Urea Clearance: Revival of an Old Analytical Technique? : A retrospective pilot study into the use of the mean clearance of creatinine and urea for more precise estimation of renal function in renal transplant recipients

Background: Chronic kidney disease (CKD) is a worldwide health problem with a rising incidence. For appropriate treatment it is important to know kidney function, which is best described by glomerular filtration rate (GFR). GFR can be measured by gold standard methods (e.g. by the clearance of 125I-iothalamate (Ciot)) or GFR can be estimated (e.g. by the creatinine-based MDRD-equation (resulting in an estimated GFR (eGFR)) or by the creatinine clearance (Ccr)), all resulting in different GFR values. Because the Ccr overestimates and the urea clearance (Cur) underestimates GFR, the mean value of these clearances provides a better substitute for Ciot as a measure of GFR. We hypothesized that this mean clearance of creatinine and urea (Ccr-ur)¬ gives a more precise estimation of GFR than the MDRD equation or Ccr, in patients with CKD stage 3 or 4. Methods: Therefore, we performed a retrospective pilot study on 44 renal transplant recipients (55% males, mean 54 ± 12 years), all transplanted in the University Medical Center Groningen with a follow-up in the Deventer Hospital. Ciot was performed and they all had CKD stage 3 or 4. The Ccr-ur¬ was compared with the eGFR (MDRD) and with the Ccr, in its approximation of Ciot. Results: Based on the eGFR (MDRD), 39 patients had CKD stage 3 and 5 had CKD stage 4. Ciot was 50 ± 17 ml/min, eGFR (MDRD) 42 ± 10 ml/min/1.732, Ccr 59 ± 16 ml/min and Ccr-ur¬ 43 ± 12 ml/min. The distribution of patients according to the stages of CKD, based on the different methods of determining GFR, showed major differences. Further analysis revealed a clear overestimation of GFR (Ciot) by the Ccr and underestimation of GFR by the Cur. In scatter plots, the Ccr-ur¬ seemed to perform best and the relatively high concordance correlation coefficient of the Ciot and the Ccr-ur¬ appeared to confirm this. Difference plots showed a good approximation of GFR (Ciot) by Ccr-ur if GFR is below 45 ml/min, but a significant underestimation (P < 0.005) above this GFR value. Conclusion: The Ccr-ur¬ offers more insight into GFR than the MDRD equation or Ccr, in renal transplant recipients with CKD stage 3B or stage 4. So it would be a waste to discard urea clearances in these patient categories: there is a role for the Ccr-ur¬ when the clinician wants more precision than the eGFR (MDRD) can offer.