The GFR represents the amount of plasma filtered by the kidneys in a unit of time; the GFR is universally considered a functional indicator, able to represent the function of the organ, and, for this reason, it has a high clinical value. In clinical practice, the direct measurement of GFR, that is the true GFR (mGFR), is unlikely and even the clearance of exogenous substances, such as inulin, 125I-Iothalamate, 51Cr-EDTA, 99TC-DPTA, cannot be used in the routine, both for the complexity of the protocols to be applied and for the critical issues affecting methods for their measurement. Some authors have recently proposed the utilization of the iohexol clearance because of the availability of reliable and fast methods for the measurement of this compound. Hence, since 2002, the international scientific community has recommended to associate the measurement of creatinine with the estimation of GFR through the application of specific equations based on some physical parameters combined arithmetically with the plasma creatinine concentration, or other plasma biomarkers, and predefined constant factors.

A plethora of formulas/equations for eGFR have been developed over the past 50 years (Fig. 1 and Table 1); for a long time, the Cockcroft–Gault formula for adults and the Schwartz formula for children were widely used worldwide, mainly because of their simplicity. However, the Cockcroft–Gault formula did not allow the estimation of GFR but was simply the estimation of creatinine clearance based on plasma creatinine. In 1999, the MDRD (Modification of Diet in Renal Disease) equation was developed in a group of participants (1628) in a randomized trial studying the effects of dietary restriction and blood pressure control on the progression of CKD. In these patients, mGFR was measured by iothalamate clearance. The original equation had two shortcomings: a universal standard calibrator for creatinine determination was not available at that time (non-trace able method) and the equation was developed only in patients with CKD and, therefore, the results were inaccurate in healthy subjects with GFR >90 mL/min/1.73 m² (systematic bias of underestimating GFR for high values). The original 1999 equation included six variables: creatinine, age, gender, ethnicity, urea, and albumin. In 2000, the equation was simplified by removing urea and albumin as variables, and in 2006, it was reexpressed using a traceable method for creatinine. In 2009, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to overcome the problems associated with the MDRD equation. The new equation was derived from a meta-analysis study that included 8254 healthy adult subjects with CKD. Numerous clinical studies in various populations have demonstrated over time that the performance of the CKD-EPI equation is significantly better than that of the MDRD equation; for these reasons, clinical laboratories are still recommended to use the CKD-EPI equation for the calculation of GFR estimation. The CKD-EPI equation based on the determination of plasma creatinine is organized according to the scheme shown in Table 1. The original 2009 CKD-EPI equation has been modified in various subsequent studies, with the aim to minimize the bias between mGFR and eGFR in different ethnic groups, especially African Americans. A recent position statement recommended the utilization of the new European Kidney Function Consortium (EKFC) equation or, alternatively, the 2009 CKD-EPI equation based on serum creatinine without applying the race correction factor. Further modifications of the CKD-EPI equation, including cystatin C, are discussed below. The CKD-EPI equation is inaccurate in people over the age of 70 years; therefore, two new equations designed specifically for populations over 70 years of age were proposed in 2012: the Berlin Initiative Study 1 (BIS1), which incorporates creatinine into the calculation, and the Berlin Initiative Study 2 (BIS2), which incorporates creatinine and cystatin C. Based on the evidence that the 1976 Schwartz equation overestimated the mGFR by approximately 20% (mGFR assessed by the iohexol clearance), in 2009 the original equation was changed by using a traceable, enzymatic method for plasma creatinine.

Fig1. Formulas for calculating the GFR estimate. (Copyright EDISES 2021. Reproduced with permission)

Table1. CKD-EPI equation based on plasma creatinine

Equation for eGFR show at least two major advantages: (1) decreased influence of extrarenal factors that influence the creatinine result and (2) increased focus by the clinicians on organ function, expressed as a dynamic parameter (mL/min/1.73 m2) rather than as a numerical value (mg/dL) of creatinine. These advantages are achievable only if the measurement of the biomarkers included in the equation (creatinine, cystatin C, or others) is accurate and standardized. Indeed, the relationship between the GFR and biomarkers, such as creatinine or cystatin C, is of the exponential type, which means that even small variations in biomarker concentration due to imprecision and bias are reflected by significant variations in the eGFR. This explains the importance of using traceable analytical methods with excellent quality specifications. Regardless of the type of equation, the calculation of estimated GFR should be interpreted with caution in all conditions of hemodynamic and metabolic instability, such as postoperative course, organ transplant follow-up, pregnancy (especially in the third trimester), obesity, malnutrition, diabetes, competitive sports activity, acute kidney injury, therapeutic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), sepsis, septic shock, and systemic infection. Some recommendations on laboratory assessment of renal function are described in Table 2.

Table2. Recommendations for laboratory evaluation of renal function

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قسم الشبابيك: تقديم أكثر من 50 ألف وجبة طعام لزائري الأربعين

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المزيد

مواضيع ذات صلة

Creatinine test for Diagnosis of Kidney Diseases

Urea test for Diagnosis of Kidney Diseases

Standard Urine Test for Diagnosis of Kidney Diseases

Diagnosis of Ventilator-Associated Pneumonia

protein C, protein S

prostate-specific antigen (PSA), prostate cancer gene 3 (PCA3), MI-prostate score (MiPS)

prolactin levels (PRLs)

Enzyme-Linked Immunosorbent Assay (ELISA)

Agglutination Reaction

Precipitation Reaction

Heparins and Fondaparinux

Activated Partial Thromboplastin Time (aPTT)