The Novelty

By implementing the 24-h urine creatinine excretion rate (U-CER) adjustment method, this study has successfully eliminated the paradoxical mortality in patients with high estimated glomerular filtration rate (eGFR). In other words, the 24-h U-CER–adjusted eGFR allowed a more accurate evaluation of mortality risk. The inclusion of muscle mass in the estimations was able to correct the bias. These results also served as the first empirical evidence proving the impact of sarcopenia on the paradoxical mortality pattern in the patients. For validation, future study may examine the effectiveness of this approach by implementing it in different ethnic populations and health care systems. Moreover, the feasibility of 24-h U-CER in monitoring excessive muscle loss over the course of chronic kidney disease (CKD) should be investigated in the future.


The Background

The GFR indicates how much blood our kidneys clean every minute based on our body size. The methods to evaluate GFR include measured glomerular filtration rate (mGFR), estimated glomerular filtration rate (eGFR), and 24-h creatinine clearance (CrCl). Although mGFR is known to be the gold standard for measuring kidney function, it is costly and inefficient. Meanwhile, 24-h creatinine clearance (CrCl) faces several setbacks, such as inaccurate estimation of GFR and being inconvenient, even though it has higher applicability for patients with sarcopenia or malnutrition. Estimated GFR (eGFR) based on equations (i.e. Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) have shown discrepancies and low feasibility. Moreover, a paradoxically increased risk of mortality was also reported. Nonetheless, the calculation of eGFR based on CKD-EPI is recognized as a good practice since 2012. Despite having various locally-derived eGFR equations, they are not systematically compared with 24-h CrCl-adjusted equation-based eGFR in terms of mortality prediction. Moreover, since decreased muscle mass is the main factor giving rise to the high eGFR–high mortality paradox, the 24-h urine creatinine excretion rate (24-h U-CER) (i.e. a 24-h CrCl method) is suitable for adjusting the equation-based eGFR for its effectiveness in measuring muscle mass. Therefore, this study compared the performance of equation methods for predicting 5-year all-cause mortality by applying 24-h CrCl, equation-based eGFRs, and 24-h U-CER. The reversal of paradoxically high mortality achieved by applying 24-h U-CER is a significant milestone towards more accurate kidney diagnosis.


The SDG Impact

10% of the global population is affected by CKD. Thus, a technique for high-precision eGFR is crucial for early diagnosis and treatment of CKD. The 24-h U-CER–adjusted eGFR developed by this study exhibits high accuracy in mortality risk evaluation and, more importantly, it is ready to be adopted by health care systems. By contributing to the enhancement of health care, this study shows good alignment with UNSDG 3: Good Health & Well-Being.