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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 31  |  Issue : 2  |  Page : 185-190

Cystatin and glomerular filtration rate equations in old renal transplant donors


Department of Internal Medicine, Faculty of Medicine, Cairo University, Giza, Egypt

Date of Submission23-Oct-2018
Date of Acceptance29-Nov-2018
Date of Web Publication28-Jun-2019

Correspondence Address:
Ahmed Y Ali
MD of internal medicine, Giza, 12827
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejim.ejim_99_18

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  Abstract 

Introduction Early detection of renal dysfunction in live kidney donors is important and needs easy reliable tools. The aim of the study is to evaluate the cystatin level and cystatin-based equation in assessment of renal function in old healthy kidney donors.
Participants and methods A total of 27 living kidney donors were selected in the study, where serum creatinine and cystatin C were measured. Measured glomerular filtration rate (GFR) was done by DTPA renal scintigraphy, and it was estimated by the following equations: Cockroft–Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration-based creatinine, cystatin, and creatinine–cystatin formulae.
Results A total of 27 kidney donors comprised 12 (44.4%) males and 15 (55.6%) females. The mean±SD age was 61±0.14 years, and mean±SD age at the time of donation was 56.9±1.7 years. The mean of cystatin level was 1.28±0.44. Serum cystatin was negatively correlated with measured filtration rate by renal scintigraphy and estimating GFR by cystatin and creatinine–cystatin formulae. The performance of Cockroft–Gault equation was better, with the highest sensitivity (70%). Serum cystatin and cystatin-based equation had higher specificity (70%) at criterion of 1.4 and 48, respectively. Area under the curve was 0.204 and 0.839, respectively, and significance level was 0.002 and 0.009, respectively.
Conclusion Serum cystatin and cystatin-based formulae could outperform as surrogate tools to monitor the renal function and estimating GFR in healthy older kidney donors. Chronic Kidney Disease Epidemiology Collaboration-based cystatin has better specificity, whereas Cockroft–Gault equation has better sensitivity with the best accuracy.

Keywords: Chronic Kidney Disease Epidemiology Collaboration, creatinine, cystatin, glomerular filtration rate, old kidney donors


How to cite this article:
Ali AY, Elkhashab SO. Cystatin and glomerular filtration rate equations in old renal transplant donors. Egypt J Intern Med 2019;31:185-90

How to cite this URL:
Ali AY, Elkhashab SO. Cystatin and glomerular filtration rate equations in old renal transplant donors. Egypt J Intern Med [serial online] 2019 [cited 2019 Aug 24];31:185-90. Available from: http://www.esim.eg.net/text.asp?2019/31/2/185/261738




  Introduction Top


Living donor kidney transplantation is the most effective treatment for end-stage renal disease [1], yet the safety of donors is not warranted particularly in older donors [2].

Healthy young donors have the same risk as the general population to develop renal dysfunction [3]. Long-term effect of kidney donation is likely related to different ethnicity, sex, age, and comorbidities of living kidney donors (LKDs) [4].

Some research studies support the idea that living kidney donation does not increase risk of chronic kidney disease (CKD) or mortality [5],[6]; however, postdonation hypertension was reported in white donors when there was more than 50% of nephron mass loss [7]. Moreover, proteinuria and loss of nocturnal blood pressure dip were found in Afro-American donors [8].

Renal assessment after donation is crucial for early detection of renal dysfunction in LKDs to maintain favorable consequence and quality of life particularly in older age group. The use of serum creatinine (SCr)-based or creatinine-based equations such as Modification of Diet in Renal Disease (MDRD) seems to be practical but is not an optimal tool owing to its fallacies through many factors such as age, sex, muscle mass, and diet [9]. Serum cystatin (Scys)-based and cystatin-based equation have been widely studied and were clearly proven to be better models in the detection of acute renal impairment [10] as well as in patients with CKD and renal transplant recipients [11],[12]. Scys is superior to SCr as it is filtered and metabolized by the kidneys but not secreted through the tubules, making it an accurate marker of renal dysfunction [13],[14],[15].

The recently emerging Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equations including CKD EPI Cys and CKD EPI creatinine–cystatin proved to have great accuracy in assessing kidney function, especially in those with glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 [16]. Scys-based and Scys-based formulae were established in many studies as an accurate means for renal function evaluation in LKDs [17],[18].

The aim of our study was to compare the performance of the aforementioned parameters with the formally measured glomerular filtration rate (mGFR) by isotope renal scan and creatinine-based equations including Cockcroft–Gault Formula (C–G), MDRD, and CKD EPI creatinine in older age renal transplant donors.


  Participants and methods Top


Study design and selected population

This cross-sectional (pilot) study included 27 healthy living-related voluntary kidney donors who underwent kidney transplantation from July 2009 to June 2016. All participants were consecutively recruited from the Nephrology Unit of Kasr Al Aini Hospital. Participants who were above 55 years at the time of donation and those of above 1 year after nephrectomy were included in the study.

Patients with cardiovascular disorders, diabetes, and liver diseases and those with thyroid dysfunction were excluded.

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

Methodology

  1. All participants were subjected to full history taking and thorough clinical examination.
  2. Laboratory work was as follows: 5 ml of blood was taken under complete resting condition and pooled into a dry tube. SCr was measured by the kinetic colorimetric method using kinetic photometric equipment (Peckman; Dade Behring Company, Deerfield, Illinois, USA). Quantitative measurement of Scys was done by enzyme-linked immunosorbent assay (ELISA) using specific kits manufactured by Dade Behring Diagnostic (Marburg, Germany) after centrifuging at 3400 rpm.
  3. Estimated glomerular filtration rate (eGFR) was calculated by the following formulae [19],[20],[21],[22]:
    • Cockroft–Gault:

    • MDRD equation:

      CKD EPI creatinine:

      CKD EPI cystatin:

      [22].
  4. Creatinine clearance was determined by measurement of creatinine in a 24-h urine specimen, and SCr in a serum specimen was obtained during the same collection period. The creatinine clearance was then calculated by the following equation [23]:
  5. Radionuclide GFR was estimated by using 99mTc-DTPA (Gate’s method):
    • 3–5 μCi of 99mTc-diethylene triaminepentaacetic acid (DTPA) was injected intravenously, and the GFR (global and differential) was calculated by a closed computer program based on Gate’s method using Phillips equipment (Philips company Amasterdam, Netherlands) [24].


Statistical analysis

Data were statistically described in terms of range, mean±SD, or summary of quantitative data and frequencies used for qualitative data. A P-value less than 0.05 was considered statistically significant. Spearman’s correlation was used to compare quantitative data. All statistical calculations were done using computer programs Microsoft Excel 2013 (Microsoft Corporation, New York, New York, USA) and statistical package for the social science, version 24 (SPSS Inc., Chicago, Illinois, USA) for Microsoft Windows. Accuracy was represented using the terms sensitivity and specificity. Receiver operating characteristic analysis was used to determine the optimum cutoff values.


  Results Top


The study included 27 elderly LKDs [12 (44.4%) males and 15 (55.6%) females]. The mean±SD age was 61±0.14, ranging from 56 to 69 years. The age range at the time of donation was 55–61 years, with mean±SD of 56.9±1.7. The mean duration of donation was 4.6±1.9 years. The clinical and laboratory characteristic of the studied participants are shown in [Table 1].
Table 1 Clinical and laboratory background of the elderly living kidney donors

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By means of DTPA renogram, about seven (25.9%) patients had decreased GFR below 90 ml/min/1.37 m2. The results revealed a negative correlation between mGFR and Scys, whereas mGFR was positively related to CKD EPI Cr–Cys equation ([Table 2]).
Table 2 Correlation of measured glomerular filtration rate by DTPA-Tc99m scintigraphy with cystatin and estimated glomerular filtration rate by other formula

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Regarding the age of participants, it was negatively correlated with eGFR by C–G equation (r=−0.480, P=0.011). The data showed that Scys and all other parameters did not differ by either sex or age at time of donation; however, there was an inverse relation between the duration of donation and MDRD, C–G, and CKD EPI creatinine (r=−0.434, −0.498, and −0.441 and P=0.024, 0.008, and 0.021, respectively). The correlations of cystatin level and other variables are shown in [Table 3].
Table 3 Correlation of cystatin and estimated glomerular filtration rate by other formulae

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As revealed in [Table 4] and [Figure 1], the performance of C–G equation was better with the highest sensitivity (70%) as compared with other formulae on its own. However, cystatin and CKD EPI Cys equation had the highest specificity (70%) at criterion of 1.4 and 84, respectively. Area under the curve was 0.204 and 0.839, and the significance level was 0.002 and 0.009, respectively.
Table 4 Results of receiver operating characteristic curve analyses of cystatin and other parameters and estimated glomerular filtration rate equations in detection of renal dysfunction (related to measured glomerular filtration rate)

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Figure 1 Receiver operating characteristic curve analyses of cystatin, creatinine, and the various glomerular filtration rate formulae.

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From receiver operating characteristic analyses, accuracy of each was yielded for MDRD, C–G, CKD EPI Cr, CKD EPI Cys, and CKD EPI Cr–Cys at 44.6, 66.6, 48.1, 66.7, and 59.2%, respectively.


  Discussion Top


This study verifies the role of cystatin and different equations for estimating GFR in healthy donors, especially those of older age who are more susceptible for renal deterioration after kidney donation.

The survival and residual renal functions in LKDs are affected by filtration capacity [25]. This study revealed that seven (25.9%) patients had decreased GFR (mGFR) less than 90 ml/min/1.37 m2 assessed by renal isotope scan. Regarding Scys, it was 1.28±0.44, and this result is similarly to earlier study, where Scys was 1.39±0.1 [26], but this was higher than reported by Ayub et al. [27] who found the mean level of cystatin was 0.88±0.12 mg/l. These contradictory findings might be related to different age group examined in the former study as the population was younger, and the mean age was 32.19±8.27 years.

Although SCr is the most easily used biomarker in assessing kidney function, it is unfortunate that it fails to detect early renal impairment. Interpretation of SCr values in the clinical sitting of frail elderly patients is of note. eGFR declines with age in linear pattern with C–G equation, whereas in MDRD, there is an exponential relation between age and eGFR [28].

Creatinine-based equations were developed and modulated progressively into CKD EPI Creatinine 2009. Yet, these equations did not improve the clinical tracing of renal affection, and the different studies were controversial and elusive [17],[29],[30]. There is a vast knowledge suggesting that cystatin C could serve as a confirmatory test with better accuracy for kidney disease in patients with muscle wasting or chronic illness. Earlier studies reported that Scys did not offer an advantage to SCr in detecting renal impairment among LKDs [31],[32]. Cystatin-based equations proved superior to those based on creatinine. Besides, CKD EPI Cystatin C formula is less effected by age or race [33], however, the evolved CKD EPI Creatinine–Cystatin C 2012 had similar bias to the creatinine or cystatin C equations but more precise of greater accuracy [34].

Attempting to find a correlation between Scys and other variables, in our study, there was a basically significant inverse correlation between Scys and eGFR by means of CKD EPI cystatin and CKD EPI Cr–Cys. Garcia-Covarrubias et al. [18] had confirmed a potential relation of Scys and eGFR by means of SCr-based and Scys-based equations. This difference may be due the small size sample and the older aged population comparable to this study.

In accordance to what was concluded by previous studies [22],[26], our study revealed that mGFR by DTPA-Tc99m was significantly related only to CKD EPI Cr–Cys equation. This finding is inconsistent with a recent study in which a significant correlation between GFR measured by DTPA-Tc99m scan and both SCr-based and Scys-based equations, with stronger association with CKD EPI Cr followed by MDRD formulae [18].Scys was not related to C–G or MDRD, which is in contrary to Jaisuresh et al. [35] and Ayub et al. [27] who found significant correlations between Scys and CrCl, MDRD, and C–G equations.

Surprisingly, in this study, none of donors’ age at the study, sex, the age at time of donation, or the duration of nephrectomy were related to Scys. These findings are in contrast to what was reported that Scys was influenced by age and sex [27],[36],[37], as elevated Scys was associated with older age [27]. These contradictory results may be related to different ethnicity.

The accuracy and performance of cystatin and cystatin-based equations compared with creatinine-based equation were addressed by many studies; the recorded data were conflicting. Unfortunately, there is no equation showing an absolute accuracy. A systematic review was widely conducted on many studies that considered different cystatin C-based equations and concluded that cystatin C-based equations were superior and most accurate than those based on creatinine [33]. In an another study, CKD EPI Cr equation appeared to be less accurate than MDRD in estimating GFR; moreover, CKD EPI Cys and CKD EPI Cr–Cys exhibited great bias and less accuracy than creatinine-based MDRD equation [38].

As for the performance of cystatin and other eGFR formulae in detecting renal dysfunction in donors comparable to mGFR by renogram, our study revealed that Scys and CKD EPI Cys had similar and better specificity (70%) than others variables, meanwhile C–G equation outperforms, with the best sensitivity (71.4%). The highest accuracy was yielded for CKD EPI Cys followed by C–G equations (66.7 and 66.6%, respectively).

The study emphasizes the importance of renal assessment in LKD especially elderly before and after donation. Upcoming researches should define and establish adequate protocol for following up the LKDs. Some study shortcomings make these results less generalizable. First is the small size of the sample, necessitating further studies on a larger scale. Second, we did not assess the confounding effect of morbidities like diabetes and hypertension on eGFR as we had excluded these candidates.


  Conclusion Top


Age at time of donation has no effect on long-term outcome of LKDs. Scys and Scys-based formulae could outperform SCr-based equations as surrogate tools to monitor the renal function and estimate GFR in healthy older kidney donors. CKD EPI Cys has better specificity, whereas C–G equation has better sensitivity for determination of decline in renal filtration rate, as well the best accuracy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pauly R, Gill JS, Rose C, Asad R, Chery A, Pierratos A et al. Survival among nocturnal haemodialysis patients compared to kidney transplant recipients. Nephrol Dial Transplant 2009; 24:2915–2919.  Back to cited text no. 1
    
2.
Ommen ES, Winston JA, Murphy B. Medical risks in living kidney donors: absence of proof is not proof of absence. Clin J Am Soc Nephrol 2006; 1:885–895.  Back to cited text no. 2
    
3.
Cherikh SW, Young JC, Kramer FB, Taranto ES, Randall HB, Fan PY. Ethnic and gender related differences in the risk of end-stage renal disease after living kidney donation. Am J Transplant 2011; 11:1650–1655.  Back to cited text no. 3
    
4.
Sommerer C, Morath C, Andrassy J, Zeier M. The long-term consequences of living-related or unrelated kidney donation. Nephrol Dial Transplant 2004; 19(Suppl 4):45–47.  Back to cited text no. 4
    
5.
Ibrahim HN, Foley R, Tan L, Rogers T, Bailey R, Guo H et al. Long-term consequences of kidney donation. N Engl J Med 2009; 360:459–469.  Back to cited text no. 5
    
6.
Budisavljevic MN, Nietert PJ, Zhai Y, Dooley MJ, Rajagopalan PR. Long-term effects of kidney donation on renal function and blood pressure in African Americans. Clin J Am Soc Nephrol 2011; 6:1474–1480.  Back to cited text no. 6
    
7.
Fehrman-Ekholm I, Elinder CG, Stenbeck M, Groth CG. Kidney donors live longer. Transplantation 1997; 64: 976–978.  Back to cited text no. 7
    
8.
Nogueira JM, Weir MR, Jacobs S, Haririan A, Breault D, Klassen D et al. A study of renal outcomes in African American living kidney donors. Transplantation 2009; 88:1371–1376.  Back to cited text no. 8
    
9.
Han HH, Choi KH, Yang SC, Han WK. Clinical assessment of follow-up cystatin C-based eGFR in live kidney donors. Korean J Urol 2012; 53:721–725.  Back to cited text no. 9
    
10.
Murty M, Sharma UK, Pandey VB, Kankare SB. Serum cystatin C as a marker of renal function in detection of early acute kidney injury. Indian J Nephrol 2013; 23:180–183.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Krishnamurthy N, Arumugasamy K, Anand U, Anand CV, 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. 11
    
12.
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
    
13.
Westhuyzen J. Cystatin C: a promising marker and predictor of impaired renal function. Ann Clin Lab Sci 2006; 36:387–394.  Back to cited text no. 13
    
14.
Filler G, Bökenkamp A, Hofmann W, Le Bricon T, Martínez-Brú C, Grubb A. Cystatin C as a marker of GFR − history, indications, and future research. Clin Biochem 2005; 38:1–8.  Back to cited text no. 14
    
15.
Ashalatha VL, Bitla AR, Kumar VS, Rajasekhar D, Suchitra MM, Lakshmi AY et al. Biomarker response to contrast administration in diabetic and nondiabetic patients following coronary angiography. Indian J Nephrol 2017; 27:20–27.  Back to cited text no. 15
[PUBMED]  [Full text]  
16.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3:1–150.  Back to cited text no. 16
    
17.
Yang Y, Kim KY, Hwang I, Yim W, Do M, Kim S et al. Cystatin C-based equation for predicting the glomerular filtration rate in kidney transplant recipients. Transplant Proc 2017; 49:1018–1022.  Back to cited text no. 17
    
18.
Garcia-Covarrubias L, Barragan J, Castro I, Hernandez K, Reding A, Hinojosa H et al. Correlation of the glomerular filtration rate measured with the use of DTPA-Tc99m in live kidney donors with equations based on creatinine and cystatin C. Transplant Proc 2018; 50:423–427.  Back to cited text no. 18
    
19.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31–41.  Back to cited text no. 19
    
20.
Levey AS, Stevens LA. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 2010; 55:622–627.  Back to cited text no. 20
    
21.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150:604–612.  Back to cited text no. 21
    
22.
Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367:20–29.  Back to cited text no. 22
    
23.
Fink JC, Blahut SA, Weir MR. Optimal strategies for modeling the 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. 23
    
24.
Gates GF. Glomerular filtration rate: estimation from fractional renal accumulation of 99mTc-DTPA (stannous). Am J Roentgenol 1882 138:565–570.  Back to cited text no. 24
    
25.
Hasan S, Ali A, Jawad F, Ahmed E, Asghar A, Naqi Z et al. living kidney donor follow-up in a dedicated clinic. Transplantation 2005; 79:1247–1251.  Back to cited text no. 25
    
26.
Issa N, Kukla A, Jackson S, Riad M, Foster M, Matas A et al. Comparison of cystatin C and creatinine-based equations for GFR estimation after living kidney donation. Transplantation 2014; 98:871–877.  Back to cited text no. 26
    
27.
Ayub S, Khan S, Ozair U, Zafar MN. Cystatin C levels in healthy kidney donors and its correlation with GFR by creatinine clearance. J Pak Med Assoc 2014; 64:286–290.  Back to cited text no. 27
    
28.
Spruill JW, Wade EW, Cobb HH. Continuing the use of the Cockcroft-Gault equation for drug dosing in patients with impaired renal function. Clin Pharmacol Ther 2009; 86:468–470.  Back to cited text no. 28
    
29.
Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT. Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 2010; 5:1003–1009.  Back to cited text no. 29
    
30.
Nguyen MT, Maynard S, Kimmel PL. Misapplications of commonly used kidney equations: renal physiology in practice. Clin J Am Soc Nephrol 2009; 4:528–534.  Back to cited text no. 30
    
31.
Hari P, Bagga A, Mahajan P, Lakshmy R. Effect of malnutrition on serum creatinine and cystatin C levels. Pediatr Nephrol 2007; 22:1757–1761.  Back to cited text no. 31
    
32.
John GT, Fleming JJ, Talaulikar GS, Selvakumar R, Thomas PP, Jacob CK. Measurement of renal function in kidney donors using serum cystatin C and beta(2)-microglobulin. Ann Clin Biochem 2003; 40:656–658.  Back to cited text no. 32
    
33.
Harman G, White CA, Ramsay T, Kokolo MB, Craig J, Knoll GA. Accuracy of cystatin C-based estimates of glomerular fi ltration rate in kidney transplant recipients: a systematic review. Nephrol Dial Transplant 2013; 28:741–57. 32.  Back to cited text no. 33
    
34.
Santos J, Martins L. Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker. World J Nephrol 2015; 4:345–353.  Back to cited text no. 34
    
35.
Jaisuresh K, Sharma R, Mehrothra S, Kumari N, Singh Badauria D, Gupta A et al. Cystatin C as a marker of glomerular filtration rate in voluntary kidney donors. Exp Clin Transplant 2012; 10:14–17.  Back to cited text no. 35
    
36.
Stevens LA, Schmid CH, Greene T, Liang L, Gerald J, Marshall M et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int 2009; 75:652–660.  Back to cited text no. 36
    
37.
Alwakeel J, Ali Memon N, Chaudhary A, Mitwalli A, Tarif N, Isnani A et al. Normal reference levels of serum cystatin C in Saudi adults. Saudi J Kidney Dis Transplant 2008; 19:361–370.  Back to cited text no. 37
    
38.
Qutb A, Syed G, Tamim HM, Al Jondeby M, Jaradat M, Tamimi W et al. Cystatin C-based formula is superior to MDRD, Cockcroft–Gault and Nankivell formulae in estimating the glomerular filtration rate in renal allografts. Exp Clin Transplant 2009; 7:197–202.  Back to cited text no. 38
    


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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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