Imbalanced STAT5 phosphorylation in conventional and regulatory CD4 T cell subsets from SLE patients is related to their Bcl‐2 expression, homeostatic‐proliferation differences, and relapsing ...disease.
Activation of the STAT5 signaling pathway up‐regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (Tcons). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA−FOXP3hi activated regulatory T cells (aTregs) were described. We assessed Tcon/Treg subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty‐one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included. Long‐term monitoring was performed in 39 patients with SLE, which were followed longitudinally for up to 1000 d. Significantly increased Bcl2 protein content in T cells from patients with SLE was associated with IL‐7–dependent STAT5 activation, expressed as increased basal levels and nuclear localization of pSTAT5. pSTAT5 levels were significantly increased in the FOXP3 low‐expressing CD4+ T cell subsets but not in the aTreg subset, which was significantly decreased in patients with SLE. In contrast to aTreg, SLE Tcon displayed significantly increased pSTAT5 and Bcl2 levels. Moreover, the percentage of Tcon‐expressing proliferation marker Ki‐67 was significantly increased in patients with SLE and was positively correlated with CD4 T cell pSTAT5 levels. Finally, a subgroup of patients characterized by an increased Tcon–pSTAT5/aTreg–pSTAT5 ratio experienced a more aggressive‐relapsing disease course and displayed higher time‐adjusted cumulative CD4 T cell pSTAT5 levels during follow‐up, which were positively correlated with time‐adjusted cumulative disease activity. Our results indicate that imbalanced STAT5 phosphorylation, which is related to Bcl2 and Ki‐67 expression, may confer survival and proliferative advantage to Tcon over aTreg and could represent a possible marker of SLE disease severity.
We evaluated cystatin‐C (cysC) in the umbilical blood as a predictor of acute kidney injury (AKI) after perinatal hypoxia/asphyxia compared with creatinine (Cr). One hundred full‐term newborns were ...enrolled in the study (50 in a group affected by perinatal hypoxia/asphyxia AS and 50 controls). CysC and Cr were measured in blood samples from the umbilical cord at birth (cysC‐umb and Cr‐umb) and from a peripheral vein 3 days later (cysC‐3 and Cr‐3). At birth, the mean level of cysC in healthy term babies was found to be 1.39 ± 0.19 mg/L and 1.34 ± 0.21 mg/L after 3 days of life, not significantly decreased (P = 0.137). The mean of cysC in the AS group was 2.12 ± 0.53 mg/L in cord blood and 1.56 ± 0.32 g/L in day 3 blood samples, also decreased (P < 0.001) and different from the control (P < 0.001). Cr levels, determined simultaneously at birth were different (P = 0.001) between the control (62.74 ± 12.84 μmol/L) and AS (72.60 ± 15.55 μmol/L) group, significantly decreased after 3 days in both groups (P < 0.001). The receiver‐operating characteristic curve analysis, comparing AS and the control group, showed area under the curve for cysC‐umb, cysC‐3, Cr‐umb and Cr‐3 (0.918; 0.698; 0.692; 0.660). The highest diagnostic accuracy was achieved with a chosen cut‐off for cysC‐umb of 1.67 mg/L (sensitivity of 84.0%, specificity of 90.0%) or 1.69 mg/L (sensitivity of 82.0%, specificity of 94.0%). Our results indicate serum CysC is a more sensitive marker of glomerular filtration rate than Cr in the newborns.
Estimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than ...serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard (51CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient 51CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD‐EPI cystatin C, CKD‐EPI creatinine‐cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean 51CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m2. Statistically significant correlations between 51CrEDTA clearance and all formulas were found (P < 0.0001). In the receiver operating characteristic (ROC) curve analysis (cut‐off for GFR 45 mL/min per 1.73 m2) no significant differences in diagnostic accuracy between all the before mentioned equations were found. Bland‐Altman analysis for the same cut‐off showed that CKD‐EPI creatinine‐cystatin C and BIS2 equation underestimated and CKD‐EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m2 showed similar ability for all equations (P = 0.24–0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.
Despite the fact that the serum creatinine level is notoriously unreliable for the estimation of glomerular filtration rate (GFR) in the elderly, the serum creatinine concentration and serum ...creatinine‐based formulas, such as the Modification of Diet in Renal Disease study equation (MDRD) are the most commonly used markers to estimate GFR. Recently, serum cystatin C‐based formulas, the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD‐EPI creatinine formula), and an equation that uses both serum creatinine and cystatin C (CKD‐EPI creatinine and cystatin formula) were proposed as new GFR markers. The aim of our study was to compare the MDRD formula, CKD‐EPI creatinine formula, CKD‐EPI creatinine and cystatin formula, and simple cystatin C formula (100/serum cystatin C) against 51Cr‐EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, 51Cr‐EDTA clearance, serum creatinine, and serum cystatin C were determined, and the GFR was calculated using the MDRD formula, CKD‐EPI formulas, and simple cystatin C formula. Statistically significant correlations between 51Cr‐EDTA clearance and all formulas were found. In the receiver operating characteristic (ROC) curve analysis with a cut‐off of GFR 45 mL/min/1.73 m2, a higher diagnostic accuracy was achieved with the equation that uses both serum creatinine and cystatin C (CKD‐EPI creatinine and cystatin formula) than the MDRD formula (P < 0.013) or CKD‐EPI creatinine formula (P < 0.01), but it was not higher than that achieved for the simple cystatin C formula (P = 0.335). Bland and Altman analysis for the same cut‐off value showed that the creatinine formulas underestimated and the simple cystatin C formula overestimated measured GFR. All equations lacked precision. The accuracy within 30% of estimated 51Cr‐EDTA clearance values differ according to the stage of CKD. Analysis of the ability to correctly predict GFR below and above 45 mL/min/1.73 m2 showed a high prediction for all formulas. Our results indicate that the simple cystatin C formula, which requires just one variable (serum cystatin C concentration), is a reliable marker of GFR in the elderly and comparable to the creatinine formulas, including the CKD‐EPI formulas.
We examined the prevalence of vitamin D deficiency in hemodialysis patients and tested the hypothesis that decreased levels of 25‐hydroxyvitamin D (25D) are associated with an increased risk for ...early all‐cause mortality. One hundred and two patients, 57 (56%) men and 45 (44%) women, mean age 60.5 ± 13.1 years, were included in our study. Serum calcium and phosphorus levels were measured by routine laboratory methods. Parathyroid hormone (PTH) was measured by immunoassay and 25D by enzyme immunoassay. Patients were divided into two groups depending on the serum concentration of 25D: below or above 50 nmol/L. Survival rates were analyzed using the Kaplan–Meier survival curves. The Cox regression model was used to define potential variables effecting all‐cause mortality. The mean level of 25D in all patients was 58 ± 35.6 nmol/L, 52% of patients had 25D levels >50 nmol/L and 48% had levels of 10.5–50 nmol/L. Compared with men, women were more likely to be 25D deficient (67% vs. 37%; P = 0.005). Patients were observed from the date of laboratory measurement until their death or to a maximum of 730 days. Kaplan–Meier survival analysis showed that mortality in patients was significantly higher in the group with 25D levels ≤50 nmol/L (P < 0.033). With Cox multivariable regression modeling, the PTH level (P < 0.029) turned out to be the only predictor of mortality in our patients. Using the definitions recommended in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, we found that our hemodialysis patients on average have vitamin D insufficiency. Our results indicate that patients with 25D levels ≤50 nmol/L are associated with higher all‐cause early mortality.
Highlights • Suicide attempt with a mix of synthetic cannabinoids and cathinones is presented. • Intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC. • GC–MS analysis of powder ...material, stomach content and urine was performed.
Background. Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C was proposed as a new ...endogenous marker of GFR and in our study its diagnostic accuracy was compared with that of other markers of GFR. Methods. In this study, 164 patients with CKD stages 2–3 (GFR 30–89 ml/min/1.73 m2), who had performed 51Cr-labelled ethylenediaminetetra-acetic acid clearance, were enrolled. In each patient, serum creatinine and serum cystatin C were determined. Creatinine clearance was calculated using the Cockcroft–Gault (C&G) and the modification of diet in renal disease (MDRD) formulas. Results. The mean 51CrEDTA clearance was 57 ml/min/1.73 m2, the mean serum creatinine 149 μmol/l and the mean serum cystatin C 1.74 mg/l. We found significant correlation between 51CrEDTA clearance and serum creatinine (R = −0.666), serum cystatin C (R = −0.792), reciprocal of serum creatinine (R = 0.628), reciprocal of serum cystatin C (R = 0.753) and calculated creatinine clearance from the formulas C&G (R = 0.515) and MDRD formulas (R = 0.716). The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that serum cystatin C had a significantly higher diagnostic accuracy than serum creatinine (P = 0.04) and calculated creatinine clearance from the C&G formula (P<0.0001), though only in female patients. No difference in diagnostic accuracy was found between serum cystatin C and creatinine clearance calculated from the MDRD formula. Conclusions. Our results indicate that serum cystatin C is a reliable marker of GFR in patients with mildly to moderately impaired kidney function and has a higher diagnostic accuracy than serum creatinine and calculated creatinine clearance from the C&G formula in female patients.
Background
The levels of serum cystatin C (CysC) and creatinine (Cr) were determined in small-for-gestational-age (SGA) babies and compared with those for normal term newborns appropriate for ...gestational age (AGA), at birth and 3 days later. We then compared a number of cysC-based, Cr-based and combined formulas for estimation of glomerular filtration rate (GFR) with the neonatal reference GFR.
Methods
Fifty full-term SGA and 50 AGA newborns were enrolled in the study. Kidney volume measurements were performed by ultrasound for each newborn.
Results
At birth, the mean level of CysC in SGA babies was 1.48 ± 0.30 mg/l in cord blood and 1.38 ± 0.18 mg/l in day 3 blood samples, and the mean Cr level, determined simultaneously, was 67.08 ± 17.62 and 55.62 ± 14.91 μmol/l, respectively. These levels did not differ significantly from those determined in AGA babies. A 10 % reduction in kidney volume was associated with an increase in CysC value of 9.3 % in cord blood. The Cr-based and Schwartz-combined equations underestimated GFR relative to CysC-based and Zappitelli-based equations at birth and 3 days later.
Conclusions
A newly constructed Cys-C based formula which includes kidney volume and body surface area in the calculations for GFR is a reliable marker of GFR compared with neonatal reference clearance values.
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