Performance comparison of estimated glomerular filtration rate equations

doi:10.1016/j.krcp.2014.07.002

To the Editor:

The glomerular filtration rate (GFR) cannot be measured by direct means, but can be assessed by urinary clearance of exogenous filtration markers such as inulin, iohexol, or iothalamate [1,2]. However, for several reasons, direct GFR measurements are not suitable for use in routine laboratory settings. Hence, it is more appropriate to derive an estimated GFR (eGFR) from various equations. However, recent reports have shown that these equations are inadequate and have greater biases in Asian populations [3].

Recently Lee et al [4] evaluated the performance of serum cystatin C-based equations in calculating GFR in chronic kidney disease (CKD) patients. As the Modification of Diet in Renal Disease (MDRD) eGFR equation is known to be inaccurate in Asians [3], I fully agree with the authors’ concept to find out the optimal eGFR equation. They suggest that the performance of equations varied based on the CKD stages. However, it is difficult to determine the real superiority of any equation among them, mainly due to a lack of measured GFR (mGFR) data [5].

Although the authors showed that the Orebro-cyst (Gentian) method was compatible with the results of MDRD equation in CKD stage 4–5, it does not mean that this method is more suitable for the evaluation of eGFR in patients of this stage. In Fig. 2 of that paper, discrepancy between cystatin-C-based eGFR and creatinine-based eGFR is generally very high; thus again, it is difficult to draw a meaningful conclusion regarding the optimal eGFR equation. For proper comparison, I would like to suggest that the authors should further study the performance of the equations using any type(s) of mGFR evaluation methods, such as radioisotope- or inulin-based methods.

Conflict of interest

The author declares no conflict of interest.

Beom Seok Kim

Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.

E-mail address: docbsk@yuhs.ac (BS Kim).

References

[1] Levey AS, Greene T, Schluchter MD, Cleary PA, Teschan PE, Lorenz RA, Molitch ME, Mitch WE, Siebert C, Hall PM: Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol 4:1159–1171, 1993
[2] Perrone RD, Steinman TI, Beck GJ, Skibinski CI, Royal HD, Lawlor M, Hunsicker LG: Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study. Am J Kidney Dis 16:224–235, 1990
[3] Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Xu JS, Huang SM, Wang LN, Huang W, Wang M, Xu GB, Wang HY: Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 17:2937–2944, 2006
[4] Lee HS, Rhee H, Seong EY, Lee DW, Lee SB, Kwak IS: Comparison of glomerular filtration rates calculated by different serum cystatin C-based equations in patients with chronic kidney disease. Kidney Res Clin Pract 33:45–51, 2014
[5] Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S: Modification of the Modification of Diet in Renal Disease (MDRD) Study equation for Japan. Am J Kidney Dis 50:927–937, 2007

In Reply:

We appreciate your interest in our recent article entitled “Comparison of glomerular filtration rates calculated by different serum cystatin C-based equations in patients with chronic kidney disease”. Traditionally, for most clinical circumstances, glomerular filtration rate (GFR) had been estimated from serum creatinine (SCr, eGFRcr). However, SCr concentration is influenced by non-GFR determinants, including muscle mass, diet, tubular secretion and extra-renal elimination by the gastrointestinal tract. Currently the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend initial use of SCr followed by a confirmatory test using cystatin C for evaluation of GFR when eGFRcr is thought to be inaccurate [1]. But recent published data suggested that, the combined creatinine-cystatin C based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is more useful as a confirmatory test than the equations based on SCr or cystatin C alone [2,3]. Although cystatin C is less affected by racial differences, race is still an important determinant of GFR estimation [4]. Thus, race-specific modification is necessary before we accept the suggested guideline. In our study, we compared six-different cystatin C based eGFR equations and tried to find out more suitable cystatin C based eGFR equation in Korean CKD patients [5]. However, as you pointed out, we could not draw a conclusion because we did not measure the reference GFR. Thus, we fully agree with your suggestion that further studies are required to decide which of the equation is more suitable for the Korean CKD patients. In our study, we found that performance of serum cystatin C is quite different to that of SCr in patients with CKD stage 4 to 5 [5], and we thought this finding might be associated with the extrarenal elimination of serum cystatin C [6]. However, in other large studies, this point has not been carefully evaluated [2,3]. Thus, in our next study, we will focus more on the performance of eGFRcys in patients with CKD stage 4 to 5, and compare its accuracy to that of eGFRcr in those patients.

Conflict of interest

None.

Harin Rhee and Ihm Soo Kwak

Division of Nephrology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.

E-mail address: iskwak@pusan.ac.kr (IS Kwak).

References

[1] Kidney Disease: Improving Global Outcome (KDIGO) CKD Work Group: KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150, 2013
[2] Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, Coresh J, Levey AS, CKD-EPI Investigators: Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29, 2012
[3] Fan L, Inker LA, Rossert J, Froissart M, Rossing P, Mauer M, Levey AS: Glomerular filtration rate estimation using cystatin C alone or combined with creatinine as a confirmatory test. Nephrol Dial Transplant 29:1195–1203, 2014
[4] Guo X, Qin Y, Zheng K, Gong M, Wu J, Shou W, Cheng X, Xia L, Xu E, Li X, Qiu L: Improved glomerular filtration rate estimation using new equations combined with standardized cystatin C and creatinine in Chinese adult chronic kidney disease patients. Clin Biochem 47:1220–1226, 2014
[5] Lee HS, Rhee H, Seong EY, Lee DW, Lee SB, Kwak IS: Comparison of glomerular filtration rates calculated by different serum cystatin C-based equations in patients with chronic kidney disease. Kidney Res Clin Pract 33:45–51, 2014
[6] Sjöström P, Tidman M, Jones I: Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand J Clin Lab Invest 65:111–124, 2005