Association of CD4 cell counts and viral load with cystatin C level in children with human immunodeficiency virus (HIV) infection

  • Wita Rostania pediatrician
  • Anggraini Alam Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung
  • Dany Hilmanto Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung
Keywords: CD4 cell counts, cystatin C, Glomerular Filtration Rate, HIV, viral load


Background The ease of access to antiretroviral therapy (ART) has improved both survival rate and comorbidities in patients with human immunodeficiency virus (HIV) infection. Impaired kidney function is one of the most common comorbidities of HIV. CD4 and viral load can be used to monitor HIV progression and to determine the effectiveness of ART. The most commonly used estimated-glomerular filtration rate (e-GFR) technique is to use serum creatinine but often causes late detection of kidney dysfunction while serum cystatin increases at the beginning of the GFR decrease. This supports cystatin C serum as an early diagnostic tool to detect kidney function or biomarker early kidney disorders.

Objective To evaluate a possible association between serum cystatin C as a marker of kidney function and HIV progression through CD4 levels and viral load.

Methods This cross-sectional study was conducted through evaluation of secondary data from medical and laboratory records of pediatric patients who had routine visits to the HIV Clinic at Dr. Hasan Sadikin General Hospital, Bandung, West Java, in January-February 2020.

Results Sixty subjects were reviewed in the study. Median cystatin C-based eGFR was 28.1mL/minute/1.73m2. Subjects were categorized by viral load result into <40 and ?40 copies/mL. The median serum cystatin C was significantly higher [3.7 (range 2.61–6.55) mg/L] in the >40 copies/mL viral load group than the <40 copies/mL group [2.4 (range 0.26–13.61) mg/L]. The median absolute CD4 count, CD4 percentage, and cystatin C were 776 (range 7–1644) cells/mm3, 27.5 (range 1.6–57.4) %, and 3 (range 0.26–13.61) mg/L, respectively. There were no significant correlations (r=-0.2; P=0.1) between CD4 and serum cystatin C

 Conclusion Higher viral load associates with higher cystatin C level, while CD4 shows no correlation to cystatin C. However, patients with low CD4 tend to have increased cystatin C level.


Author Biographies

Anggraini Alam, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung

Assistant Professor, Doctorate, Attending, Lecturer; Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung

Dany Hilmanto, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung

Professor, Attending, and Lecturer Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/ Dr Hasan Sadikin General Hospital, Bandung


1. UNAIDS. Global HIV & AIDS statistics, fact sheet. 2019. [cited 2020 Desember 20th].
Available from:
2. Calza L, Vanino E, Magistrelli E, Salvadori C, Cascavilla A, Colangeli V, et al. Prevalence of renal disease within an urban HIV-infected cohort in northern Italy. Clin Exp Nephrol. 2014;18:104–12. DOI:
3. Ekat MH, Courpotin C, Diafouka M, Akolbout M, Mahambou-Nsonde D, Bitsindou PR, et al. Prevalence and factors associated with renal disease among patients with newly diagnoses of HIV in Brazzaville, Republic of Congo. Med Sante Trop. 2013;23:176–80. DOI:
4. Gupta V, Gupta S, Sinha S, Sharma SK, Dinda AK, Agarwal SK, et al. HIV associated renal disease: a pilot study from north India. Indian J Med Res. 2013;137:950–6.
5. Adih WK, Selik RM, Hu X. Trends in diseases reported on US death certificates that mentioned HIV infection, 1996-2006. J Int Assoc Physicians AIDS Care. 2011;10:5–11. DOI:
6. Ross MJ. Advances in the pathogenesis of HIV-associated kidney diseases. Kidney Int. 2014;86:266–74. DOI:
7. Jindal AK, Tiewsoh K, Pilania RK. A review of renal disease in children with HIV infection. Infect Dis (Lond). 2018;50:1-12. DOI:
8. Bhimma R, Purswani MU, Kala U. Kidney disease in children and adolescents with perinatal HIV-1 infection. J Int AIDS Soc. 2013;16:18596. DOI:
9. Kooij KW, Vogt L, Wit FWNM, van der Valk M, van Zoest RA, Goorhuis A, et al. Higher prevalence and faster progression of chronic kidney disease in human immunodeficiency virus-infected middle-aged individuals compared with human immunodeficiency virus uninfected controls. J Infect Dis. 2017;216:622–31. DOI:
10. Trullas J, Mart A, Jofre R, Rivera M, Mart J, Ros S, et al. Outcome and prognostic factors in HIV-1–infected patients on dialysis in the cART era: a GESIDA / SEN cohort study. J Acquir Immune Defic Syndr. 2011;57:276–83. DOI:
11. Coll E, Botey A, Alvarez L, Poch E, Quintó L, Saurina A, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis. 2000;36:29–34. DOI:
12. Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L. Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function. Nephrol Dial Transplant. 2006;21:1855–62. DOI:
13. Narvaez-Sanchez R, Gonzalez L, Salamanca A, Silva M, Rios D, Arevalo S, et al. Cystatin C could be a replacement to serum creatinine for diagnosing and monitoring kidney function in children. Clin Biochem. 2008;41:498–503. DOI:
14. Cho SY, Lee HJ, Suh JT, Cho BS, Suh JS. Cystatin C/creatinine ratio in pediatric kidney disease. Clin Exp Nephrol. 2011;15:976–7. DOI:
15. Bökenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J. Cystatin C - A new marker of glomerular filtration rate in children independent of age and height. Pediatrics. 1998;101:875–81. DOI:
16. Krieser D, Rosenberg AR, Kainer G, Naidoo D. The relationship between serum creatinine, serum cystatin C and glomerular filtration rate in pediatric renal transplant recipients: A pilot study. Pediatr Transplant. 2002;6:392–5. DOI:
17. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function - measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473–83. DOI:
18. 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. DOI:
19. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40:221–6. DOI:
20. Andersen TB, Eskild-Jensen A, Frøkiær J, Brøchner-Mortensen J. Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review. Pediatr Nephrol. 2009;24:929–41. DOI:
21. Reinhard M, Erlandsen EJ, Randers E. Biological variation of cystatin C and creatinine. Scand J Clin Lab Invest. 2009;69:831–6. DOI:
22. Shoko C, Chikobvu D. A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy. BMC Infectious Diseases. 2019;19. DOI:
23. Salazar-Vizcaya L, Keiser O, Technau K, Davies MA, Haas AD, Blaser N, et al. Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: cohort-based modelling study. AIDS 2014;28:2451–60. DOI:
24. World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Geneva: WHO;2007. p. 52. ISBN 9789241595629.
25. Rizal RA, Rahayuningsih SE, Alam A. Korelasi nilai CD4 dengan left ventricular mass index pada anak dengan infeksi human immunodeficiency virus. Sari Pediatr. 2020;22:37. DOI:
26. Mofenson , Williams P, Brady M, van Dyke R, Dankner W, Oleske J (2008) Trends in mortality in HIV-infected children in the United States—1994–2006. AIDS 2008 – XVII International AIDS conference: Abstract no. MOPE0230.
27. Leão FVF, de Menezes Succi RC, Machado DM, Gouvêa A de FTB, do Carmo FB, Beltrão SV, et al. Renal abnormalities in a cohort of HIV-infected children and adolescents. Pediatr Nephrol. 2016;31:773–8. DOI:
28. Fredrick F, Francis JM, Ruggajo PJ, Maro EE. Renal abnormalities among HIV infected children at Muhimbili National Hospital (MNH) - Dar es Salaam, Tanzania. BMC Nephrol. 2016;17:30. DOI:
29. Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, Gordin FM, et al. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS. 2010;24:1877–86. DOI:
30. Esezobor CI, Iroha E, Oladipo O, Onifade E, Soriyan OO, Akinsulie AO, et al. Kidney function of HIV-infected children in Lagos, Nigeria: using Filler’s serum cystatin C-based formula. J Int AIDS Soc. 2010;13:17. DOI:
31. Abiodun MT, Iduoriyekemwen NJ, Abiodun PO. Cystatin C-based evaluation of kidney function of HIV-infected children in Benin City, Southern Nigeria. Int J Nephrol. 2012;2012:861296. DOI:
32. Jones CY, Jones CA, Wilson IB, Knox TA, Levey AS, Spiegelman D, et al. Cystatin C and creatinine in an HIV cohort: the nutrition for healthy living study. Am J Kidney Dis. 2008;51:914–24. DOI:
33. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011;22:2129–37. DOI:
34. Zhang J, Fedick A, Wasserman S, Zhao G, Edelmann L, Bottinger EP, et al. Analytical validation of a personalized medicine APOL1 genotyping assay for nondiabetic chronic kidney disease risk assessment. J Mol Diagn. 2016;18:260–6. DOI:
35. Kasembeli AN, Duarte R, Ramsay M, Mosiane P, Dickens C, Dix-Peek T, et al. APOL1 risk variants are strongly associated with HIV-associated nephropathy in black South Africans. J Am Soc Nephrol. 2015;26:2882–90. DOI:
36. Merati TP, Ryan CE, Spelmen T, Wirawan DN, Bakta IM, Otto B, et al. CRF01-AE dominates the HIV-1 epidemic in Indonesia. Sex Health. 2012;9:414–21. DOI:
37. Khairunisa SQ, Masyeni S, Witaningrum AM, Muhammad Qushai Yunifiar M, Indriati DW, Kotaki T, et al. Genotypic characterization of human immunodeficiency virus type 1 isolated in Bali, Indonesia in 2016. HIV AIDS Rev. 2018;17:81–90. DOI:
38. Roselinda, Jekti RP. Genotype and transmission human immunodeficiency virus-1 in seven provinces in Indonesia. Health Sci Indones. 2012;3:27-30.
39. Chu M, Zhang W, Zhang X, Jiang W, Huan X, Meng X, et al. HIV-1 CRF01-AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China. Sci Rep. 2017;7:1570. DOI:
40. Dondo V, Mujuru HA, Nathoo KJ, Chirehwa M, Mufandaedza Z. Renal abnormalities among HIV-infected, antiretroviral naive children, Harare, Zimbabwe: a cross-sectional study. BMC Pediatr. 2013;13:75. DOI:
41. Shah I, Gupta S, Shah DM, Dhabe H, Lala M. Renal manifestations of HIV infected highly active antiretroviral therapy naive children in India. World J Pediatr. 2012;8:252–5. DOI:
42. Winston JA, Bruggeman LA, Ross MD, Jacobson J, Ross L, D’Agati VD, et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med. 2001;344:1979–84. DOI:
43. Choi A, Scherzer R, Bacchetti P, Tien PC, Saag MS, Gibert CL, et al. Cystatin C, albuminuria, and 5-year all-cause mortality in HIV-infected persons. Am J Kidney Dis. 2010;56:872–82. DOI:
44. Finney H, Newman DJ, Thakkar H, Fell JM, Price CP. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child. 2000;82:71–5. DOI:
45. 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. 2013;3(suppl.3):1–150.
How to Cite
Rostania W, Alam A, Hilmanto D. Association of CD4 cell counts and viral load with cystatin C level in children with human immunodeficiency virus (HIV) infection. PI [Internet]. 11Apr.2023 [cited 29Feb.2024];63(2):88-5. Available from:
Pediatric Nephrology
Received 2021-12-23
Accepted 2023-04-11
Published 2023-04-11