Sebastjan Bevc

Serum cystatin C-based equation compared to serum creatinine-based equations for estimation of glomerular filtration rate in patients with chronic kidney disease.

Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG) and modification of diet in renal disease (MDRD) formulas are serum creatinine-based equations, and the most widely used tests for renal function. Recently, serum cystatin C-based equations were proposed as markers for estimation of GFR. The present study compares our serum cystatin C-based equation (cystatin C formula) and serum creatinine-based equations for a large group of patients with CKD. In this study, 592 adult patients with CKD were enrolled. In each patient, serum creatinine was determined and creatinine clearance was calculated using the CG and MDRD formulas. The serum cystatin C was determined by an immunonephelometric method and our own cystatin C formula (GFR = 90.63 x cystatin C-1.192) for estimation of GFR was developed. GFR was measured using 51CrEDTA clearance, and the correlation, accuracy, bias and precision were determined. Ability to correctly estimate the patients GFR with different equations compared to gold standard below and above 60 ml/min/1.73 m2; was analyzed. The mean 51CrEDTA clearance was 47 ml/min/1.73 m2, the mean serum creatinine was 269 micromol/l and the mean serum cystatin C was 2.68 mg/l. Statistically significant correlation between 51CrEDTA clearance with the CG (r = 0.861) and MDRD (r = 0.909) formulas and the cystatin C formula (r = 0.899) was found. The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that the cystatin C formula had a significantly higher diagnostic accuracy than the CG formula (p < 0.003). All equations underestimated the measured GFR and lacked precision. Analysis of ability to correctly predict the patients GFR below or above 60/ml/min/1.73 m2 showed a higher prediction for the cystatin C formula than the MDRD formula (91.6 versus 84.1%, p < 0.0005) and a higher prediction trend than the CG formula (91.6 versus 88.3%, p = 0.078). Our results indicate that serum cystatin C-based equation is a reliable marker of GFR with a very high diagnostic accuracy and ability to predict patients with CKD and GFR under 60/ml/min/1.73 m2.

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.

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 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.

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 × cystatin C–1.192). The actual GFR was measured using 51CrEDTA clearance. Results: The mean 51CrEDTA clearance was 47 ml/min/1.73 m2; the mean serum cystatin C concentration was 2.68 mg/l. Receiver operating characteristic curve analysis (cutoff for GFR: 60 ml/min/ 1.73 m2) 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.

Atherosclerosis in Hemodialysis Patients—the Role of Microinflammation

Introduction. Cardiovascular diseases (CVDs) are the most frequent cause of morbidity and mortality in patients with end-stage renal disease, and the risk for coronary heart disease is higher among the hemodialysis (HD) patients than in the general population. This excess risk for coronary heart disease is not entirely explained by traditional risk factors for CVDs. The aim of the study was to determine possible correlations between asymptomatic atherosclerosis and inflammatory markers (high sensitivity CRP [hsCRP], interleukin 6 [IL-6], tumor necrosis factor-alpha [TNF-α], interleukin 2 receptor [IL-2R], and selective adhesion molecules ICAM-1 and VCAM-1) in HD patients. Patients and methods. In our study, 95 HD patients, 56 (59%) male and 39 (41%) female, were included. The mean age was 60 ± 13 years, ranging from 22–81 years. Using B-mode ultrasonography (US), we measured intima-media thickness (IMT) and plaque occurrence (markers of asymptomatic atherosclerosis) in carotid arteries in these patients. In the 1–4 weeks after US examination, we took blood samples from patients to determine serum concentrations of inflammatory markers. Results. The mean IMT value was 0.83 ± 0.21 mm, ranging from 0.5 to 2 mm. The plaques were found in 63 (84%) of HD patients. Correlations between IMT values and serum concentrations of IL-2R (r = 0.269; p < 0.022) and VCAM-1 (r = 0.290; p < 0.014) were found. Multiple linear regression analysis showed relationship between IMT values and IL-2R (p = 0.049). No relationship between inflammatory markers and plaques was found. Conclusion. The results indicate that atherosclerosis in HD patients correlates with some nontraditional risk factors—the markers of inflammation.

Kidney function estimating equations in patients with chronic kidney disease

Background:  The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C‐based equations and serum creatinine‐based equations in patients with chronic kidney disease (CKD).

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.

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 51CrEDTA clearance in 252 patients with CKD and GFR <90 mL/min/1.73 m2. 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.

Biomarkers of Renal Disease and Progression in Patients with Diabetes

Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase), markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines) and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

Mortality of patients with renal dysfunction after percutaneous coronary intervention.

Aim: To determine the impact of stages of renal dysfunction on mortality after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Patients and Methods: A total of 449 patients (mean age 63 ± 11.9 years) with ACS after PCI were included. Serum creatinine was determined and creatinine clearance was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Results: The prevalence of chronic kidney disease (CKD) defined as glomerular filtration rate (GFR) <60 mL/min per 1.73 m2 was 26.3%. After up to 787 days of follow-up, 40 patients had died. Kaplan-Meier survival analysis showed progressively higher risk for cardiovascular death from stage 1 to stage 4 of renal dysfunction. In an adjusted Cox model, gender (P < .009), age (P < .0001), total cholesterol level (P < .01), and stage of renal dysfunction (P < .04) were predictors of mortality. Conclusions: In patients with ACS after PCI, a higher stage of renal dysfunction was directly associated with higher mortality of these patients.