The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately. The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m²). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of mGFR] were compared. The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m², P₁₀ 40%/35%/35% and P₃₀ 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m², most pronounced among men. In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)‐markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5–30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine‐based GFR‐estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor‐blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C‐based GFR‐estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.

Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEAN_LM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEAN_CKD-EPI), and the composite CKD-EPI equation (CKD-EPI_CREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine. Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008–2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m²). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates ±30% of mGFR; P₃₀) were compared. Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEAN_LM-REV+CAPA/MEAN_CKD-EPI/CKD-EPI_CREA+CYSC were: median bias –2.2%/–0.5%/–1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m², and P₃₀ 91.3%/91.0%/91.1%. The P₃₀ figures were about 7–14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P₃₀ ≥90% and never <80%. Combined equations reached P₃₀ of 95% when the difference between eGFR_CREA and eGFR_CYSC was <10% but decreased to 82% at a difference of ≥40%. Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P₃₀ ≥90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.

The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.