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 Table of Contents  
Year : 2019  |  Volume : 19  |  Issue : 3  |  Page : 75-79

Cystatin: assessment of renal function in chronic kidney disease and postrenal transplant patients

Department of Internal Medicine, Cairo University, Cairo, Egypt

Date of Submission08-Sep-2018
Date of Acceptance15-Apr-2019
Date of Web Publication2-Aug-2019

Correspondence Address:
MD Ahmed Y Ali
MD of Internal Medicine, Giza, 12511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jesnt.jesnt_22_18

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Objectives Cystatin C is an alternative parameter for the assessment of renal function. The objective of the study is to evaluate the efficacy of serum cystatin C as a marker of renal dysfunction among different chronic kidney disease (CKD) and postrenal transplant patients.
Patients and methods A total of 60 postrenal transplants patients and 60 patients with CKD were compared with 30-old aged patients regarding serum cystatin and through evaluating cystatin-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR equations versus measured GFR using 99mTc diethylene-triamine-penta-acetate method.
Results Serum cystatin is significantly higher in the CKD group. Cystatin is negatively correlated with measured GFR in all groups, with P value less than 0.01, serum cystatin is a better parameter than serum creatinine to rule out renal dysfunction (sensitivity 95.1 and 80.3%, respectively). Cystatin eGFR (Larsson equation) has less sensitivity and specificity than creatinine eGFR formulae namely modified diet in renal disease and Gault–Cockcroft.
Conclusion Serum cystatin C is a useful parameter in recognizing individuals with early renal impairment and can be used as a screening tool with significant performance

Keywords: chronic kidney disease, creatinine, cystatin C, transplant

How to cite this article:
Ali AY, Elkhashab SO. Cystatin: assessment of renal function in chronic kidney disease and postrenal transplant patients. J Egypt Soc Nephrol Transplant 2019;19:75-9

How to cite this URL:
Ali AY, Elkhashab SO. Cystatin: assessment of renal function in chronic kidney disease and postrenal transplant patients. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2020 May 28];19:75-9. Available from: http://www.jesnt.eg.net/text.asp?2019/19/3/75/263900

  Introduction Top

Assessment of renal function fundamentally depends on the estimation of serum or urinary biomarkers and radiological tools; however, histopathological studies may be needed in certain cases [1].

Cystatin C is a 122-amino acid basic protein synthesized by all nucleated cells and is filtered freely through the glomeruli; thereafter, it is reabsorbed and metabolized totally in renal tubular cells and not excreted by the kidneys to any significant degree, so it could be a surrogate marker for glomerular filtration rate (GFR) [2]. Moreover, it could reflect properly the renal dysfunction in its early stage.

Unlike creatinine, cystatin C is not affected by different variables such as age, diet, muscle mass, and inflammation which makes it a better indicator of renal dysfunction [3].

Variable equations have been developed to assess the GFR based on anthropometric and biochemical data, as early recognition and stage classification of chronic kidney disease (CKD) can help in early intervention with avoiding the disease progression and complications [4].

Cystatin C has been addressed in kidney transplant recipients and it outperforms other biomarkers in prediction of acute kidney injury in renal transplants. Thus, cystatin C-based equations are more suitable and more accurate than creatinine-based equations for early detection of renal allograft rejection and other functional impairments [5].

The aim of this work was to evaluate cystatin C level as a reliable marker of renal affection in patients with CKD as well as renal transplant recipients and its relation to renal isotopes and different estimated glomerular filtration rate (eGFR) equations.

  Patients and methods Top

Study design and population

A cross-sectional study

The participants are enrolled from the Nephrology Department of Kasr Alainy Hospital and divided into three groups:
  • Group 1: 60 patients who underwent renal transplant within 1–2 years, with serum creatinine less than 1.4 mg/dl.
  • Group II: 60 patients with CKD not on dialysis who were followed up in Kasr Alainy Hospital clinic.
  • Group III: 30 elderly (>60years of age) patients.

Patients with cardiovascular disorders, liver diseases, myopathies, thyroid disorders, malignancies, and pregnant women were excluded from the study.

The study protocol conformed to the ethical guidelines of the 1975 Helsinki Declaration and was approved by the Ethical Committee of Internal Medicine, Faculty of Medicine, Cairo University. Written informed consents were obtained from the participants in this study.


All participants were subjected to the following:

(1) Laboratory workup: 5 ml of blood was taken via a peripheral vein from each patient under complete resting condition and pooled into a dry tube.

Serum creatinine is measured by the kinetic colorimetric method using kinetic photometric equipment.

Quantitative measurement of serum cystatin C is done by enzyme-linked immunosorbent assay using specific kits manufactured by Dade Behring Diagnostic (Marburg, Germany) after obtaining serum by centrifuging the blood at 3400 rpm.

(2) eGFR:

(a) The creatinine-based equation is as follows:[6],[7].

(b) Cystatin C-based equation is as follows [8]

(3) Creatinine clearance

Creatinine clearance is determined from measurement of creatinine in a 24-h urine specimen and from a serum specimen obtained during the same collection period. The creatinine clearance is then calculated by the following equation:[9]

(4) Radionuclide GFR estimation using 99mTc diethylene-triamine-penta-acetate (DTPA) (Gate’s method):

Overall, 3–5 μCi of 99mTc DTPA is injected intravenously, and the GFR (global and differential) is calculated by a closed computer program based on Gate’s method using Phillips (Philadelphia, USA) equipment [10].

GFR measured by the modified Gate’s method was calculated using the following equation:

Pre, precount; Post, postcount; R, right kidney counts; RB, right kidney background counts; L, left kidney counts; LB, left kidney background counts; χR, right kidney depth; χL: left kidney depth; µ, attenuation coefficient of 99mTc in soft tissue (0.153/cm); e, constant [11].

Statistical analysis

Data were statistically described in terms of mean±SD. Comparison of quantitative variables between the study groups was done using Kruskal–Wallis for nonparametric variables and analysis of variance test for parametric variables. χ2 was used for comparison of nominal data, Mann–Whitney U test for independent samples, and post-hoc multiple tests for three group comparisons. A P value less than 0.05 was considered statistically significant. All statistical calculations were done using Statistical Package for the Social Science (SPSS, Chicago, Illinois, USA), version 15, for Microsoft Windows.

  Results Top

The patients’ age varied from 9 to 75 years (45.12±29.53 years). A total of 82 (54.66%) patients were males whereas 68 (45.3%) were females.

Demographic, anthropometric, and laboratory parameters among studied groups are summarized in [Table 1].
Table 1 Demographic and laboratory parameters among studied groups

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As illustrated in [Table 2], there is no correlation between measured GFR by DTPA renogram versus modified diet in renal disease (MDRD), Cockcroft–Gault, and creatinine clearance in both groups I and III, but there is a correlation in group II. There is a significant negative correlation between measured GFR by DTPA versus serum cystatin, cystatin eGFR, and serum creatinine in all groups.
Table 2 Correlations of measured glomerular filtration rate by diethylene-triamine-penta-acetate with different variables among the studied groups

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Results depicted in [Table 3] show the diagnostic performance of cystatin, creatinine and other measurable calculations for the identification of renal dysfunction. Data demonstrated that cystatin had higher sensitivity (95.1%), so it is a better positive than negative test to rule in renal impairment at cut off value more than or equal to 1.050, whereas serum creatinine is a better negative (specificity 90.5%) to exclude renal dysfunction. However, the eGFR formula, namely, MDRD, had higher sensitivity and specificity than Cockcroft–Gault and cystatin eGFR (Larsson equation).
Table 3 Validity of cystatin and other parameters and estimated glomerular filtration rate equations in detection of renal dysfunction (related to measured glomerular filtration rate by diethylene-triamine-penta-acetate) among the studied patients

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  Discussion Top

The current study concluded that serum cystatin level is significantly correlated to renal dysfunction and decreased GFR measured by DTPA renogram, as well as cystatin has higher sensitivity than serum creatinine and other traditional calculations in ruling out the presence of renal dysfunction among the study groups.

Owing to the morbid problems developed by CKD, early detection of renal dysfunction is mandatory. Inulin and 51 Cr-EDTA plasma clearance are the most accurate methods for the measuring of GFR, but they are not practical because of methodological limitations [12].

Albeit serum creatinine still being a rapid easy measurable parameter of renal impairment, it has some pitfalls. Muscle mass, age, chronic illness, diets phenotypes, and certain medications are confounding factors that may misestimate creatinine and thus GFR [13].

Despite cystatin having been studied multiply as a marker with superiority over creatinine, there has been renewed interest in evaluating it as an alternate, reliable, reproducible independent marker of renal dysfunction.

The current study assessed serum cystatin in postrenal transplant patients and patients with CKD and compared it with measured GFR by DTPA renogram and different eGFR equations to identify the better clinical diagnostic implementation of different tools.

Herein, cystatin and creatinine are increased in patients with CKD compared with postrenal transplant and old age patients.

The present study found that measured GFR by DTPA is inversely correlated to serum cystatin and creatinine in all groups, and cystatin is better correlated than serum creatinine. This matches with Krishnamurthy and colleagues who conducted the study on renal transplant patients and concluded that serum cystatin is a better parameter than serum creatinine in assessing renal function in renal transplant recipient [14]. This is also in concordance with other studies that found a better correlation between serum cystatin and GFR [15],[16].

Creatinine-based equations (MDRD and Cockcroft–Gault formulae) which are currently used, were designed and developed from hospitalized patients with CKD. Thereby, the application of these equations on normal persons is debatable.

Cystatin-based equations were derived and validated in fewer patients than creatinine-based equations [17]. Christine et al. [4] showed that Filler and Le Bricon (cystatin-based equations) were a bit indicator of renal dysfunction among stable renal transplant recipient (RTRs) rather than the standard creatinine-based equations. Hither in our study, Larsson equation has been used because it was generated on assembly of patients with diverse age and sex and using iohexol, a radiocontrast material, which is one of the gold standard methods [8].

Besides, measured GFR by DTPA renogram is proportionately correlated to cystatin eGFR in all groups, whereas it is significantly related to eGFR by MDRD, and Cockroft–Gault, and creatinine clearance equations in only patients with CKD. These results are in agreement with White and colleagues who precluded that the Le Bricon (cystatin based) formula was suitable for RTR. Krishnamurthy [14] noted similar findings. This denotes the low performance of these equations in early detection of renal dysfunction, which highlights the importance of serum cystatin and cystatin eGFR as an instrument of early assessment of renal dysfunction and rapid tracer of renal function deterioration in postrenal transplant patients or patients of high risk to develop nephropathy.

The present study evaluated the diagnostic performance of serum cystatin and creatinine as well as cystatin eGFR and creatinine-based formulae. The data found that serum cystatin has better sensitivity (95.1%) and creatinine has better specificity (90.5%).

Cystatin eGFR had lower sensitivity and specificity than MDRD and Cockroft–Gault equations as the area under the curve was 0.049 and this is consisting with Mira and colleagues who conducted a study on renal transplant patients and concluded that eGFR cystatin C-based equations (cystatin C CKD-EPI equations) had more bias and less accuracy than those of eGFR MDRD, eGFR creatinine-cystatin C, and eGFR creatinine, whereas the performance of the eGFR creatinine-cystatin C was superior in the term of accuracy [18].

In contrast to Mira and colleagues, a systematic study on postrenal transplant patients done by Masson and colleagues, showed that cystatin C estimated equations were superior to creatinine-based eGFR equations [19]; however, the performance of the eGFR cystatin C did not have a significant effect compared with eGFR Cr and eGFR creatinine-cystatin C formulae [20].

Notably, one study declared that serum cystatin has better sensitivity and specificity than creatinine and Le Bricon equations is significantly more valid than MDRD equation [14].

The contradiction of our results and those of aforementioned studies may be explained by the heterogeneity of the current study populations, including patients with CKD, and postrenal transplant patients and old individuals, whereas the others were conducted only on RT recipients. Moreover, we used measured GFR by DTPA scan and not inulin clearance as used by Masson [19].

The limitations of the study were first the small-sized sample and second the lack of follow up of patients, necessitating further studies on larger scale and various population samples for more confirmatory results and to evaluate the generalizability and validity of cystatin as an early marker of renal disorders in different clinical presentations.

  Conclusion Top

Serum cystatin C is an alternative, and reliable marker of renal affection in variable characteristic groups. It seems to be able to identify early decline of glomerular filtration, thus a good predictor of preclinical state of kidney dysfunction. However, cystatin-based eGFR equation’s performance is inferior to other equations.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Janice D, Sukanya S, Roopa R, Ashalatha V. Association between serum cystatin C and creatinine in chronic kidney disease subjects attending a tertiary health care centre. J Clin Diagn Res 2017; 11:BC09–BC12.  Back to cited text no. 1
Fink JC, Blahut SA, Weir MR. Optimal strategies for modeling reciprocal of creatinine versus time in renal transplant recipients and patients with native chronic renal disease. Am J Kidney Dis 2002; 39:753–761.  Back to cited text no. 2
Coresh J, Astor B, McQuillan G, Kusek J, Greene T, Van Lente F, Levey AS. Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 2002; 39:920–929.  Back to cited text no. 3
Christine W, Ayub A, Naser H, Laurent D, Guido F, Nathalie L et al. Chronic kidney disease stage in renal transplantation—classification using cystatin C and creatinine-based equations. Nephrol Dial Transplant 2007; 22:3013–3020.  Back to cited text no. 4
Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, Haase M. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery a prospective cohort study. Crit Care Med 2009; 37:553–560.  Back to cited text no. 5
Cockcroft D, Gault M. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31–41.  Back to cited text no. 6
Levey A, Stevens L, Schmid C, Zhang Y, Castro A, Feldman H et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150:604–612.  Back to cited text no. 7
Larsson A, Malm J, Grubb A, Hansson L. Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L. Scand J Clin Lab Invest 2004; 64:25–30.  Back to cited text no. 8
Marie EK, Cristi RC. Glomerular filtration rate and renal scintigraphy. J Vet Med Sci 2005; 20:31–38.  Back to cited text no. 9
Gates GF. Glomerular filtration rate: estimation from fractional renal accumulation of 99 Tcm-DTPA (stannous). Am J Roentgenol 1982; 138:565–570.  Back to cited text no. 10
Ma YC, Zuo L, Zhang CL, Wang M, Wang RF, Wang HY. Comparison of 99mTc‐DTPA renal dynamic imaging with modified MDRD equation for glomerular filtration rate estimation in Chinese patients in different stages of chronic kidney disease. Nephrol Dial Transplant 2007; 22:417–423.  Back to cited text no. 11
Ogawa Y, Goto T, Tamasawa N, Matsui J, Tando Y, Sugimoto K et al. Serum cystatin C in diabetic patients. Not only an indicator for renal dysfunction in patients with overt nephropathy but also a predictor for cardiovascular events in patients without nephropathy. Diabetes Res Clin Pract 2008; 79:357–361.  Back to cited text no. 12
Rajiv A. Estimating GFR from serum creatinine concentration: pitfalls of GFR-estimating equations. Am J Kidney Dis 2005; 45:610–613.  Back to cited text no. 13
Krishnamurthy N, Arumugasamy K, Usha A, Anand V, Aruna V, Venu G. Serum cystatin C levels in renal transplant recipients. Indian J Clin Biochem 2011; 26:120–124.  Back to cited text no. 14
Keevil BG, Kilpatrick ES, Nicholus SP, Maylor PW. Biological variation of cystatin C: implications for the assessment of glomerular filtration rate. Clin Chem 1998; 44:1535–1539.  Back to cited text no. 15
Risch L, Blumberg A, Huber A. Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C. Nephrol Dial Transplant 1999; 14:1991–1996.  Back to cited text no. 16
Rosenthal S, Bokenkamp A, Hofmunn W. How to estimate GHR − serum creatinine. Serum cystatin C or equations? Clin Biochem 2008; 40:1531–1561.  Back to cited text no. 17
Mira T, Hatem A, Nikolay V, Walter K, Andrew D, John C. Creatinine-based and cystatin C-based GFR estimating equations and their non-GFR determinants in kidney transplant recipients. Clin J Am Soc Nephrol 2016; 11:1640–1649.  Back to cited text no. 18
Masson I, Maillard N, Tack I, Thibaudin L, Dubourg L, Delanaye P et al. GFR estimation using standardized cystatin C in kidney transplant recipients. Am J Kidney Dis 2013; 61:279–284.  Back to cited text no. 19
White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N, Knoll GA. Estimating glomerular filtration rate in kidney transplantation. A comparison between serum creatinine and cystatin C-based methods. J Am Soc Nephrol 2006; 16:3763–3770.  Back to cited text no. 20


  [Table 1], [Table 2], [Table 3]


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