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 is used in equations (e.g. Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) to provide estimated GFR. We studied 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/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 (CVI) expressed as a percentage [95% CI] 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. CVI values for MDRD and CKD- EPIcreatinine+cystatinC were lower (p=0.027 and p=0.022 respectively) than that of measured GFR (6.7% [5.6-8.2]). Reference change values (RCV), the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated: using the MDRD equation, positive and negative RCVs were 15.1% and 13.1% respectively. If an individual’s baseline MDRD estimated GFR (mL/min/1.73 m2) was 59, significant increases or decreases would be to values >68 or <51 respectively. Within-subject variability of estimated GFR is lower than measured GFR. RCVs can be used to understand GFR changes in clinical practice

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing - A Systematic Review.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. AIMS: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. METHODS: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. RESULTS: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. CONCLUSION: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis