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1.
Clin Nephrol ; 75(3): 226-32, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21329633

RESUMO

OBJECTIVE: Relaxin, a potent pregnancy-related hormone, has been proposed to be a major mediator of renal physiology in normal pregnancy. We wished to test relaxin levels in pregnancy and preeclampsia. METHODS: We performed precise physiologic measurements of kidney function in 38 normal peripartum women and 58 women with preeclampsia. We measured serum relaxin levels prior to delivery and over the first 4 postpartum weeks utilizing a modern, validated ELISA. Results were compared to those of 18 normal women of childbearing age. RESULTS: Relaxin levels were substantially elevated in women prior to delivery (364 ± 268 vs. 15 ± 16 pg/ml) and fell rapidly over the first postpartum week reaching normal non pregnant levels by Week 2 (32 ± 64 vs. 15 ± 16 pg/ml). No differences were seen between relaxin levels in normal pregnancy as compared to preeclampsia (364 ± 268 vs. 376 ± 241 pg/ml) despite substantial and persistent abnormalities in GFR (149 ± 33 vs. 89 ± 25 ml/min), albuminuria (14 vs. 687 mg/g) and mean arterial pressure (80 ± 8 vs. 111 ± 18). Furthermore no correlation could be established between physiologic measures (GFR, MAP, RBF, RVR) and relaxin levels (p > 0.3), either in the overall population or any of the subgroups. CONCLUSION: Relaxin is indeed significantly elevated in the serum of women during late pregnancy and the early puerperium. However, serum relaxin does not appear to influence BP, renal vascular resistance, renal blood flow or GFR in late pregnancy or in women with preeclampsia.


Assuntos
Rim/fisiopatologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Relaxina/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea , California , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Período Pós-Parto , Gravidez , Terceiro Trimestre da Gravidez , Circulação Renal , Fatores de Tempo , Regulação para Cima , Resistência Vascular , Adulto Jovem
2.
Can J Cardiol ; 24(6): 491-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18548147

RESUMO

BACKGROUND: Clinical practice recommendations for hypertension do not make recommendations specific to men or women. However, the sex hormones appear to modulate differently the renin-angiotensin system (RAS), which plays a central role in the regulation of blood pressure. Today, little is known about the effects of sex on the efficacy of therapies that antagonize the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). OBJECTIVE: To identify randomized controlled trials evaluating the efficacy of ACEIs and ARBs in preventing major cardiovascular outcomes, determine what proportion of the trial participants were female, and evaluate whether there was any evidence of a sex difference in the efficacy of these agents. METHODS: A systematic review of the literature was conducted to identify randomized controlled trials that used either ACEIs or ARBs for the treatment of hypertension. RESULTS: Thirteen ACEI trials and nine ARB trials were identified. Sex-specific outcome data were available in six of the ACEI trials and three of the ARB trials. These trials enrolled 74,105 patients; 39.1% were women. Seven of the nine trials indicated that ACEIs or ARBs may be slightly more beneficial in men. The magnitude of these differences, in most trials, was small. CONCLUSIONS: Sex-specific data are reported in 43% of large hypertension clinical trials. Review of the trials reporting sex-specific effect sizes indicates that ACEIs and ARBs may be more effective in men.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Hipertensão/tratamento farmacológico , Morbidade/tendências , Cooperação do Paciente , Distribuição por Sexo , Fatores Sexuais , Resultado do Tratamento
3.
Am J Physiol Renal Physiol ; 294(3): F614-20, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18199600

RESUMO

We evaluated the early postpartum recovery of glomerular function over 4 wk in 57 women with preeclampsia. We used physiological techniques to measure glomerular filtration rate (GFR), renal plasma flow, and oncotic pressure (pi(A)) and computed a value for the two-kidney ultrafiltration coefficient (K(f)). Compared with healthy, postpartum controls, GFR was depressed by 40% on postpartum day 1, but by only 19% and 8% in the second and fourth postpartum weeks, respectively. Hypofiltration was attributable solely to depression, at corresponding postpartum times, of K(f) by 55%, 30%, and 18%, respectively. Improvement in glomerular filtration capacity was accompanied by recovery of hypertension to near-normal levels and significant improvement in albuminuria. We conclude that the functional manifestations of the glomerular endothelial injury of preeclampsia largely resolve within the first postpartum month.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Glomérulos Renais/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Biológicos , Período Pós-Parto/fisiologia , Gravidez
4.
Obstet Gynecol ; 107(4): 886-95, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16582128

RESUMO

OBJECTIVE: To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia. METHODS: Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups. RESULTS: No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria. CONCLUSION: Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery. LEVEL OF EVIDENCE: I.


Assuntos
Arginina/uso terapêutico , Rim/efeitos dos fármacos , Pré-Eclâmpsia/tratamento farmacológico , Resultado da Gravidez , Administração Oral , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Idade Gestacional , Taxa de Filtração Glomerular , Humanos , Recém-Nascido , Rim/fisiopatologia , Idade Materna , Paridade , Período Pós-Parto , Pré-Eclâmpsia/diagnóstico , Gravidez , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Am J Physiol Renal Physiol ; 286(3): F496-503, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14612381

RESUMO

We evaluated the glomerular filtration rate (GFR) during the second postpartum week in 22 healthy women who had completed an uncomplicated pregnancy. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). We compared these findings with those in pregnant women previously studied on the first postpartum day as well as nongravid women of reproductive age. Healthy female transplant donors of reproductive age permitted the morphometric analysis of glomeruli and computation of the single-nephron K(f). The aforementioned physiological and morphometric measurements were utilized to estimate transcapillary hydraulic pressure (Delta P) from a mathematical model of glomerular ultrafiltration. We conclude that postpartum day 1 is associated with marked glomerular hyperfiltration (+41%). A theoretical analysis of GFR determinants suggests that depression of glomerular capillary oncotic pressure, the force opposing the formation of filtrate, is the predominant determinant of early elevation of postpartum GFR. A reversal of the gestational hypervolemia and hemodilution, still evident on postpartum day 1, eventuates by postpartum week 2. An elevation of oncotic pressure in the plasma that flows axially along the glomerular capillaries to supernormal levels ensues; however, GFR remains modestly elevated (+20%) above nongravid levels. An analysis of filtration dynamics at this time suggests that a significant increase in Delta P by up to 16%, an approximately 50% increase in K(f), or a combination of smaller increments in both must be invoked to account for the persistent hyperfiltration.


Assuntos
Taxa de Filtração Glomerular , Período Pós-Parto/fisiologia , Adulto , Feminino , Humanos , Glomérulos Renais/anatomia & histologia , Glomérulos Renais/fisiologia , Pessoa de Meia-Idade , Pressão
6.
Am J Physiol Renal Physiol ; 284(5): F1014-22, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12527555

RESUMO

We evaluated the glomerular filtration rate (GFR) in 34 subjects with membranous nephropathy (MN) of new onset. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). A morphometric analysis of glomeruli in the diagnostic biopsy permitted computation of the single-nephron ultrafiltration coefficient (SNK(f)). MN subjects were divided into two groups: moderate or severe, according to whether GFR was depressed by less or more than 50%. SNK(f) was subnormal but similar in moderate and severe MN. In contrast, two-kidney K(f) was significantly more depressed in severe than in moderate MN. We estimated the total number of functioning glomeruli (N(g)) by dividing two-kidney K(f) by SNK(f). Whereas mean N(g) was similar in controls and moderate MN (1.5 and 1.4-1.7 x 10(6), respectively), it was significantly lower in severe MN (0.5 x 10(6)). This degree of glomerulopenia was not reflected in the rate of global sclerosis. We conclude that a combination of depressed SNK(f) (due to foot process broadening) and profound glomerulopenia accounts for GFR depression of >50% early in the course of MN. The cause of the glomerulopenia remains to be elucidated.


Assuntos
Taxa de Filtração Glomerular , Glomerulonefrite Membranosa/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Glomerulonefrite Membranosa/patologia , Humanos , Glomérulos Renais/patologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Modelos Biológicos , Valores de Referência , Circulação Renal , Índice de Gravidade de Doença
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