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1.
Anal Chim Acta ; 1099: 26-38, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-31986274

RESUMO

Kidney transplantation is one of the renal replacement options in patients suffering from end-stage renal disease (ESRD). After a transplant, patient follow-up is essential and is mostly based on immunosuppressive drug levels control, creatinine measurement and kidney biopsy in case of a rejection suspicion. The extensive analysis of metabolite levels offered by metabolomics might improve patient monitoring, help in the surveillance of the restoration of a "normal" renal function and possibly also predict rejection. The longitudinal follow-up of those patients with repeated measurements is useful to understand changes and decide whether an intervention is necessary. The time modality, therefore, constitutes a specific dimension in the data structure, requiring dedicated consideration for proper statistical analysis. The handling of specific data structures in metabolomics has received strong interest in recent years. In this work, we demonstrated the recently developed ANOVA multiblock OPLS (AMOPLS) to efficiently analyse longitudinal metabolomic data by considering the intrinsic experimental design. Indeed, AMOPLS combines the advantages of multilevel approaches and OPLS by separating between and within individual variations using dedicated predictive components, while removing most uncorrelated variations in the orthogonal component(s), thus facilitating interpretation. This modelling approach was applied to a clinical cohort study aiming to evaluate the impact of kidney transplantation over time on the plasma metabolic profile of graft patients and donor volunteers. A dataset of 266 plasma metabolites was identified using an LC-MS multiplatform analytical setup. Two separate AMOPLS models were computed: one for the recipient group and one for the donor group. The results highlighted the benefits of transplantation for recipients and the relatively low impacts on blood metabolites of donor volunteers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31774122

RESUMO

CONTEXT: α-klotho is an integral membrane protein, that serves as a co-receptor for fibroblast growth factor 23 (FGF23) in conjunction with cognate fibroblast growth factor receptors. Proteolytic cleavage sheds the ectodomain of α-klotho (soluble α-klotho) as an endocrine substance into blood, urine and cerebrospinal fluid. OBJECTIVE: To study the relationship of soluble α-klotho to mineral metabolism in the general population with mainly preserved kidney function. DESIGN: Cross-sectional analysis of the associations between soluble α-klotho with laboratory markers of markers of mineral metabolism in a population-based cohort. SETTING: Three centers in Switzerland including 1128 participants. MEASURES: Soluble full-length α-klotho levels by a specific immunoassay and markers of mineral metabolism. RESULTS: The median serum level of soluble α-klotho was 15.0 pmol/L. Multivariable analyses using α-klotho as outcome variable revealed a sex-by-parathyroid hormone (PTH) interaction: In men, PTH was positively associated with α-klotho levels whereas this association was negative in women. Plasma phosphate associated with soluble α-klotho levels in an age-dependent manner, changing from a positive association in young adults gradually to a negative association in the elderly. The decline of 1,25 (OH)2 vitamin D3 levels in parallel to the gradual impairment of kidney function was greatly attenuated in the setting of high circulating soluble α-klotho levels. CONCLUSIONS: Soluble α-klotho level is associated with plasma phosphate in an age-dependent manner and with PTH in a sex-dependent manner. Furthermore, our data reveal soluble α-klotho as a modulator of 1,25 (OH)2 vitamin D3 levels in individuals with preserved renal function.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31738424

RESUMO

BACKGROUND: Cardiovascular morbidity and mortality is high in patients starting dialysis and could be related to modifications of calcification inducers and inhibitors by dialysis, promoting cardiovascular events. The impact of dialysis initiation on serum calcification propensity evolution and arterial stiffness is unknown. We therefore prospectively determined the evolution of the one-half maximal transition time (T50) value and its main determinants as well as pulse wave velocity over the first 3 months of dialysis initiation. METHODS: We analysed the evolution of T50, fetuin-A and mineral metabolism parameters before dialysis initiation (M0) and monthly until Month 3 (M3) in incident patients starting haemodialysis (HD) or peritoneal dialysis (PD) in two tertiary Swiss university hospitals. Arterial stiffness was assessed by pulse tonometry at M0 and M3 and biological parameters were compared between M0 and M3 and before/after HD. Linear mixed models were used to assess parameter evolution over time, taking into account repeated measures and other influencing variables. RESULTS: Forty-six patients on HD and 12 on PD were followed. Among them, 45 were male (78%) with a median age of 67 years (25th-75th quartile range 54-77). T50 significantly increased between M0 and M3 from 183 (120-266) to 246 min (175-330) (P < 0.001). Fetuin-A, calcium and magnesium also increased while phosphate decreased. Factors associated with T50 changes over time were fetuin-A, phosphate and magnesium (P < 0.001). Fetuin-A changes were associated with inflammation-related factors (albumin, C-reactive protein) but not calcium and phosphate levels. Arterial stiffness was not significantly modified over 3 months. PD and HD initiation showed similar trends. CONCLUSIONS: Dialysis initiation significantly improves calcification propensity and fetuin-A levels. These modifications do not explain the high mortality related to dialysis initiation. The clinical relevance of using T50 values to initiate dialysis awaits further studies.

5.
Rev Med Suisse ; 15(662): 1625-1628, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508914

RESUMO

The salt sensitivity of the blood pressure (SSBP) is defined as a rise or fall in blood pressure induced by a change in sodium intake. There is an interindividual variation and no strong diagnostic criteria exist to date. The SSBP may lead to underestimation of the beneficial effect of sodium restriction in some patients in meta-analyzes. High sodium intake in salt sensitive patients results in an increase in the prevalence of hypertension and target organ damage. The etiology seems to be a failure of one or more natriuretic mechanisms. Some environmental, genetic and epidemiological factors increase its susceptibility. Per se, SSBP cannot be treated, but its identification may help in preventing hypertension and adapt the treatment in some populations.


Assuntos
Variação Biológica Individual , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico
6.
Rev Med Suisse ; 15(662): 1629-1632, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508915

RESUMO

Arterial hypertension (HT) affects hundreds millions of people suffering from chronic kidney disease: it could be a cause or a consequence. HT can aggravate their prognosis and then lead to a very high cardiovascular morbidity and mortality. HT must be systematically screened and optimally taken care of. However, general practitioners actually lack unambiguous guidelines regarding patients with kidney diseases. This article underlines the necessity and modalities of a precise diagnosis, and aims to discuss the last studies supporting new and better therapeutic targets. The pathophysiological aspects of HT in chronic kidney diseases are also discussed.


Assuntos
Hipertensão/complicações , Hipertensão/terapia , Insuficiência Renal Crônica/complicações , Humanos , Hipertensão/mortalidade , Guias de Prática Clínica como Assunto , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Fatores de Risco
7.
J Am Heart Assoc ; 8(18): e013558, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31510823

RESUMO

Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (<38 years; P=0.62), whereas it was significant in older age groups (38-55 and >55 years; P=0.016 and P<0.001, respectively). Conclusions Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.

8.
Kidney Int ; 96(4): 890-905, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301888

RESUMO

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease is independently associated with all-cause mortality. Since inflammation is characteristic of chronic kidney disease and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of chronic kidney disease showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of chronic kidney disease.

9.
Swiss Med Wkly ; 149: w20090, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31154659

RESUMO

The objectives were to determine urinary iodine concentration (UIC) in day and night samples collected over a 24-hour period and evaluate the usual dietary iodine intake distribution from this collection. We propose a method by which the prevalence of inadequacy can be calculated from a single 24-hour collection, reducing the burden on participants and the study costs. The samples from 1128 participants were collected between 2009 and 2013 within the framework of the Swiss Kidney Project on Genes observational cohort study; 1024 samples were suitable for statistical evaluation of iodine analysis. Participants were over 18, resident in Switzerland and of European ancestry. Over 24 hours, urine was collected as night-time (bedtime until and including first morning urine) and day-time (the remainder) samples. Associations with variables, in particular to estimated glomerular filtration rate (eGFR), were investigated using mixed models. The 24-hour median UICs were 73 and 96 µg/l for women (n = 542) and men (n = 482), respectively; 24-hour median intakes (derived from the corresponding excretion) were 127 and 156 µg/d, respectively. Day and night excretions were normalised to 24-hour excretion values and the usual intake distribution calculated by the US National Cancer Institute method. The Estimated Average Requirement cut-point method was used to calculate the prevalence of inadequacy, estimated at 14% for women and 4% for men; above the target of 2-3%. We conclude that segregating 24-hour urine into day and night collections is sufficient to determine the prevalence of iodine inadequacy in the population and reduces the burden on participants by sparing a second 24-hour collection. No association between iodine intake and eGFR was found.

10.
Artigo em Inglês | MEDLINE | ID: mdl-30951967

RESUMO

The prevalence of chronic kidney disease (CKD) is increasing worldwide. New technical approaches are needed to improve early diagnosis, disease understanding and patient monitoring, and to evaluate new therapies. Metabolomics, as a prime candidate in the field of CKD research, aims to comprehensively analyze the metabolic complexity of biological systems. An extensive analysis of the metabolites contained in biofluids is therefore needed, and the combination of data obtained from multiple analytical platforms constitutes a promising methodological approach. This study presents an original workflow based on complementary chromatographic conditions, reversed-phase and hydrophilic interaction chromatography hyphenated to mass spectrometry to improve the polar metabolome coverage coupled with a univocal metabolite annotation strategy enabling a rapid access to the biological interpretation. This multiplatform workflow was applied in a CKD cohort study to assess plasma metabolic profile modifications related to renal disease. Multivariate analysis of 278 endogenous annotated metabolites enabled patient stratification with respect to CKD stages and helped to generate new biological insights, while also confirming the relevance of tryptophan metabolism pathway in this condition.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Metaboloma/fisiologia , Reprodutibilidade dos Testes
11.
J Hypertens ; 37(9): 1853-1860, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30964826

RESUMO

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing worldwide in part due to population ageing. Identifying risk factors for age-related kidney function decline could help in understanding mechanisms for kidney ageing. Sodium and potassium intakes are associated with CKD progression in the renal population, but little is known on their role in renal function decline [mean estimated glomerular filtration rate variation (ΔeGFR)] in the general adult population. METHOD: We therefore explored the association of urinary sodium and potassium excretions with ΔeGFR in a longitudinal population-based cohort. We estimated 24-h urinary sodium (eUNa), potassium (eUK) and sodium-to-potassium ratio (eUNa/K) from spot urine using Kawasaki formulae. We performed multivariate linear regression models studying the association of eUNa, eUK and eUNa/K with yearly ΔeGFR, taking several covariates into account, including baseline eGFR and albuminuria. RESULTS: There were 4141 white participants from which 54.3% were women. Median age was 51.5 [43.6-60.6] years and mean baseline eGFR 88 (SD 15) ml/min per 1.73 m. During a median follow-up of 5.4 years, mean ΔeGFR was -0.59 (SD 1.68) ml/min per 1.73 m per year. In the fully adjusted model, high eUNa and eUNa/K were associated with faster renal function decline with standardized coefficients ß = -0.07 (95% confidence interval: -0.11 to -0.04) and ß = -0.05 (95% confidence interval: -0.08 to -0.02), respectively. By contrast, eUK, taken alone, showed no association. CONCLUSION: These results suggest that dietary sodium and potassium intakes may play a role in kidney function decline in the general adult population. Whether lowering sodium and increasing potassium in the diet may help in CKD prevention needs further exploration.

12.
PLoS One ; 14(3): e0214549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30925175

RESUMO

OBJECTIVE: Urinary steroid metabolomics by GC-MS is an established method in both clinical and research settings to describe steroidogenic disorders. However, population-based reference intervals for adults do not exist. METHODS: We measured daytime and night time urinary excretion of 40 steroid metabolites by GC-MS in 1128 adult participants of European ancestry, aged 18 to 90 years, within a large population-based, multicentric, cross-sectional study. Age and sex-related patterns in adjacent daytime and night time urine collections over 24 hours were modelled for each steroid metabolite by multivariable linear mixed regression. We compared our results with those obtained through a systematic literature review on reference intervals of urinary steroid excretion. RESULTS: Flexible models were created for all urinary steroid metabolites thereby estimating sex- and age-related changes of the urinary steroid metabolome. Most urinary steroid metabolites showed an age-dependence with the exception of 6ß-OH-cortisol, 18-OH-cortisol, and ß-cortol. Reference intervals for all metabolites excreted during 24 hours were derived from the 2.5th and 97.5th percentile of modelled reference curves. The excretion rate per period of metabolites predominantly derived from the adrenals was mainly higher during the day than at night and the correlation between day and night time metabolite excretion was highly positive for most androgens and moderately positive for glucocorticoids. CONCLUSIONS: This study gives unprecedented new insights into sex- and age-specificity of the human adult steroid metabolome and provides further information on the day/night variation of urinary steroid hormone excretion. The population-based reference ranges for 40 GC-MS-measured metabolites will facilitate the interpretation of steroid profiles in clinical practice.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/urina , Metabolômica/normas , Caracteres Sexuais , Esteroides/biossíntese , Esteroides/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Esteroides/metabolismo , Fatores de Tempo , Adulto Jovem
13.
Rev Med Suisse ; 15(639): 432-435, 2019 Feb 20.
Artigo em Francês | MEDLINE | ID: mdl-30785676

RESUMO

Hepatorenal syndrome is a serious and frequent complication in patients suffering from liver cirrhosis. Its most severe type is characterized by the rapid occurrence of a functional acute kidney injury. However it is mainly an exclusion diagnosis. Although the pathophysiology is not yet fully understood, the principal hypothesis is a splanchnic vasodilatation leading to a systemic and renal vasoconstriction associated with sodium and water retention and progressive cardiac failure. Intravenous albumin associated with systemic vasoconstrictors, terlipressin or noradrenaline, is recommended. Because this pathology is associated with high mortality rate, liver transplantation should be discussed. A multidisciplinary approach is mandatory due to the renal disease but also to multiorganic failure.


Assuntos
Síndrome Hepatorrenal , Cirrose Hepática , Transplante de Fígado , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/terapia , Humanos , Rim , Vasoconstritores
14.
J Clin Endocrinol Metab ; 104(6): 2195-2215, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690465

RESUMO

CONTEXT: Sex steroid hormones exhibit anabolic effects whereas a deficiency engenders sarcopenia. Moreover, supraphysiological levels of glucocorticoids promote skeletal muscle atrophy, whereas physiologic levels of glucocorticoids may improve muscle performance. OBJECTIVE: To study the relationship between both groups of steroid hormones at a physiological range with skeletal muscle mass and function in the general population. DESIGN: Cross-sectional analysis of the associations between urinary excreted androgens, estrogens, glucocorticoids, and steroid hormone metabolite ratios with lean mass and handgrip strength in a population-based cohort. SETTING: Three centers in Switzerland including 1128 participants. MEASURES: Urinary steroid hormone metabolite excretion by gas chromatography-mass spectrometry, lean mass by bioimpedance analysis, and isometric handgrip strength by dynamometry. RESULTS: For lean mass a strong positive association was found with 11ß-OH-androsterone and with most glucocorticoids. Androsterone showed a positive association in middle-aged and older adults. Estriol showed a positive association only in men. For handgrip strength, strong positive associations with androgens were found in middle-aged and older adults, whereas positive associations were found with cortisol metabolites in young to middle-aged adults. CONCLUSIONS: Sex steroids and glucocorticoids are strongly positively associated with skeletal muscle mass and strength in the upper limbs. The associations with muscle strength appear to be independent of muscle mass. Steroid hormones exert age-specific anabolic effects on lean mass and handgrip strength. Deficits in physical performance of aged muscles may be attenuated by androgens, whereas glucocorticoids in a physiological range increase skeletal muscle mass at all ages, as well as muscle strength in particular in younger adults.

15.
Rev Med Suisse ; 15(N° 632-633): 69-73, 2019 Jan 09.
Artigo em Francês | MEDLINE | ID: mdl-30629374

RESUMO

Major advances in the treatment of ANCA associated-renal vasculitides, IGA nephropathy and renal autosomal dominant polycystic disease were published within the past year. There is neither clear benefit of early initiation of renal replacement therapy in the intensive care unit nor with the use of chloride-poor solutions to prevent kidney failure. Maintenance parenteral iron supplementation in hemodialysis patients is neither associated with infectious nor cardiovascular risks. Cognitive decline may be more associated with hemodialysis than peritoneal dialysis. In transplantation, the persistence of complement-binding donor-specific antibodies after treatment is predictor of graft loss. Tocilizumab is a promising treatment for chronic antibody-mediated rejection.


Assuntos
Falência Renal Crônica , Transplante de Rim , Nefrologia , Diálise Peritoneal , Humanos , Falência Renal Crônica/terapia , Nefrologia/tendências , Diálise Renal , Terapia de Substituição Renal
16.
Nephrology (Carlton) ; 24(2): 170-180, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29369449

RESUMO

AIM: Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. METHODS: A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its aetiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). RESULTS: We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. CONCLUSIONS: In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI aetiology. It could also improve AKI diagnosis and prognosis.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Cirrose Hepática/complicações , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Idoso , Creatinina/sangue , Cistatina C/sangue , Diagnóstico Precoce , Feminino , Humanos , Pacientes Internados , Lipocalina-2/sangue , Lipocalina-2/urina , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/etiologia , Proteinúria/urina , Circulação Renal , Fatores de Risco , Índice de Gravidade de Doença , Sódio/urina , Resistência Vascular
17.
Physiol Rep ; 6(21): e13900, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30426716

RESUMO

Anemia is defined according to decreased blood hemoglobin concentration ([Hb]), which is considered a marker of low total red blood cell volume (RBCV). Alterations of plasma volume (PV) may also modify [Hb] without concomitant changes in RBCV. Since anemia and fluid retention are frequent complications of chronic kidney disease (CKD), we hypothesized that anemia during CKD may in part be related to expanded PV without a simultaneous decrease in RBCV. We quantified hemoglobin mass, RBCV, PV, and total blood volume (BV) using an automated carbon monoxide device in 40 consecutive stage 3-5 CKD patients not on dialysis and in seven healthy male controls of the same age range. These were compared within and to predicted volumes according to Nadler's formula. Arterial stiffness and NT-proBNP were measured. RBCV was similar to predicted values range in anemic CKD patients 2073 (1818-2704) versus, 2061 (1725-2473) mL, P > 0.05. In contrast, PV was largely increased in anemic CKD patients (3881 (3212-4352) vs. 2916 (2851-3201)), P = 0.01. Of 26 anemic patients, only six had a >20% decrease in RBCV as the cause for their anemia, whereas 14 had a >20% increase of PV as a cause for their anemia. NT-pro BNP correlated with eGFR but neither with PV nor BV, whereas arterial stiffness was not correlated to blood volumes. Anemia in CKD as diagnosed by low [Hb] is not necessarily associated to low RBCV but may reflect increased PV. This finding has implications for the treatment of CKD patients and may refrain from normalizing [Hb] levels in all CKD patients.


Assuntos
Anemia/sangue , Volume de Eritrócitos , Insuficiência Renal Crônica/sangue , Idoso , Anemia/etiologia , Anemia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Rigidez Vascular
18.
PLoS One ; 13(10): e0203903, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308019

RESUMO

BACKGROUND: Although the polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women with vast metabolic consequences, its etiology remains unknown and its diagnosis is still made by exclusion. This study aimed at characterizing a large number of urinary steroid hormone metabolites and enzyme activities in women with and without PCOS in order to test their value for diagnosing PCOS. METHODS: Comparative steroid profiling of 24h urine collections using an established in-house gas-chromatography mass spectrometry method. Data were collected mostly prospectively. Patients were recruited in university hospitals in Switzerland. Participants were 41 women diagnosed with PCOS according to the current criteria of the Androgen Excess and PCOS Society Task Force and 66 healthy controls. Steroid profiles of women with PCOS were compared to healthy controls for absolute metabolite excretion and for substrate to product conversion ratios. The AUC for over 1.5 million combinations of metabolites was calculated in order to maximize the diagnostic accuracy in patients with PCOS. Sensitivity, specificity, PPV, and NPV were indicated for the best combinations containing 2, 3 or 4 steroid metabolites. RESULTS: The best single discriminating steroid was androstanediol. The best combination to diagnose PCOS contained four of the forty measured metabolites, namely androstanediol, estriol, cortisol and 20ßDHcortisone with AUC 0.961 (95% CI 0.926 to 0.995), sensitivity 90.2% (95% CI 76.9 to 97.3), specificity 90.8% (95% CI 81.0 to 96.5), PPV 86.0% (95% CI 72.1 to 94.7), and NPV 93.7% (95% CI 84.5 to 98.2). CONCLUSION: PCOS shows a specific 24h urinary steroid profile, if neglected metabolites are included in the analysis and non-conventional data analysis applied. PCOS does not share a profile with hyperandrogenic forms of congenital adrenal hyperplasias due to single steroid enzyme deficiencies. Thus PCOS diagnosis by exclusion may no longer be warranted. Whether these findings also apply to spot urine and serum, remains to be tested as a next step towards routine clinical applicability.


Assuntos
Metabolômica/métodos , Síndrome do Ovário Policístico/diagnóstico , Esteroides/urina , Adolescente , Adulto , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/urina , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
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