Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for identifying and monitoring moderate chronic kidney disease: the eGFR-C study.

Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Setting: Primary, secondary and tertiary care. Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration: This trial is registered as ISRCTN42955626. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Chronic kidney disease, which affects approximately 14% of the adult population, often has no symptoms but, in some people, may later develop into kidney failure. Kidney disease is most often detected using a blood test called creatinine. Creatinine does not identify everyone with kidney disease, or those most likely to develop more serious kidney disease. An alternative blood test called cystatin C may be more accurate, but it is more expensive than the creatinine test. We compared the accuracy of these two tests in more than 1000 people with moderate kidney disease. Participants were tested over 3 years to see if the tests differed in their ability to detect worsening kidney function. We also wanted to identify risk factors associated with loss of kidney function, and how much the tests normally vary to better understand what results mean. We compared the accuracy and costs of monitoring people with the two markers. Cystatin C was found slightly more accurate than the creatinine test at estimating kidney function when comparing the baseline single measurements (95% accurate compared to 90%), but not at detecting worsening function over time. This means that the additional cost of monitoring people over time with cystatin C to detect kidney disease progression could not be justified. Kidney test results could vary by up to 20% between tests without necessarily implying changes in underlying kidney function ­ this is the normal level of individual variation. Cystatin C marginally improved accuracy of kidney function testing but not ability to detect worsening kidney function. Cystatin C improves identification of moderate chronic kidney disease, but our results do not support its use for routine monitoring of kidney function in such patients.

Acceptability and Feasibility of an Isometric Resistance Exercise Program for Abdominal Cancer Surgery: An Embedded Qualitative Study.

Although it is recognized in the early stages of cancer recovery that changes in lifestyle including increases in physical activity improves physical function, there are no clear findings whether low versus moderate intensity activity or home or gym exercise offer optimal benefit. Isometric-resistance exercises can be carried out with very little equipment and space and can be performed while patients are bed-bound in hospital or at home. This embedded qualitative study, based in an English hospital trust providing specialist cancer care, was undertaken as a component of a feasibility trial to evaluate the acceptability and feasibility of an isometric-resistance exercise program and explore the suitability of functional assessments by drawing from the experiences of abdominal cancer patients following surgery. Telephone interviews were undertaken with 7 participants in the intervention group, and 8 interviews with the usual care group (n = 15). The gender composition consisted of 11 females and 4 males. Participants' ages ranged from 27 to 84 (M = 60.07, SD = 15.40). Interviews were conducted between August 2017 and May 2018, with audio files digitally recorded and data coded using thematic framework analysis. Our results show that blinding to intervention or usual care was a challenge, participants felt the intervention was safe and suitable aided by the assistance of a research nurse, yet, found the self-completion questionnaire tools hard to complete. Our study provides an insight of trial processes, participants' adherence and completion of exercise interventions, and informs the design and conduct of larger RCTs based on the experiences of abdominal cancer surgery patients.

Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.

When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m2). Patients underwent weekly GFR measurement by iohexol clearance over four consecutive weeks. Simultaneously, GFR was estimated using the MDRD, CKD-EPIcreatinine, CKD-EPIcystatinC and CKD-EPIcreatinine+cystatinC equations. Within-subject biological variation expressed as a percentage [95% confidence interval] for the MDRD (5.0% [4.3-6.1]), CKD-EPIcreatinine (5.3% [4.5-6.4]), CKD-EPIcystatinC (5.3% [4.5-6.5]), and CKD-EPIcreatinine+cystatinC (5.0% [4.3-6.2]) equations were broadly equivalent. The within-subject biological variation for MDRD and CKD- EPIcreatinine+cystatinC estimated GFR were each significantly lower than that of the measured GFR (6.7% [5.6-8.2]). Reference change values, the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated. By the MDRD equation, positive and negative reference change values were 15.1% and 13.1% respectively. If an individual's baseline MDRD estimated GFR (ml/min per 1.73 m2) was 59, significant increases or decreases would be to values over 68 or under 51 respectively. Within-subject variability of estimated GFR was lower than measured GFR. Reference change values can be used to understand GFR changes in clinical practice. Thus, estimates of GFR are at least as reliable as measured GFR for monitoring patients over time.

Effects of preoperative and postoperative resistance exercise interventions on recovery of physical function in patients undergoing abdominal surgery for cancer: a systematic review of randomised controlled trials.

OBJECTIVE: To systematically review the effects of preoperative and postoperative resistance exercise training on the recovery of physical function in patients undergoing abdominal surgery for cancer. DATA SOURCES: A systematic review of English articles using Medline, Physiotherapy Evidence Database, CINAHL and the Cochrane Library electronic databases was undertaken. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they used a randomised, quasi-randomised or controlled trial study design and compared the effects of a muscle-strengthening exercise intervention (±other therapy) with a comparative non-exercise group; involved adult participants (≥18 years) who had elected to undergo abdominal surgery for cancer; and used muscle strength, physical function, self-reported functional ability, range of motion and/or a performance-based test as an outcome measure. RESULTS: Following screening of titles and abstracts of the 588 publications retrieved from the initial search, 24 studies met the inclusion criteria and were accessed for review of the full-text version of the article, and 2 eligible studies met the inclusion criteria and were included in the review. One exercise programme was undertaken preoperatively and the other postoperatively, until discharge from hospital. The exercise interventions of the included studies were performed for five and eight sessions, respectively. There were no differences between groups in either study. CONCLUSION: The only two studies designed to determine whether preoperative or postoperative resistance muscle-strengthening exercise programmes improved or negatively affected physical function outcomes in patients undergoing abdominal surgery for cancer provide inconclusive results.