Radovan Hojs

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.

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.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study

BACKGROUND AND OBJECTIVES Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. RESULTS Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. CONCLUSIONS Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

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.

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.

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).

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.

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.