STAT5 phosphorylation in CD4 T cells from patients with SLE is related to changes in their subsets and follow-up disease severity.

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.

Increased Levels of STAT1 Protein in Blood CD4 T Cells from Systemic Lupus Erythematosus Patients Are Associated with Perturbed Homeostasis of Activated CD45RA-FOXP3hi Regulatory Subset and Follow-Up Disease Severity.

In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4+FOXP3+ regulatory T cells (Tregs) were described. In the present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity. The highest STAT1 MFI was found in CD45RA-FOXP3hi-activated Treg (aTreg) subset, which demonstrated the highest STAT1 phosphorylation responses among SLE CD4 T cells and significant decrease in proliferation marker Ki-67 expression after IFN-alpha stimulation. Percentage of Ki-67+ aTregs was significantly decreased in SLE patients and was negatively correlated with CD4 T cell STAT1 MFI. A subgroup of SLE patients characterized by lower aTreg counts experienced more severe relapsing disease course during 1,000 days of follow-up. Mean CD4 T cell STAT1 MFI in follow-up samples from SLE patients was negatively correlated with mean of follow-up aTreg counts. Our findings indicate that augmented STAT1 signaling may be involved in perturbed aTreg homeostasis, which could represent a possible marker of SLE disease severity.

Estimation of Glomerular Filtration Rate in Elderly Chronic Kidney Disease Patients: Comparison of Three Novel Sophisticated Equations and Simple Cystatin C Equation.

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 (51 CrEDTA 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 51 CrEDTA 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 51 CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m2 . Statistically significant correlations between 51 CrEDTA 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.

Determinants of maternal vitamin D concentrations in Slovenia : A prospective observational study.

OBJECTIVE: To analyze the vitamin D status of pregnant women in Slovenia and the factors influencing it. METHODS: The study was performed in Maribor University Medical Centre (location 46°N). Maternal serum 25-hydroxy-vitamin D (25(OH)D) in 4 groups of 100 pregnant women in 4 different seasons of the year was measured at the time of delivery. Data on life style, eating habits, sunbathing and intake of vitamin D supplements during pregnancy were obtained using a questionnaire. Information on maternal outcome was acquired from medical records. Duration of sunlight and average temperature in the month preceding delivery were calculated from meteorological data. RESULTS: The average maternal 25(OH)D concentration ranged from 28.5 ± 17.1 nmol/l in March to 54.8 ± 24.1 nmol/l in June (p < 0.001). Severe vitamin D deficiency, i.e. <25 nmol/l 25(OH)D was present in 23.6% of women overall. In multiple regression analysis supplements containing vitamin D (ß = 0.225, p < 0.001) and duration of intentional exposure to sunlight (ß = 0.192, p = 0.026) were associated with maternal 25(OH)D status. Significantly lower vitamin D levels were observed in women who had a cesarean section (t = 2.053, p = 0.041) and those with premature delivery (t = 2.296, p = 0.022). Vitamin D levels were not associated with the occurrence of gestational diabetes, gestational hypertension or infections during pregnancy. CONCLUSION: A high prevalence of vitamin D deficiency was detected at the end of pregnancy, especially in the months following autumn and winter and in women who did not take supplements containing vitamin D.

Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC.

We report on a case of intoxication with a mix of new psychoactive substances. A 38-year-old male was brought to the emergency department (ED) following the ingestion of an unknown drug in a suicide attempt. During the transport, he became progressively more somnolent and unresponsive to painful stimuli. Urine and stomach content were collected on admission to be screened for drugs of abuse and medicinal drugs. After admission, the patient's next of kin presented five small grip seal plastic bags containing different powders/crystals, and they were sent for analysis along with urine and stomach content to the toxicology laboratory. An easy and rapid sample preparation technique was applied for the extraction of urine and stomach content. Samples were extracted with liquid-liquid extraction (LLE) technique and analysed using gas chromatography-mass spectrometry (GC-MS). A small amount of powder material from the bags was diluted in methanol and injected directly into the GC-MS instrument. Obtained spectra (EI) were evaluated against SWGDRUG library. Five different designer drugs were identified in the powder material, including synthetic cannabinoids (AB-CHMINACA, AB-FUBINACA) and synthetic cathinones (alpha-PHP, alpha-PVP and 4-CMC). With the exception of 4-CMC, all of these substances were also detected in the stomach content along with the prescription drugs. This is the first time that a positive identification of these five drugs has been made by a clinical laboratory in Slovenia.

The role of urine neutrophil gelatinase--associated lipocalin (NGAL) in acute heart failure in patients with ST--elevation myocardial infarction.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a novel early marker of acute kidney injury for which has been shown that it can also be released from the injured myocardium. Our aim was to correlate urine NGAL with markers of in-hospital heart failure in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: We prospectively included 61 consecutive STEMI patients after primary percutaneous coronary intervention and estimated admission and in-hospital urine NGAL, serum creatinine, troponin I, leucocytes, CRP, N-terminal pro brain natriuretic peptide (NT-proBNP) levels and ejection fraction by echocardiography. Urine NGAL levels were compared between patients with and without HF defined as serum NT-proBNP > 400 pmol/l and were correlated to markers of heart failure, inflammations and of kidney function. RESULTS: Urine NGAL levels and CRP was significantly higher in participants with heart failure compared to those with NT-proBNP below 400 pmol/l. Urine NGAL level of 50 ng/ml had 90 % specificity for HF, the sensitivity was low at 25 %. Comparison of participants with NGAL levels < 50 ng/ml and ≥ 50 ng/ml at admission and after 12 h revealed a significant difference in NT-proBNP levels, left ventricle ejection fraction, markers of inflammation and of kidney function. Urine NGAL level was independently associated with NT-proBNP level. CONCLUSIONS: The level of urine NGAL early after myocardial infarction is associated with NT-proBNP concentration and even NGAL levels below 137 ng/ml, the usually reported normal cut-off value, had high specificity for HF in our sample.

A new serum cystatin C formula for estimating glomerular filtration rate in newborns.

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.

Seasonal variations of vitamin D concentrations in pregnant women and neonates in Slovenia.

OBJECTIVE: While foreign research shows a high prevalence of vitamin D deficiency in pregnant women and consequently in neonates, we do not have any data on vitamin D concentration in these risk groups for Slovenia. We performed a prospective study to evaluate vitamin D concentration in pregnant women and neonates in Maribor region. STUDY DESIGN: We determined 25-hydroxy-vitamin D concentration from blood samples taken before delivery from 100 pregnant women who gave birth in Maribor University Clinical Centre in September and December 2013, respectively, and from the cord blood of their neonates. We collected data on nutrition and sun exposure during pregnancy. We calculated the vitamin D concentrations in pregnant women and neonates according to season of birth and use of nutrition supplements, determined the vitamin D levels in some pregnancy complications and checked the correlation of maternal and neonatal vitamin D concentrations. RESULTS: The average vitamin D concentration in the September group was 54.3±25.2nmol/L, and in the December group 33.3±18.6nmol/L (p<0.001). Optimal vitamin D concentration (>80nmol/L) was reached by 12.0% of pregnant women in September and by only 2.0% in December. Women who took nutrition supplements containing vitamin D during pregnancy had significantly higher vitamin D levels than those who did not (September 68.9±27.0nmol/L vs. 46.5±20.3nmol/L, p<0.001; December 38.7±17.9nmol/L vs. 30.2±18.4nmol/L, p=0.028). Neonates had higher average levels of vitamin D than their mothers but there was a good correlation between maternal and neonatal vitamin D values. CONCLUSION: Vitamin D deficiency is very common in pregnant women in Slovenia as well, especially in winter and in those women who do not take nutrition supplements containing vitamin D.

Serum cystatin-C as a marker of acute kidney injury in the newborn after perinatal hypoxia/asphyxia.

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.

Simple cystatin C formula compared to serum creatinine-based formulas for estimation of glomerular filtration rate in patients with mildly to moderately impaired kidney function.

BACKGROUND: Serum cystatin C (SCC)-based formulas and the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)) were proposed as improved glomerular filtration rate (GFR) markers. The aim of our study was to compare serum creatinine (SCr)-based and SCC-based equations against (51)Cr-EDTA clearance in patients with mildly to moderately impaired kidney function. METHODS: 255 adult Caucasian patients with chronic kidney disease (GFR 89-30 ml/min/1.73 m(2)) were enrolled. In each patient, (51)Cr-EDTA clearance, SCr and SCC were determined. GFR was calculated using the Cockcroft-Gault (C&G), Modification of Diet in Renal Disease (MDRD), CKD-EPI formulas and simple cystatin C formula (SCCF) (100/SCC). RESULTS: The receiver-operating characteristic curve analysis (cut-off for GFR 60 ml/min/1.73 m(2)) showed that the SCCF had a higher diagnostic accuracy than C&G but not than MDRD or CKD-EPI formulas. The Bland-Altman analysis for the same cut-off value showed that creatinine formulas underestimated and SCCF overestimated the measured GFR. Analysis of ability to correctly predict a patient's GFR <60 or >60 ml/min/1.73 m(2) showed the higher ability for the SCCF compared to all creatinine-based formulas. CONCLUSION: Our results indicate that the SCCF is a reliable marker of GFR and comparable to creatinine formulas including the CKD-EPI formula.

Investigation of unusual high serum indices for lipemia in clear serum samples on siemens analysers dimension.

INTRODUCTION: We present our work of monitoring 202 different patients with markedly elevated serum index for lipemia whereby serum samples were clear. We tried to clarify the cause of occurrence of these indices which were detected in the years 2006-2010 on Siemens Dimension analyzers. MATERIALS AND METHODS: In samples with unusual lipemia index we measured the concentration of lipids (total cholesterol, triglycerides, HDL and LDL cholesterol, Lp(a), ApoA1, ApoB), total proteins and checked for possible interferents (rheumatoid factor, immunoglobulins). We performed serum protein and immuno- electrophoresis. We investigated the repeatability of unusual lipemia indices during the day and after different time periods and we compared them on four different analyzers (RXL Max, Vista, Hitachi 911 and former Olympus AU640). RESULTS: In 87% of 202 samples we found a monoclonal or biclonal peak in serum protein electrophoresis. Different types of paraproteins were confirmed with immunofixation electrophoresis. In the remaining 13%, polyclonal elevated concentrations of immunoglobulins were measured. Other parameters had no influence on appearing of these indices. The repeatability of indices was good during the first day of measurements (P values > 0.05) and markedly lower in the next days or after 3 and 12 months (P values <0.05). The indices were elevated only on Dimension analyzers, but not on Hitachi and former Olympus analysers. CONCLUSION: A markedly elevated lipemia index in a clear serum sample measured on Siemens analyzers Dimension indicates a high possibility for the presence of a paraprotein in the sample.

Simple cystatin C formula for estimation of glomerular filtration rate in overweight patients with diabetes mellitus type 2 and chronic kidney disease.

In clinical practice the glomerular filtration rate (GFR) is estimated from serum creatinine-based equations like the Cockcroft-Gault formula (C&G) and Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C-based equations, the newer creatinine formula (The Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed as new GFR markers. Present study compares serum creatinine-based equations, combined (including both serum creatinine and cystatin C) equation, and serum simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in 113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD). The results of present study demonstrated that the simple cystatin C formula could be a useful tool for the evaluation of renal function in overweight patients with DM2 and impaired kidney function in daily clinical practice in hospital and especially in outpatients. Despite the advantages of the simple cystatin C formula, cystatin C-based equations cannot completely replace the "gold standard" for estimation of the GFR in a population of DM2 patients with CKD, but may contribute to a more accurate selection of patients requiring such invasive and costly procedures.

Simple cystatin C formula compared to sophisticated CKD-EPI formulas for estimation of glomerular filtration rate in the elderly.

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 (51) Cr-EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, (51) Cr-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 (51) Cr-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 m(2), 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 (51) Cr-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 m(2) 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.

Fetuin-A as a risk factor for mortality in hemodialysis patients.

OBJECTIVES: Fetuin A, a circulating inhibitor of calcification, is regulated as a negative acute-phase protein. However, its relationship with outcomes of patients undergoing hemodialysis has not been well evaluated. The aim of our study was to determine the association between fetuin-A and some factors of metabolism and their impact on all-cause mortality in hemodialysis patients. PATIENTS AND METHODS: The study comprised 106 hemodialysis patients, 45 of whom were women. Levels of serum fetuin-A were measured by ELISA and serum intact parathyroid hormone (iPTH) by immunoassay in each patient. Serum Ca, serum P, Ca x P product, alkaline phosphatase, cholesterol, triglycerides, bicarbonate, albumin, homocysteine and C-reactive protein (CRP) were measured using routine laboratory methods. Survival rates were analyzed using Kaplan-Meier survival curves. A Cox regression model was used to access the possible influence of variables on all-cause mortality. RESULTS: The mean value of fetuin-A was 15.3 +/- 3.8 g/l, range 5.5-23.7 g/l. Significant correlations were found between serum fetuin-A and serum iPTH (r = -0.239; P = 0.014), alkaline phosphatase (r = -0.240; P = 0.013), triglycerides (r = +0.236; P = 0.015) and serum albumin level (r = +0.286; P = 0.003). Patients were followed-up prospectively from the first day of the laboratory measurement for a maximum of 752 days or until death. A total of 24 patients died. Surviving patients had higher levels of fetuin-A (P = 0.005), serum cholesterol (P = 0.0001), triglycerides (P = 0.004), albumin (P = 0.0001) and homocysteine (P = 0.028). Kaplan-Meier survival analysis showed higher mortality in the first tertile of fetuin-A than in the third tertile (P = 0.0297). In our patients, serum Ca (P = 0.025), serum P (P = 0.040) and the Ca x P product (P = 0.039) were found to be predictors of mortality in the Cox multivariable regression model. CONCLUSIONS: In patients undergoing hemodialysis, lower fetuin-A levels are associated with higher mortality. Metabolism of Ca and P were directly associated with higher mortality.

Serum cystatin C-based formulas for prediction of glomerular filtration rate in patients with chronic kidney disease.

BACKGROUND: The present study, involving a large group of patients with chronic kidney disease (CKD), compares different serum cystatin C-based equations for prediction of the glomerular filtration rate (GFR). METHODS: A total of 592 adult patients with CKD were enrolled in the study. Serum cystatin C was determined in each patient by an immunonephelometric method. Their GFR was estimated using 5 equations based on serum cystatin C: (1) the Larsson formula, (2) the Hoek formula, (3) the Grubb formula, (4) the simple cystatin C formula (GFR = 100/cystatin C) and (5) our own cystatin C formula (GFR = 90.63 x cystatin C(-1.192)). The actual GFR was measured using (51)CrEDTA clearance. RESULTS: The mean (51)CrEDTA clearance was 47 ml/min/1.73 m(2); the mean serum cystatin C concentration was 2.68 mg/l. Receiver operating characteristic curve analysis (cutoff for GFR: 60 ml/min/ 1.73 m(2)) showed no difference between the cystatin C formulas with regard to diagnostic accuracy. All equations underestimated the measured GFR except the simple cystatin C formula, which slightly overestimated the measured GFR. All equations lacked precision. The ability to correctly estimate the patient's GFR was high for all equations (87.3-91.9%), except for the Larsson formula, with which 29.2% of subjects were misclassified. CONCLUSIONS: Our results indicate that all serum cystatin C-based equations, excluding the Larsson formula, are reliable markers of the GFR in patients with CKD, and for daily clinical practice the simplest formula (100/cystatin C) could be accurate enough for GFR estimation.

Vitamin D as a novel nontraditional risk factor for mortality in hemodialysis patients.

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 < or =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 < or =50 nmol/L are associated with higher all-cause early mortality.

Serum cystatin C as an endogenous marker of renal function in patients with chronic kidney disease.

The estimation of the glomerular filtration rate (GFR) is an essential part of the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C has been proposed as a new endogenous marker of GFR. Authors compared serum creatinine, creatinine clearance calculated from Cockcroft and Gault formula and serum cystatin C against (51)CrEDTA clearance in 252 patients with CKD and GFR <90 mL/min/1.73 m(2). Analysis of correlations and diagnostic accuracy (receiver operating characteristic curves) of different GFR markers indicate that serum cystatin C is a more reliable marker of GFR in patients with CKD than serum creatinine.

Cystatin C versus creatinine as a marker of glomerular filtration rate in the newborn.

AIM: Serum cystatin C (cysC) has been proposed as a promising endogenous marker of glomerular filtration rate (GFR) in adults and children. The aim of this study was to determine the reference values of cysC at birth and three days later in comparison with creatinine (Cr) and Schwartz's estimated clearance. PATIENTS AND METHODS: 75 newborns (42 boys, 33 girls) were enrolled in the study. The gestational age ranged from 34 to 41 weeks, and the birth weight from 2070 to 4410 g. Blood samples were taken from the umbilical cord at birth and from a peripheral vein three days after birth. CysC and Cr were measured in all serum samples and values analyzed in different subgroups of neonates according to sex, gestational age, birth weight, umbilical blood pH, the influence of bilirubin, hemoglobin and hydration state. The Mann-Whitney U-test and Wilcoxon's analysis were used. RESULTS: At birth, serum cysC values ranged from 1.38 to 3.23 mg/l, not significantly decreasing after 3 days of life. Cr levels, determined simultaneously at birth, ranged from 34 to 99 mumol/l and were also not significantly different from day 3 levels. Both CysC and Cr levels were independent of sex, gestational age, birth weight, bilirubin levels and hydration state. CysC correlated positively only with the hemoglobin level (r = 0.28, P = 0.01) and negatively with cord blood pH (r = -0.40, P = 0.001), similarly to Cr. Significant correlation was found between cysC and Cr in umbilical cord blood (r = 0.30, P = 0.006) and day 3 blood samples (r = 0.37, P = 0.001). No correlation was found between 1/cysC and Schwartz GFR in cord blood (r = 0.18, P = 0.18), but correlation became significant in day 3 blood samples (r = 0.27, P = 0.02). CONCLUSION: This study suggests that cysC is not more sensitive than Cr as a marker of GFR in the newborn.

Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function.

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 micromol/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.