The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C.

Human cystatin C (hCC), a member of the superfamily of papain-like cysteine protease inhibitors, is the most widespread cystatin in human body fluids. Physiologically active hCC is a monomer, which dimerization and oligomerization lead to the formation of the inactive, insoluble amyloid form of the protein, strictly associated with cerebral amyloid angiopathy, a severe state causing death among young patients. It is known, that biological membranes may accelerate the oligomerization processes of amyloidogenic proteins. Therefore, in this study, we describe an influence of membrane mimetic environment-mixed dodecylphosphocholine:sodium dodecyl sulfate (DPC:SDS) micelle (molar ratio 5:1)-on the effect of the hCC oligomerization. The hCC-micelle interactions were analyzed with size exclusion chromatography, circular dichroism, and nuclear magnetic resonance spectroscopy. The experiments were performed on the wild-type (WT) cystatin C, and two hCC variants-V57P and V57G. Collected experimental data were supplemented with molecular dynamic simulations, making it possible to highlight the binding interface and select the residues involved in interactions with the micelle. Obtained data shows that the mixed DPC:SDS micelle does not accelerate the oligomerization of protein and even reverses the hCC dimerization process.

Estimación de la tasa de filtración glomerular en adultos mayores mediante las ecuaciones CKD-EPI / Estimate of the glomerular filtration rate in aged adults through the CKD-EPI equations

Introducción: La tasa de filtración glomerular se considera el mejor índice para evaluar la función renal, ya que su reducción aparece mucho antes que cualquier manifestación clínica derivada de la disfunción renal. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 92 pacientes sin enfermedad renal y con esta, atendidos en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, de febrero a noviembre de 2017, a fin de evaluar las ecuaciones insuficiencia renal crónica-colaboración epidemiológica (CKD-EPI) para estimar el filtrado glomerular en adultos mayores. Resultados: Se halló menor promedio de filtrado con orina de 24 horas en el grupo sin nefropatía (64,8 mL/min) y mayor en el grupo de nefrópatas (25,8 mL/min) respecto a dichas ecuaciones. Aunque no hubo diferencias significativas en el filtrado según edad, sexo y peso corporal, en ambos grupos al emplear CKD-EPI, los valores mayores se obtuvieron con CKD-EPI cistatina C. Conclusiones: En los ancianos sin marcadores de daño renal la utilización de las fórmulas CKD-EPI con cistatina permite una mejor estimación de la función renal.

Introduction: The glomerular filtration rate is considered the best index to evaluate the renal function, since its reduction is evidenced much time before any clinical manifestation which derives from the renal failure. Methods: A descriptive, cross-sectional and observational study of 92 patients without and with renal disease, assisted in Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from February to November, 2017, was carried out in order to estimate glomerular filtrate in older adults by means of the CKD-EPI equations. Results: Lower average filtrate with 24 hours urine was found in the group without nefropathy (64.8 mL/min) and it was higher in the kidney disease group (25.8 mL/min) regarding these equations. Although in both groups there were no significant differences in the filtrate according to age, sex and corporal weight, when using the equations CKD-EPI, the higher values were obtained with CKD-EPI cystatine C. Conclusions: The use of the formulas CKD-EPI with cystatine allows a better estimate of the renal function in aged patients without markers of renal damage.

[Glomerular filtration rate estimation and measurement: The quest for precision]. / Estimation et mesure du débit de filtration glomérulaire : en quête de précision.

Glomerular filtration rate measurement is still the best way to assess the global renal function. In daily practice, glomerular filtration rate is estimated by creatinine-based equations. Serum creatinine as a renal biomarker has however several limitations. We discuss the current recommended creatinine-based equations. The potential added value of a new biomarker, cystatin C, and alternative equations will be discussed. Finally, the potential interest of measured glomerular filtration rate by a reference method in specific patients and/or situations will be discussed and justified.

[Measurement and estimation of glomerular filtration rate]. / Mesure et estimation du débit de filtration glomérulaire.

Glomerular filtration rate is the best quantitative marker of renal function. It allows diagnosis and classification of severe chronic kidney disease into five stages. Theoretically, the measurement of glomerular filtration rate is based on the calculation of urinary clearance of exogenous substances such as chromium 51-labeled inulin or ethylenediaminetetraacetic acid ([51Cr]-EDTA). In practice, glomerular filtration rate is most often estimated from equations derived from plasma creatinine. This article reviews the range of methods used to measure or approximate glomerular filtration rate and attempts to describe recent developments in this area, including those related to plasma creatinine assay methods, creatinine and cystatin C concentration-derived estimations. Measurement of glomerular filtration rate by the clearance of exogenous tracers is also discussed.

Clinical Investigation for Blood Levels of Cystetine C and Superoxide Dismutase in Patients With Obstructive Sleep Apnea Syndrome Related Hypertension / 中国循环杂志

Objective: To observe blood levels of cystetine C (Cys C) and superoxide dismutase (SOD) in patients with obstructive sleep apnea syndromes (OSAS) related hypertension (HP). Methods: A total of 102 HP patients received polysomgography (PSG) in our hospital from 2013-01 to 2013-12 were studied. According to apnea hypopnea index (AHI), the patients were divided into 2 groups: OSAS with HP (OH) group, n=55 patients with AHI≥5 and HP group,n=47 patients with AHI0.05. Conclusion: Blood levels of Cys C in OH and HP groups were higher than Control group, Cys C in OH group was higher than HP group; SOD levels in OH and HP groups were lower than Control group, SOD in OH group was lower than HP group. The relationships between Cys C, SOD and OH severity were unclear.

[Exploration of renal glomerular function: estimation of glomerular filtration rate]. / Exploration de la fonction glomérulaire rénale: estimation du débit de filtration glomérulaire.

In addition to direct measurement methods of glomerular filtration rate, there are many formulas whose purpose is to estimate glomerular filtration rate from endogenous markers, of which the most used is serum creatinine. The latest recommendations the French health agency Haute Autorité de santé (HAS) unambiguously endorse the use of the CKD-EPI equation. The assessment of glomerular filtration rate from this equation however remains approximate in many situations where the plasma creatinine concentration poorly reflects the glomerular filtration rate. In these situations, plasma cystatin C could potentially be a more reliable alternative to endogenous plasma creatinine marker, especially since a reference standard for the determination of serum cystatin C concentration has recently been developed. Use of serum cystatin C concentration in clinical practice begins to be mentioned, but still needs to be fully validated.