Mohamed I. A, Elzein A. O. M. Determination of Cystatin C and Creatinine S in Sudanese Patients with Chronic Kidney Disease. Biomed Pharmacol J 2025;18(3).

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Manuscript received on :27-08-2024
Manuscript accepted on :02-06-2025
Published online on: 03-09-2025

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Plagiarism Check: Yes
Reviewed by: Dr. Priya Gayathri
Second Review by: Dr. Thirunahari Sravanthy
Final Approval by: Dr. Prabhishek Singh

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Ibtihal Ahmed Mohamed^1*and Amna Osman M.Elzein²

Faculty of medical laboratory (clinical chemistry), Alzaeim Alazhari University, Khartoum-Sudan.

Corresponding Author E-mail:ebtihala885@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/3268

Abstract

Cystatin c is single non glycated polypeptide chains which is recently   considered as markers in the renal dialysis. Our study aimed to estimate cystatin c and creatinine reduction in Sudanese patients with chronic kidney disease on dialysis. A cohort of forty patients was selected for this study creatinine and cystatin were estimated pre and post dialysis, three ml of blood were drowned by standard methods twice from each patient pre and post dialysis. 20 out of 40 patients with CKD were males while 20 were females, the most patients were more than 50years old 45.5% , 42.5% between 25-50years while 12.5% were less than 25 years. The mean and std of creatinine and cystatin c were reduced significantly in post haemodialysis than pre haemodialysis, the haemodialysis, the reduction ratio were 14.93%(pvalue 0.000) , and 58.50% (p.value0.000) for cystatin C and creatinine respectively.  The pre and post haemodialysis cystatin c were not correlated with haemodialysis duration in years while pre haemodialysis creatinine level were significantly correlated with duration p.value 0.009. In conclusion cystatin C is another sensitive marker beside urea and creatinine reduction ratio further studies were required in different dialysis machine.

Keywords

CKD; Creatinine; Cystatin C; Dialysis; GFR

Introduction  

The chronic kidney disease (CKD), and end-stage renal diseases (ESRD) are main  health concerns affects all nation worldwide with gradual  raising rates  and prevalence.¹

CKD predominately having no symptoms, and thus, a laboratory estimation  of renal function is needed. the most parameter used to assess CKD were , serum creatinine as crucial  indicators of glomerular filtration (GFR).²

Serum creatinine level have low sensitivity to early predict CKD and unable to predict half of patients in stage three CKD (GFR of 30-59 mL/min/1.73m2),³  in which serum creatinine level  may not change until approximately 50% of the kidney function has been changes .⁴In addition, creatinine production is also affected  by factors like  age, gender, muscle mass, physical activity and dietary intake.⁵ Moreover, many factors encountered with measurements of creatinine and its use as a GFR estimate, cystatin C (CysC) has been proposed as an alternative marker of renal function. ⁵

Cystatin c recently has emerged as biomarkers for assessing the renal function, especially in the context of dialysis. Moreover, cystatin C was demonstrated to estimate GFR with better adequacy than creatinine in many studies ^6-7

Beside traditional markers such as serum creatinine, cystatin C is a small, non-glycosylated protein produced at a constant rate by all nucleated cells and is freely filtered by the glomerulus. In addition , serum levels of cystatin C is  primarily determined by glomerular filtration rate (GFR), making it a reliable indicator of kidney function. ⁸

In dialysis, accurate assessment of renal function is crucial for monitoring disease progression, optimizing treatment strategies, and predicting outcomes. Conventional dialysis assessment parameters such as (Serum creatinine), may be influenced by factors such as muscle mass, diet, and medications, leading to variability in the test interpretation. Cystatin C, on the other hand, is less influenced by extra-renal factors and has been shown to provide a more adequate and accurate  estimation of GFR in patients with end-stage renal disease (ESRD).⁹

Many studies have been demonstrated the utility of cystatin C as a dialysis biomarker, with elevated levels correlating with reduced GFR and increased mortality risk in dialysis patients.^10-11 Furthermore, cystatin C has shown promise in identifying early renal dysfunction and predicting progression to ESRD, allowing for timely intervention and improved patient outcomes.¹²

In addition to its role in assessing renal function, cystatin C is considered as  potential marker of cardiovascular risk in dialysis patients. High level of cystatin C have been associated with cardiovascular diseases , including myocardial infarction, stroke, and heart failure, independent of traditional risk factors.¹³All these make  cystatin C as a biomarker, encompassing both renal and cardiovascular health in the dialysis population.

Despite this roles, several challenges remain in the clinical implementation of cystatin C as a dialysis biomarker. Standardization of assay methods, establishment of reference ranges, and consideration of patient characteristics are essential for accurate interpretation of cystatin C levels.¹⁴

Here in this study we estimated the cystatin level beside conventional dialysis estimator(creatinine level) pre and post haemodialysis to detect reduction ratio.

Materials and Methods

A cohort study was done in White Nile State,Al­­_Dieum city Al­­_Dieum Dialysis Center, from 28May to 4June 2017, forty patient on dialysis was selected for this study to determine the level of cystatin C and creatinine after dialysis. Total 40 heamodialysis  Patients, age ranged from (15-70) years were selected for this study while patients with severe illness were excluded , Questioner was used to obtain initial information about the Heamodialysis  Patients, The study was approved from ALzaeim Alazhari University faculty of medical laboratory sciences with code (1—0017) , blood was collected after by standard methods after patient informed about the aim of the study and consented to contribute to this study. 3 ml heparinized blood samples   heparin  blood samples were collected from the patients  and centrifuged and frozen in -20 and cystatin C was estimated within one week duration of storage in I Chroma, serum creatinine and urea was estimated by spectrophotometer , all test was performed under quality control protocol , the reduction was used with published formula reduction ratio =100*(1-( post test result/ pre test result) we used this formula for all creatinine and urea and cystatin C

Ethical approval and consents

The study approved from Alzaeim Alazhari  University faculty of medical sciences with ethical committee code (1-0017)all patient signed informed consents   after informed about the aim of the study and consented to contribute to this study

Data analysis

The data was entered and analyzed  social package of social sciences version 20 SPSS  p.value <0.050 valued as significants

Results

Of 40 study participants 20 were males and 20 were females , the most patients were more than 50years old 45.5% , 42.5% between 25-50years while 12.5% were less than 25 years .The mean and STD of creatinine and cystatin c were reduced significantly in post haemodialysis than pre haemodialysis p.value 0.000. The haemodialysis  reduction ratio were 14.93%(pvalue 0.000) , and 58.50% (p.value0.000) for cystatin C and creatinine respectively table(1).  The higher reduction rate were achieved in females creatinine 60.29972% table (1). The pre and post haemodialysis cystatin c were not correlated with haemodialysis duration in years while pre haemodialysis creatinine  level were significantly correlated with duration p.value 0.009 table(2) and figure (1).

Table 1: Show statistics and mean differences of Cystatin C and Creatinine in pre and post dialysis with reduction ratio

Table 2: Correlation of duration in Cystatin C and creatinine pre/post heamodialysis:

Figure 1: Showed the association between pre and post level of the tests A) Showed cystatin level pre-dialysis and duration in years B) Post dialysis Cystatin C and duration in yearsClick here to view Figure

Discussion

In this study the  reduction ratios of cystatin C and creatinine were  measured from pre-dialysis to post-dialysis levels, which provide valuable insights into the efficiency of hemodialysis in removing these waste products from the bloodstream. Fist of all our study confirmed higher level of cystatin level in patient with CKD, as urea and creatinine impaired in CKD consequently the cystatin C was also impaired. Our study observed a significant decrease in cystatin C reduction ratio post-dialysis compared to pre-dialysis levels, whereas creatinine reduction ratio showed a substantial reduction both pre- and post-dialysis which is consistent with meta analysis  that found cystatin c is reduced after hemodialysis.¹⁵ Moreover lower reduction of cystatin C than creatinine have been proposed in many studies. ^6-16 The observed decrease in cystatin C reduction ratio post-dialysis suggests a less efficient removal of this biomarker during the hemodialysis session. Cystatin C, being a low-molecular-weight protein, is freely filtered by the glomerulus and predominantly cleared through renal excretion. However, hemodialysis may not effectively remove cystatin C due to its larger size and protein-bound nature, resulting in a lower reduction ratio compared to creatinine.¹⁰ This discrepancy highlights the limitations of cystatin C as a dialysis biomarker and underscores the need for alternative markers of renal function in the dialysis population.

In contrast, creatinine reduction ratio exhibited a significant reduction both pre- and post-dialysis, indicating effective removal of this small molecule during hemodialysis. Creatinine, a byproduct of muscle metabolism, is readily filtered by the glomerulus and efficiently removed by hemodialysis, making it a standard marker for assessing dialysis adequacy.¹⁷ The observed decrease in creatinine reduction ratio post-dialysis reflects the successful clearance of creatinine from the bloodstream during the dialysis session.

Interestingly, our findings are consistent with those of other studies that have reported a reduction in cystatin C levels post-hemodialysis compared to pre-hemodialysis levels. For example, Huang et.al ¹⁸  observed a significant decrease in cystatin C levels following hemodialysis sessions in a cohort of nephrotic  patients. Similarly, another study  reported a decrease in cystatin C levels post-hemodialysis in patients on dialysis with high flux haemodialysis.¹⁹ The differences between cystatin C reduction ratio and traditional markers such as  creatinine which is estimated here  highlights the need for alternative markers of renal function in hemodialysis patients. While urea and creatinine are small molecules that are readily cleared by dialysis, cystatin C may exhibit different clearance kinetics and removal efficiency due to its unique properties.¹¹ Physicians  should interpret cystatin C reduction ratio in conjunction with other markers and clinical parameters to assess dialysis adequacy and monitor renal function in hemodialysis patients until adjust their reference range and other factors affect cystatin reduction ratio.

The discrepancy between cystatin C and creatinine reduction ratios underscores the complex dynamics of solute removal during hemodialysis. While creatinine serves as a reliable marker of dialysis adequacy, cystatin C may not accurately reflect changes in renal function or dialysis clearance due to its unique properties and clearance mechanisms.

Conclusion

In conclusion, our findings highlight the differences in reduction ratios of cystatin C and creatinine pre- and post-dialysis, reflecting variations in their clearance kinetics and removal efficiency during hemodialysis. More  research is needed for assessing dialysis adequacy and monitoring renal function in dialysis patients.

Acknowledgement

We would like to thanks all patients participate in this study head Departments clinical chemistry university of Alzaeim Alazhri University.

Funding Sources

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

The author(s) do not have any conflict of interest.

Data Availability Statement

This statement does not apply to this article.

Ethics Statement

This research did not involve human participants, animal subjects, or any material that requires ethical approval.

Informed Consent Statement

This study did not involve human participants, and therefore, informed consent was not required.

Clinical Trial Registration

This research does not involve any clinical trials.

Permission to reproduce material from other sources

Not Applicable 

Author contributions

• Ibtihal Ahmed- Conceptualization, data collection, laboratory procedures, data analysis, write original draft, and approved final draft.
• Amna Osman- Conceptualization, supervision, reviewing , editing of the final draft, and approved final draft.

References

1. Hooi LS, Ong LM, Ahmad G, et al. A population-based study measuring the prevalence of chronic kidney disease among adults in West Malaysia. Kidney Int. 2013;84(5). doi:10.1038/ki.2013.220
   CrossRef
2. McCredie M. Geographic, ethnic, age-related and temporal variation in the incidence of end-stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002. Nephrology Dialysis Transplantation. 2006;21(8). doi:10.1093/ndt/gfl145
   CrossRef
3. Bostom AG, Kronenberg F, Ritz E. Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. Journal of the American Society of Nephrology. 2002;13(8). doi:10.1097/01.ASN.0000022011.35035.F3
   CrossRef
4. Bennett MR, Devarajan P. Characteristics of an Ideal Biomarker of Kidney Diseases. In: Biomarkers of Kidney Disease. ; 2017. doi:10.1016/B978-0-12-803014-1.00001-7
   CrossRef
5. Hsu CY, Chertow GM, Curhan GC. Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency. Kidney Int. 2002;61(5). doi:10.1046/j.1523-1755.2002.00299.x
   CrossRef
6. 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. In: Clinical Biochemistry. Vol 38. ; 2005. doi:10.1016/j.clinbiochem.2004.09.025
   CrossRef
7. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. American Journal of Kidney Diseases. 2002;40(2). doi:10.1053/ajkd.2002.34487
   CrossRef
8. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. American Journal of Kidney Diseases. 2002;40(2). doi:10.1053/ajkd.2002.34487
   CrossRef
9. Grubb AO. Cystatin C-Properties and use as diagnostic marker. Adv Clin Chem. 2001;35. doi:10.1016/s0065-2423(01)35015-1
   CrossRef
10. Shlipak MG, Sarnak MJ, Katz R, et al. Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons. New England Journal of Medicine. 2005;352(20). doi:10.1056/nejmoa043161
    CrossRef
11. Stevens LA, Schmid CH, Greene T, et al. Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2. American Journal of Kidney Diseases. 2010;56(3). doi:10.1053/j.ajkd.2010.03.026
    CrossRef
12. Taglieri N, Koenig W, Kaski JC. Cystatin C and cardiovascular risk. Clin Chem. 2009;55(11). doi:10.1373/clinchem.2009.128397
    CrossRef
13. Peralta CA, Shlipak MG, Judd S, et al. Detection of chronic kidney disease with creatinine, cystatin c, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA. 2011;305(15). doi:10.1001/jama.2011.468
    CrossRef
14. Laterza OF, Price CP, Scott MG. Cystatin C: An improved estimator of glomerular filtration rate? Clin Chem. 2002;48(5). doi:10.1093/clinchem/48.5.699
    CrossRef
15. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. American Journal of Kidney Diseases. 2002;40(2). doi:10.1053/ajkd.2002.34487
    CrossRef
16. Gottlieb ER, Estiverne C, Tolan N V., Melanson SEF, Mendu ML. Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study. Kidney Med. 2023;5(3). doi:10.1016/j.xkme.2023.100600
    CrossRef
17. Gotch FA. The current place of urea kinetic modelling with respect to different dialysis modalities. Nephrology Dialysis Transplantation. 1998;13(SUPPL. 6). doi:10.1093/ndt/13.suppl_6.10
    CrossRef
18. Huang SHS, Filler G, Yasin A, Lindsay RM. Cystatin C reduction ratio depends on normalized blood liters processed and fluid removal during hemodialysis. Clinical Journal of the American Society of Nephrology. 2011;6(2). doi:10.2215/CJN.05290610
    CrossRef
19. Maheshwari KU, Santhi S, Malar R. Cystatin C: An alternative dialysis adequacy marker in high flux hemodialysis. Indian J Nephrol. 2015;25(3). doi:10.4103/0971-4065.139489
    CrossRef