Maša Knehtl

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 ≤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.

Albuminuria is Associated With Subendocardial Viability Ratio in Chronic Kidney Disease Patients.

Background/Aims: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA) employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR) and ejection duration (ED). SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD) patients. Methods: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1%) were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP) monitoring were performed. The following parameters were calculated: (1) aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75), (2) SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3) ED, (4) estimated central aortic systolic and diastolic pressure and (5) central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR) were analyzed; UACR values were natural log transformed (lnUACR). Results: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73m2 (mean 32.6; SD±24.6). We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004), eGFR (r=-0.219; P=0.04), hemoglobin (r=-0.255; P=0.02), phosphorus (r=0.222; P=0.04), iPTH (r=0.268; P=0.01), SEVR (r=-0.254; P=0.02) and ED (r=0.315; P=0.003). No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic BP and 24h ABP values were found. Using multiple regression analysis statistically significant association was found between SEVR as dependent variable and lnUACR (β=-0.223, P=0.039), sex (β=-0.216, P=0.035), and diabetes (β=0.332, P=0.001). Multiple regression analysis with ED as dependent variable has shown statistically significant association with lnUACR (β=0.242, P=0.031) and diabetes (β=-0.275, P=0.01). Patients were stratified into tertiles according to the lnUACR. Statistically significant differences in serum creatinine (P=0.001), cystatin C (P=0.012), hemoglobin (P=0.03), calcium (P=0.036), iPTH (P=0.008), SEVR (P=0.007) and ED (P=0.004) were found between tertiles. In post hoc analysis we found statistically significant differences between first and third tertile in SEVR (P=0.002; 95% CI:10.5-45) and in ED (P=0.001; 95% CI:-6.89-(-1.87)). Conclusions: Nondialysis CKD patients with higher levels of albuminuria have lower SEVR and higher ED and our results have shown the importance of central hemodynamic parameters like are SEVR and ED as a better or earlier noninvasive hemodynamic indexes in these patients.

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.

Exit-site infection and acute peritonitis due to peritoneal dialysis catheter rupture.

The patient started with continuous ambulatory peritoneal dialysis (CAPD) in 2007 due to hypertension as a cause of endstage renal disease (ESRD) after placement of a silicone PD catheter (Swan Neck Missouri PD catheter, Kendall, a Division of Tyco Healthcare group LP, Mansfield, USA) via a standard open surgical procedure. After 6 months, she changed to APD. Exit-site care was performed routinely with soap, saline, and a product for skin disinfection, occasionally with Mupirocin as well. She had an episode of acute peritonitis with Difteroides in 2010. On admission in December 2012, she reported 2 days of vomiting, abdominal pain and a fever (37.8°C). In the last 6 months before her admission, intermittent problems with negative ultrafiltration were noted, although the regime of PD had been changed several times. However, the patient’s weight was stable. Two months before her admission, she had a hernioplasty. She reported falling on the stairs on her back a few weeks before her admission. On initial evaluation, she had a temperature of 37.2°C, the abdominal examination revealed generalized tenderness, the external part of the PD catheter appeared normal, with no breaks or kinks, but there were signs of ESI with a green discharge. Peritoneal fluid demonstrated 5,308 leukocytes/μL, with a predominance of polymorphonuclear cells. She was initially treated with Ceftazidime 1,800 mg daily and Cefazolin 1,400 mg daily intraperitoneally. Later, the Ceftazidime was discontinued when coagulase-negative Staphylococcus aureus grew in hemoculture and from the exit-site culture as well. She responded well, but the drainage was slow, the volumes were gradually decreasing to zero, and fluid leakage was noted. An abdominal X-ray confirmed a wellpositioned PD catheter tip, but a disruption of the catheter was noted (Figure 1). Surgical removal revealed that the PD catheter was transected and split in 2 parts with the fracture site located 3 cm in front of the catheter cuff within the abdominal rectus musculature (Figure 2). The patient discontinued APD and hemodialysis was initiated.

Ankle‐Brachial Index and Long‐Term (10 Years) Survival of Nondiabetic Hemodialysis Patients

Low (<0.9) and high (>1.4) ankle brachial index (ABI) is associated with a higher cardiovascular (CV) mortality in the general and hemodialysis (HD) population. The aim of our study was to determine the impact of ABI on long‐term survival of 52 non‐diabetic HD patients. The ABI was determined using an automated, non‐invasive waveform analysis device. Patients were divided into three groups: low (<0.9), normal (0.9–1.4) and high (>1.4) ABI. Patients were observed from the date of ABI measurement until their death or ten years. Survival analysis showed higher risk for CV death in HD patients with high ABI compared to normal ABI (log rank test P < 0.027). In Cox regression model adjusted for arterial hypertension, smoking, serum cholesterol and triglycerides, high ABI (P < 0.049) remained a predictor of mortality. The results indicate an association between ABI and long‐term survival of non‐diabetic HD patients and only high ABI was associated with higher CV mortality.

Cystatin C as a predictor of mortality in elderly patients with chronic kidney disease

Abstract Background: The prevalence of chronic kidney disease (CKD) in the elderly is high. Serum cystatin C is an accurate marker of kidney function and it also has prognostic utility in CKD patients. The aim of our study was to determine the prediction of serum cystatin C and other markers of kidney function on long-term survival in elderly CKD patients. Methods: Fifty eight adult Caucasian patients, older than 65 years, without known malignancy, thyroid disease and/or not on steroid therapy were enrolled in the study. In each patient, 51CrEDTA clearance, serum creatinine, serum cystatin C, and estimated glomerular filtration rate using different equations were determined on the same day and patients were then followed for 11 years or until their death. Results: The means are as follows: 51CrEDTA clearance 53.3 ± 17.4 ml/min/1.73 m2, serum creatinine 1.62 ± 0.5 mg/dl, serum cystatin C 1.79 ± 0.5 mg/l, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 40.1 ± 14 ml/min/1.73 m2, Berlin Initiative Study 2 (BIS2) equation 38.9 ± 10.7 ml/min/1.73 m2, full age spectrum (FAS) creatinine equation 43.8 ± 13.8 ml/min/1.73 m2, FAS cystatin C equation 40.1 ± 11.7 ml/min/1.73 m2. In the follow up period, 47 (81%) patients died. Cox regression analysis showed different hazard ratios (HRs) for death: for 51CrEDTA clearance HR 1.022 (95% CI 1.004–1.042; p = .015), serum creatinine HR 1.013 (95% CI 1.006–1.019; p = .001), serum cystatin C HR 2.028 (95% CI 1.267–3.241; p = .003), CKD-EPI creatinine equation HR 1.048 (95% CI 1.019–1.076; p = .001), BIS2 equation HR 1.055 (95% CI 1.021–1.088; p = .001), FAS creatinine equation HR 1.046 (95% CI 1.017–1.074; p = .001), FAS cystatin C equation HR 1.039 (95% CI 1.010–1.071; p = .009). Conclusions: Our results showed the highest HR for serum cystatin C among kidney function markers for prediction of outcome in elderly CKD patients.