Comparison of bias and accuracy using cystatin C and creatinine in CKD-EPI equations for GFR estimation

Background: The directly measured glomerular filtrate rate (mGFR) is the gold standard for kidney function, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR, however, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. We performed this meta-analysis to assess the bias and accuracy of eGFR using equations of CKD-EPI_crea, CKD-EPI_cys, and CKD-EPI_crea/cys in adult populations relevant to primary health care.Methods: Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for related studies.Results: A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included. The difference in the bias of eGFR using CKD-EPI_cys was 4.84 mL/min/1.73 m² (95% CI, 1.88~7.80) lower than using CKD-EPI_crea, and 1.50 mL/min/1.73 m² (95% CI, 0.05~2.95) lower than using CKD-EPI_crea/cys. These gaps increased in subgroups of low mGFR (<60 mL/min/1.73 m²). CKD-EPI_crea/cys eGFR achieved the highest accuracy, 7.50% higher than CKD-EPI_crea (95% CI, 4.81~10.18), and 3.21% higher than CKD-EPI_cys (95% CI, -0.43~6.85); and the best correlation with mGFR, with Fisher's z transformed R of 1.20 (95% CI, 0.89-1.50).Conclusions: CKD-EPI_crea/cys and CKD-EPI_cys gave less bias and more accurate estimates of mGFR than CKD-EPI_crea. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.     

Performance of the Cockcroft-Gault,MDRD, and New CKD-EPI Formulas in Relation to GFR,Age, and Body Size

Background and objectives: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using ¹²⁵I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI).Design, setting, participants, & measurements: For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis.Results: Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m² [SD 30.4 ml/min per 1.73 m²]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies.Conclusions: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD.With the increasing incidence of kidney dysfunction, the use of formulas to estimate kidney function is implemented more frequently in clinical practice (1). The most frequently used formulas are the Cockcroft-Gault and (abbreviated) Modification of Diet in Renal Disease (MDRD) equations (2). The Cockcroft-Gault equation estimates clearance of creatinine (3), whereas the MDRD estimates GFR (2). At present, for subgroups of people who are old, underweight, or overweight, no clear-cut advice exists regarding which formula is best used for optimal estimation of kidney function. Both Cockcroft-Gault and abbreviated MDRD have been compared in the same population against a gold standard method for estimating GFR (4–8). These studies show conflicting results because of different study populations, different gold standard GFR measurements, and differences in creatinine assay calibration (9). Furthermore, the recently developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula has not been validated yet, outside pf the original publication (10); therefore, a pragmatic study to evaluate the most often used formulas, in a study population in which a GFR measurement is requested, is needed. Furthermore, these formulas need to be compared with an excellent gold standard GFR measurement.In our center, GFR is measured by a method that can be considered the gold standard in the absence of bladder catheterization, for clinical reasons with a continuous infusion of ¹²⁵I-iothalamate (11–13). ¹³¹I-hippuran is added to correct for inaccurate urine collections without using a bladder catheter to optimize GFR measurement further (13). The aim of this study was to assess the agreement between kidney function as estimated by the Cockcroft-Gault, MDRD, and CKD-EPI equations and the GFR as measured by a gold standard method using ¹²⁵I-iothalamate. To examine whether the agreement is influenced by the level of GFR, gender, age, body weight, and body mass index (BMI), we also analyzed the agreement within clinically relevant strata of these variables.     

The Spatial QRS-T Angle: Implications in Clinical Practice

The ventricular gradient (VG) as a concept was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. The contemporary spatial QRS-T angle is based on the concept of the VG and defined as its mathematical and physiological integral. Its current major clinical use is to assess the cardiac primary repolarization abnormalities in 3-dimensional spatial vectorial plans which are normally untraced in the presence of secondary electrophysiological activity in a 2-dimensional routine electrocardiogram (ECG). Currently the calculation of the spatial QRS-T angle can be easily computed on the basis of a classical ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local heterogeneity of the myocardial ventricular action potention duration. Recent population-based studies suggest that the spatial QRS-T angle is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary cardiovascular prevention efforts and should be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial QRS-T angle. The main focus is its role in ECG assessment of dispersion of repolarization, a key factor in arrythmogeneity.     

IL28B: Implications for Clinical Practice

The discovery of genetic variants near the gene for IL28B has provided new insight into the biology of hepatitis C infection and response to treatment with pegylated interferon alpha and ribavirin. Patients that carry the favorable CC genotype for SNP rs12979860 or TT genotype for SNP rs8099917 are more likely to spontaneously clear the virus after acute infection and to respond to therapy with pegylated interferon alpha and ribavirin. IL28B genotype may also have a relationship with the natural history of chronic hepatitis and has implications for organ allocation in liver transplantation. Now that the protease inhibitors telaprevir and boceprevir have improved the response rates to hepatitis c treatment, the applicability of IL28B genotyping in clinical practice is limited. However, further understanding of the mechanism underlying the relationship between IL28B and treatment response is likely to provide valuable insight into the pathophysiology of hepatitis c infection and response to therapy.     

Comparative performance of FAS equation and Asian modified CKD-EPI in the determination of GFR in Chinese patients with CKD with the 99mTc-DTPA plasma clearance as the reference method

BackgroundGlomerular filtration rate (GFR) is a useful index in many clinical conditions. However, very few studies have assessed the performance of full age spectrum (FAS) equation and the Asian modified Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation in the approximation of GFR in Chinese patients with chronic kidney disease.ObjectiveThis study aimed to compare the diagnostic performance of the above two creatinine-based equations.MethodsA well designed single-center cross-sectional study was performed and the GFR was determined by 3 methods separately in the same day: technetium-99m-diethylene triamine pentaacetic acid (^99mTc-DTPA) dual plasma sample clearance method (mGFR); FAS equation method; Asian modified CKD-EPI equation method. The gold standard method was the mGFR. Equations performance criteria considered correlation coefficient, bias, precision, accuracy and the ability to detect the mGFR less than 60 ml/min/1.73 m².ResultsA total of 160 patients were enrolled. The diagnostic performance of FAS showed no significant difference in the correlation coefficient (0.89 vs 0.89), precision (15.9 vs 16.1 ml/min/1.73 m²), accuracy (75.0% vs 76.3%) and the ability to detect the mGFR less than 60 ml/min/1.73 m² (0.94 vs 0.94) compared with the Asian modified CKD-EPI equation in all participants. The FAS showed a negative bias, while the new CKD-EPI equation showed a positive bias (?1.20 vs 1.30 ml/min/1.73 m², P < 0.001). However, they were all near to zero. In the mGFR < 60 ml/min/1.73 m² subgroup and mGFR > 60 ml/min/1.73 m² subgroup were consistent with that in the whole cohort. The precision and accuracy decreased when GFR > 60 ml/min/1.73 m² in both equations.ConclusionsThe FAS equation and the Asian modified CKD-EPI equation had similar performance in determining the glomerular filtration rate in the Chinese patients with chronic kidney disease. Both the FAS equation and Asian modified CKD-EPI can be a satisfactory method and may be the most suitable creatinine-based equation.     

Gender Differences in Colonoscopy: Implications for Clinical Practice and Female Gastroenterologists

Digestive Diseases and Sciences - Performing colonoscopy can be technically challenging in female patients. Female patients may prefer having a female endoscopist. This preference, coupled with the...     

Estimation of renal function by three CKD-EPI equations in Chinese HIV/AIDS patients: A STROBE-compliant article

Assessing renal function accurately is important for human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recommended three equations to calculate estimated glomerular filtration rate (eGFR). There is evidence that eGFR based on the combination of serum creatinine and cystatin C is the most accurate of the three equations. But there is limited data on the comparison of three CKD-EPI equations in Chinese HIV/AIDS patients. The aim of our study was to compare the three CKD-EPI equations in Chinese HIV/AIDS population and assess renal function.Cross-sectional, single center, prospective study.One hundred seventy two Chinese adult HIV/AIDS patients were enrolled, including 145 (84.3%) males and 27 (15.7%) females. Mean age was 40(±12) years old. Overall mean eGFR based on serum creatinine, cystatin C and the combination of the 2 markers was 112.6(±19.0) mL/min/1.73 m², 92.0(±24.2)mL/min/1.73 m², and 101.7(±21.8)mL/min/1.73 m², respectively (P = .000). The eGFR calculated by serum creatinine alone is higher than eGFR calculated by combination of serum creatinine and cystatin C, and eGFR calculated by cystatin C individual is lower than eGFR calculated by combination of the 2 markers.Of the 3 CKD-EPI equations, the CKD-EPI_scr-cys equation may have the most accuracy in evaluating renal function in Chinese HIV/AIDS patients while the CKD-EPI_scr equation may overestimate renal function and the CKD-EPI_cys equation may underestimate renal function.     

The Implications of Acute Clinical Care Responsibilities on the Contemporary Practice of Interventional Cardiology

The responsibilities of the interventional cardiologist (IC) have evolved in contemporary practice to include substantial acute care clinical duties outside of the cardiac catheterization laboratory. In particular, the IC has assumed a central role in the global management of myocardial infarction and other acute coronary syndromes in the intensive care unit and beyond. These duties have expanded to include many nonprocedural tasks. The Interventional Section Leadership Council (ISLC) of the American College of Cardiology (ACC) therefore recommends: 1) these implications should be directly considered in the ACC’s future planning and policy statements concerning manpower, competence, education, and reimbursement; 2) the development of an acute care cardiology subspecialty should be undertaken; 3) steps should be taken to adjust the number of ICs primarily on the basis of optimizing procedural volume and quality; and 4) the annual number of coronary interventions performed should not solely define competence in the future, but should include the performance of acute cardiology responsibilities.     

Estimation of the glomerular filtration rate in older individuals with serum creatinine-based equations: A systematic comparison between CKD-EPI and BIS1

AimCKD-EPIcr (Chronic Kidney Disease Epidemiology Collaboration creatinine) and BIS1 (Berlin Initiative Study) are two serum creatinine-based formulae for the estimation of glomerular filtration rate (GFR). However, their comparative accuracy in older people has not been well established. Our aim was to conduct a systematic comparative study of the accuracy of estimation of GFR in older people with these two formulae.MethodsWe conducted a systematic search in Pubmed, EMBASE and Central databases on the validity of the CKD-EPIcr and BIS1 formulae in people aged 60 or more years. The search ranged from 2009 and 2012 for CKD-EPIcr and BIS1, respectively, until May 2017. The validity criterion for comparing the formulae was to have a P30 accuracy level equal to or greater than 80%.ResultsOf 1295 identified studies, 16 met our inclusion criteria. Out of 16 studies reporting the accuracy of the CKD-EPIcr formula, only 5 (31.3%) had P30 scores ≥80% (mean P30 was 77.1 ± 7.711 range 55.5–91.7), and out of 9 studies on accuracy using the BIS1 formula, 6 (66.7%) were ≥80% (mean P30 was 83.88 ± 9.37, range 67.0–95.8).ConclusionOur results suggest that for the estimation of the GFR in older people, BIS1 formula may be more accurate than CKD-EPIcr.     

肾小球滤过率评估方程在少数民族和汉族慢性肾脏病患者中的适用性研究

目的评价肾小球滤过率（glomerular filter rate,GFR）评估方程在少数民族和汉族慢性肾脏病（chronic kidney disease。CKD）患者中的适用性。方法选择174例慢性肾脏病患者（包括少数民族和汉族患者）,将Cockcroft—Gauh方程、MDRD7方程、简化MDRD方程计算的GFR值用体表面积（BSA）标准化,与BSA标准化的^99mTc—DTPA测得的GFR在不同CKD分期进行比较。结果方程计算的GFR（cGFR、7GFR、aGFR）与^99mTc—GFR（sGFR）分别在少数民族及汉族具有显著的相关性,相关性较好的依次为MDRD7、简化MDRD、Cockcrofi—Gauh方程;Roe曲线下的面积也表明MDRD7方程诊断的敏感性最好,简化MDRD次之。但是7GFR、aGFRc、cGFR与^99mTc—GFR差异均有显著意义（P〈0．01）。结论上述方程用于我国少数民族和汉族CKD患者时,应对三个方程进行修正。     

Screening for Chronic Kidney Disease Complications in US Adults: Racial Implications of a Single GFR Threshold

Background and objectives: An ideal and effective screening tool should perform equally across ethnic groups. The objective of this study was to determine whether the widely advocated creatinine-based estimated GFR (eGFR) threshold of 60 ml/min per 1.73 m² identifies the typical metabolic abnormalities related to chronic kidney disease equally well in minority and nonminority adults.Design, setting, participants, & measurements: This objective was addressed using data for 8918 minority and nonminority adult participants in the National Health and Nutrition Examination Survey 2003 through 2006, which used stratified, multistage, probability sampling methods to assemble a nationwide probability sample of the noninstitutionalized population of the United States. Metabolic abnormalities including BP, potassium, hemoglobin, bicarbonate, uric acid, calcium, phosphorus, and parathyroid hormone were defined by fifth or 95th percentile values.Results: Among participants with eGFR <60 ml/min per 1.73 m², black individuals were more likely than white individuals to have low hemoglobin (adjusted odds ratio [aOR] 3.76; 95% confidence interval [CI] 1.94 to 7.28), elevated uric acid (aOR 2.15; 95% CI 1.26 to 3.68), and elevated parathyroid hormone (aOR 3.93; 95% CI 2.33 to 6.66).Conclusions: Metabolic consequences of reduced eGFR are more common in black individuals and seem to be present at levels well above 60 ml/min per 1.73 m²; thus, black individuals should be screened for the metabolic complications of chronic kidney at higher GFR levels.Creatinine-based estimates of GFR (eGFR) are widely used to define chronic kidney disease (CKD), because they are believed to offer the combination of acceptable accuracy, convenience, and low cost (1–3). Current guidelines recommend that physicians begin screening for the metabolic disturbances of CKD once the creatinine-based eGFR reaches 60 ml/min per 1.73 m². Recent data, however, suggest that a strategy of using this single eGFR threshold, 60 ml/min per 1.73 m², may disadvantage minority populations. Using the US Third National Health and Nutrition Examination Survey (NHANES III; 1988 through 1994) database, we found that a case definition of CKD with a single eGFR value of 60 ml/min per 1.73 m² seemed to disadvantage minority populations, because metabolic abnormalities such as high BP, anemia, and elevated phosphorus and uric acid were already considerably more prevalent at higher eGFR values in black than in white participants (4). We believe that confirmation of these findings in a more recent, nationally representative population is of public health relevance, not least because of the changes in the demographic profile that have occurred since the conclusion of NHANES III (5). In addition, unlike more recent iterations of NHANES, parathyroid hormone (PTH) levels were not measured in NHANES III, preventing assessment of a classic metabolic complication of CKD. The objective of this study, therefore, was to determine whether a creatinine-based eGFR threshold of 60 ml/min per 1.73 m², as calculated by the re-expressed Modification of Diet in Renal Disease (MDRD) Study formula and the African American Study of Kidney Disease and Hypertension (AASK) formula, identifies metabolic abnormalities equally well in minority and nonminority adult NHANES participants studied between 2003 and 2006 (n = 8918).     

Complex Determinants of Work Ability in Adults With Congenital Heart Disease and Implications for Clinical Practice

Background“Work ability” is the employees’ capacity to meet the demands of their job. As more patients with complex congenital heart disease (CHD) are now reaching adulthood, we assessed work ability and factors impacting livelihood in adult CHD.MethodsThe work ability index (WAI) questionnaire and patient health questionnaire-9 (PHQ-9) were administered at 2 Midwest adult CHD centres from February 2017 to 2018.ResultsOf the 267 participants (n = 157 males, 59%) with an average age of 35 ± 13 years, the majority (n = 204, 76%) were employed. Patients with complex CHD (n = 103, 39%) were less likely to have enrolled in college or completed a graduate degree (P = 0.0115), and more likely to have an annual income of < $50,000 (P = 0.0056) and lower WAI scores (P = 0.0026) than patients with simple and moderate CHD. Unemployed patients (n = 63, 24%) with complex CHD (n = 27, 43%) were more likely to have higher PHQ-9 scores (P = 0.0242) indicating mild, moderate, or severe depression (P = 0.0482) than unemployed patients with simple and moderate CHD. Patients with complex CHD had lower self-perception of work ability compared with patients with simple and moderate CHD (P = 0.0007). Finally, patients in NYHA Functional Class I had higher WAI scores than NYHA Class III-IV (P < 0.0001).ConclusionsThis study demonstrates that employed patients with complex CHD have lower education level, income, and work ability. Unemployed patients are more likely to exhibit symptoms of depression and have low self-perception of work ability. Occupational health programs focusing on promoting general health perception, increasing exercise capacity, and improving psychosocial health must be considered to improve work ability in patients with adult CHD to maintain livelihood.     

Relative Performance of the MDRD and CKD-EPI Equations for Estimating Glomerular Filtration Rate among Patients with Varied Clinical Presentations

Summary

Background

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed using both CKD and non-CKD patients to potentially replace the Modification of Diet in Renal Disease (MDRD) equation that was derived with only CKD patients. The objective of our study was to compare the accuracy of the MDRD and CKD-EPI equations for estimating GFR in a large group of patients having GFR measurements for diverse clinical indications.

Design, setting, participants, and measurements

A cross-sectional study was conducted of patients who underwent renal function assessment for clinical purposes by simultaneous measurements of serum creatinine and estimation of GFR using the MDRD and CKD-EPI equations and renal clearance of iothalamate (n = 5238).

Results

Bias compared with measured GFR (mGFR) varied for each equation depending on clinical presentation. The CKD-EPI equation demonstrated less bias than the MDRD equation in potential kidney donors (−8% versus −18%) and postnephrectomy donors (−7% versus −15%). However, the CKD-EPI equation was slightly more biased than the MDRD equation in native CKD patients (6% versus 3%), kidney recipients (8% versus 1%), and other organ recipients (9% versus 3%). Among potential kidney donors, the CKD-EPI equation had higher specificity than the MDRD equation for detecting an mGFR <60 ml/min per 1.73 m² (98% versus 94%) but lower sensitivity (50% versus 70%).

Conclusions

Clinical presentation influences the estimation of GFR from serum creatinine, and neither the CKD-EPI nor MDRD equation account for this. Use of the CKD-EPI equation misclassifies fewer low-risk patients as having reduced mGFR, although it is also less sensitive for detecting mGFR below specific threshold values used to define CKD stages.     

Clinical Implications of the Solitary Functioning Kidney

Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.     

Advances in the Genetics of Spondyloarthritis and Clinical Implications

Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases whose main clinical feature is inflammation of the axial spine. Articular, periarticular, and extra-articular manifestations can also occur, depending on the type of spondyloarthritis. The most common clinical subsets of SpA are ankylosing spondylitis (AS) and psoriatic arthritis (PsA). SpA is a major health challenge given the propensity to affect young adults and the potential requirement for lifelong treatment. Although the precise etiology of SpA is unknown, there is mounting evidence that these diseases are a result of complex interplay of genetic, environmental, and immunological factors. In this review on SpA, we will discuss genetic variants with genome-wide significance, highlight potential clinical application of genetic variants, and discuss challenges in further elucidating the genetic basis of SpA.