Bökenkamp, Arend

ABSTRACT Background Creatinine-based equations are the most used to estimate glomerular filtration rate (eGFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the re-expressed Lund-Malmö Revised (r-LMR) and the European Kidney Function Consortium (EKFC) equations are the most validated. The EKFC and r-LMR equations have been suggested to have better performances in young adults, but this is debated. Methods We collected data (GFR) measured by clearance of an exogenous marker (reference method), serum creatinine, age and sex from 2366 young adults (aged between 18 and 25 years) both from Europe and the USA. Results In the European cohorts (n = 1892), the bias (in mL/min/1.73 m²) was systematically better for the EKFC and r-LMR equations compared with the CKD-EPI equation [2.28, 95% confidence interval (1.59; 2.91), –2.50 (–3.85; –1.76), 17.41 (16.49; 18.47), respectively]. The percentage of estimated GFR within 30% of measured GFR (P30) was also better for EKFC and r-LMR equations compared with the CKD-EPI equation [84.4% (82.8; 86.0), 87.2% (85.7; 88.7) and 65.4% (63.3; 67.6), respectively]. In the US cohorts (n = 474), the bias for the EKFC and r-LMR equations was better than for the CKD-EPI equation in the non-Black population [0.97 (–1.69; 3.06), –2.62 (–5.14; –1.43) and 7.74 (5.97; 9.63), respectively], whereas the bias was similar in Black US individuals. P30 results were not different between the three equations in US cohorts. Analyses in sub-populations confirmed these results, except in individuals with high GFR levels (GFR ≥120 mL/min/1.73 m²) for whom the CKD-EPI equation might have a lower bias. Conclusions We demonstrated that both the EKFC and r-LMR creatinine-based equations have a better performance than the CKD-EPI equation in a young population. The only exception might be in patients with hyperfiltration.

AimThe Cockcroft‐Gault (CG) creatinine‐based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over‐ or underdosing.MethodsIn a cross‐sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification‐of‐Diet‐in‐Renal‐Diseases (MDRD), Chronic‐Kidney‐Disease‐Epidemiology (CKD‐EPI), Lund‐Malmö‐Revised (LMR) and European‐Kidney‐Function‐Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.ResultsThe CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD‐EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5‐25 kg/m2, all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30‐accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG.ConclusionsThe CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine‐based equations.

Abstract In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, Black race, disagreement between creatinine- and cystatin C–based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m 2 . This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 . Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.