Abstract
Glomerular filtration rate (GFR) is commonly used in daily practice for diagnosing kidney disease and for the follow-up of kidney disorders and potential nephrotoxic treatment. There are several formulas for an approximate estimation of GFR (eGFR), based on the concentration of plasma markers. Commonly used are those based on creatinine and/or cystatin C. The plasma elimination of iohexol, a non-ionic contrast agent, is widely used for a more accurate measurement of GFR (mGFR). The aims of the thesis were to 1) evaluate different eGFR-formulas, 2) find the optimal time point and formula when using a single blood sample for mGFR, 3) explore the possibility of using dried capillary blood spots instead of venous sampling and 4) investigate the relationship between mGFR and non-renal diagnostic markers as well as examining to what extent this could affect their decision limits. 96 children (age 0.3-17.5 years) with chronic kidney disease (CKD) stage 1-5 were recruited. For evaluation of GFR based on natural biomarkers we recommend using Schwartz’ eGFR-formulas including cystatin C when available. Simplified mGFR based on one blood sampling after iohexol injection may be an alternative to multipoint mGFR gold standard procedures when using Fleming formula and sampling at 3h, especially in clinical trials and in children with cancer. If GFR < 30 mL/min/1.73m2, a mGFR procedure with a minimum of two blood samples is recommended. mGFR based on capillary blood spots sampling is an alternative with accuracy limitations. Non-renal diagnostic biomarkers, e.g. biomarkers used in screening for Inborn errors of metabolism, may be influenced by reduced renal function and lead to clinical misinterpretation. Overall, the optimal choice for GFR determination is measurement based on iohexol clearance with two blood samples in general, at 2 and 5 hours after injection. In everyday practice, the use of Schwartz’cysC or Schwartz’CKiD formula for eGFR in children is recommended.
List of papers
Paper I: Estimating Glomerular Filtration Rate in Children: evaluation of creatinine- and cystatin C based equations. Cathrin Lytomt Salvador, Camilla Tøndel, Alexander Dominic Rowe, Anna Bjerre, Atle Brun, Damien Brackman, Lars Mørkrid. Pediatr Nephrol, 2019;34:301-311. DOI: 10.1007/s00467-018-4067-3. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1007/s00467-018-4067-3 |
Paper II: Iohexol plasma clearance in children: validation of multiple formulas and single-point sampling times. Camilla Tøndel, Cathrin Lytomt Salvador, Karl Ove Hufthammer, Bjørn Bolann, Damien Brackman, Anna Bjerre, Einar Svarstad, Atle Brun. Pediatr Nephrol, 2018;33:683-696. DOI: 10.1007/s00467-017-3841-y. The article is included in the thesis. Also available at: https://doi.org/10.1007/s00467-017-3841-y |
Paper III: Glomerular filtration rate measured by iohexol clearance: A comparison of venous samples and capillary blood spots. Cathrin Lytomt Salvador, Camilla Tøndel, Lars Mørkrid, Anna Bjerre, Atle Brun, Bjørn Bolann, Damien Brackman, Stein Bergan. Scand J Clin Lab Invest, 2015; 75:710-716. DOI: 10.3109/00365513.2015.1091091. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.3109/00365513.2015.1091091 |
Paper IV: Renal Function Influences Diagnostic Markers in Serum and Urine: A Study of Guanidinoacetate, Creatine, Human Epididymis Protein 4, and Neutrophil Gelatinase–Associated Lipocalin in Children. Cathrin Lytomt Salvador, Camilla Tøndel, Alexander Dominic Rowe, Anna Bjerre, Atle Brun, Damien Brackman, Nils Bolstad, Lars Mørkrid. The Journal of Applied Laboratory Medicine, 2017; 2:297-308. DOI: 10.1373/jalm.2016.022145. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1373/jalm.2016.022145 |