Chronic Kidney Disease Epidemiology Collaboration Formula Research Articles

Assessment of renal and cardiovascular risks in patients with type 2 diabetes when using non-steroidal mineralocorticoid receptor antagonists

Background. Given the proven excessive activation of the renin-angiotensin-aldosterone system and the clinical manifestations of hypertension, mostly of renal origin, there is a need to optimize antihypertensive therapy aimed at an active nephroprotection. The purpose of the study is to carry out a comprehensive assessment of kidney and heart risk factors in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) and to justify the administration of non-steroidal mineralocorticoid receptor antagonists to these patients. Materials and methods. In a prospective cohort study, 88 patients with type 2 diabetes were examined: group 1 — estimated glomerular filtration rate (eGFR) < 60 ml/min/m2, group 2 — eGFR ≥ 60 ml/min/m2. eGFR was evaluated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Colla­boration) formula based on serum creatinine. GFR category was defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The albumin-creatinine ratio was calcula­ted. The level of glycated hemoglobin (HbA1c) was assessed by the method of high-performance liquid chromatography. Aldosterone was evaluated by immunoenzymatic method. Results. In patients with eGFR < 60 ml/min/m2, the albumin-creatinine ratio in daily urine is statistically significantly higher compared to group 2. Patients with eGFR < 60 ml/min/m2 had an average uric acid level of 410.3 ± 98.8 μmol/l, which is statistically significantly higher than in those with eGFR ≥ 60 ml/min/m2 — 321.10 ± 74.54 μmol/l. A statistically significant correlation between the level of uric acid and markers of renal dysfunction was found only in patients with eGFR < 60 ml/min/m2. Aldosterone levels were higher in the first group. No statistical difference was found between the average value of HbA1c in the studied groups. Conclusions. Numerous factors of unfavorable prognosis regarding kidney and heart risks have been identified: hypertension, increased albumin-creatinine ratio and cholesterol, unsatisfactory compensation of diabetes, obesity. There is an increase in the frequency of resistant hypertension, hyperuricemia, and hyperaldosteronism in patients with decreased eGFR. In patients with diabetic kidney damage on the background of type 2 diabetes, the administration of finerenone, a non-steroidal mine­ralocorticoid receptor antagonist, at a dose of 10–20 mg/day is pathogenetically justified.

Abstract 15604: Dietary Patterns, Blood Pressure and Proteinuria in a West African Chronic Kidney Disease Population

Introduction: There is little known about the impact of dietary patterns on blood pressure (BP) in West Africa. Our study describes associations of dietary patterns with BP and albuminuria and is the first study to do so in a well-phenotyped West African CKD cohort. Research question: What are the associations of dietary patterns with BP and proteinuria in West African CKD patients? Methods: We performed a cross-sectional analysis of participants from the Diet, Apolipoprotein L1, and CKD study; an ancillary study under the H3 Africa Network. We analyzed 24-hour dietary recalls in 583 participants. Dietary patterns were derived via principal component analysis, and the first 3 principal components with eigenvalues > 1 were selected. We measured proteinuria using 24-hour urine samples. Mixed effect linear regression models were used to estimate the β coefficient and 95% confidence interval for the quartiles of the dietary patterns with BP and proteinuria after adjusting for covariates. Results: The mean age was 49±17 years with 51% males and the mean eGFR (2009 CKD-Epidemiology collaboration formula) was 68±39 mL/min/1.73m 2 . The median 24-hour urine protein was 0.31g (IQR=0.13-1.07). We identified the Dried fish, Oils and vegetables; Poultry and Cereal; and the Fruit and Cereal dietary patterns . Compared to Q1 (lowest consumption), higher quartiles of intake of the Poultry and Cereal dietary pattern were associated with lower systolic BP (SBP) and diastolic (DBP). Higher consumption of the Poultry and Cereal dietary pattern was associated with lower 24hr urine protein, with a significant p for trend (p=0.05). Compared to Q1, Q4 of this pattern was associated with reduced odds of proteinuria ( Table 1 ). Conclusions: Consuming a Poultry and Cereal dietary pattern may be beneficial for BP and proteinuria in West African CKD patients.

Role of beta 2 microglobulin in chronic kidney disease

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p>0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

#6668 PREDICTION OF REMAINING RENAL FUNCTION IN PATIENTS UNDERGOING RADICAL NEPHRECTOMY DUE TO RENAL TUMOUR MASS AND AFTER NEPHRECTOMY IN LIVING DONORS

Abstract Background and Aims Accurate assessment of renal function is of great importance in clinical practise, in particular in patients undergoing nephrectomy due to tumor nephrectomy or in potential living kidney donors. In both cases, residual renal function is dependent on the remaining nephron number and their function. A reliable prediction of the post-nephrectomy kidney function would be of great help to identify the patient with an increased functional risk. The aim of this study was to assess if the short-term kidney function after nephrectomy can be reliably predicted. Method We performed a retrospective study in 68 living kidney donors (LD-Nx) and 43 patients undergoing nephrectomy due to a renal tumour (Tu-Nx) between 1st of January 2011 to 31st of December 2015 at the University Hospital Zurich. Baseline serum creatinine was defined as lowest observed serum creatinine value before LD-Nx and Tu-Nx and was used for calculation of estimated glomerular filtration rate (eGFR) by the Cockroft-Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. The expected post-nephrectomy kidney function was calculated based on the formula (expected eGFRpost = 0.6 * eGFRpre + 8.7) described in detail in: (Prediction of kidney function after nephrectomy was performed by using the formulas previosly established by our group [1]). Expected eGFR was calculated for CG and CKD-EPI formulas and expected serum creatinine was calculated from the expected eGFR based on CG formula. The expected kidney function was then compared to the observed kdiney function based on lowest observed serum creatinine (LoObsSCr) during the first year after nephrectomy and the corresponding eGFR values for CG and CKD-EPI were calculated. Results Patients with nephrectomy due to renal tumour had significantly higher baseline serum creatinine levels compared to living donors (100±50 umol/l vs. 70±12 umol/l, respectively) with 35% having proteinuria, 58% hypertension and 14% diabetes mellitus. In addition Tu-Nx patients were significantly older and had a higher body weight. Living donors had a higher percentage of smokers (31%) compared to the other group. Predonation eGFR CKD-EPI was 71±23 ml/min/1.73 m2 for Tu-Nx and 94±12 ml/min/1.73 m2 for LD-Nx patients. Both groups showed an adaptive increase in kidney function calculated by eGFR CKD-EPI: 29% for Tu-Nx and 14% for LD-Nx. LD-Nx patients had less bias in prediction of post-nephrectomy kidney function (Table 1). Lowest observed serum creatinine after nephrectomy did not significantly differ between the groups. A significant correlation between expected and observed serum creatinine values, as well as between expected and observed eGFR post-nephrectomy, was seen in both groups of patients. Conclusion Despite older age, higher body weight and more comorbidities, patients with tumor nephrectomy show an adaptive increase in kidney function. Prediction of kidney function after nephrectomy is possible for both groups, however more accurate for living donor patients.

Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach.

The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV) or oral administration of valganciclovir (VGCV), both adjusted to the renal function. In both instances, there is a high interindividual pharmacokinetic variability, mainly owing to the wide range of variation of both the renal function and body weight. Therefore, accurate estimation of the renal function is crucial for GCV/VGCV dose optimization. This study aimed to compare three different formulas for estimating the renal function in solid organ transplantation patients with cytomegalovirus infection, for individualizing antiviral therapy with GCV/VGCV, using a population approach. A population pharmacokinetic analysis was performed using NONMEM 7.4. A total of 650 plasma concentrations obtained after intravenous GCV and oral VGCV administrations were analyzed, from intensive and sparse sampling designs. Three different population pharmacokinetic models were built with the renal function given by Cockcroft-Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formulas. Pharmacokinetic parameters were allometrically scaled to body weight. The CKD-EPI formula was identified as the best predictor of between-patient variability in GCV clearance. Internal and external validation techniques showed that the CKD-EPI model had better stability and performed better compared with the others. The model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.

Creatinine Clearance Measurement with Bioelectrical Impedance Analysis in Heart Failure Patients: Comparison with Estimated-Creatinine Clearance Formulas.

Kidney disease is common in patients with heart failure (HF). The Donadio equation combines plasma creatinine and bioimpedance vector analysis (BIVA) to estimate creatinine clearance. This study aimed to compare the Donadio formula to the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD-4), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in patients with HF. We analysed data from 900 patients (mean age: 76 ± 10 years) with HF. All of them underwent clinical, laboratory, BIVA, and echocardiographic evaluations. Donadio equation overestimated eGFR as compared to CG and CKD-EPI formulas (+6.8 and +12 mL/min/1.73 m2, respectively) while computing similar results to MDRD-4 (overestimation: +0.1 mL/min/1.73 m2). According to the different formulas, the prevalence of renal insufficiency (eGFR< 30 ml/min/1.73 m2) in relation to the different formulas was as follows: 24% with Donadio, 21% with CG, 13% with MDRD-4, and 23% with CKD-EPI formulas. All the equations demonstrated a high precision rate (r>0.8 for all). There was a "good" agreement between the Donadio and CG/MDRD-4 formulas and "fair" with the CDK-EPI formula. The Donadio equation showed a high accuracy in predicting severe renal dysfunction (eGFR< 30 mL/min/1.73 m2) in patients with HF (AUC > 0.9), showing comparable performances to CG. The Donadio formula provided an estimation of GFR comparable to MDRD-4 in HF patients, independently from acute or chronic HF conditions. The use of BIVA in HF patients may be adopted both for HF management and for evaluating kidney function.

Estimation of glomerular filtration rate in children: interest of FAS formula

The recommended equation to estimate the value of glomerular filtration rate (eGFR) among children is Schwartz equation updated in 2009. However, it is few frequently used because involves height, a factor rarely documented for laboratories, especially hospital laboratories. The FAS (Full Aged Spectrum) formula developed by a European group, allows to get away from this factor. We compared CKD-EPI (Chronic Kidney Disease-EPIdemiology collaboration) and FAS formulas to Schwartz equation to estimate GFR in children. We realized a retrospective study included 1.668 children between 2 and 14 years old, whose serum creatinine had been measured during their hospitalization stay. We showed that FAS formula is correlated to Schwartz (r = 0.88), with a mean underestimation of eGFR at 6.2% versus CKD-EPI which has a correlation coefficient equal to 0.45 and overestimates eGFR to approximatively 42.0% compared to Schwartz formula. Furthermore, concordance at 30% is 99% with FAS whereas it’s only 35% with CKD-EPI. Thus, we recommend using the FAS formula to estimate GFR in children between 2 and 14 years old when their height is not available.

Clinical Relevance of a Vancomycin 24 h Area under the Concentration-Time Curve Values Using Different Renal Function Equations in Bayesian Dosing Software.

With the updated 2020 vancomycin therapeutic drug monitoring (TDM) guidelines suggesting a ratio of area under the curve over 24 h to a minimum inhibitory concentration (AUC24/MIC) as a target from the Infectious Diseases Society of America, an accurate estimation of AUC24 has become more critical. We aim to compare the AUC24 using Bayesian dosing software according to various estimated glomerular filtration rate (eGFR) equations in order to analyze the clinical impact of eGFR in vancomycin TDM. We reviewed the TDM dataset of 214 adult patients and analyzed the AUC24 values from various renal function equations, including the Cockcroft-Gault (C-G), the modification of diet in renal disease (MDRD), the chronic kidney disease epidemiology collaboration (CKD-EPI), and the revised Lund−Malmö. The AUC24/MIC results (assuming a MIC of 1 mg/L) were divided into three groups as follows: <400, 400−600, and >600. Additionally, we compared the group agreement between the C-G and the three eGFR formulas. Although there was a statistically significant difference in the AUC24 of the MDRD and the CKD-EPI formulas compared to the C-G, the group concordance rate of the eGFR formula was 95.2−100%, which indicates no clinical significance. The clinical impact of the eGFR formula type on drug dosing recommendations in vancomycin TDM using Bayesian software was insignificant in clinical practice.

Evaluating Equations for Estimated Glomerular Filtration Rate (eGFR) in Patients with Sickle Cell Disease (SCD)

Background: Assessment of kidney function in sickle cell disease poses a unique dilemma, both due to the presence of hyperfiltration and the increased tubular secretion of creatinine, the metabolite most often used in eGFR assessment. In the general population, formulae utilizing serum creatinine have been developed to estimate GFR. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have developed the most recent formulae. Until recently, the CKD-EPI-2009 creatinine-based formula has been the standard for estimating eGFR and included black race as a variable in the formula. This formula has been noted to overestimate eGFR in SCD patients, but its bias is improved when the black race variable is excluded. Among available formulae, the CKD-EPI-2012 cystatin C-based formula was shown to have the least bias in SCD patients compared to radionucleotide measured GFR but loses its accuracy when combined with creatinine. The recently developed CKD-EPI-2021 formula which excludes race as a variable is becoming the standard formula in most clinical laboratories. In this multicenter study, we sought to evaluate the agreement of various CKD-EPI formulae in SCD patents. Methods: Patients with HbSS or HbSb0 thalassemia between ages 18 and 65 years were enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with bone marrow transplantation, diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, and end-stage kidney disease on dialysis. Participants were enrolled during routine clinical visits at four centers. At baseline, blood samples and urine were obtained, and kidney function was assessed using each sites clinical laboratory to measure serum creatinine. Serum cystatin C was also measured at baseline using a commercially available ELISA kit. We calculated eGFR using each of the CKD-EPI formula, excluding the race variable in the CKD-EPI-2009 formula. Spearman's rank correlation coefficients were calculated for each formula compared to the others. Prevalence of CKD was assessed using the CKD-EPI-2009, CKD-EPI-2012 (cystatin C) and CKD-EPI-2021 formulae and defined as the presence of albuminuria or an eGFR ≤ 90 ml/min/1.73m2. Prevalence of CKD derived from the CKD-EPI-2012 was compared to the other two formulae using McNemar's Chi-squared test with 95% confidence intervals determined using bootstrap replications. Results: Our cohort enrolled 284 subjects with HbSS or HbSb0 thalassemia. For these analyses, 277 patients with baseline serum creatinine were included. The mean age of included subjects was 32.9 (SD ±11.5) years and 57% were female (N=158). The median eGFR of these subjects using the creatinine-based CKD-EPI-2009 formula was 123.9 (IQR 105.9, 134.0) ml/min/1.73m2. Cystatin C was available in 270 patients and had median value of 0.72 (IQR 0.59, 0.92) mg/L. Correlation between the several eGFR formulae are presented in Table 1. CKD-EPI-2009 and CKD-EPI-2021 creatinine-based formulae were very highly correlated with each other; both had similar but less correlation with the CKD-EPI-2012 cystatin C-based formula, which has been shown previously to have the least bias when compared to measured GFR. The prevalence of CKD using the creatinine-based CKD-EPI-2009 formula was 51.3% and 50.5% using the creatinine-based CKD-EPI-2021 formula. When assessed with the cystatin C-based CKD-EPI-2012 formula, CKD prevalence was higher at 55.7% (p<0.0001) than that seen with both of creatinine-based CKD-EPI formulae. Conclusions: When comparing the new CKD-EPI-2021 creatinine-based formula to the CKD-EPI-2009 formula (excluding the black race variable), eGFR calculation remains very similar in SCD patients. The CKD-EPI-2009 formula is well recognized to overestimate eGFR in SCD patients. Our data would suggest the newer formula would have similar bias. Using the cystatin C-based CKD-EPI-2012 formula, the prevalence of CKD is higher in this SCD cohort than using creatinine-based CKD-EPI formulae, although our data are limited by lack of directly measured GFR. We anticipate the newer CKD-EPI-2021 creatinine-based formula would similarly underestimate prevalence of CKD in SCD. Use of cystatin C for assessing kidney function in SCD patients should be considered, and resources should be utilized to make this measure more widely and readily available. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Estimated glomerular filtration rate derived from different formulas and prognosis in acute coronary syndrome: Findings from the improving care for cardiovascular disease in China-acute coronary syndrome project

BackgroundThe optimal formula for the estimation of glomerular filtration rate (GFR) in patients with acute coronary syndrome (ACS) in terms of predicting in-hospital mortality and adverse events remains unclear. MethodsA nationwide registry study, Improving CCC (Care for Cardiovascular Disease in China) ACS project, was launched in 2014 as a collaborative study of the American Heart Association and Chinese Society of Cardiology. The Cockcroft-Gault, modification of diet in renal disease (MDRD) formula for Chinese (C-MDRD), Mayo, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate estimated GFR in 61,545 ACS patients (38,734 with ST-segment elevation myocardial infarction [STEMI] and 22,811 with non-ST-segment-elevation ACS [NSTE-ACS]). ResultsPrevalence of moderate to severe renal dysfunction was inconsistent among four formulas, ranging from 11.6% to 22.4% in NSTE-ACS and from 8.3% to 16.8% in STEMI, respectively. The in-hospital mortality rate in patients with ACS was inversely associated with estimated GFR. In STEMI, the Mayo-derived eGFR exhibited the highest predictive power for in-hospital death compared with the Cockcroft-Gault-derived eGFR (area under the curve [AUC]: 0.782 vs. 0.768, p=0.004), C-MDRD-derived eGFR (AUC: 0.782 vs. 0.740, p<0.001) and CKD-EPI-derived eGFR (AUC: 0.782 vs. 0.767, p<0.001). In NSTE-ACS, the Mayo-derived eGFR exhibited a similar predictive value with the Cockcroft-Gault (AUC: 0.781 vs. 0.787, p>0.05) and CKD-EPI-derived eGFR (AUC: 0.781 vs. 0.784, p>0.05). ConclusionsThe Mayo formula was superior to Cockcroft-Gault, C-MDRD, and CKD-EPI formulas for predicting in-hospital mortality in ACS patients, especially for STEMI. The Mayo-derived eGFR may serve as a risk-stratification tool for in-hospital adverse events in ACS patients. Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616.

Which glomerular filtration rate estimation formula should be used for nephrological evaluation in patients with common variable immune deficiency

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. In addition to renal complications of the disease, there may be an increased likelihood of renal dysfunction due to sucrose in immunoglobulin replacement therapies or other drugs used in treatment. In CVID patients, it is important to monitor patients for renal complications at routine intervals. We compared creatinine-based calculation methods for estimated glomerular filtration rate (eGFR) such as Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with 24-hour urine creatinine clearance measurement. We aimed to investigate which calculation method was more reliable and consistent in this patient population. Methods: The records of 14 patients who had clinical follow-up at our hospital were retrospectively reviewed. Patients’ eGFR values were measured by three different methods (CKD-EPI, MDRD , and CG formulas). The 24-hour urinary creatinine clearance of all patients and e-GFR calculated by the formula were compared. Results: The eGFR calculated using the MDRD formula was 122.99±41.22 mL/min/1.73 m2, whereas the eGFR measured using the 24-hour urinary creatinine clearance was 99.64(83.35-156.58) mL/min/1.73 m2. Moreover, eGFR calculated by CKD-EPI formula was 113.83±26.46 mL/min/1.73 m2, while eGFR calculated by CG formula was 133.52±45.35 mL/min/1.73 m2. 24-hour urinary creatinine clearance was positively correlated with MDRD, CKD-EPI and CG formulas (r=0.726, p=0.003, r=0.634, p=0.015, r=0.806, p=0.001, respectively). Conclusions: We found that all creatinine-based formulas used in clinical practice for eGFR measurement correlate with 24-hour urine creatinine clearance in patients with CVID. In addition, we have shown that eGFR calculated with the formula CKD-EPI is more closely related to 24-hour urinary creatinine clearance. Therefore, we believe that the eGFR measurement calculated with CKD-EPI is more useful for nephrological follow-up of patients with CVID. It should be noted that our study has some limitations due to the small number of patients.

MO1026: Performance of Creatinine and Cystatin-Based Estimates of GFR in Paediatric Kidney Transplant Recipients. Comparison of the CKD-EPI Age- Adjusted Creatinine eGFR with Previous Formulas

Abstract BACKGROUND AND AIMS Estimation of glomerular filtration rate (GFR) is essential for renal function evaluation and the surveillance of kidney transplant recipients. We aimed to compare the GFR estimation by different formulas using creatinine and/or cystatin C, in paediatric kidney transplant recipients and to compare the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation with age-adjusted creatinine values for height-independent estimated GFR (eGFR) calculation. We also intend to evaluate the impact of body mass index (BMI) influence on eGFR. METHOD Data on paediatric renal transplant patients (n = 35) with stable graft function for more than 6 months post-transplantation were enrolled. eGFR was calculated using the revised Schwartz (bedside Cr), CKD-EPI (Cr), CKiD (CysC), Zappitelli (CysC), combined Schwartz (Cr/CysC) and combined Zappitelli (Cr/CysC) formulas. The estimation by CKD-EPI formula used age and sex-adjusted creatinine values to adult levels with 40 as assigned age (CKD-EPI40). RESULTS A total of 35 patients were included, 26 (76%) were male, with a median age of 16 (4–18) years and a median BMI of 21.27 (15.20–32.29) with a Z-score median of 3.26 (2–5). The median eGFR obtained by the Schwartz [64.39 (23.96–115.16) mL/min/1.73 m2] and by the CKD-EPI40 equation [64.99 (13.98-141.80) mL/min/1.73 m2] was similar (P = .176). When compared with the Schwartz estimation, Cys-based eGFR were significantly lower (by CKiD-CysC, 49.48 (25.47–84.68) (P &amp;lt; .001), by Zappitelli formula 51.31 (24.74–92.61) (P &amp;lt; .001), by combined Schwartz 51.37 (24.07–85.31), (P &amp;lt; .001), by combined Zappitelli 54.83 (20.64–109.68).The correlations between eGFR by all formulas were strong and statistically significant, especially between the combined Schwartz and the combined Zappitelli (r = 0.97). The same pattern of differences between the eGFR estimations was observed when BMI groups (normal versus overweight) were analysed separately, with all formulas being significantly different for Schwartz except for CKD-EPI. CONCLUSION As expected, formulas with creatinine were similar to each other but significantly different when compared with formulas that included cystatin. As demonstrated in previous studies, the combined formulas appear to be the closest estimates of the GFR calculated by exogenous methods. Thus, estimates that consider only creatinine may overestimate the GFR. The eGFR obtained by the adjusted CDK-EPI formula is similar to that obtained by the Schwartz bedside, unlike the other formulas. In this study, we did not find differences regarding the BMI, probably due to the number of this sample.

Comparison of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula based eGFR (estimated glomerular filtration rate) with C-G (Cockcroft-Gaul) and MDRD (Modification of Diet in Renal Disease) formula based eGFR in adult Bangladeshi population

Glomerular filtration rate (GFR) is the most important and accurate measure of overall kidney functions both in good health and disease because it is the sum of the filtration rates in each of the functioning nephrons .Different GFR measuring methods have some limitations.The objective of this study was to compare the CKD-EPI formula based eGFR with that of Cock- croft- Gault formula &amp; 4 variable MDRD formula based eGFR.This Cross-sectional analytical study was done in the Department of Biochemistry &amp; Molecular biology, BSMMU September during the period of July 2017 to August 2018. Serum creatinine was measured and eGFR by MDRD, CKD-EPI and Cockcroft-Gault formula was calculated using the respective equations on online calculator. Comparison of eGFR values between CKD-EPI &amp; MDRD formula and between CKD-EPI &amp; Cockcroft-Gault formula were done among different groups. Compari- son was done by Bland Altman agreement test to see the agreement on the measurement of GFR between three equation based eGFR method. Pearson‘s correlation test revealed a positive correlation between C-G and CKD-EPI (r = 0.779), but a stronger correlation between MDRD and CKD-EPI (r = 0.934). Bland-Altman plot showed strong agreement between CKD-EPI &amp; 4–variable MDRD than between CKD-EPI &amp; C-G formula. From this study we may conclude CKD-EPI and MDRD formula showed better agreement than between CKD-EPI and Cockcroft-Gault formula. So, this study suggests that CKD-EPI and MDRD equations can be used to estimate GFR more effectively than Cockcroft-Gault equation in Bangladeshi population. BSMMU J 2021; 14(4): 152-156

Kidney Function According to Different Equations in Patients Admitted to a Cardiology Unit and Impact on Outcome.

Background: This paper aims to evaluate the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and alternative equations and to assess their predictive power for all-cause mortality in unselected patients discharged alive from a cardiology ward. Methods: We retrospectively included patients admitted to our Cardiology Division independently of their diagnosis. The total population was classified according to Kidney Disease: Improving Global Outcomes (KDIGO) categories, as follows: G1 (estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2); G2 (eGFR 89–60 mL/min/1.73 m2); G3a (eGFR 59–45 mL/min/1.73 m2); G3b (eGFR 44–30 mL/min/1.73 m2); G4 (eGFR 29–15 mL/min/1.73 m2); G5 (eGFR <15 mL/min/1.73 m2). Cockcroft-Gault (CG), CG adjusted for body surface area (CG-BSA), Modification of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS-1), and Full Age Spectrum (FAS) equations were also assessed. Results: A total of 806 patients were included. Good agreement was found between the CKD-EPI formula and CG-BSA, MDRD, BIS-1, and FAS equations. In subjects younger than 65 years or aged ≥85 years, CKD-EPI and MDRD showed the highest agreement (Cohen’s kappa (K) 0.881 and 0.588, respectively) while CG showed the lowest. After a median follow-up of 407 days, overall mortality was 8.2%. The risk of death was higher in lower eGFR classes (G3b HR4.35; 95%CI 1.05–17.80; G4 HR7.13; 95%CI 1.63–31.23; G5 HR25.91; 95%CI 6.63–101.21). The discriminant capability of death prediction tested with ROC curves showed the best results for BIS-1 and FAS equations. Conclusion: In our cohort, the concordance between CKD-EPI and other equations decreased with age, with the MDRD formula showing the best agreement in both younger and older patients. Overall, mortality rates increased with the renal function decreasing. In patients aged ≥75 years, the best discriminant capability for death prediction was found for BIS-1 and FAS equations.

Evaluation of Four eGFR Calculating Formulae in Predicting Postoperative Acute Kidney Injury in Adult Patients Undergoing Open‐Heart Surgery with Cardiopulmonary Bypass

Objective There are four widely-used formulae to calculate the perioperative glomerular filtration rate (GFR) of patients undergoing cardiac surgery. We assessed the predictive values of these formulae in the occurrence of postoperative acute kidney injury (AKI). Methods Patients who underwent open-heart valvular surgery with cardiopulmonary bypass from January 2015 to October 2017 were enrolled in this retrospective study. Demographic data and perioperative serum creatinine levels were collected. The estimated GFR (eGFR) was calculated using four formulae: Cockcroft Gault (CG), body surface area (BSA) corrected CG, simplified modification of diet in renal disease (MDRD), and chronic kidney disease-epidemiology collaboration (CKD-EPI) formula. The incidence of post-operative AKI was calculated and the predictive capability of these formulae was evaluated. Results A total of 290 patients were included. 136 patients (46.90%) developed AKI after surgery. The eGFR in the AKI group was significantly lower than those in the non-AKI group at all investigated time points. In addition, the eGFR in the non-AKI group increased temporarily on the day of operation, then decreased on the following days, and returned to preoperative level about one week after surgery. However, in the AKI group, the eGFR decreased from the day of operation, which still did not recover to the preoperative level by the end of the first week after surgery. The eGFR calculated by the BSA-standardized CG formula had the highest AUC ROC curves of 0.699 and 0.774 before operation and on the day of operation, respectively. While eGFR calculated by CKD-EPI formula had the highest AUC ROC of 0.874 and 0.887 at the first and second postoperative day. Conclusions The eGFR formula is a powerful tool for perioperative renal function assessment. The BSA-corrected CG and CKD-EPI formula have better performance in predicting postoperative AKI after cardiopulmonary bypass than serum creatinine level and other formulae.

284 Worsening renal function as an outcome predictor in patients with new onset atrial fibrillation on direct oral anticoagulant

Abstract Aims In patients with atrial fibrillation (AF), baseline kidney function is used to guide oral anticoagulant (OA) selection and dosing, and chronic kidney disease (CKD) is a significant outcome predictor. However, the incidence of worsening renal function (WRF) and its prognostic role during treatment with direct oral anticoagulants (DOACS) has been poorly explored. To assess the prognostic role of WRF in terms of bleedings and major adverse cardiovascular events (MACEs) in a cohort of patients with newly diagnosed non-valvular AF (NVAF) treated with DOACs. Methods and results Between January 2017 and March 2019, we enrolled all the patients with newly diagnosed NVAF and OA indication, treated with DOACs. Renal function was assessed using the mean value of the estimated glomerular filtration rates (eGFR) calculated using Cockcroft–Gault (CG), modification of diet in renal disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. CHA2DS2-VASc and HAS-BLED scores were used at baseline to estimate the ischaemic and haemorrhagic risk, respectively. At follow-up, WRF was identified as a decrease in eGFR of at least 20% while bleedings were classified according to the international society of thrombosis and haemostasis (ISTH) criteria. Finally, we defined AF progression as the transition from paroxysmal to persistent or permanent AF or from persistent to permanent AF. 1009 patients with newly diagnosed NVAF started on DOAC were enrolled. They were followed-up for 21.6 ± 9.5 months. Overall, WRF was observed in 181 cases (18%). Patients with WRF had higher rates of progression of AF (18.5% vs. 11.8%, P = 0.02), MACEs (20.4% vs. 12.9%, P = 0.09) and major bleedings (MBs) (9.4% vs. 4.7%, P = 0.013). WRF did not correlate with all bleedings, stroke, or acute coronary syndrome (ACS). However, those who presented WRF using CKD-EPI formula had higher ACS incidence (6.1% vs. 2.5%, P = 0.015), and generally better-predicted MACEs. At multivariate analysis adjusted for age, hypertension, baseline HAS-BLED score and WRF, the latter emerged as an independent predictor of MB (OR: 1.9, 95% CI: 1.059–3.51). Conclusions In patients with newly diagnosed NVAF treated with DOACs, WRF is associated with AF progression and MACEs, and emerged as an independent predictor of major bleedings. WRF evaluated with CKD-EPI formula better predicted MACEs.

Worsening renal function as an outcome predictor in patients with new onset atrial fibrillation on direct oral anticoagulant

Abstract Background In patients with atrial fibrillation (AF), baseline kidney function is used to guide oral anticoagulant (OA) selection and dosing, and chronic kidney disease (CKD) is a significant outcome predictor. However, the incidence of worsening renal function (WRF) and its prognostic role during treatment with direct oral anticoagulants (DOACS) has been poorly explored. Purpose To assess the prognostic role of WRF in terms of bleedings and major adverse cardiovascular events (MACEs) in a cohort of patients with newly diagnosed non-valvular AF (NVAF) treated with DOACs. Methods Between January 2017 and March 2019, we enrolled all the patients with newly diagnosed NVAF and OA indication, treated with DOACs. Renal function was assessed using the mean value of the estimated glomerular filtration rates (eGFR) calculated using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. CHA2DS2-VASc and HAS-BLED scores were used at baseline to estimate the ischemic and hemorrhagic risk, respectively. At follow-up, WRF was identified as a decrease in eGFR of at least 20% while bleedings were classified according to the international society of thrombosis and hemostasis (ISTH) criteria. Finally, we defined AF progression as the transition from paroxysmal to persistent or permanent AF or from persistent to permanent AF. Results 1009 patients with newly diagnosed NVAF started on DOAC were enrolled. They were followed-up for 21.6±9.5 months. Overall, WRF was observed in 181 cases (18%). Patients with WRF had higher rates of progression of atrial fibrillation (18.5% vs 11.8%, p=0.02), MACEs (20.4% vs 12.9%, p=0.09) and major bleedings (MB) (9,4% vs 4,7%, p=0.013). WRF did not correlate with all bleedings, stroke, or acute coronary syndrome (ACS). However, those who presented WRF using CKD-EPI formula had higher ACS incidence (6.1% vs 2.5%, p=0.015), and generally better-predicted MACEs. At multivariate analysis adjusted for age, hypertension, baseline HAS-BLED score and WRF, the latter emerged as an independent predictor of MB (OR 1.9 95% C.I, 1,059–3,51). Conclusion In patients with newly diagnosed NVAF treated with DOACs, WRF is associated with atrial fibrillation progression and MACEs, and emerged as an independent predictor of major bleedings. WRF evaluated with CKD-EPI formula better predicted MACEs. Funding Acknowledgement Type of funding sources: None.

Potential risks of substituting estimated glomerular filtration rate for estimated creatinine clearance for dosing of direct oral anticoagulants in atrial fibrillation and chronic kidney disease

Abstract Background In the clinical trials with direct oral anticoagulants (DOAC) estimates of creatinine clearance (CrCl) with Cockcroft-Gault equation were used to assess renal functions. Recently, most laboratories report renal function estimated with the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, which may lead to impaired dosing of DOACs by physicians. Purpose To compare estimated glomerular filtration rate and estimated creatinine clearance in a large group of patients with atrial fibrillation and chronic kidney disease. Methods Physicians from 423 institutions in the Czech Republic were asked to enroll 5 consecutive outpatients with atrial fibrillation (AF) treated by a DOAC with stage 3 chronic kidney disease and glomerular filtration rate (eGFR) 30–59 ml/min estimated by MDRD or CKD EPI equations into the registry. Besides eGFR, serum creatinine values were recorded and CrCl calculated by the Cockroft-Gault formula. Results of CrCl and eGFR obtained in individual patients were compared and statistically analyzed using two-sample t-test. Results A total of 2115 patients were enrolled. Mean CrCl was 47.43 ml/min, mean eGFR calculated by MDRD and CKD-EPI was lower 43.88 and 43.53 ml/min (P for difference &amp;lt;0.001 for both). Mean difference between CrCl and eGFR in individual patients calculated by MDRD and CKD-EPI was 8.8 and 9.41 ml/min. A difference beween CrCl and eGFR &amp;gt;10 ml/min was found in 31.5% and 34.8% patients when using MDRD and CKD-EPI formulas. The respective differences between CrCl and eGFR between 4.1 and 10 ml/min were found in 28.5% (MDRD) and 30.8% (CKD-EPI). At CrCl above or below 50 ml/min, 24.0% and 24.2% were misclassified when using eGFR calculated by MDRD and CKD-EPI. At CrCl above or below 30 ml/min, 9.8% (MDRD) and 10.0% (CKD-EPI) patients were misclassified (please see Figures). Conclusions When eGFR estimated by MDRD or CKD-EPI is used to assess renal function and guide DOAC dosing instead of CrCl calculated by the Cockroft-Gault formula in patients with AF and stage 3 CKD, more than a third of patients is misclassified and wrong DOAC dose can be recommended. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer-Ingelheim Differences between CrCl and CKD-EPIDifferences between CrCl and MDRD

Arterial stiffness measured according to the cardio-ankle vascular index in the persons with pre-diabetes and diabetes mellitus in the population sample of the Russian Federation

Abstract Aims To study the characteristics of the cardio-ankle vascular index (CAVI) and predictors of increased arterial stiffness in patients with carbohydrate metabolism disorders (CMD). Methods A cross-sectional study was conducted within the framework of the multicenter epidemiological study “Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation” (ESSE-RF) from March to October 2013. The object was a random population sample of the adult male and female population of the Kemerovo region (Western Siberia, Russia) aged of 25–64 years. The standard protocol of the ESSE-RF has been expanded with investigation of peripheral arteries wall stiffness (VaSeraVS-1000, Fukuda Denshi, Japan) with automatic CAVI calculation. A total of 1617 subjects were divided into three groups: group 1 – patients with type 2 diabetes mellitus (n=272), group 2 – patients with pre-diabetes (n=44), group 3 –without any confirmed CMD (n=1301). Results A trend for the similarity of clinical, instrumental (including arterial stiffness measured by CAVI) and laboratory characteristics in patients with type 2 diabetes and prediabetes was revealed, with a significant difference from patients without CMD. A direct correlations of CAVI with age (p&amp;lt;0.001), male gender (p&amp;lt;0.001), type 2 diabetes (p&amp;lt;0.001), prediabetes (p=0.002), visceral obesity (p&amp;lt;0.001), level of total cholesterol (p&amp;lt;0.001), triglycerides (p&amp;lt;0.001), low density lipoprotein cholesterol (p&amp;lt;0.001), and inverse correlations of CAVI with the glomerular filtration rate (GFR) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula (p&amp;lt;0.001) were revealed in the general sample. Further, the patients were divided into 2 groups - with disorders of carbohydrate metabolism (prediabetes and diabetes) and normoglycemia, and in each group, predictors of increased arterial stiffness (pathological CAVI) were analyzed. According to the results of multivariate regression analysis in both groups, age, arterial hypertension, systolic and diastolic blood pressure, and a decrease in GFR CKD-EPI were predictors of pathological CAVI (Table). Male gender became a predictor of increased arterial stiffness only among patients with normoglycemia, and there was no effect among patients with CMD (Table). Conclusions An increase in CAVI is associated with diabetes mellitus 2, prediabetes, increasing age, systolic and diastolic blood pressure and decreased GFR. An increase in arterial stiffness occurs already in the prediabetes stage. Identifying of prediabetes is important because prediabetes and type 2 diabetes are similar in many ways. Funding Acknowledgement Type of funding sources: None. Correlations of CAVIPredictors of pathological CAVI

The Prognostic Impact of Estimated Creatinine Clearance by Bioelectrical Impedance Analysis in Heart Failure: Comparison of Different eGFR Formulas.

The estimation of glomerular filtration rate (eGFR) provides prognostic information in patients with heart failure (HF). Bioelectrical impedance analysis may calculate eGFR (Donadio formula). The aim of this study was to evaluate the impact of the Donadio formula in predicting all-cause mortality in patients with HF as compared to Cockroft-Gault, MDRD-4 (Modification of Diet in renal Disease Study), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. Four-hundred thirty-six subjects with HF (52% men; mean age 75 ± 11 years; 42% acute HF) were enrolled. Ninety-two patients (21%) died during the follow-up (median 463 days, IQR 287–669). The area under the receiver operator characteristic curve for eGFR, as estimated by Cockroft-Gault formula (AUC = 0.75), was significantly higher than those derived from Donadio (AUC = 0.72), MDRD-4 (AUC = 0.68), and CKD-EPI (AUC = 0.71) formulas. At multivariate analysis, all eGFR formulas were independent predictors of death; 1 mL/min/1.73 m2 increase in eGFR—as measured by Cockroft-Gault, Donadio, MDRD-4, and CKD-EPI formulas—provided a 2.6%, 1.5%, 1.2%, and 1.6% increase, respectively, in mortality rate. Conclusions. eGFR, as calculated with the Donadio formula, was an independent predictor of mortality in patients with HF as well as the measurements derived from MDRD4 and CKD-EPI formulas, but less accurate than Cockroft-Gault.