin: 2055 ± 310.6 ?%/min; P = 0.005) and potassium (NaCl: 460.4 ± 100 ?%/min; 126 ng insulin: 669.2 ± 60.8 ?%/min; P = 0.025). The urinary sodium excretion response to icv 126 ng insulin microinjection was significantly attenuated by combined administration of L-NAME (126 ng insulin: 1935 ± 258.3 ?%/min; L-NAME + 126 ng insulin: 582.3 ± 69.6 ?%/min; P = 0.01). Insulin induced natriuresis occurred by increasing post-proximal sodium excretion, despite an unchanged glomerular filtration rate. Although the rationale for decreased urinary sodium excretion induced by combined icv L-NAME and insulin administration is unknown, it is tempting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature / Doutorado / Clinica Medica / Doutor em Clínica Médica