INTRODUÇÃO: A nefrite lúpica é uma complicação frequente e de alta morbimortalidade do lúpus eritematoso sistêmico (LES). A evolução para insuficiência renal crônica terminal varia entre 8 e 15% dos casos, após um período de 5 anos. A fase inicial da nefrite se deve a uma atividade imunológica exacerbada que leva a sequelas renais, como a fibrose intersticial, sinéquias glomerulares, e glomeruloesclerose. Uma vez instalada, vários fatores aceleram a velocidade de progressão da insuficiência renal, como a presença de proteinúria residual, hipertensão arterial sistêmica e a etnia do paciente. Estudos recentes mostraram que a presença de polimorfismos do MYH9 são altamente prevalentes em pacientes com GESF (glomeruloesclerose focal e segmentar), nefropatia do HIV e em pacientes com doença renal crônica não diabética. Os polimorfismos do MYH9 mais relacionados com essas doenças são os do haplótipo E1, causados pelos polimorfismos rs4821480, rs2032487, rs4821481 e rs3752462, presentes principalmente na população negra e de hispano-americanos. No Brasil não há estudos sobre a prevalência desse gene. MÉTODOS: Nosso estudo analisou retrospectivamente 196 pacientes com nefrite lúpica, acompanhadas no ambulatório de glomerulopatias do Hospital das Clínicas da USP. Foram recuperados os dados clínicos e laboratoriais dos pacientes de janeiro de 1999 a dezembro de 2010. Foi feita análise dos polimorfismos do haplótipo E1 do gene do MYH9 (rs4821480, rs2032487, rs4821481 e rs3752462) e correlacionados com suas características clínicas e laboratoriais, apresentando como desfecho a duplicação da creatinina ou a evolução para doença renal crônica terminal. RESULTADOS: O tempo de seguimento médio dos pacientes foi de 6,1 anos, com a creatinina inicial média de 1,6 g/dL e proteinúria média de 3,9 g/dia. Dezenove pacientes não recuperaram função renal, mantendo-se em diálise. Dos 177 pacientes restantes 43 (24%) apresentaram o desfecho de duplicação (DC) da creatinina, ou necessidade de diálise (DRCT). Pacientes progressores eram tinham maior SLEDAI renal (10 vs 8,9 p=0,04), maior índice de cronicidade renal à biópsia (5 vs 2, p<0,001) e maior frequência de reativações da doença renal (flare renal) (82,9% x 53,8%, p=0,002), assim menores índices de remissão completa ou parcial (p<0,0001). Os 4 polimorfismos se segregam em conjunto, ou seja, como um haplótipo, pelo modelo de Hardy-Weinberg. Analisando separadamente cada polimorfismo, apenas o rs3752462, apresenta associação com o desfecho DC/DRCT, na análise por genótipo (CC/CT/TT, p=0,03) e quando feita análise TT/CT vs CC (p=0,02). Não houve relação dos polimorfismos com a etnia negra ou parda. Pacientes com haplótipo E1 eram progressores em 28% dos casos, conferindo um OR de 1,79 (IC 1,02 a 3,0) de DC/DRC. DISCUSSÃO: A presença do haplótipo E1 têm alta prevalência em pacientes portadores de nefrite lúpica no Brasil, sendo fator de risco para progressão da doença renal crônica / BACKGROUND: Lupus nephritis (LN) is a frequent complication with high morbidity and mortality of systemic lupus erythematosus (SLE). Chronic renal failure is observed in 8 to 15% of the patients after 5 years of follow up. LN is an inflammatory disease after a systemic autoimmune activation. Once inflammation is shutdown several renal and nonrenal factors, such as residual proteinuria, hypertension and ethnicity of the patient, may emerge and impose to the kidney a chronic phenotype (interstitial fibrosis, glomerular adhesions and glomerulosclerosis. Recently E1 haplotype (rs4821480, rs2032487, rs4821481 and rs3752462 polymorphisms) of the MYH9 gene was associated to progressive kidney diseases in patients with FSGS (focal segmental glomerulosclerosis), HIV nephropathy and non-diabetic chronic kidney disease, in african american and spanic american patients. In Brazil there is no data on this subject. METHODS: Retrospective analysis of 196 patients with LN followed in our outpatient glomerular disease ward were enrolled glomerulopathies. Patients clinical data from January 1999 to December 2010 were retrieved and MYH9 rs4821480, rs2032487, rs4821481 and rs3752462 polymorphisms were genotyped. Outcome was defined as doubling of serum creatinine, or end stage renal disease (ESRD). RESULTS: The mean follow-up of patients was 6.1 years, with an initial mean creatinine of 1.6 g/dL and mean proteinuria 3.9 g/day. On enrollment nineteen patients were on dialysis and did not recover renal function, they were withdraw from analyses of progressive kidney disease. On follow up, from 177 remaining patients, 43 (24%) showed the composite outcome: dialysis, or doubling creatinine. Progressors had higher renal SLEDAI (10 vs 8.9, p = 0.04), higher chronicity index at biopsy (5 vs 2, p <0.001) and more frequently renal flares (82, 9% vs. 53.8%, p=0.002), as well as lower rates of complete or partial remission (p <0.0001). The four polymorphisms segregate as a haplotype, according the Hardy-Weinberg model. Analysing each polymorphism, only TT/CT genotype from rs3752462 polymorphism was associated with the outcome of DC/ESRD (p = 0.02). E1 haplotype were associated with progression with an OR of 1.79 (CI 1.02 to 3.0). DISCUSSION: The presence of the E1 haplotype is associated with worse prognosis of chronic renal failure in lupus nephritis patients

Introdução: Não há estudos que avaliem o impacto da reutilização do dialisador na remoção de solutos em sessões de hemodiafiltração online curta diária (HDF-OL-D). Objetivo: Avaliar o impacto do reuso do dialisador na dose do tratamento, na cinética de beta2-microglobulina e na extração de solutos em sessões de HDF-OL-D e comparar com sessões de hemodiálise curta diária de alto fluxo (HD-D). Métodos: Foram incluídos 14 pacientes do programa de HD-D. Foram coletadas amostras de sangue pré, no meio e pós-diálise e amostras do dialisato no 1º, 7º e 13º usos do dialisador em sessões de HD-D e de HDF-OL-D. Resultados: A massa total extraída (MTDQ) e a depuração (KDQ) diretamente quantificada dos solutos pequenos (ureia, fósforo, creatinina e ácido úrico), bem como a dose de diálise ofertada, foram semelhantes quando o 1º, 7º e 13º usos do dialisador em sessões de HD-D foram comparados, respectivamente, ao 1º, 7º e 13º usos em sessões de HDF-OL-D. A MTDQ e a KDQ dos solutos pequenos e a dose de diálise foram semelhantes entre os usos do dialisador tanto em sessões de HD-D e quanto em sessões de HDF-OL-D. A MTDQ, a KDQ e o Kt/V diretamente quantificado (Kt/VDQ) de beta2-microglobulina foram maiores em sessões de HDF-OL-D do que nos respectivos usos do dialisador em sessões de HD-D. Não houve diferença quanto à cinética de beta2-microglobulina, avaliada pela MTDQ, KDQ ou Kt/VDQ, entre o 1º, 7º e 13º usos do dialisador em sessões de HD-D nem em sessões de HDF-OL-D. Na HDF-OL-D, a perda intradialítica de albumina foi significativamente diferente entre os usos do dialisador (p < 0,001), estando reduzida no 7º e 13º usos, quando comparados ao 1º uso do dialisador. Não houve correlação entre o volume de enchimento do dialisador e a MTDQ e a KDQ de moléculas pequenas em nenhum dos métodos dialíticos estudados. Em sessões de HDF-OL-D, foi observada uma correlação fraca entre o volume de enchimento do dialisador e a KDQ de beta2-microglobulina, não percebida com a MTDQ ou o Kt/VDQ de beta2-microglobulina. Conclusão: O reprocessamento de dialisadores de alto fluxo e alta eficiência não resulta em comprometimento da dose do tratamento, da cinética de beta2-microglobulina nem da extração de solutos em sessões de HDF-OL-D. A extração de beta2-microglobulina foi maior em sessões de HDF-OL-D do que em sessões de HD-D, sem diferenças significativas na remoção dos demais solutos. O reprocessamento do filtro, em sessões de HDF-OL-D, resultou numa redução significativa da perda intradialítica de albumina. Não parece haver influência do volume de enchimento do filtro na extração de solutos em nenhum dos métodos de diálise estudados / Introduction: There no studies evaluating the impact of dialyzer reutilization on solute removal in daily online hemodiafiltration (D-OL-HDF) sessions. Objectives: Our aim was to evaluate the impact of dialyzer reuse on solute extraction, beta2-microglobulin kinetics and dialysis dose in D-OL-HDF and compare to those in high-flux short daily hemodialysis (D-HD). Methods: 14 patients undergoing a D-HD program were included. Pre, middle and post-dialysis blood samples and effluent dialysate were collected in the 1st, 7th and 13th dialyzer uses in D-HD sessions and in D-OL-HDF sessions. Results: Directly quantified small solute (urea, phosphorus, creatinine and uric acid) total mass removal (TMDQ) and clearance (KDQ), as well as dialysis dosis, were similar when the 1st, 7th and 13th dialyzer D-HD uses were compared to the 1st, 7th and 13th D-OL-HDF uses. TMDQ and KDQ of small solutes and dialysis dose were similar among dialyzer uses in D-HD sessions and also in D-OL-HDF sessions. beta2-microglobulin TMDQ, KDQ and directly quantified Kt/V (Kt/VDQ) were statistically higher in D-OL-HDF dialyzer uses than in the respective D-HD uses. There was no difference in beta2-microglobulin kinetics, evaluated by TMDQ, KDQ or Kt/VDQ, among 1st, 7th and 13th uses in D-OL-HDF sessions or in D-HD sessions. In D-OL-HDF, albumin loss was significantly different among studied dialyzer uses (p < 0.001), being reduced in the 7th and 13th dialyzer uses, when compared to the first use. There was no correlation between dialyzer priming volume and small molecules TMDQ, KDQ in neither analyzed dialytic method. In D-OL-HDF sessions, it was observed a week correlation between dialyzer priming volume and beta2-microglobulin KDQ, not observed with beta2-microglobulin MTDQ or Kt/VDQ. Conclusion: High flux, high efficiency dialyzer reprocessing did not did result in a reduction of the offered dialysis dose, beta2-microglobulin kinetics or solute extraction in D-OL-HDF. beta2-microglobulin removal was greater in D-OL-HDF than in D-HD sessions, without difference in other solutes extraction. There was a significant reduction in intradialytic albumin loss with dialyzer reprocessing in D-OL-HDF sessions. Dialyzer priming volume does not appear to influence solute removal in neither analyzed dialytic method

Complicações renais e urológicas incluindo nefrolitíase, cristalúria, cólica renal e lombalgia, são eventos adversos bem conhecidos do indinavir (IDV), um inibidor de protease (IP) largamente utilizado no tratamento de pacientes infectados com o vírus da imunodeficiência humana (HIV). Prévios estudos em ratos demonstraram que o IDV, um potente IP capaz de provocar uma sustentada supressão da carga viral do HIV, induz vasoconstricção renal, diminui a filtração glomerular (RFG) e reduz a excreção urinária de nitrito (NO2-), sugerindo que a vasoconstricção causada pelo IDV deve ser mediada pelo óxido nítrico (NO). Os objetivos deste estudo foram investigar a ocorrência de insuficiência renal (clearance de creatinina < 80ml/min) em pacientes com infecção pelo HIV tratados com terapia anti-retroviral altamente potente incluindo o inibidor de protease IDV, e mensurar a excreção urinária de nitrato (NO3-) nestes pacientes, comparando-os com outro grupo de pacientes tratados com efavirenz (EFV), um inibidor de transcriptase reversa não-análogo de nucleosídeo (NNRTI). No período compreendido entre março de 2000 e outubro de 2003, estudamos 36 pacientes infectados pelo HIV que estavam em terapia com IDV na dose de 800 mg de 8/8 horas por pelo menos 12 meses. Os pacientes foram avaliados para uma variedade de parâmetros clínicos e laboratoriais: idade, peso, tempo de infecção, tempo de uso de IDV, uso de sulfametoxazol-trimetoprim (SMX-TMP) ou sulfadiazina, exames bioquímicos (colesterol total, triglicérides, magnésio, sódio, potássio e creatinina), exame do sedimento urinário, clearance de creatinina, osmolaridade urinária, volume urinário de 24 h, fração de excreção de sódio (FENa), fração de excreção de potássio (FEK) e fração de excreção de água (FEH2O). NO3 urinário foi mensurado em 18 pacientes recebendo terapia anti-retroviral com IDV e 8 pacientes recebendo terapia com EFV. Leucocitúria ocorreu em 78.8% dos pacientes tratados com IDV. Clearance de creatinina diminuído foi observado em 21 pacientes e foi associado com menor peso e uso de derivados de sulfa. Nestes pacientes com diminuição da função renal, também detectamos menor osmolaridade urinária e uma FEH2O mais alta. A excreção urinária de NO3- foi significativamente menor nos pacientes tratados com IDV (908 ± 181) quando comparados aos pacientes do grupo EFV (2247 ± 648, p<0.01). Nossos resultados mostram que insuficiência renal ocorreu em 58% dos pacientes tratados com IDV e foi associada com menor peso corpóreo e uso de derivados de sulfa. A menor excreção urinária de NO3- e as alterações na osmolaridade e FEH2O sugerem que o IDV diminui a produção de óxido nítrico e causa dano tubular, respectivamente. Sugerimos então que os pacientes em uso de IDV sejam monitorados routineiramente para função renal através do clearance de creatinina. / Renal and urological complications including nephrolithiasis, crystalluria, renal colic and flank pain are significant side effects of the HIV protease inhibitor indinavir (IDV), and IDV has been widely used in the treatment of human immunodeficiency virus (HIV) infection. Previous studies in rats demonstrated that IDV, a potent protease inhibitor that causes profound and sustained supression of HIV replication, also induces renal vasoconstriction, decreases glomerular filtration rate (GFR) and reduces urinary excretion of nitrite (NO2-), suggesting that IDV-vasoconstriction may be mediated by nitric oxide (NO). The objectives of this study were to investigate the occurrence of renal failure (creatinine clearance <80ml/min) in human HIV patients treated with highy active antiretroviral therapy (HAART), including IDV, and to measure urinary excretion of nitrate (NO3-) in those patients, comparing it with that of another group of patients treated with the non-nucleoside reverse-transcriptase inhibitor efavirenz (EFV). From March 2000 through October 2003, we evaluated 36 patients infected with HIV who was receiving IDV 800 mg q8h for at least 12 months. The patients were assessed for a variety of clinical and laboratory parameters including age, body weight, duration of infection, time of IDV treatment, trimethoprim/sulfamethoxazole (TMP/SMX) or sulfadiazine use, biochemistry (total cholesterol, triglycerides, magnesium, sodium, potassium and creatinine), urinalysis, creatinine clearance, urine osmolality, 24-hour urine volume, fractional excretion of sodium (FENa), potassium (FEK) and water (FEH2O). Urinary NO3 was measured in 18 IDV-treated patients and compared with that of 8 EFV-treated patients. Leukocyturia occurred in 78.8% of the IDV-treated patients. Reduced creatinine clearance was observed in 21 patients and was associated with lower body weight and sulfa-derivated use. In these renal failure patients, we also detected a lower osmolality and a higher FEH2O. Excretion of NO3- was significantly lower in IDV-treated patients (908 ± 181) than in EFV-treated patients (2247 ± 648, p<0.01). Our data show that renal failure occurred in 58% of IDV-treated patients and was associated with lower body weight and sulfa administration. The lower NO3- excretion suggests that this drug decreases nitric oxide production, and the alterations in osmolality and FEH2O indicate that it also causes tubular damage. Based on our findings, we suggest that the renal function of patients under IDV treatment should be closely monitored with creatinine clearance.

Made available in DSpace on 2016-01-26T12:51:24Z (GMT). No. of bitstreams: 1 fernandonestor_tese.pdf: 1042593 bytes, checksum: af0a555c2adb2f553fd7214a6ca2774b (MD5) Previous issue date: 2006-03-14 / The aim of the present study was to investigate the effects of the use of the anti-inflammatory protein annexin 1 (Anx-A1), which is found in most cells. It is characterized by its ability in binding to calcium and phospholipids, conferring protection against the initial effects of ischemia-reperfusion injury. Right nephrectomy was performed on 48 adult males Wistar rat, with sizes ranging between 250-300 g, maintained on a diet normosodic , normoprotein and with water ad libitum. The animals was divided into 3 groups: Annexin-1/Ischemia (Anx-A1-I/R) (n=16), vehicle (PBS40)-Ischemia (Vehicle-I/R) (n=16) and Sham Group (n=16). The endovenous administration of Anx-A1 was made 30 minutes before ischemia of the left renal artery. The animals of each group were divided and studied at 2 and 7 days post-reperfusion, in respect to the glomerular, tubular and renal structure functions. The results showed that there was a reduction in the glomerular filtration rate (GFR) in the Vehicle-I/R Groups at 2 and 7 days post-reperfusion (0.42 ± 0.02 mL/min-100g and 0.48 ± 0.05 mL/min-100g, respectively). There was a significantly greater filtration rate in the Anx-A1-I/R Groups compared to the Vehicle-I/R Groups (0.86 ± 0.05 mL/min-100g and 0.73 ± 0.04 mL/min-100g, respectively). A significant difference between the Anx-A1-I/R and Sham Groups (p-value < 0.01) was also observed (7days). The fractional sodium excretion (FeNa) was significantly higher in the Vehicle-I/R Groups when compared to the Anx-A1-I/R and Sham Groups on the 2nd and 7th post-perfusion days. On the 2nd day of the study, the fractional sodium excretion was 0.17 ± 0.01% for the Anx-A1-I/R, 0.42 ± 0.03% for the Vehicle-I/R and 0.21 ± 0.01% for the Sham groups (p-value < 0.001). On the 7th day, the values were 0.27 ± 0.03%, 0.52 ± 0.03% and 0.29 ± 0.01%, respectively (p-value < 0.001). The potassium excretion fraction (FeK) on the 2nd and 7th post-perfusion days did not differentiate between the Anx-A1-I/R and Sham Groups, but it was significantly higher in the Vehicle-I/R Groups. The urinary-plasmatic osmolality ratio (U/Posm) showed a significant reduction in the Vehicle-I/R Groups after 2 and 7 days when compared with the Anx-A1-I/R and Sham Groups. A histopathologic evaluation of renal cortex samples, taken on the 2nd and 7th post-perfusion days, revealed a significant increase in the intravascular and transmigrated neutrophils in ischemic areas of the Vehicle-I/R Groups. Additionally, high rates of transmigrated neutrophils were identified in the ischemia-reperfusion areas of samples of renal medulla from the Vehicle-I/R Group taken on the 2nd and 7th days. There was a significant reduction of the neutrophil transmigration in samples of renal medulla on the 2nd and 7th post-perfusion days in the Anx-A1-I/R Groups, as well as a lower intravascular neutrophil rate. On the 2nd and 7th post-perfusion days, the Sham Group presented with structures of distal and proximal convoluted tubules and well-preserved brush-border structures in the renal cortex and medulla samples as seen by light microscopy. Similar results were evidenced in the Anx-A1-I/R Groups with preserved structures in the tubules, basal membrane and glomeruli. In the Vehicle-IR Groups, numerous monocytes, cellular debris inside proximal convoluted tubules, dilated capillaries and alterations in the basal membrane structure were seen. These results suggest that the administration of annexin-1 thirty minutes before renal ischemia in rat , prevents the transmigration of neutrophils and confers protection against the initial effects of ischemia-reperfusion injury, as well as providing protection to the glomerular, tubular and renal structure functions. / O presente estudo objetivou investigar os efeitos do uso da anexina 1 (Anx-A1), considerada proteína antiinflamatória e que está presente na maioria das células. Caracteriza-se pela sua habilidade em ligar-se ao cálcio e fosfolipídeos, conferindo proteção contra os efeitos iniciais da lesão por isquemia e reperfusão. Realizou-se nefrectomia à direita em 48 ratos (Wistar-adultos-machos), pesando entre 250-300 gramas, mantidos com dieta normosódica , normoprotéica e água ad libitum. Os animais foram divididos em 3 grupos: Anexina 1-Isquemia (Anx-A1-I/R) (n=16), Veículo(PBS-40)-Isquemia (Veic-I/R) (n=16) e grupo Sham (n=16). A administração de anexina1 endovenosa foi realizada 30 minutos antes do clampeamento da artéria renal esquerda. Após reperfusão, os animais de cada grupo foram divididos e estudados com 2 e 7 dias, quanto às funções glomerulares , tubulares e à estrutura renal. Os resultados mostraram que houve redução da taxa de filtração glomerular (RFG) nos grupos veículo-I/R com 2 e 7 dias de experimento (0,42 ± 0,02 ml-min-100g e 0,48 ± 0,05 ml-min-100g, respectivamente) e verificamos aumento significativo da taxa de filtração glomerular nos grupos Anx-A1-I/R comparados aos grupos veículo-I/R (0,86 ± 0,05ml-min-100g e 0,73 ± 0,04ml-min-100g, respectivamente). Observou-se diferença significativa entre os grupos Anx-A1-I/R e Sham com 7 dias (p<0,01). A excreção fracional de sódio (FeNa) apresentou-se significantemente aumentada nos grupos veículo-I/R, comparada aos grupos Anx-A1-I/R e Sham nos 2º e 7º dias de experimento; apresentando assim no 2º dia de estudo,Anx-A1-I/R (0,17 ± 0,01%), Veic-I/R (0,42 ± 0,03%) e Sham (0,21 ± 0,01%) (p<0,001); e no 7º dia, Anx-A1-I/R (0,27 ± 0,03%), Veic-I/R (0,52 ± 0,03%) e Sham (0,29 ± 0,01%) (p<0,001). A fração de excreção de potássio (FeK) com 2 e 7 dias de experimento não diferiram entre os grupos Anx-A1-I/R e Sham, mas a FeK aumentou significativamente nos grupos Veic-IR. A razão das osmolalidades urinário-plasmáticas (U/Posm) mostraram uma redução importante nos grupos Veic-I/R em experimentos com 2 e 7 dias, comparados aos grupos Anx-A1-I/R e Sham. A avaliação histopatológica revelou aumento significativo de neutrófilos intravasculares e transmigrados, em áreas isquêmicas dos grupos Veic-I/R, de amostras avaliadas da porção do córtex renal com 2 e 7 dias. Verificaram-se altas taxas de transmigração de neutrófilos nas áreas de isquemia-reperfusão nos grupos Veic-I/R com 2 e 7 dias, em amostras avaliadas de medula renal. Houve significativa redução do extravasamento de neutrófilos em análise quantitativa, nas amostras de medula renal com 2 e 7 dias de estudo, nos grupos anexina 1-I/R, bem como menor taxa de neutrófilos no espaço intravascular. À microscopia de luz, verificou-se que, em amostras de córtex e medula renal, com 2 e 7 dias, o grupo Sham apresentou estruturas dos túbulos contorcidos proximais, distais e borda em escova bem preservados. Notou-se resultados semelhantes nos grupos de anexina1-I/R, com estruturas preservadas nos túbulos, membrana basal e glomérulos. Nos grupos Veic-I/R, verificou-se a presença de debris celulares no interior de túbulos contorcidos proximais, capilares dilatados e alterações na estrutura da membrana basal. Estes resultados sugerem que a administração da anexina1, trinta minutos antes da isquemia renal em ratos, previne a transmigração de neutrófilos e confere proteção contra os efeitos iniciais da lesão por isquemia e reperfusão, bem como proteção das funções glomerulares, tubulares e da estrutura renal.

Made available in DSpace on 2011-05-04T12:36:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2009 / O objetivo deste estudo foi realizar uma análise de custo-efetividade de propostas para o adiamento da fase terminal da doença renal crônica (ADRC) associada à hipertensão arterial e ao diabetes mellitus no contexto nacional, sob a perspectiva do Sistema Único de Saúde. Dentre as possibilidades de manejo da doença analisadas constam a experiência do ambulatório de DRC da Universidade do Estado do Rio de Janeiro e aabordagem clínica tradicional, representada pela atenção fornecida hoje pelo SUS. As alternativas estudadas foram: Tratamento Tradicional do SUS com o uso de Inibidor da enzima conversora de angiotensina (IECA) para o controle da pressão arterial; ADRC 1, representado pelo Programa de ADRC da UERJ; ADRC 2, como uma proposta de programa de ADRC de acordo com as diretrizes clínicas incluindo o uso do ARA II; ADRC 3, como uma proposta de programa de ADRC de acordo com as diretrizes clínicas incluindo com o uso de estatina; ADRC 4 como uma proposta de ADRC completa incluindo o uso de ARA II e estatina . O ADRC UERJ foi uma alternativa avaliada como um referencial para o SUS de um programa que oferece cuidado integral ao paciente portador de DRC com abordagem multiciplinar. Os resultados mostraram que pacientes com nefropatia diabética no SUS, teriam uma expectativa de vida aproximada de 6,66 anos, enquanto que na UERJ a expectativa de vida seria de 11,56 anos. As alternativas ADRC 3 e ADRC 4 proporcionariam uma expectativa de vida de cerca de 16 anos, e 10 QALYS extras com relação ao SUS. Ao relacionar as dimensões custo e efetividade aplicando-se uma taxa de desconto de 5 por cento ao ano, verificou-se que a alternativa mais vantajosa foi o ADRC 3, apresentando economia da ordem de R$ 10.525,27 com relação ao SUS para cada ano adicional sobre a expectativa de vida, isto porque os pacientes prescindiriam de hemodiálise. A conclusão deste estudo é de que a simples disponibilização de medicamentos de eficácia reconhecida para o ADRC não é suficiente como estratégia para o cuidado adequado aos pacientes portadores de DRC no âmbito do SUS, mas que é fundamental a implementação efetiva das práticas já definidas pelo Ministério da Saúde para o manejo clínico dos pacientes. / The objective of this study was to estimate the cost-effectiveness for some alternatives of Conservative Management of Chronic Kidney Disease (CKD) related to hypertension and diabetes mellitus under Brazilian Public Health System (SUS) perspective. These options include an experience of a conservative management based on a multidisciplinary approach performed by the University of Rio de Janeiro (UERJ) and the current practice that have been carried out in SUS. The point was to evaluate both, benefits and incremental costs that would result from a full coverage of technologies that are not still largely available in brazilian primary care, like Angiotensin II-Receptor Antagonists (ARA II) and Statins. The alternatives assessed were: Current practice in SUS including Angiotensin-converting enzyme (ACE) inhibitors to treat hypertension; ADRC 1 represented by UERJ Program; ADRC 2 as a hypothetical program based on current guidelines, including the prescription of statins; ADRC 3 as a hypothetical program based on current guidelines, including the prescription of ARA II; and ADRC 4 as a hypothetical program based on current guidelines, including the prescription of ARA II and statins. The UERJ program was an alternative evaluated as a reference to SUS and as an example of a clinical management that offers a whole care to their CKD patients with a multidisciplinary team support. Results showed that SUS patients with diabetic nephropahy have a life expectancy of 6,66 years while UERJ patients have 11,56 years. Both alternatives ADRC 3 and 4, increase the SUS quality-adjusted life expectancy in about 10 years. The results of cost-effectiveness ratios discounted at 5% a.a. showed that the dominant strategy was ADRC 3 indicating costs savings of R$ 10.525,27 for each year of life added compared to SUS. This occurs because in this alternative patients would not need hemodialysis during their lifetime. The conclusion is that, the addition of new drugs with efficacy evidence is not a sufficient strategy to provide an adequate management of CKD patients in SUS. Instead of it, it is essential the effective implementation of the practices that are already defined by the Ministry of Health for the manegement of CKD patients.

Complicações renais e urológicas incluindo nefrolitíase, cristalúria, cólica renal e lombalgia, são eventos adversos bem conhecidos do indinavir (IDV), um inibidor de protease (IP) largamente utilizado no tratamento de pacientes infectados com o vírus da imunodeficiência humana (HIV). Prévios estudos em ratos demonstraram que o IDV, um potente IP capaz de provocar uma sustentada supressão da carga viral do HIV, induz vasoconstricção renal, diminui a filtração glomerular (RFG) e reduz a excreção urinária de nitrito (NO2-), sugerindo que a vasoconstricção causada pelo IDV deve ser mediada pelo óxido nítrico (NO). Os objetivos deste estudo foram investigar a ocorrência de insuficiência renal (clearance de creatinina < 80ml/min) em pacientes com infecção pelo HIV tratados com terapia anti-retroviral altamente potente incluindo o inibidor de protease IDV, e mensurar a excreção urinária de nitrato (NO3-) nestes pacientes, comparando-os com outro grupo de pacientes tratados com efavirenz (EFV), um inibidor de transcriptase reversa não-análogo de nucleosídeo (NNRTI). No período compreendido entre março de 2000 e outubro de 2003, estudamos 36 pacientes infectados pelo HIV que estavam em terapia com IDV na dose de 800 mg de 8/8 horas por pelo menos 12 meses. Os pacientes foram avaliados para uma variedade de parâmetros clínicos e laboratoriais: idade, peso, tempo de infecção, tempo de uso de IDV, uso de sulfametoxazol-trimetoprim (SMX-TMP) ou sulfadiazina, exames bioquímicos (colesterol total, triglicérides, magnésio, sódio, potássio e creatinina), exame do sedimento urinário, clearance de creatinina, osmolaridade urinária, volume urinário de 24 h, fração de excreção de sódio (FENa), fração de excreção de potássio (FEK) e fração de excreção de água (FEH2O). NO3 urinário foi mensurado em 18 pacientes recebendo terapia anti-retroviral com IDV e 8 pacientes recebendo terapia com EFV. Leucocitúria ocorreu em 78.8% dos pacientes tratados com IDV. Clearance de creatinina diminuído foi observado em 21 pacientes e foi associado com menor peso e uso de derivados de sulfa. Nestes pacientes com diminuição da função renal, também detectamos menor osmolaridade urinária e uma FEH2O mais alta. A excreção urinária de NO3- foi significativamente menor nos pacientes tratados com IDV (908 ± 181) quando comparados aos pacientes do grupo EFV (2247 ± 648, p<0.01). Nossos resultados mostram que insuficiência renal ocorreu em 58% dos pacientes tratados com IDV e foi associada com menor peso corpóreo e uso de derivados de sulfa. A menor excreção urinária de NO3- e as alterações na osmolaridade e FEH2O sugerem que o IDV diminui a produção de óxido nítrico e causa dano tubular, respectivamente. Sugerimos então que os pacientes em uso de IDV sejam monitorados routineiramente para função renal através do clearance de creatinina. / Renal and urological complications including nephrolithiasis, crystalluria, renal colic and flank pain are significant side effects of the HIV protease inhibitor indinavir (IDV), and IDV has been widely used in the treatment of human immunodeficiency virus (HIV) infection. Previous studies in rats demonstrated that IDV, a potent protease inhibitor that causes profound and sustained supression of HIV replication, also induces renal vasoconstriction, decreases glomerular filtration rate (GFR) and reduces urinary excretion of nitrite (NO2-), suggesting that IDV-vasoconstriction may be mediated by nitric oxide (NO). The objectives of this study were to investigate the occurrence of renal failure (creatinine clearance <80ml/min) in human HIV patients treated with highy active antiretroviral therapy (HAART), including IDV, and to measure urinary excretion of nitrate (NO3-) in those patients, comparing it with that of another group of patients treated with the non-nucleoside reverse-transcriptase inhibitor efavirenz (EFV). From March 2000 through October 2003, we evaluated 36 patients infected with HIV who was receiving IDV 800 mg q8h for at least 12 months. The patients were assessed for a variety of clinical and laboratory parameters including age, body weight, duration of infection, time of IDV treatment, trimethoprim/sulfamethoxazole (TMP/SMX) or sulfadiazine use, biochemistry (total cholesterol, triglycerides, magnesium, sodium, potassium and creatinine), urinalysis, creatinine clearance, urine osmolality, 24-hour urine volume, fractional excretion of sodium (FENa), potassium (FEK) and water (FEH2O). Urinary NO3 was measured in 18 IDV-treated patients and compared with that of 8 EFV-treated patients. Leukocyturia occurred in 78.8% of the IDV-treated patients. Reduced creatinine clearance was observed in 21 patients and was associated with lower body weight and sulfa-derivated use. In these renal failure patients, we also detected a lower osmolality and a higher FEH2O. Excretion of NO3- was significantly lower in IDV-treated patients (908 ± 181) than in EFV-treated patients (2247 ± 648, p<0.01). Our data show that renal failure occurred in 58% of IDV-treated patients and was associated with lower body weight and sulfa administration. The lower NO3- excretion suggests that this drug decreases nitric oxide production, and the alterations in osmolality and FEH2O indicate that it also causes tubular damage. Based on our findings, we suggest that the renal function of patients under IDV treatment should be closely monitored with creatinine clearance.

Introdução: Não há estudos que avaliem o impacto da reutilização do dialisador na remoção de solutos em sessões de hemodiafiltração online curta diária (HDF-OL-D). Objetivo: Avaliar o impacto do reuso do dialisador na dose do tratamento, na cinética de beta2-microglobulina e na extração de solutos em sessões de HDF-OL-D e comparar com sessões de hemodiálise curta diária de alto fluxo (HD-D). Métodos: Foram incluídos 14 pacientes do programa de HD-D. Foram coletadas amostras de sangue pré, no meio e pós-diálise e amostras do dialisato no 1º, 7º e 13º usos do dialisador em sessões de HD-D e de HDF-OL-D. Resultados: A massa total extraída (MTDQ) e a depuração (KDQ) diretamente quantificada dos solutos pequenos (ureia, fósforo, creatinina e ácido úrico), bem como a dose de diálise ofertada, foram semelhantes quando o 1º, 7º e 13º usos do dialisador em sessões de HD-D foram comparados, respectivamente, ao 1º, 7º e 13º usos em sessões de HDF-OL-D. A MTDQ e a KDQ dos solutos pequenos e a dose de diálise foram semelhantes entre os usos do dialisador tanto em sessões de HD-D e quanto em sessões de HDF-OL-D. A MTDQ, a KDQ e o Kt/V diretamente quantificado (Kt/VDQ) de beta2-microglobulina foram maiores em sessões de HDF-OL-D do que nos respectivos usos do dialisador em sessões de HD-D. Não houve diferença quanto à cinética de beta2-microglobulina, avaliada pela MTDQ, KDQ ou Kt/VDQ, entre o 1º, 7º e 13º usos do dialisador em sessões de HD-D nem em sessões de HDF-OL-D. Na HDF-OL-D, a perda intradialítica de albumina foi significativamente diferente entre os usos do dialisador (p < 0,001), estando reduzida no 7º e 13º usos, quando comparados ao 1º uso do dialisador. Não houve correlação entre o volume de enchimento do dialisador e a MTDQ e a KDQ de moléculas pequenas em nenhum dos métodos dialíticos estudados. Em sessões de HDF-OL-D, foi observada uma correlação fraca entre o volume de enchimento do dialisador e a KDQ de beta2-microglobulina, não percebida com a MTDQ ou o Kt/VDQ de beta2-microglobulina. Conclusão: O reprocessamento de dialisadores de alto fluxo e alta eficiência não resulta em comprometimento da dose do tratamento, da cinética de beta2-microglobulina nem da extração de solutos em sessões de HDF-OL-D. A extração de beta2-microglobulina foi maior em sessões de HDF-OL-D do que em sessões de HD-D, sem diferenças significativas na remoção dos demais solutos. O reprocessamento do filtro, em sessões de HDF-OL-D, resultou numa redução significativa da perda intradialítica de albumina. Não parece haver influência do volume de enchimento do filtro na extração de solutos em nenhum dos métodos de diálise estudados / Introduction: There no studies evaluating the impact of dialyzer reutilization on solute removal in daily online hemodiafiltration (D-OL-HDF) sessions. Objectives: Our aim was to evaluate the impact of dialyzer reuse on solute extraction, beta2-microglobulin kinetics and dialysis dose in D-OL-HDF and compare to those in high-flux short daily hemodialysis (D-HD). Methods: 14 patients undergoing a D-HD program were included. Pre, middle and post-dialysis blood samples and effluent dialysate were collected in the 1st, 7th and 13th dialyzer uses in D-HD sessions and in D-OL-HDF sessions. Results: Directly quantified small solute (urea, phosphorus, creatinine and uric acid) total mass removal (TMDQ) and clearance (KDQ), as well as dialysis dosis, were similar when the 1st, 7th and 13th dialyzer D-HD uses were compared to the 1st, 7th and 13th D-OL-HDF uses. TMDQ and KDQ of small solutes and dialysis dose were similar among dialyzer uses in D-HD sessions and also in D-OL-HDF sessions. beta2-microglobulin TMDQ, KDQ and directly quantified Kt/V (Kt/VDQ) were statistically higher in D-OL-HDF dialyzer uses than in the respective D-HD uses. There was no difference in beta2-microglobulin kinetics, evaluated by TMDQ, KDQ or Kt/VDQ, among 1st, 7th and 13th uses in D-OL-HDF sessions or in D-HD sessions. In D-OL-HDF, albumin loss was significantly different among studied dialyzer uses (p < 0.001), being reduced in the 7th and 13th dialyzer uses, when compared to the first use. There was no correlation between dialyzer priming volume and small molecules TMDQ, KDQ in neither analyzed dialytic method. In D-OL-HDF sessions, it was observed a week correlation between dialyzer priming volume and beta2-microglobulin KDQ, not observed with beta2-microglobulin MTDQ or Kt/VDQ. Conclusion: High flux, high efficiency dialyzer reprocessing did not did result in a reduction of the offered dialysis dose, beta2-microglobulin kinetics or solute extraction in D-OL-HDF. beta2-microglobulin removal was greater in D-OL-HDF than in D-HD sessions, without difference in other solutes extraction. There was a significant reduction in intradialytic albumin loss with dialyzer reprocessing in D-OL-HDF sessions. Dialyzer priming volume does not appear to influence solute removal in neither analyzed dialytic method

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-18T17:29:53Z No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-22T15:11:02Z (GMT) No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) / Made available in DSpace on 2016-07-22T15:11:02Z (GMT). No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) Previous issue date: 2011-02-24 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Justificativa e Objetivo: Independente da etiologia, a doença renal crônica (DRC) envolve fibrose generalizada e progressiva do tecido, atrofia tubular e a perda da função renal. Atualmente, as terapias eficazes para esta condição são escassas. Neste estudo, foram investigados os efeitos da terapia laser de baixa intensidade (LLLT) sobre a fibrose intersticial, que ocorre após obstrução ureteral unilateral (OUU) em ratos, um modelo experimental de doença renal crônica. Materiais e Métodos: Foram utilizados 32 ratos Wistar, 8 em cada grupo, machos, com 250 a 300g de peso aproximadamente e 8 semanas de idade. O rim obstruído de metade dos ratos, submetidos à OUU receberam dose única intra-operatória do LLLT (AlGaAs laser, 780 nm, 22,5 J / cm ², 30 mW, 30 segundos em cada um dos nove pontos). Após 14 dias, a fibrose renal foi avaliada pela coloração por picrosírius e medição da área transversal sob luz polarizada. Análise imunohistoquímica quantificou células do tecido renal que expressam marcadores de fibroblastos (FSP-1) e miofibroblastos (α-SMA). RT-PCR foi realizado para determinar a expressão de mRNA de genes chaves relacionados com a fibrose: TGF-β1, Smad3 e colágeno I (Col I). Resultados: No grupo OUU e tratado pelo LLLT os animais apresentaram menos fibrose renal do que os animais obstruídos (OUU). α-SMA, TGF-β1 e Smad3 foram aumentados no interstício renal de ratos OUU. LLLT reduziu a expressão de todas essas moléculas. LLLT não parece ter um efeito significativo no Col I ou FSP-1, que também foram induzidos por OUU. Conclusão: Pela primeira vez, nós mostramos que LLLT tem um efeito protetor em relação à fibrose intersticial renal. Entende-se que, atenuando a inflamação, a laserterapia pode impedir a ativação tubular e transdiferenciação, que são os dois processos principais que formam a fibrose renal no modelo OUU. / Background and Objective: Regardless of the etiology, chronic kidney disease (CKD) involves progressive widespread tissue fibrosis, tubular atrophy and loss of kidney function. At present, effective therapies to this condition are lacking. We investigated the effects of low level laser therapy (LLLT) on the interstitial fibrosis that occurs after unilateral ureteral obstruction (UUO) in rats, an experimental model of CKD. Study Design/Materials and Methods: We used 32 Wistar rats, 8 in each group, males, 250 to 300g weight and 8 weeks old. The occluded kidney of half of the Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm², 30 mW, 30 seconds on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining and measurement of the cross-sectional area under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. RT-PCR was performed to determine the mRNA expression of key fibrosis-related genes, namely TGF-β1, Smad3 and collagen I (Col I). Results: The UUO-LLLT animals had less severe renal fibrosis than OUU animals. α- SMA, TGF-β1 and Smad3 were increased in the renal interstitium of UUO rats. LLLT reduced the expression of all of these molecules. LLLT did not appear to have a significant effect on Col I or FSP-1, which were also induced by UUO. Conclusion: For the first time, we showed LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.