Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of urinary haptoglobin level as a biomarker of diabetic nephropathy in children with type 1 diabetes

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Type 1 diabetes mellitus (T1DM) is a common endocrine disease in children. Early recognition of complications of T1DM is important for preventing long-term morbidity and mortality. We aimed to investigate whether urinary haptoglobin level is a biomarker of diabetic nephropathy in children with T1DM.

Methods

Ninety T1DM patients, aged between 2–18 years, and 60 healthy age-matched children were included in the study. Glycosylated hemoglobin (HbA1c), spot urine creatinine, microalbumin, protein and haptoglobin levels of all cases were measured and compared. Correlations between HbA1c level, duration of diabetes, spot urine microalbumin/creatinine (uACR), protein/creatinine (uPCR), and haptoglobin/creatinine (uHCR) ratios in the T1DM group were evaluated.

Results

T1DM and control groups were homogeneous in terms of age, sex, and anthropometric measurements. uACR was higher in the T1DM group than in the control group (14 mg/g vs. 6 mg/g) while uHCR was not elevated in T1DM patients. Nevertheless, uHCR was higher in the microalbuminuria group when compared to the normoalbuminuria group. In the T1DM group, moderate positive correlations between uPCR with uACR and uHCR, and weak correlation between uACR and uHCR were found (r = 0.60, p < 0.001; r = 0.55, p < 0.001; r = 0.24, p = 0.03, respectively). No significant relationship was found between diabetes duration, HbA1c levels and uACR, uPCR, and uHCR.

Conclusions

Although uHCR in the T1DM group was similar to the control group, uHCR was higher in the microalbuminuria group than in the normoalbuminuria group. These results show that the uHg level could be a biomarker of diabetic nephropathy, but not earlier than albuminuria in the disease course.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

The data of this study are available from the corresponding author, Diğdem Bezen, upon reasonable request.

References

  1. Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX et al (2018) ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 19:7–19

    Article  PubMed  PubMed Central  Google Scholar 

  2. Perrin N, Torbjörnsdotter T, Jaremko GA, Berg UB (2010) Risk markers of future microalbuminuria and hypertension based on clinical and morphological parameters in young type 1 diabetes patients. Pediatr Diabetes 11:305–311

    Article  PubMed  Google Scholar 

  3. Umanath K, Lewis JB (2018) Update on Diabetic Nephropathy: Core Curriculum 2018. Am J Kidney Dis 71:884–895

    Article  PubMed  Google Scholar 

  4. Gluhovschi C, Gluhovschi G, Petrica L, Timar R, Velciov S, Ionita I et al (2016) Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy. J Diabetes Res 2016:4626125

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brosius FC, Pennathur S (2013) How to Find Prognostic Biomarker for Progressive Diabetic Nephropathy. Kidney Int 83:996–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fu WJ, Xiong SL, Fang YG, Wen S, Chen M, Deng RT et al (2012) Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross- sectional study. Endocrine 41:82–88

    Article  CAS  PubMed  Google Scholar 

  7. Mohammed IY, Busari AO, Ahmad MB (2019) Assessing the Clinical Utility of Haptoglobin to Creatinine Ratio as a Test for Detecting Nephropathy among Type 2 Diabetic Patients. J B Med Res Clin Pract 2:180–184

    Article  Google Scholar 

  8. Wang Y, Zhou Q, Zhang L, Dai Y, Huang Z, Zhang H et al (2019) Urine Haptoglobin/Creatinine Ratio Correlates with Tubular Injury Biomarkers and Severity of Albuminuria in Type 2 Diabetes Patients. Horm Metab Res 51:595–601

    Article  CAS  PubMed  Google Scholar 

  9. MacKellar M, Vigerust DJ (2016) Role of Haptoglobin in Health and Disease: A Focus on Diabetes. Clin Diabetes 34:148–157

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hafez HM, El-Mougy FA, Makar SH, Abd El Shaheed SS (2015) Detection of an Earlier Tubulopathy in Diabetic Nephropathy Among Children with Normoalbuminuria. Iran J Kidney Dis 9:126–131

    PubMed  Google Scholar 

  11. Currie G, McKay G, Delles C (2014) Biomarkers in diabetic nephropathy: Present and future. World J Diabetes 5:763–776

    Article  PubMed  PubMed Central  Google Scholar 

  12. Demir K, Konakçı E, Özkaya G, Kasap Demir B, Özen S, Aydın M et al (2020) New Features for Child Metrics: Further Growth References and Blood Pressure Calculations. J Clin Res Pediatr Endocrinol 12:125–129

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    Article  CAS  PubMed  Google Scholar 

  14. KDOQI (2007) KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis 49:12–154

    Article  Google Scholar 

  15. Ariceta G (2011) Clinical practice: proteinuria. Eur J Pediatr 170:15–20

    Article  CAS  PubMed  Google Scholar 

  16. Leung AKC, Wong AHC (2010) Proteinuria in children. Am Fam Physician 82:645–651

    PubMed  Google Scholar 

  17. Mukaka MM (2012) Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Med J 24:69–71

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C (2017) Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 33:e2841

    Article  Google Scholar 

  19. Omar MA, Rezk MM, El-Kafoury KMS (2015) Microalbuminuria and glycated hemoglobin in children with type 1 diabetes mellitus. Alexandria J Med 51:83–88

    Article  Google Scholar 

  20. Daniels M, DuBose SN, Maahs DM, Beck RW, Fox LA, Gubitosi-Klug R et al (2013) Factors associated with microalbuminuria in 7,549 children and adolescents with type 1 diabetes in the T1D Exchange Clinic Registry. Diabetes Care 36:2639–2645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Er E, Ata A, Evin F, Altınok YA, Demir G, Özen S et al (2020) Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 33:1533–1537

    Article  CAS  PubMed  Google Scholar 

  22. Nazim J, Fendler W, Starzyk J (2014) Metabolic control and its variability are major risk factors for microalbuminuria in children with type 1 diabetes. Endokrynol Pol 65:83–89

    Article  PubMed  Google Scholar 

  23. Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R, Dolan L, Imperatore G et al (2017) Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence with Complications During Teenage Years and Young Adulthood. JAMA 317:825–835

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dağdeviren ÇA, Saygılı SK, Canpolat N, Konukoğlu D, Turan H, Çalışkan S et al (2021) Elevated urinary VEGF-A, Transferrin, and Angiotensinogen Levels in Normoalbuminuric Children and Adolescents with Type 1 Diabetes: Can They Be Early Markers of Diabetic Kidney Disease? Horm Res Paediatr 94:426–432

    Article  Google Scholar 

  25. Metwalley KA, Farghaly HS, Gabri MF, Abdel-Aziz SM, Ismail AM, Raafat DM et al (2021) Midkine: Utility as a Predictor of Early Diabetic Nephropathy in Children with Type 1 Diabetes Mellitus. J Clin Res Pediatr Endocrinol 13:293–299

    Article  PubMed  PubMed Central  Google Scholar 

  26. Costacou T, Ferrell RE, Ellis D, Orchard TJ (2009) Haptoglobin genotype and renal function decline in type 1 diabetes. Diabetes 58:2904–2909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Costacou T, Evans RW, Orchard TJ (2015) Does the concentration of oxidative and inflammatory biomarkers differ by haptoglobin genotype in type 1 diabetes? Antioxid Redox Signal 23:1439–1444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Guh JY (2010) Proteinuria versus albuminuria in chronic kidney disease. Nephrology 15:53–56

    Article  CAS  PubMed  Google Scholar 

  29. Cade WT (2008) Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 88:1322–1335

    Article  PubMed  PubMed Central  Google Scholar 

  30. Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G (2006) Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway. Pediatr Diabetes 7:239–246

    Article  PubMed  Google Scholar 

  31. Basiratnia M, Abadi SF, Amirhakimi GH (2012) Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria. Saudi J Kidney Dis Transplant 23:311–315

  32. Lind M, Pivodic A, Svensson AM, Ólafsdóttir AF, Wedel H, Ludvigsson J (2019) HbA1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study. BMJ 366:l4894

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The authors recieved no funding for the study.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Pediatric Endocrinology, University of Health Sciences, Prof. Dr. Cemil Tascioglu City Hospital, Darulaceze Street No. 27, Sisli, 34360, Istanbul, Turkey

    Diğdem Bezen

  2. Department of Medical Biochemistry, University of Health Sciences, Prof. Dr. Cemil Tascioglu City Hospital, Darulaceze Street No. 27, Sisli, Istanbul, Turkey

    Eren Vurgun

  3. Department of Pediatrics, Pediatric Nephrology, University of Health Sciences, Prof. Dr. Cemil Tascioglu City Hospital, Darulaceze Street No. 27, Sisli, Istanbul, Turkey

    Hasan Dursun

Authors
  1. Diğdem Bezen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eren Vurgun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hasan Dursun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.B., H.D. and E.V. designed the study. D.B., H.D., and E.V. collected and analyzed the data. D.B. wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Diğdem Bezen.

Ethics declarations

Disclosure

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Graphical abstract (PPTX 63 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bezen, D., Vurgun, E. & Dursun, H. Evaluation of urinary haptoglobin level as a biomarker of diabetic nephropathy in children with type 1 diabetes. Pediatr Nephrol 38, 3693–3698 (2023). https://doi.org/10.1007/s00467-023-06012-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-023-06012-x

Keywords

Search

Navigation