Breda Pečovnik Balon

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

SummaryAIM: 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 Schwartzs 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 Wilcoxons 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 μmol/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.

Bone mineral density in patients beginning hemodialysis treatment.

Background: Our study was designed to determine bone mineral density (BMD) in patients beginning hemodialysis (HD) treatment, a possible correlation with the duration of renal failure prior to treatment, a possible correlation with the basic disease and the association with the concentration of intact parathormone (iPTH). Methods: Our prospective clinical trial included 50 patients beginning HD treatment. Cortical bone mineral density (BMDc) was measured at the left femoral neck and trabecular bone mineral density (BMDt) in the region of the lumbosacral spine. Bone mineral density (BMD) was measured by quantitative digital radiography using a Hologic 2000 plus device belonging to the third generation of densitometers based on dual-energy X-ray absorptiometry. Results: In patients (PTS) beginning HD, the average BMDc was 82 ± 15% of BMDc in a healthy population of corresponding age and sex. The average BMDt was 91 ± 16% of BMDt in a healthy population of corresponding age and sex. The difference was statistically significant (p < 0.05). There is a negative correlation between iPTH and BMDc r = –0.34 (p < 0.02). Patients with chronic glomerulonephritis (GN) had a statistically significantly higher BMDc (g/cm2) (p < 0.01) than those with analgetic nephropathy (AN). PTS with AN have lower BMDc (g/cm2, %) (p < 0.02) and BMDt (p < 0.005) than the rest of the PTS, iPTH in PTS with AN is higher than in the rest of the PTS (p < 0.05). Conclusions: In PTS at the beginning of HD, BMD is lower than in healthy people of corresponding age and sex. This means that BMD already decreases prior to HD. BMDc was statistically significantly lower than BMDt (p < 0.00005). PTS with AN have lower BMD than those with GN and all remaining PTS. A negative correlation between iPTH and BMDc was found.

Atherosclerosis in patients with end-stage renal failure prior to initiation of hemodialysis.

Background. In dialysis patients cardiovascular mortality is 10 to 20 times higher than in general population. It remains uncertain whether atherosclerosis of dialysis patients is effectively accelerated because many of dialysis patients have more or less marked vascular lesions already at the start of dialysis treatment. Subjects and methods. Using B-mode ultrasonography (ATL HDI 3000), we compared intima-media thickness (IMT) and plaque occurrence (indicators of atherosclerosis) in the common carotid arteries (CC), in the area of bifurcation (CB) and in the proximal part of internal carotid arteries (CI) in 28 hemodialysis patients (14 men and 14 women; mean age 49.4 years; mean duration of HD treatment 66.6 months) with that in 28 age-sex matched patients prior to initiation of hemodialysis. We also investigated possible differences in atherosclerotic risk factors in both groups. Results. The IMT values of CC (0.71 vs. 0.70 mm; p = 0.937), CB (0.81 vs. 0.77 mm; p = 0,423) and CI (0.72 vs. 0.71 mm; p = 0.935) were not significantly different in dialysis patients and patients starting dialysis treatment. We also found no difference in plaque occurrence (61% vs. 54%; p = 0.787) and in atherosclerotic risk factors (hypertension, smoking, lipids) between both groups. Conclusions. In our study we found no difference in atherosclerotic lesions in carotid arteries between dialysis patients and patients with end-stage renal failure starting dialysis treatment. Patients with chronic renal failure are at high risk for cardiovascular diseases so we should intervene earlier and more actively long before dialysis treatment in order to reduce the atherosclerotic risk factors.

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.

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

SummaryOBJECTIVES: 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 × 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 × 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.

Asymptomatic atherosclerosis and hypertension in nondiabetic patients with chronic kidney disease.

Atherosclerosis is accelerated in dialysis patients, but less is known about asymptomatic atherosclerosis and major risk factors in patients with different stages of chronic kidney disease (CKD). We compared intima media thickness (IMT) and plaque occurrence in the carotid arteries in 104 nondiabetic patients (stages 1-5 of CKD; mean age: 51.6 years) with those in 40 healthy control subjects. The IMT values (0.69 vs. 0.59 mm; P < 0.002) were higher in patients. More patients had plaques (46.2 vs. 17.5%; P < 0.002), and number of plaques was higher (P < 0.003). Negative correlation between IMT (P < 0.0001), presence of plaques (P < 0.0001), their number (P < 0.040), and chromium 51-labeled ethylenediaminetetraacetate ((51)Cr-EDTA) clearance were found in patients. With multiple regression analysis, relationship between IMT and (51)Cr-EDTA clearance (P < 0.001) and presence of hypertension (P < 0.001) was found. Nondiabetic patients with CKD showed advanced atherosclerosis and IMT, plaque occurrence, and number increased directly with the level of renal dysfunction. Another important risk factor was hypertension.

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.

Prognostic Value of 48-Hour Ambulatory Blood Pressure Measurement and Cardiovascular Mortality in Hemodialysis Patients

Background: Hypertension is common and contributes to high cardiovascular morbidity and mortality in hemodialysis (HD) patients. It is unknown which blood pressure (BP) better defines the influence on cardiovascular mortality. The purpose of our study was to analyze the relationship between various BP measurements, traditional risk factors, markers of asymptomatic atherosclerosis [left ventricular mass (LVM), carotid intima media thickness (IMT)], and cardiovascular mortality in HD patients. Methods: Seventy-three patients (44 males and 29 females; mean age: 54.2 years) were included. BP was measured before and after HD and 48-hour ambulatory blood pressure monitoring (ABPM) was performed. Using sonography, the LVM index and carotid IMT were measured. Results: During a follow-up period up to 3,664 days, 28 patients died – 16 of them from cardiovascular causes. In a Cox regression model, which included age, gender, smoking, diabetes, sensitive C-reactive protein, albumin, hemoglobin, troponin T, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, calcium, phosphorus, carotid IMT, and LVM index, only 48-hour systolic ABPM (p = 0.037) and 48-hour diastolic ABPM (p = 0.006) turned out to be independent predictors of cardiovascular death. Conclusion: Only 48-hour ABPM and not single BP measurements before or after HD were associated with cardiovascular mortality in HD patients.

Radiographic Assessment of Vascular Calcification, Aortic Pulse Wave Velocity, Ankle‐Brachial Index and Fibroblast Growth Factor‐23 in Chronic Hemodialysis Patients

Vascular calcification is a frequent complication of chronic kidney disease and end stage renal disease. In both the general population and patients with end stage renal disease, vascular calcification is related to arterial stiffness and is a predictor of cardiovascular morbidity and mortality. Various diagnostic methods are currently used to assess vascular calcification. There is a preference for simple, reliable methods that can be used in daily practice. Therefore, several imaging and laboratory methods are investigated. Twenty‐eight patients with mean age of 62 years on chronic hemodialysis were enrolled in the study. The mean duration of hemodialysis treatment was 70 months (range 3 to 350 months). Vascular calcification was assessed with coronary computed tomography and lateral lumbar, pelvic and hand radiographs. Vascular stiffness was evaluated using aortic pulse wave velocity and ankle‐brachial index measurements, and finally serum levels of fibroblast growth factor‐23 were followed. A statistically significant correlation was demonstrated between all the following parameters: coronary artery calcification score, aortic pulse wave velocity, abdominal aortic calcification score, simple vascular calcification scores in pelvis and hand. A statistically significant correlation of ankle‐brachial index >1.3 to coronary artery calcification score was found. There was no correlation between the previous parameters and fibroblast growth factor‐23. The results of our study indicate that simple imaging methods could provide confident vascular damage assessment and therefore potentially guide therapy adjustments. An association between fibroblast growth factor‐23 and the other diagnostic modalities in our study was not found.

Paricalcitol reduces proteinuria in non-dialysis chronic kidney disease patients.

Existing treatment of proteinuria is not sufficient to halt the chronic kidney disease (CKD) epidemic. Therefore the aim of our study was to evaluate the effect of paricalcitol on proteinuria in non‐dialysis CKD patients with secondary hyperparathyroidism treated according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Forty‐one non‐dialysis CKD patients with secondary hyperparathyroidism (iPTH >65 pg/mL), serum calcium <2.6 mmol/L, serum phosphate <1.8 mmol/L and proteinuria (>150 mg/day) were treated with paricalcitol 1 μg/day. Most were treated for 6 months, with the exception of three patients having iPTH <30 pg/mL after 3 months, in whom therapy was stopped. All patients were followed for 6 months. 24‐h ambulatory blood pressure (24hABP) monitoring was performed at 0 and 6 months. Fixed doses of ACE inhibitors and/or ARBs and/or statins were kept for 3 months before and during the study. Forty‐one patients (30 men, 11 women; age 62.44 ± 11.93 years) with different primary causes of CKD were enrolled in the study. Urinary albumin/creatinine ratio (UACR), 24‐h urinary albuminuria (24hUA) and 24‐h urinary quantitative proteinuria (24hUQP) were measured. Values at 0 and 6 months of these parameters were log‐transformed for statistical analysis. After treatment with paricalcitol, statistically significant reduction (paired t‐test) in 24hUA (P < 0.011) and 24hUQP (P < 0.0001) were found. The reduction of UACR was not significant (P = 0.074). In the observational period no statistically significant reduction in 24hABP was found. Treatment with 1 μg paricalcitol daily according to clinical practice in non‐dialysis CKD patients with secondary hyperparathyroidism and proteinuria significantly reduces 24hUA and 24hUQP without significant change in 24hABP.