Estimation and measurement of glomerular filtration rate in children

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.